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Author:
Diane E Pappas, MD, JD
Section Editor:
Morven S Edwards, MD
Deputy Editor:
Mary M Torchia, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Sep 25, 2015.
INTRODUCTION The common cold is an acute, self-limiting viral infection of the upper
respiratory tract, involving, to variable degrees, sneezing, nasal congestion and discharge
(rhinorrhea), sore throat, cough, low grade fever, headache, and malaise. It can be caused
by members of several families of viruses; the most common are the more than 100
serotypes of rhinoviruses.
The common cold is the most frequent human illness. An estimated 25 million individuals
seek medical care for uncomplicated upper respiratory tract infections (URI) annually in
the United States [1,2]. Approximately 30 percent of these visits result in a prescription for
antibiotics. Inaccurate perceptions that colds are caused by bacteria and that antibiotics
improve outcome fuel the number of visits and requests for antibiotics [3]. Infants and
children are affected more often and experience more prolonged symptoms than adults.
The common cold accounts for approximately 22 million missed days of school and 20
million absences from work, including parents time away from work while caring for ill
children [2,4].
The epidemiology, clinical features, complications, and diagnosis of the common cold in
children will be discussed here. The treatment and prevention of the common cold in
children and the common cold in adults are discussed separately. (See "The common cold
in children: Management and prevention" and "The common cold in adults: Diagnosis and
clinical features" and "The common cold in adults: Treatment and prevention".)
VIROLOGY The symptoms of the common cold can be caused by a variety of viruses.
Rhinoviruses, which include more than 100 serotypes, cause up to 50 percent of colds in
children and adults [2]. Other common causes of colds in preschool children include
respiratory syncytial virus (RSV), influenza viruses, parainfluenza viruses, and
adenoviruses (table 1). (See "Epidemiology and clinical manifestations of adenovirus
infection" and "Epidemiology, clinical manifestations, and pathogenesis of rhinovirus
infections" and "Seasonal influenza in children: Clinical features and diagnosis", section on
'Clinical features' and "Parainfluenza viruses in children", section on 'Clinical
presentation' and "Respiratory syncytial virus infection: Clinical features and diagnosis",
section on 'Clinical manifestations'.)
Many of the viruses that cause colds also cause other characteristic clinical syndromes in
children [7]:
RSV Bronchiolitis in children younger than the age of two years (see "Bronchiolitis
in infants and children: Clinical features and diagnosis", section on 'Clinical
features' and "Respiratory syncytial virus infection: Clinical features and diagnosis",
section on 'Clinical manifestations')
Influenza viruses Influenza, pneumonia, and croup (see "Seasonal influenza in
children: Clinical features and diagnosis", section on 'Clinical features')
Parainfluenza viruses Croup (see "Croup: Clinical features, evaluation, and
diagnosis", section on 'Clinical presentation' and "Parainfluenza viruses in children",
section on 'Clinical presentation')
Coxsackievirus A (an enterovirus) Herpangina (fever and ulcerated papules on the
posterior oropharynx) (see "Clinical manifestations and diagnosis of enterovirus and
parechovirus infections", section on 'Herpangina' and "Hand, foot, and mouth disease
and herpangina: An overview", section on 'Herpangina')
Other nonpolio enteroviruses Aseptic meningitis (see "Viral meningitis: Clinical
features and diagnosis in children", section on 'Clinical features')
Adenoviruses Pharyngoconjunctival fever (palpebral conjunctivitis, watery eye
discharge, and pharyngeal erythema) (see "Epidemiology and clinical manifestations
of adenovirus infection")
Human metapneumovirus Pneumonia and bronchiolitis [5,6] (see "Human
metapneumovirus infections", section on 'Children')
EPIDEMIOLOGY
Seasonal patterns The common cold may occur at any time of year, but there is
typically a high prevalence during the fall and winter months as the different viruses move
through the community in a predictable manner. In the northern hemisphere, this yearly
epidemic begins with an increase in the number of rhinovirus infections in September [9],
followed by parainfluenza viruses in October and November. The winter months are
characterized by an increase in respiratory syncytial virus (RSV), influenza viruses, and
coronaviruses [10]. Adenovirus infections are continuously present at a low rate throughout
the common cold season. The epidemic finally ends with a small wave of rhinovirus
infections in March and April [11]. Enteroviruses most often cause illness in the summer,
but can be detected throughout the year.
Transmission Viruses that cause colds are spread by three mechanisms [7]:
The most successful means of viral spread for the majority of upper respiratory infections
(URI), including rhinoviruses, is transmission of infectious secretions from contaminated
fingers and hands to the mucous membranes of the nose or eyes of a susceptible recipient
[12]. The risk of person-to-person transfer is dependent upon the amount of time people
spend together, the proximity of their contact with one another, and the amount of virus
shed by the infected patient. In experimental studies, rhinovirus was efficiently transferred
from hand-to-hand after minimal contact (10 seconds) and subsequent contact with nasal
or conjunctival mucosa resulted in infection [13]. Particle aerosols were an inefficient
method of rhinovirus transmission [13,14]. However, both influenza virus and coronavirus
can be transmitted via aerosols. (See "Seasonal influenza in children: Clinical features and
diagnosis", section on 'Transmission' and "Coronaviruses", section on 'Epidemiology'.)
Substantial titers of rhinovirus are present in nasal secretions of infected individuals. Low
titers of rhinovirus are present in saliva in approximately one-half of infected individuals.
Viral contamination of the hands of infected individuals is common. Rhinoviruses may
remain viable on human skin for as long as two hours [15]. Rhinoviruses also can survive
for up to one day on inanimate surfaces although porous materials such as tissues and
cotton handkerchiefs do not appear to support virus survival [15-18].
Surface contamination of pediatric office toys with respiratory viral RNA does not appear to
be an important method of transfer. In an observational study, approximately 20 percent of
the toys in a pediatric office waiting room were contaminated with picornavirus RNA
(rhinovirus or enterovirus). Cleaning with a disposable germicidal wipe (containing
quaternary ammonium with alcohol) was only modestly effective in removing the viral RNA,
but transfer from the toys to the fingers was inefficient [19].
Period of infectivity Viral shedding peaks on the third day after inoculation; this
coincides with a peak in symptoms [20,21]. In experimental studies, viral titers in nasal
washings returned to near baseline values by five days after inoculation [20]. Low levels of
viral shedding may persist for up to two weeks.
Incubation period The incubation period (time between contact with infectious material
until the onset of symptoms) for most common cold viruses is 24 to 72 hours.
PATHOPHYSIOLOGY Symptoms of the common cold are largely due to the innate
immune response to infection, rather than to direct viral damage to the respiratory tract
[22]. After deposition on nasal or conjunctival mucosa, cold viruses attach to receptors on
epithelial cells in the nasopharynx and enter the cells [7]. During rhinovirus infection, viral
replication occurs in only a small number of nasal epithelial cells [23,24]. The infected cells
release cytokines, including interleukin (IL)-8, which attracts polymorphonuclear cells
(PMNs) [25-27]. Large numbers of PMNs (100-fold increase) accumulate in the nasal
secretions and mucociliary clearance is slowed [28].
Symptoms usually appear one to two days after viral inoculation, coinciding with the influx
of PMNs in the nasal submucosa and epithelium [28-30]. The severity of symptoms
correlates with mucosal IL-8 concentrations. A change in the character of the nasal
discharge from clear to yellow/white or green correlates with the increase in PMNs, but not
with an increase in positive bacterial cultures [31]. The colored discharge may signify the
presence of PMNs (yellow or white) or of PMN enzymatic activity (green color).
Histologic studies in young adults with natural and experimentally induced colds
demonstrate that the nasal epithelium remains intact, although there is an influx of PMNs
into the nasal submucosa and epithelium [29,30]. In vitro, rhinoviruses and coronaviruses
do not cause gross destruction of nasal epithelial cells; however, adenoviruses and
influenza A have a cytopathic effect, with resultant destruction of nasal epithelial cells [34].
CLINICAL FEATURES
Frequency and duration Children younger than six years have an average of six to
eight colds per year (up to one per month, September through April), with a typical
symptom duration of 14 days [2,35,36]. Young children in daycare appear to have more
colds than children cared for at home. However, when they enter primary school, children
who attended daycare are less vulnerable to colds than those who did not [37,38].
Older children and adults have an average of two to four colds per year, with a typical
symptom duration of five to seven days [2,11]. The duration of symptoms is increased
among cigarette smokers [39].
Overview The symptom profile of the common cold varies from patient to patient, in
part due to age, and in part due to the causative virus, although the wide range and
overlapping manifestations of the various cold-causing viruses make it impossible to
determine the specific causative virus without laboratory testing [2,8,36].
In school-aged children, nasal congestion, nasal discharge and cough are the predominant
symptoms. In a prospective study of 81 colds in school-aged children (5 to 12 years),
parents recorded signs and symptoms during the first 10 days of illness [36]. Signs and
symptoms included cough, sneeze, feverish (defined as ill-appearing, flushed, warm to
touch), congestion, nasal discharge, and headache; sore throat and hoarseness were not
evaluated. Rhinovirus RNA was detected in 46 percent of episodes. The frequency and
duration of the various manifestations were as follows (figure 1):
Nasal congestion was reported in 59 percent at the onset of illness, peaked (88
percent) on day 3, and persisted in 75 percent on day 7
Runny nose peaked (72 percent) on day 3 and persisted in 50 percent on day 6
Cough was reported in 46 percent at onset, peaked (69 percent) on day 1, and
persisted in 50 percent on day 8
Sneezing was reported in 36 percent at the onset of illness, peaked (55 percent) on
day 1, and persisted in 35 percent on day 6
Feverishness was reported in 15 percent at the onset of illness and declined over
the first three days
Headache was reported in 15 percent at the onset of illness, 20 percent on day 1,
and approximately 15 percent through day 4
Fever Fever may be the predominant manifestation of the common cold during the
early phase of infection in young children. It is uncommon in older children and adults.
(See "The common cold in adults: Diagnosis and clinical features", section on 'Clinical
features'.)
New onset of fever or recurrence of fever (if one was present at the onset of illness) may
indicate secondary bacterial infection (eg, acute otitis media, sinusitis, pneumonia).
(See 'Complications' below.)
Nasal manifestations Nasal congestion, nasal discharge, and sneezing are common
in children [36]. Examination may reveal erythema and swelling of the nasal mucosa and
nasal discharge. Nasal discharge may be clear initially, but often becomes colored (yellow
or green) within a few days [7]. Coloring of the nasal discharge is probably related to the
increase in number or enzymatic activity of polymorphonuclear cells [31]. Coloring of the
nasal discharge does not indicate bacterial superinfection or acute bacterial sinusitis
[2,31]. (See 'Pathophysiology' above.)
Acute bacterial sinusitis may be indicated by persistence of nasal discharge for more than
10 days without improvement, severe symptoms, or worsening symptoms (as defined
below). (See 'Sinusitis' below.)
Cough Cough occurs in more than two-thirds of children with the common cold and
may be the most bothersome symptom for the childs caregivers [36,40]. Cough may affect
the childs sleep, school performance, and ability to play; it also may disturb the sleep of
other family members and be disruptive in the classroom [41]. The cough may linger for an
additional week or two after other symptoms have resolved, but should gradually improve.
Diagnoses other than the common cold should be considered if the cough worsens or fails
to improve. (See 'Differential diagnosis' below.)
Other symptoms and signs Other symptoms and signs of the common cold may
include sore throat (typically an early manifestation), hoarseness, headache, irritability,
difficulty sleeping, decreased appetite, anterior cervical adenopathy, and conjunctival
injection. Vomiting and diarrhea are uncommon [2,7,36].
Middle ear abnormalities Middle ear abnormalities are common during the course of
an uncomplicated cold [42,43]. In an observational study of 86 children (2 to 12 years) with
colds, two-thirds had abnormal middle ear pressure (assessed by tympanometry) at some
point during the two weeks after onset [42]. Abnormal middle ear pressures were most
common during the first week. They shifted from ear to ear and were present only
intermittently during the course of the cold.
Abnormal middle ear pressure may predispose to the development of acute otitis media.
The development of acute otitis media is not affected by treatment with combination
decongestant-antihistamines [44]. (See 'Acute otitis media' below.)
The cause of abnormal middle ear pressure during the common cold is unknown. Viral
nasopharyngitis may result in Eustachian tube dysfunction and abnormal middle ear
pressure, or abnormal middle ear pressure may result from the viral infection of the
mucosa of the middle ear and/or Eustachian tube.
Radiographic features Self-limiting radiographic abnormalities of the paranasal
sinuses are common during the course of an uncomplicated cold:
In a study of 31 healthy young adults with the recent onset of cold symptoms,
abnormalities of the paranasal sinuses were evident on computed tomographic (CT)
scans during the acute phase of illness in 27 (87 percent) [45]. Antibiotics were not
administered, and follow-up CT scans two weeks later showed complete resolution or
marked improvement in 11 of the 14 subjects evaluated (79 percent).
In another study, 37 (62 percent) of 60 children (4 to 7 years old) with a cold had
major abnormalities (more than one-third volume loss or air-fluid level) in their
maxillary and/or ethmoid sinuses by magnetic resonance imaging (MRI). Twenty-six
of the 37 had a follow-up MRI at two weeks; 30 percent had a new cold and two had
received an antibiotic. At follow-up, the major abnormalities were no longer present in
54 percent of ethmoid and 65 percent of maxillary sinuses [46].
It is unknown whether these abnormalities are the result of impaired sinus drainage or the
result of actual viral infection of the sinus mucosa. Nose blowing has been demonstrated
to propel nasal secretions into the paranasal sinuses [47]. However, the degree to which
this contributes to the accumulation of fluid in the sinuses is uncertain.
COMPLICATIONS
Acute otitis media The majority of children with a cold have abnormal middle ear
pressure at some point during its course. (See 'Middle ear abnormalities' above.) Abnormal
middle ear pressure may predispose to acute otitis media (AOM).
The risk of secondary acute otitis media is greatest among children 6 to 11 months of age
[7]. Approximately one-third to one-half of colds in young children are complicated by
development of AOM as defined by acute onset of symptoms, inflammation of the
tympanic membrane, and fluid in the middle ear [48-50]. However, bacterial or suppurative
otitis media, defined as a bulging tympanic membrane with purulent material behind it or
purulent otorrhea from perforation of the tympanic membrane [51], occurs in only 5 to 19
percent of colds in young children [50]. In a prospective study, the frequency of AOM was
increased among children who had middle ear effusion before they developed the cold
[50].
AOM may be indicated by new-onset fever and earache after the first few days of cold
symptoms. (See "Acute otitis media in children: Diagnosis", section on
'Diagnosis' and "Acute otitis media in children: Epidemiology, microbiology, clinical
manifestations, and complications", section on 'Clinical manifestations'.)
Sinusitis Viral URI is the most important risk factor for the development of bacterial
sinusitis. Between 6 and 13 percent of viral URIs in children are complicated by acute
bacterial sinusitis [49]. (See "Acute bacterial rhinosinusitis in children: Clinical features and
diagnosis", section on 'Predisposing factors'.)
Secondary bacterial infection of the paranasal sinuses may be indicated by (see "Acute
bacterial rhinosinusitis in children: Clinical features and diagnosis", section on 'Clinical
features'):
Other complications Other complications of the common cold in children may include
epistaxis, conjunctivitis, and pharyngitis. (See "Epidemiology and etiology of epistaxis in
children", section on 'Mucosal irritation' and "Conjunctivitis", section on 'Viral
conjunctivitis' and "Group A streptococcal tonsillopharyngitis in children and adolescents:
Clinical features and diagnosis", section on 'Viral infections'.)
DIAGNOSIS The diagnosis of the common cold is made clinically, based upon history
and examination findings, including exposure to someone with a cold, nasal congestion,
nasal discharge, sore throat, fever (in young children), anterior cervical adenopathy, and
erythema of nasal mucosa and oropharynx [7]. Laboratory tests are not helpful in making
the diagnosis. (See 'Clinical features' above.)
Clinical features that may indicate a diagnosis other than an uncomplicated cold include
persistent fever, high-fever (>39C [102.2F]), ill-appearance, absence of nasal symptoms,
oral mucosal lesions (eg, the posterior vesicles of herpangina), wheezing, focal findings on
lung examination (eg, dullness to percussion, reduced air entry, crackles, bronchial
breathing), hemoptysis, acute onset or difficulty breathing (may suggest inhaled foreign
body), and/or features of a chronic respiratory disorder (eg, failure to thrive, finger
clubbing, over-inflated chest, chest deformity, atopy) [41,52,53]. Chest radiography may be
warranted in children with focal findings on lung examination, relentlessly progressive
cough, hemoptysis, or features of an undiagnosed chronic respiratory disorder [41].
(See 'Complications' above and 'Differential diagnosis' below.)
Laboratory testing can identify the viral pathogen if it is necessary to do so [2]. The wide
range and overlapping manifestations of the various cold-causing viruses make it
impossible to clinically determine the causative virus in an individual patient [2].
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on patient info and the keyword(s) of interest.)
Basics topics (see "Patient education: Giving your child over-the-counter medicines
(The Basics)" and "Patient education: Cough in children (The Basics)")
Beyond the Basics topic (see "Patient education: The common cold in children
(Beyond the Basics)")
SUMMARY
The common cold is an acute, self-limiting viral syndrome of the upper respiratory
tract, involving, to variable degrees, sneezing, nasal congestion and discharge, sore
throat, cough, low grade fever, headache, and malaise. (See 'Introduction' above.)
The symptoms of the common cold can be caused by a variety of viruses (table 1).
Rhinoviruses cause up to 50 percent of colds in children and adults. Other common
causes of colds in preschool children include respiratory syncytial virus (RSV),
influenza viruses, parainfluenza viruses, and adenoviruses. (See 'Virology' above.)
The majority of colds are transmitted by hand contact; cold-inducing viruses may
remain viable on human skin for at least two hours and on inanimate surfaces for a
day. (See 'Transmission' above.)
Children younger than six years have an average of six to eight colds per year with
typical symptom duration of 14 days. Nasal congestion, nasal discharge, and cough
are the predominant symptoms (figure 1). Yellow or green coloring of the nasal
discharge does not indicate bacterial superinfection or acute bacterial sinusitis.
(See 'Symptoms and signs' above.)
Abnormal middle ear pressure occurs frequently during the course of the common
cold, particularly during the first week. Radiographic abnormalities of the paranasal
sinuses (rhinosinusitis) also occur frequently during the course of the common cold
and resolves without antibiotic treatment. (See 'Middle ear abnormalities' above
and 'Radiographic features' above.)
Complications of the common cold include acute otitis media, acute bacterial
sinusitis, asthma exacerbation, and lower respiratory tract disease.
(See 'Complications' above.)
The diagnosis of the common cold is made clinically, based upon history and
examination findings, including exposure to someone with a cold, nasal congestion,
nasal discharge, sore throat, fever (in young children), anterior cervical adenopathy,
and erythema of nasal mucosa and oropharynx. Other diagnoses should be
considered if the child has fever >39C (102.2F), ill-appearance, absence of nasal
symptoms, oral mucosal lesions, wheezing, focal findings on lung examination,
hemoptysis, or features of a chronic respiratory disorder (eg, failure to thrive, finger
clubbing, over-inflated chest, chest deformity, atopy). Laboratory tests are not helpful
in making the diagnosis. (See 'Diagnosis' above.)
The differential diagnosis of the common cold includes other causes of rhinitis
(allergic, seasonal, vasomotor, rhinitis medicamentosa), acute bacterial sinusitis,
nasal foreign body, inhaled foreign body, pertussis, structural abnormalities of the
nose or sinuses, influenza, and bacterial pharyngitis or tonsillitis. These conditions
usually can be differentiated from the common cold by history and physical
examination. (See 'Differential diagnosis' above.)
Author:
Diane E Pappas, MD, JD
Section Editor:
Morven S Edwards, MD
Deputy Editor:
Mary M Torchia, MD
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Jan 24, 2017.
INTRODUCTION The common cold is an acute, self-limiting viral infection of the upper
respiratory tract characterized by variable degrees of sneezing, nasal congestion and
discharge (rhinorrhea), sore throat, cough, low grade fever, headache, and malaise.
The management and prevention of the common cold in children will be discussed here.
The epidemiology, clinical features, and diagnosis of the common cold in children and the
common cold in adults are discussed separately. (See "The common cold in children:
Clinical features and diagnosis" and "The common cold in adults: Diagnosis and clinical
features" and "The common cold in adults: Treatment and prevention".)
CAREGIVER EDUCATION The common cold is usually a mild and self-limiting viral
illness, usually caused by rhinoviruses. Caregiver education is the mainstay of
management [1,2] and is recommended by the American Academy of Pediatrics (AAP) [3],
the United Kingdom's National Institute for Health and Care Excellence (NICE) [4,5], and
British Thoracic Guidelines for the assessment and management of cough in children [6].
Antiviral therapy is not available for the viruses that cause the common cold with the
exception of influenza virus. The clinical features of influenza and treatment of influenza
with antiviral agents are discussed separately. (See "Seasonal influenza in children:
Prevention and treatment with antiviral drugs", section on 'Antiviral therapy'.)
Expected course of illness In infants and young children, the symptoms of the
common cold usually peak on day 2 to 3 of illness and then gradually improve over 10 to
14 days (figure 1) [7,8]. The cough may linger in a minority of children, but should steadily
resolve over three to four weeks. In older children and adolescents, symptoms usually
resolve in five to seven days (longer in those with underlying lung disease or who smoke
cigarettes) [9-11].
In randomized trials, systematic reviews, and meta-analyses, OTC medications have not
been proven to work any better than placebo in children and may have serious side effects
[34-43]. OTC cough and cold medications have been associated with fatal overdose in
children younger than two years [44-46]. OTC medications have the potential for enhanced
toxicity in young children because metabolism, clearance, and drug effects may vary
according to age. Safe dosing recommendations have not been established for children
[17]. (See "Over-the-counter cough and cold preparations: Approach to pediatric
poisoning".)
If parents choose to administer OTC medications to treat the common cold in children >6
years, they should be advised to use single-ingredient medications for the most
bothersome symptom and be provided with proper dosing and administration instructions
to avoid potential toxicity [17]. As an example, inverting the container rather than holding it
upright when administering intranasal medication may provide a dose that is 20 to 30
times greater than recommended [42]. (See 'Symptomatic therapy' below and "Over-the-
counter cough and cold preparations: Approach to pediatric poisoning".)
SYMPTOMATIC THERAPY Symptoms of the common cold need not be treated unless
they bother the child or other family members (eg, interrupting sleep, interfering with
drinking, causing discomfort) [47]. Symptomatic therapies have associated risks and
benefits, particularly in young children (table 2).
Discomfort due to fever We suggest that discomfort due to fever in the first few days
of the common cold be treated with acetaminophen (for children older than three months)
or ibuprofen (for children older than six months) [48]. (See "Fever in infants and children:
Pathophysiology and management", section on 'Management of fever'.)
Our second-line interventions for bothersome nasal symptoms that do not improve with
supportive care vary according to age:
<6 years For children <6 years with bothersome nasal symptoms that persist
despite supportive interventions, we generally suggest increasing the frequency of
nasal suction, sprays, or irrigation. We do not use OTC medications for nasal
symptoms in children <6 years. The benefits are unproven and there are associated
risks. (See 'Over-the-counter medications' above.)
Ipratropium nasal spray 0.06% is available by prescription for children older than five
years and may be warranted on a case-by-case basis. Two sprays are administered
to each nostril three times per day for four days.
6 to 12 years For children age 6 to 12 years with bothersome nasal symptoms
that do not respond to supportive interventions, we generally suggest increasing the
frequency of nasal suction, sprays, or irrigation rather than other interventions. We
suggest not using OTC decongestants or decongestant/antihistamine combinations.
The benefits are unproven and there are associated risks [43]. Ipratropium nasal
spray is available by prescription and may be warranted on a case-by-case basis.
The regimen varies according to age:
6 through 11 years Ipratropium 0.06% nasal spray, two sprays in each nostril
three times per day for four days
12 years Ipratropium 0.06% nasal spray, two sprays in each nostril three to
four times per day for four days
In a systematic review of seven randomized trials comparing ipratropium nasal spray
with placebo in children 5 years and adults, ipratropium was effective in reducing
subjective nasal discharge but not nasal congestion [49]. Adverse effects
(nosebleeds, nasal dryness, mouth dryness) were approximately two to four times as
common in patients treated with ipratropium.
12 years For children 12 years with bothersome nasal symptoms that do not
respond to supportive interventions, we suggest OTC decongestants (oral or topical)
or ipratropium nasal spray.
Decongestants (oral or topical) cause vasoconstriction of the nasal mucosa.
We prefer oral pseudoephedrine to phenylephrine and other oral OTC nasal
decongestants. Side effects of oral decongestants may include tachycardia,
elevated diastolic blood pressure, and palpitations [50].
Commonly used topical decongestants include oxymetazoline, xylometazoline,
and phenylephrine [1]. Side effects of topical decongestants include nosebleeds
and drying of the nasal membranes. Topical decongestants should only be used
for two to three days; longer use may result in rebound nasal congestion after
discontinuation [1,13].
A 2016 systematic review found low-quality evidence that multiple doses of
oral and/or topical decongestants subjectively improved nasal congestion in adults
[51]. No studies directly compared oral with topical decongestants. In randomized
trials in adult patients with allergic rhinitis, oral pseudoephedrine was more effective in
reducing nasal congestion than phenylephrine or placebo, whereas phenylephrine
was no more effective than placebo [52-54].
Diagnoses other than the common cold should be considered in children whose nasal
symptoms persist or worsen despite second line interventions. (See 'Persistent
symptoms' below.)
Cough Cough may affect the child's sleep, school performance, and ability to play; it
also may disturb the sleep of other family members and be disruptive in the classroom [6].
Although caregivers frequently seek interventions to suppress cough, they should
understand that cough clears secretions from the respiratory tract and suppression of
cough may result in retention of secretions and potentially harmful airway obstruction
[3,15].
We suggest that airway irritation contributing to cough be relieved with oral hydration,
warm fluids (eg, tea, chicken soup), honey (in children older than one year), or cough
lozenges or hard candy (in children in whom they are not an aspiration risk) rather than
OTC or prescription antitussives, antihistamines, expectorants, or mucolytics. Fluids,
honey, cough lozenges, and hard candy are inexpensive and unlikely to be harmful,
although they may provide only placebo effect [55]. (See 'Unproven therapies' below.)
Oral hydration and warm fluids are discussed above. (See 'Supportive
care' above.)
Honey We suggest honey as an option for treating cough in children 1 year with
the common cold. The honey (2.5 to 5 mL [0.5 to 1 teaspoon]) can be given straight
or diluted in liquid (eg, tea, juice [47]). Corn syrup may be substituted if honey is not
available. Honey has a modest beneficial effect on nocturnal cough and is unlikely to
be harmful in children older than one year of age. Honey should be avoided in
children younger than one year because of the risk of botulism. (See "Botulism",
section on 'Infant botulism'.)
In a randomized trial, 300 children (one to five years of age) with upper respiratory
infection and nocturnal cough were assigned to receive a single dose (10 g) of honey
(eucalyptus, citrus, or labiatae) or placebo (a date extract similar to honey in
appearance and taste) before bedtime; caregivers completed a symptom survey on
the days before and after the intervention; 270 children completed the study [56].
Symptoms improved in all children after the intervention. However, children who
received honey had greater mean improvement in cough frequency (1.77 to 1.85
versus 1.00 points), severity (1.78 to 1.94 versus 0.99 points) and bothersomeness
(2.00 to 2.16 versus 1.25 points) than those who received placebo. Adverse effects
(abdominal pain, nausea, vomiting) occurred in five patients, approximately evenly
distributed among each of the honey and the placebo groups. The findings of this trial
were confirmed in a 2014 systematic review and meta-analysis (mean difference in
cough frequency -1.85, 95% CI -3.36 to -0.33) [57]. Honey also reduced cough
frequency compared with no treatment and diphenhydramine, but not compared
with dextromethorphan.
Given the relative safety and low cost of honey, the World Health Organization (WHO)
and American Academy of Pediatrics (AAP) suggest it as a potential treatment for
upper respiratory infection in young children who are older than one year [15,47].
Lozenges We suggest hard candy or lozenges as an option for treating cough in
children in children in whom they are not an aspiration risk. Although there is no
evidence from controlled trials that cough lozenges and hard candy are effective in
decreasing cough, they are unlikely to be harmful [15]. The AAP suggests that cough
lozenges or hard candy may be used to coat the irritated throat for children older than
six years [47].
We do not use codeine or other antitussive agents (eg, dextromethorphan) for the
treatment of cold-related cough in children. They have potential harms with no proven
benefit [58]. Adverse effects of codeine in children include somnolence, respiratory
depression, and even death [59]; adverse effects of dextromethorphan include behavioral
disturbances and respiratory depression [3].
Sore throat Symptomatic relief of sore throat in children and adolescents is discussed
separately. (See "Sore throat in children and adolescents: Symptomatic treatment".)
Middle ear abnormalities We do not suggest decongestants or decongestant-
antihistamine combinations for symptoms of middle ear abnormalities (eg, conductive
hearing loss) in children with the common cold. Although abnormalities of middle ear
pressure associated with the common cold may predispose to development of acute otitis
media, in a prospective cross-over study, treatment with a decongestant-antihistamine did
not prevent the development of acute otitis media [62]. (See "Acute otitis media in children:
Epidemiology, microbiology, clinical manifestations, and complications", section on
'Pathogenesis'.)
PERSISTENT SYMPTOMS
Persistent nasal symptoms Diagnoses other than the common cold should be
considered in children who have nasal discharge that is more severe or prolonged
than expected with the common cold (eg, persists for more than 10 days without
improvement or is worsening). (See "The common cold in children: Clinical features
and diagnosis", section on 'Differential diagnosis'.)
Alternative diagnoses include:
Nasal foreign body (see "Diagnosis and management of intranasal foreign
bodies")
Allergic rhinitis, nonallergic rhinitis, medication-induced rhinitis (see "An
overview of rhinitis")
Acute bacterial sinusitis (see "Acute bacterial rhinosinusitis in children: Clinical
features and diagnosis")
Persistent cough Diagnoses other than the common cold should be considered
in children who have cough that is more severe or prolonged than expected with the
common cold (eg, persists for more than two weeks without improvement or is
worsening) [61]. Alternative diagnoses include pneumonia, asthma, pertussis, cystic
fibrosis, inhaled foreign body, among others. (See "The common cold in children:
Clinical features and diagnosis", section on 'Differential diagnosis' and "Causes of
chronic cough in children" and "Approach to chronic cough in children".)
UNPROVEN THERAPIES
Antibiotics There is no role for antibiotics in the treatment of the common cold [6].
Antibiotics do not alter the course of the common cold and do not prevent secondary
complications, but may cause significant side effects and contribute to increasing
bacterial antimicrobial resistance [63]. The use of antibiotics should be reserved for
clearly diagnosed secondary bacterial infections, including bacterial otitis media,
sinusitis, and pneumonia. (See "The common cold in children: Clinical features and
diagnosis", section on 'Complications'.)
Antihistamines We do not suggest antihistamines for the treatment of the
common cold. In randomized trials, neither antihistamines nor combination
antihistamine-decongestants have been effective in relieving nasal symptoms or
cough in children with the common cold [35,37,38,64], but these medications may
have adverse effects, including sedation, paradoxic excitability, respiratory
depression, and hallucinations (table 2).
Intranasal glucocorticoids We do not suggest intranasal corticosteroids for the
treatment of nasal symptoms of the common cold. A 2015 systematic review of three
trials (353 participants) found no benefit [65].
Antitussives We do not suggest prescription (codeine) or OTC
(dextromethorphan) antitussive medications to treat cough in children with the
common cold. Their efficacy has not been proven and they have the potential for
enhanced toxicity [3,35,39,44,60,66]. (See "Dextromethorphan abuse and poisoning:
Clinical features and diagnosis", section on 'Epidemiology' and "Opioid intoxication in
children and adolescents", section on 'Clinical manifestations'.)
Expectorants and mucolytics We do not suggest OTC expectorants
(eg, guaifenesin) or mucolytics (eg, acetylcysteine, bromhexine, letosteine) to treat
cough in children with the common cold. Expectorants and mucolytics increase
mucus production and thin respiratory secretions, respectively, to make the secretions
easier to expel [41]. Neither expectorants nor mucolytics are of proven benefit in
children [13,15,41]. By itself, guaifenesin alone is relatively safe, causing only mild
gastrointestinal irritation, but in OTC medications guaifenesin is usually combined
with other ingredients [61]. Adverse effects of mucolytics include bronchospasm,
gastrointestinal disturbance, and fever [15].
Bronchodilators We do not suggest bronchodilators to treat cough in
nonasthmatic children with the common cold. Bronchodilators are not effective for
acute cough in nonasthmatic children [6,67,68]. However, children with asthma who
develop a cold should use their bronchodilator rescue agent as indicated according to
their asthma action plan. (See "Asthma in children younger than 12 years: Rescue
treatment for acute symptoms", section on 'Summary'.)
Aromatic vapors (for external rub) We do not suggest topical
aromatic agents/external rubs (eg, menthol, camphor, eucalyptus oil) for the
treatment of nasal congestion or cough in children with the common cold.
In a randomized crossover trial comparing menthol and eucalyptus oil in 42 healthy
school children, menthol increased the perception of nasal patency, but did not affect
spirometry [69].
In another randomized trial that compared a vapor rub combination (camphor,
menthol, and eucalyptus oils) with petrolatum and no treatment, vapor rub had no
effect on rhinorrhea, but reduced cough severity, improved child and parent sleep,
and reduced a combined symptom score; all outcomes were parent-reported [70].
The vapor rub combination was associated with at least one mild irritant effect in
nearly one-half of children. Because the study was not well blinded (86 percent of
parents applying the vapor rub correctly guessed that they were applying it), the
likelihood of a significant placebo effect cannot be eliminated [71]. In addition, parent
report of cough must be interpreted with caution; parental reporting of the frequency
and severity of cough is unreliable compared with objective measures [72-74].
Vitamins, minerals, and herbal products
Vitamin C We suggest not using vitamin C for the treatment of the common
cold in children. In a 2013 meta-analysis of randomized trials, vitamin C (
200 mg/day) initiated after the onset of symptoms did not reduce the duration
(seven trials, 3249 cold episodes) or severity (four trials, 2708 cold episodes) of
cold symptoms [75]. No serious adverse effects were reported.
Zinc We suggest not using zinc for the treatment of the common cold in
children. The efficacy of zinc in reducing the duration or severity of cold
symptoms in children remains unclear and side effects are common [76].
Although several systematic reviews of randomized trials suggest that zinc may
shorten the duration of cold symptoms, there was significant heterogeneity
among the individual trials [76,77]. In a 2012 systematic review and meta-
analysis of eight trials (934 participants: 371 adults and 563 children), zinc
reduced the duration of symptoms (mean difference -1.65 days, 95% CI -2.5 to
-0.8) [76]. In subgroup analysis, zinc reduced the duration of symptoms in adults
(mean difference -2.63 days, 95% CI -3.69 to -1.58), but not in children (mean
difference -0.26 days, 95% CI -0.78 to 0.25). The effects of zinc also differed by
formulation (zinc acetate was effective; zinc gluconate and zinc sulfate were not)
and dose of ionic zinc (dose of 75 mg were more effective than lower doses).
Adverse effects, including bad taste and nausea, were common and may
contribute to the limited usefulness of zinc in children [76,78].
Zinc nasal products, including homeopathic intranasal zinc gluconate, have been
associated with long-standing or permanent loss of sense of smell and are not
recommended for children [79-81].
Echinacea purpurea We suggest not using Echinacea purpurea for the
treatment of the common cold in children. Several rigorously designed
randomized trials and a meta-analysis of randomized trials in adults found that
echinacea is no better than placebo for the treatment of upper respiratory
infections (URI) [82-85]. Similarly, a randomized trial in children (age 2 to 11
years) found no differences in the duration or severity of URI symptoms in
children treated with echinacea or placebo [86]. However, children treated with
echinacea had an increased rate of rash (7 versus 2.7 percent). (See "Clinical
use of echinacea", section on 'Upper respiratory tract infection'.)
Pelargonium sidoides (Umckaloabo, South African geranium) extract We
suggest not using Pelargonium sidoides extract for the treatment of the common
cold in children. Although a systematic review found one study suggesting that
10 days of therapy was effective in adults, the evidence was very low quality
[87]. Evidence regarding the safety of P. sidoides in children is limited. In pooled
analysis of trials evaluating P. sidoides for the treatment of acute respiratory
infections, adverse events were rarely reported but slightly more common among
recipients of P. sidoides than placebo.
PREVENTION
Child care and school Most children with colds need not be excluded from out-of-
home child care or school because transmission is likely to have occurred before the child
became symptomatic [88]. The risk of spread can be decreased by following common
sense prevention measures, discussed in the following sections.
Hygiene The best methods for preventing transmission of the common cold are
frequent handwashing and avoiding touching one's mouth, nose, and eyes. In
observational studies, alcohol-based hand sanitizers and virucidal hand treatments (eg,
iodine, salicylic acid, pyroglutamic acid) were associated with decreased transmission [89-
91]. (See "The common cold in children: Clinical features and diagnosis", section on
'Transmission'.)
Cold viruses can be transmitted from the hands to objects in the environment or to other
people. To avoid contaminating their hands, children with the common cold can be
instructed to cough into a tissue or the crook of their elbow rather than into their hands.
Used tissues should be discarded in a waste basket.
Yearly influenza immunization is recommended for all individuals older than six months to
prevent influenza infection and its complications. (See "Seasonal influenza in children:
Prevention with vaccines", section on 'Target groups'.)
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
Basics topics (see "Patient education: Giving your child over-the-counter medicines
(The Basics)" and "Patient education: Cough in children (The Basics)")
Beyond the Basics topics (see "Patient education: The common cold in children
(Beyond the Basics)")
The common cold is usually a mild and self-limiting viral illness. Caregiver education
is the mainstay of management and should include information about the expected
course, indications for reevaluation, supportive interventions, the potential dangers of
over-the-counter (OTC) medications for young children, and symptomatic therapy.
(See 'Caregiver education' above.)
In infants and young children, the symptoms of usually peak on day 2 to 3 of illness
and then gradually improve over 10 to 14 days (figure 1). In older children and
adolescents, symptoms usually resolve in five to seven days. Re-evaluation may be
warranted if the symptoms worsen or exceed the expected duration. (See 'Expected
course of illness' above and 'Indications for re-evaluation' above.)
OTC cough and cold medications should be avoided in children <6 years. We
suggest not using OTC cough and cold medications in children between 6 and 12
years of age (Grade 2B). These medications have no proven benefit for children and
may have serious adverse effects (table 2). (See 'Over-the-counter
medications' above.)
Symptomatic therapy may be warranted if the symptoms bother the child (eg,
interrupting sleep, interfering with drinking, causing discomfort) or other family
members. (See 'Symptomatic therapy' above.)
For first-line therapy of bothersome nasal symptoms, we suggest one or more
supportive interventions (eg nasal suction; saline nasal drops, spray, or irrigation;
adequate hydration; cool mist humidifier) rather than OTC medications or topical
aromatic therapies (Grade 2C). (See 'Nasal symptoms' above and 'Unproven
therapies' above.)
Second-line interventions for bothersome nasal symptoms vary according to
age:
-For children <6 years, we generally suggest increasing the frequency of
nasal suction, sprays, or irrigation (Grade 2C).
-For children 6 to 12 years, we generally suggest increasing the frequency
of nasal suction, sprays, or irrigation rather than other interventions (Grade
2C).
-For children 12 years, we suggest either ipratropium nasal spray or OTC
decongestants (oral or topical) (Grade 2C).
We suggest that airway irritation contributing to cough be relieved with oral
hydration, warm fluids (eg, tea, chicken soup), honey (in children older than one
year), or cough lozenges or hard candy (in children in whom they are not an
aspiration risk) rather than OTC or prescription antitussives, antihistamines,
expectorants, or mucolytics (Grade 2C). (See 'Cough' above and 'Unproven
therapies' above.)
Symptomatic relief of sore throat is discussed separately. (See "Sore throat in
children and adolescents: Symptomatic treatment".)
We suggest not using zinc, Echinacea purpurea, or vitamin C for the treatment of
the common cold in children (Grade 2B). (See 'Unproven therapies' above.)
Most children with the common cold need not be excluded from out-of-home child
care or school. The risk of spread can be decreased through frequent hand washing
and appropriate cough hygiene. (See 'Prevention' above.)
We suggest not using Echinacea purpurea, Allium sativum (garlic), vitamin
D, vitamin C, or zinc for the prevention of the common cold in children (Grade 2B).
(See 'Unproven preventive measures' above.)
Author:
Diane E Pappas, MD, JD
Section Editor:
Morven S Edwards, MD
Deputy Editor:
Mary M Torchia, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Aug 04, 2015.
COMMON COLD OVERVIEW The common cold is the most common illness in the
United States. Infants and children are affected more often and experience more
prolonged symptoms than adults. The common cold accounts for approximately 22 million
missed days of school and 20 million absences from work, including time away from work
caring for ill children.
This topic review discusses the causes, symptoms, and treatment of the common cold in
children. The common cold in adults is discussed separately. (See "Patient education: The
common cold in adults (Beyond the Basics)".)
COMMON COLD CAUSES The common cold is a group of symptoms caused by a
number of different viruses. There are more than 100 different varieties of rhinovirus, the
type of virus responsible for the greatest number of colds. Other viruses that cause colds
include enteroviruses (echovirus and coxsackieviruses) and coronavirus. Because there
are so many viruses that cause the symptoms of the common cold, people may have
multiple colds each year and dozens over a lifetime.
Children under six years average six to eight colds per year (up to one per month,
September through April), with symptoms lasting an average of 14 days. This means that a
child could be ill with intermittent cold symptoms for nearly half of the days in this time
period, without cause for concern. Young children in daycare appear to suffer from more
colds than children cared for at home. However, when day-care children enter primary
school, they catch fewer colds, presumably because they are already immune to a larger
number.
Seasonal patterns The common cold may occur at any time of year, although most
colds occur during the fall and winter months, regardless of the geographic location. Colds
are not caused by cold climates or being exposed to cold air.
Direct contact People with colds typically carry the cold virus on their hands, where it
is capable of infecting another person for at least two hours. If a child with a cold touches
another child or adult, who then touches their eye, nose, or mouth, the virus can later
infect that person.
Infection from particles on surfaces Some cold viruses can live on surfaces (such as
countertops, door handles, or toys) for up to one day.
Inhaling viral particles Droplets containing viral particles can be exhaled into the air by
breathing or coughing. Rhinoviruses are not usually transmitted as a result of contact with
infected droplets, although influenza virus and coronavirus can be transmitted via small
droplets. Cold viruses are not usually spread through saliva.
COMMON COLD SYMPTOMS The signs and symptoms of a cold usually begin one to
two days after exposure. In children, nasal congestion is the most prominent symptom.
Children can also have clear, yellow, or green-colored nasal discharge; fever (temperature
higher than 100.4F or 38C) is common during the first three days of the illness. The table
describes how to take a child's temperature (table 1). (See "Patient education: Fever in
children (Beyond the Basics)".)
Other symptoms may include sore throat, cough, irritability, difficulty sleeping, and
decreased appetite. The lining of the nose may become red and swollen, and the lymph
nodes (glands) in the neck may become slightly enlarged.
The symptoms of a cold are usually worst during the first 10 days. However, some children
continue to have a runny nose, congestion, and a cough beyond 10 days. In addition, it is
not unusual for a child to develop a second cold as the symptoms of the first cold are
resolving; this can make it seem as if the child has a single cold that lasts for weeks or
even months, especially during the fall and winter. This is not a cause for concern, unless
the child has any of the more serious symptoms, discussed below. (See 'When to seek
help' below.)
Symptoms of allergies (allergic rhinitis) are slightly different than those of a cold, and may
include bothersome itching of the nose and eyes.
COMMON COLD COMPLICATIONS Most children who have colds do not develop
complications. However, parents should be aware of the signs and symptoms of potential
complications.
Ear infection Between 5 and 19 percent of children with a cold develop a bacterial or
viral ear infection. If a child develops a fever (temperature higher than 100.4F or 38C)
after the first three days of cold symptoms, an ear infection may be to blame. (See "Patient
education: Ear infections (otitis media) in children (Beyond the Basics)".)
Asthma Colds can cause wheezing in children who have not wheezed before, or
worsening of asthma in children who have a history of this condition.
Sinusitis Children who have nasal congestion that does not improve over the course of
10 days may have a bacterial sinus infection.
Pneumonia Children who develop a fever after the first three days of cold symptoms
may have bacterial pneumonia, especially if the child also has a cough and is breathing
rapidly.
Symptomatic treatment The treatment of an infant or child with a cold is different than
treatment recommended for adults. Antihistamines, decongestants, cough medicines, and
expectorants, alone and in combinations, are all marketed for the symptoms of a cold.
However, there have been few clinical trials of these products in infants and children, and
there are no studies that demonstrate any benefit in infants or children.
The United States Food and Drug Administration (FDA) advisory panel has recommended
against the use of these medications in children younger than six [1]. We agree with this
recommendation because these medications are not proven to be effective and have the
potential to cause dangerous side effects. For children older than 6 years, cold
medications may have fewer risks; however, there is still no proven benefit.
Parents may give acetaminophen (sample brand name: Tylenol) to treat a child (older than
three months) who is uncomfortable because of fever during the first few days of a cold.
Ibuprofen (sample brand names: Advil, Motrin) can be given to children older than six
months. Aspirin should not be given to any child under age 18 years. There is no benefit of
these medications if the child is comfortable. Parents should speak with their child's
healthcare provider about when and how to treat fever. (See "Patient education: Fever in
children (Beyond the Basics)".)
Humidified air may improve symptoms of nasal congestion and runny nose. For infants,
parents can try saline nose drops to thin the mucus, followed by bulb suction to temporarily
remove nasal secretions (table 2). An older child may try using a saline nose spray.
Honey may be helpful for nighttime cough in children older than 12 months.
Parents should encourage their child to drink an adequate amount of fluids; it is not
necessary to drink extra fluids. Children often have a reduced appetite during a cold, and
may eat less than usual. If an infant or child completely refuses to eat or drink for a
prolonged period, the parent should contact their child's healthcare provider.
Antibiotics Antibiotics are not effective in treating colds. They may be necessary if the
cold is complicated by a bacterial infection, like an ear infection, pneumonia, or sinusitis.
Parents who think their child has developed one of these infections should contact their
child's healthcare provider.
Inappropriate use of antibiotics can lead to the development of antibiotic resistance, and
can possibly lead to side effects, such as an allergic reaction.
Hand washing is an essential and highly effective way to prevent the spread of
infection. Hands should be wet with water and plain soap, and rubbed together for 15
to 30 seconds. It is not necessary to use antibacterial hand soap. Teach children to
wash their hands before and after eating and after coughing or sneezing.
Alcohol-based hand rubs are a good alternative for disinfecting hands if a sink is not
available. Hand rubs should be spread over the entire surface of hands, fingers, and
wrists until dry, and may be used several times. These rubs can be used repeatedly
without skin irritation or loss of effectiveness.
It may be difficult or impossible to completely avoid people who are ill, although
parents should try to limit direct contact.
Most children with colds need not be excluded from day care or school. It is likely
that they spread the virus before they developed cold symptoms.
Using a household cleaner that kills viruses, such as phenol/alcohol (sample brand
name: Lysol), may help to reduce viral transmission.
WHEN TO SEEK HELP If a child develops any of the following features, the parent
should call their healthcare provider, regardless of the time of day or night.
Parents should call the healthcare provider if the following symptoms develop, or if there
are general concerns about the child:
Fever greater than 101F (38.4C) lasts more than three days. The table describes
how to take a child's temperature (table 1).
Nasal congestion does not improve or worsens over the course of 14 days.
The eyes become red or develop yellow discharge.
There are signs or symptoms of an ear infection (pain, ear pulling, fussiness).
SUMMARY
WHERE TO GET MORE INFORMATION Your healthcare provider is the best source of
information for questions and concerns related to your medical problem.
Patient level information UpToDate offers two types of patient education materials.
The Basics The Basics patient education pieces answer the four or five key questions
a patient might have about a given condition. These articles are best for patients who want
a general overview and who prefer short, easy-to-read materials.
Patient education: Cough, runny nose, and the common cold (The Basics)
Patient education: Sore throat in children (The Basics)
Patient education: Sinusitis in adults (The Basics)
Patient education: Giving your child over-the-counter medicines (The Basics)
Patient education: Eustachian tube problems (The Basics)
Patient education: Pneumonia in children (The Basics)
Patient education: Swollen neck nodes in children (The Basics)
Patient education: Adenovirus infections (The Basics)
Patient education: Mycoplasma pneumonia in children (The Basics)
Patient education: Enterovirus D68 (The Basics)
Beyond the Basics Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are best for patients who want in-depth
information and are comfortable with some medical jargon.
[1-6]
Authors:
Jerome O Klein, MD
Stephen Pelton, MD
Section Editors:
Sheldon L Kaplan, MD
Glenn C Isaacson, MD, FAAP
Deputy Editor:
Mary M Torchia, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Sep 29, 2016.
The risk factors, microbiology, clinical features, and complications of AOM will be reviewed
here. Related topics are presented separately:
EPIDEMIOLOGY AOM is the most frequent diagnosis in sick children visiting clinicians'
offices and the most common reason for administration of antibiotics [8-10]. AOM occurs at
all ages but is most prevalent between 6 and 24 months of age, after which it begins to
decline [11].
Incidence Nearly 80 percent of children in the United States <2 years of age have at
least one episode of AOM annually, and most continue to have episodes through age five
years [12-16]. AOM is slightly more common in boys than girls. An observational study that
reviewed claims data from a nationwide managed health care plan (2001 to 2011) found a
declining incidence of AOM following the introduction of the 13-valent pneumococcal
conjugate vaccine (PCV13), which accelerated beginning in 2009. In 2011, the incidence
of AOM was 0.82 episodes per child per year in children younger than two years [16].
Early onset AOM is the most important predictor of recurrent disease [11]. Children who
have had little or no experience with AOM by the age of three years are unlikely to have
subsequent severe or recurrent disease. AOM is infrequent in school-age children,
adolescents, and adults. (See "Acute otitis media in adults (suppurative and serous)",
section on 'Epidemiology of AOM'.)
Risk factors A number of risk factors for AOM have been established, the most of
important of which is age.
Age The age-specific attack rate for AOM peaks between 6 and 18 months of age
[20]. After that, the incidence declines with age, although there is a small increase
between five to six years (the time of school entry). AOM is infrequent in school-age
children, adolescents, and adults. (See "Acute otitis media in adults (suppurative and
serous)", section on 'Epidemiology of AOM'.)
The occurrence of disease early in life is probably a result of a number of factors,
including immature anatomy, physiology, genetic predisposition, and immunologic
naivet. Some of these factors are identifiable (eg, the change in skull configuration
and vectors of the eustachian tube, development of antibodies following exposure to
bacterial pathogens), but others remain to be defined.
Family history Pooled analysis of three studies (1240 children) found that the risk
of AOM was increased if any other member of the family had history of AOM (relative
risk [RR] 2.63, 95% CI 1.86-3.72) [21].
The role of genetic factors in the development of AOM is suggested by a two-year
prospective study of same-sex twins and triplets [22]. The estimate of discordance for
an episode of AOM was greater among dizygotic than monozygotic twins (0.49 versus
0.04 percent). Potential pathogenetic mechanisms for the heritability of AOM include
anatomic, physiologic, and/or immunologic features. Polymorphisms in
proinflammatory cytokine genes and genes involved in innate and adaptive immunity
that increase susceptibility to otitis media and recurrent AOM have been identified
[23-26].
Day care The transmission of bacterial and viral pathogens is common in day care
centers. Multiple observational studies indicate that children attending day care
centers, especially with four or more other children, have a higher incidence of AOM
than children who receive care at home [14,27-29]. In pooled analysis of six studies
(1972 children), the RR of AOM for children who attended day care outside the home
compared with children who received care at home was 2.45 (95% CI 1.51-3.98) [21].
In pooled analysis of four studies (1030 children), the RR of AOM for children who
attended family day care versus home care was 1.59 (95% CI, 1.19-2.13) [21].
Lack of breastfeeding Lack of or limited breastfeeding is associated with an
increased risk of AOM [14,15,21,30,31]. In pooled analysis of six studies (2548
children), the risk of AOM was decreased among children who were breastfed for at
least three months (RR 0.87, 95% CI 0.79-0.95) [21].
Breastfeeding diminishes colonization of the nasopharynx by bacterial otopathogens
[21,30]. Additional reasons for the lower incidence of AOM among breastfed infants
are uncertain but may be related to immunologic or nonimmune protective factors in
breast milk, the facial musculature associated with breastfeeding, or the position
maintained during feeding from the breast contrasted with bottle feeding [32,33]. An
observational study suggests that the nasopharyngeal microbiome in breast fed
children is different from that in formula fed children, with a reduction in colonization
patterns with high densities of Streptococcus pneumoniae or
nontypeable Haemophilus influenzae [34]. (See "Infant benefits of breastfeeding",
section on 'Anti-microbial components'.)
Tobacco smoke and air pollution Exposure to tobacco smoke and ambient air
pollution increases the risk of AOM. In pooled analysis of three studies (1784
children), the RR of AOM was 1.66 (95% CI 1.33-2.06) among children whose
parents smoked [21]. In another pooled analysis, the odds ratio for recurrent AOM
was 1.48 (95% CI 1.08-2.04) if either parent smoked [35]. The mechanism for this
association is not entirely clear but may be related to increased nasopharyngeal and
oropharyngeal carriage of S. pneumoniae [36,37]. (See "Secondhand smoke
exposure: Effects in children", section on 'Middle ear disease'.)
Data are lacking regarding an association between ambient air pollution and middle
ear disease in children. Several observational studies have noted modest
associations between some air pollutants and otitis media in children, but the findings
are inconsistent [38-41]. Community-wide surveillance in a large city identified an
association between levels of sulfur dioxide (a marker for air pollution) and higher
ragweed pollen counts and invasive pneumococcal infections in children and adults
[42].
Pacifier use In pooled analysis of two studies (4110 children), children who used
a pacifier had a slightly higher incidence of AOM than children who did not (RR 1.24,
95% CI 1.06-1.46) [21].
Race and ethnicity Native Americans, Alaskan and Canadian Inuit children, and
indigenous Australian children have a higher incidence of severe and recurrent AOM
than do children of Caucasian descent [43,44]. In some indigenous populations, 40
percent of the children may have chronic perforation of the tympanic membrane by 18
months of age [45]. In a prospective study, severe otitis media was also more likely to
be reported in Bedouin than in Jewish children in Israel [46]; the authors attributed the
recurrent, nonresponsive, or chronic OM to crowded living conditions and colonization
early in life among Bedouin children, however, genetic differences were not
investigated. (See 'TM perforation' below.)
Developing areas Lack of access to medical care and local environmental factors
lead to severe suppurative episodes of OM in children living in developing areas [47].
The prevalence of chronic suppurative otitis media is discussed separately.
(See "Chronic suppurative otitis media (CSOM): Clinical features and diagnosis",
section on 'Epidemiology'.)
Other risk factors Other important risk factors in the development of single and
recurrent episodes of AOM include [20]:
Social and economic conditions (poverty and household crowding increase the
risk)
Season (increased incidence during the fall and winter months)
Altered host defenses and underlying disease (eg, cleft palate, Down syndrome,
allergic rhinitis)
PATHOGENESIS The middle ear is a narrow box that is part of an aerated system that
includes the nares, the eustachian tube, and the mastoid air cells (figure 1). The system is
lined with respiratory mucosa; events affecting one part of the system are usually reflected
in similar changes throughout the system. Extension of the suppurative process to
adjacent structures may lead to complications such as mastoiditis, labyrinthitis, petrositis,
meningitis, and lateral sinus thrombosis. (See 'Complications and sequelae' below.)
The pathogenesis of AOM in at-risk children generally involves the following sequence of
events [48-51]:
The patient has an antecedent event (usually a viral upper respiratory tract infection)
while colonized with an otopathogen(s) [15]. Some evidence suggest that co-
colonization with bacterial otopathogens only, in the absence of viral respiratory tract
infection, may be sufficient to trigger the cascade of events [50,52,53].
The event results in inflammatory edema of the respiratory mucosa of the nose,
nasopharynx, and eustachian tube.
Inflammatory edema obstructs the narrowest portion of the eustachian tube, the
isthmus.
Obstruction of the isthmus causes poor ventilation and resultant negative middle ear
pressure. This leads to the accumulation of secretions produced by the middle ear
mucosa.
The secretions have no egress and accumulate in the middle ear space.
Viruses and bacteria that colonize the upper respiratory tract enter the middle ear
via aspiration, reflux, or insufflation.
Microbial growth in the middle ear secretions often progresses to suppuration with
clinical signs of AOM (bulging tympanic membrane [TM], middle ear fluid,
erythematous TM).
The middle ear effusion may persist for weeks to months following sterilization of the
middle ear infection. (See "Acute otitis media in children: Treatment", section on
'Clinical course'.)
MICROBIOLOGY
Overview The microbiology of AOM has been documented by cultures of middle ear
effusion obtained by needle aspiration (table 1) [54]. Similar studies have been performed
to identify viral etiologies of AOM.
Bacterial and/or viral respiratory tract pathogens can be isolated from most middle ear
aspirates from children with AOM when a variety of microbiologic methods are used
[55,56]. In one series, bacteria (with or without viruses) were detected in 92 percent,
viruses (with or without bacteria) in 70 percent, and both bacteria and viruses in 66 percent
[55].
The finding of combined bacterial and viral infections in two-thirds of cases has important
clinical implications [57]. Mixed viral and bacterial infections may respond differently to
antibiotic therapy than purely bacterial infections [58,59]. The presence of viruses may
increase middle ear inflammation [60,61], decrease neutrophil function [62], and reduce
antibiotic penetration into the middle ear [63].
Bacteria Three species of bacteria account for most of the bacterial isolates from
middle ear fluid: S. pneumoniae, nontypeable H. influenzae (NTHi), and Moraxella
catarrhalis (table 1). This continues to be true even after the introduction of the conjugate
pneumococcal vaccines to the routine childhood immunization schedule [9,56,64-67].
However, the relative importance of the species has changed, and the pneumococcal
serotypes causing AOM have evolved to predominantly nonvaccine serotypes.
Several studies have examined the microbiology and clinical features of bilateral versus
unilateral AOM [70,71]. Children with bilateral AOM were more likely to have bacteria
isolated from middle ear aspirate than children with unilateral AOM. H. influenzae was
isolated more often in children with bilateral than unilateral AOM, whereas S.
pneumoniae was isolated with equal frequency in children with bilateral and unilateral
AOM.
Widespread use of PCV7 has changed the S. pneumoniae serotypes responsible for AOM.
Before the introduction of PCV7 (table 2), serotypes included in the vaccine accounted for
60 to 70 percent of AOM isolates in the 6- to 59-month age group [76]. Following universal
immunization of infants with PCV7, most isolates recovered from the nasopharynx of
asymptomatic children and the middle ear of children with AOM are nonvaccine serotypes
[66,68,77-79]. Specifically, serotype 19A emerged as an important cause of both
respiratory tract infection and invasive disease. Of specific concern, multidrug-resistant
19A pneumococcus has been reported as the cause of recalcitrant AOM [77,79,80] and
coalescent mastoiditis [81]. PCV13, which was licensed in 2010, includes serotype 19A
(table 2). Surveillance after licensure of PCV13 has documented a decline in the
prevalence of nasopharyngeal colonization with serotypes unique to PCV13 including 19A
[82-84]. A decline in AOM episodes due to vaccine serotypes, including serotype 19A, has
also been reported in Israeli children referred for tympanocentesis following the
introduction of PCV13 [72]. Declines in AOM have also been seen in the first months of
life, suggesting herd benefit from decreased transmission of vaccine serotypes in the
community [85]. (See "Impact of universal infant immunization with pneumococcal
(Streptococcus pneumoniae) conjugate vaccines in the United States".)
Universal immunization of infants with the conjugate H. influenzae type b vaccine has had
little effect on Haemophilus AOM because more than 90 percent of Haemophilus AOM is
caused by nontypeable strains. However, studies of the microbiology of AOM after the
introduction of the pneumococcal conjugate vaccine suggest the proportion of cases due
to H. influenzae is increasing. It is unclear how the incidence of disease due to NTHi has
changed. Some studies suggest an increase in incidence following introduction of
pneumococcal conjugate vaccines, while others suggest declines in NTHi AOM in early
episodes but increased incidence in recurrent disease [9,17,66,68,85,88].
Other pathogens Mycoplasma pneumoniae rarely has been isolated from middle ear
fluids of children with AOM. Chlamydia trachomatis has been associated with otitis media
in infants younger than six months of age. C. pneumoniae has been isolated from some
patients with acute and chronic otitis media [54]. (See "Chlamydia trachomatis infections in
the newborn" and "Mycoplasma pneumoniae infection in children", section on 'Clinical
features'.)
In young infants The microbiology of AOM in infants younger than two months has
been evaluated in several observational studies, the most recent of which is from the
1990s [93,94,100-106]. Bacterial pathogens isolated from the middle ear aspirates of
young infants with AOM most commonly are similar to those identified in older children
(eg, S. pneumoniae and H. influenzae). In infants younger than two weeks, pathogens that
cause neonatal sepsis (group B Streptococcus, enteric gram-negative bacilli, and S.
aureus) also may be found.
CLINICAL MANIFESTATIONS
Symptoms and signs Children with AOM, particularly infants, may present with
nonspecific symptoms and signs, including fever, irritability, headache, apathy, disturbed or
restless sleep, poor feeding/anorexia, vomiting, and diarrhea [110-114]. Fever occurs in
one- to two-thirds of children with AOM, though temperature >40C (104F) is unusual
unless accompanied by bacteremia or other focus of infection [115]. The lack of specificity
of symptoms of AOM in young children, particularly in infants, makes the diagnosis
challenging. (See "Acute otitis media in children: Diagnosis", section on 'Diagnosis'.)
Ear pain (otalgia) is the most common complaint in children with AOM and the best
predictor of AOM [110,111,113]. However, ear pain and other ear-related symptoms (eg,
ear rubbing) are not always present [110,111,116]. In a prospective study of 335
consecutive episodes of AOM, otalgia was severe in 42 percent, mild to moderate in 40
percent, and absent in 17 percent [116]. Children older than two years complained of ear
pain more often than children younger than two years (25 versus 7 percent) [116]. Other
causes of ear pain in children are discussed separately. (See "Evaluation of earache in
children".)
The most important sign for distinguishing AOM from OM with effusion and normal is the
presence of bulging of the tympanic membrane (TM) (picture 1) [4-6]. Other signs and
symptoms of AOM include otorrhea and hearing loss. Findings that may be associated
with complications of AOM include vertigo, nystagmus, tinnitus, swelling about the ear, and
facial paralysis [113]. (See 'Complications and sequelae' below.)
Clinical syndromes
Signs and symptoms of middle ear inflammation (eg, bulging of the tympanic
membrane [TM], distinct erythema of the TM or otalgia, fever) (picture 1), and
Middle ear effusion (eg, TM opacity, decreased or absent TM mobility (movie 1), an
air-fluid level, or otorrhea)
Thus, a diagnosis of AOM can be made in a child with moderate to severe bulging of the
TM; new onset of otorrhea not due to acute otitis externa; or mild bulging of the TM and
recent onset (<48 hours) of ear pain or intense erythema of the TM (picture 3) [1].
The diagnosis of AOM is discussed separately. (See "Acute otitis media in children:
Diagnosis".)
Clues to etiology Despite the lack of specificity of most ear-related findings in the
diagnosis of AOM, some clinical features correlate with particular organisms.
Eye findings, particularly conjunctivitis, are more common with H. influenzae [73]
(see 'Otitis-conjunctivitis' above)
H. influenzae is isolated more often from children with bilateral than unilateral AOM,
whereas S. pneumoniae is isolated with equal frequency in bilateral and unilateral
AOM [70,71]
Although spontaneous TM perforation can occur in all types of bacterial AOM, AOM
caused by group A streptococci (GAS) is associated with higher rates of TM
perforation than AOM caused by other pathogens [89,90]
AOM caused by S. pneumoniae is more likely to present with severe symptoms
(high fever and moderate to severe pain) [73,75].
Hearing loss Most patients with middle ear effusion have persistent or fluctuating
conductive hearing loss. Fluid filling the middle ear space prevents the TM from vibrating
adequately, thereby diminishing movement of the ossicular chain. The hearing loss
remains as long as fluid fills the middle ear space. The median loss is 25 dB, which is
equivalent to putting plugs in the child's ears. (See "Hearing impairment in children:
Etiology", section on 'Infection'.)
Despite treatment with appropriate antimicrobial agents, middle ear fluid may persist for
weeks to months after the onset of signs of AOM (see "Acute otitis media in children:
Treatment", section on 'Clinical course'). Some studies have noted that children with
prolonged time spent with middle ear effusion have lower scores on tests of speech,
language, and cognitive abilities than children without prolonged middle ear effusion [134-
137]. Other studies found no significant differences in developmental outcome between
children with and without prolonged middle ear effusion [138-142]. Systematic reviews and
meta-analyses have found either inconclusive evidence or small to no negative effects of
prolonged middle ear effusion on speech and language development [143-145]. However,
the findings may not be generalizable to children at increased risk of speech and language
delay (eg, those with craniofacial anomalies, pre-existing developmental delays, persistent
bilateral OM, etc).
Balance and motor problems Children with AOM may have balance, motor, or
vestibular problems related to vestibular dysfunction or labyrinthitis [133,146-149].
(See "Pathophysiology, etiology, and differential diagnosis of vertigo", section on 'Otitis
media'.)
TM perforation The increased pressure in the middle ear can result in central
ischemia, necrosis, and spontaneous perforation of the TM, usually accompanied by
otorrhea (picture 7) [132].
The treatment of TM perforation associated with AOM is discussed separately. (See "Acute
otitis media in children: Treatment", section on 'AOM with perforation'.)
Mastoiditis Because the mastoid air cells are connected to the distal end of the middle
ear through a small canal or antrum (figure 2), most episodes of AOM are associated with
some inflammation of the mastoid. In rare cases, resolution of the mastoid infection does
not occur, and acute mastoiditis develops with pus filling the air cells. (See "Acute
mastoiditis in children: Clinical features and diagnosis", section on 'Pathogenesis'.)
Petrositis (extension of the infection into the petrous portion of the mastoid bone)
(see "Acute mastoiditis in children: Clinical features and diagnosis", section on
'Complications')
Labyrinthitis (extension of infection into the cochlear and vestibular apparatus)
(see "Pathophysiology, etiology, and differential diagnosis of vertigo", section on 'Otitis
media')
Facial paralysis (the facial nerve courses through the middle ear and mastoid); facial
paralysis also may occur as a complication of acute mastoiditis or chronic suppurative
otitis media (see "Facial nerve palsy in children", section on 'Otitis media')
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
Basics topics (see "Patient education: Ear infections (otitis media) (The Basics)")
Beyond the Basics topics (see "Patient education: Ear infections (otitis media) in
children (Beyond the Basics)")
SUMMARY
Acute otitis media (AOM) is defined by the presence of fluid in the middle ear
accompanied by acute signs of illness and signs or symptoms of middle ear
inflammation, including bulging (picture 1). (See 'Introduction' above
and 'Definition' above.)
Viral upper respiratory infection is the most common predisposing factor for the
development of AOM. The incidence of AOM in the United States is highest between
6 and 18 months of age and during the respiratory virus season. In addition to young
age, other risk factors for AOM include family history, day care attendance, not having
been breastfed, exposure to tobacco smoke, pacifier use, and ethnicity (Native
Americans and Alaskan and Canadian Inuit populations). (See 'Risk factors' above.)
Inflammation of the upper respiratory tract predisposes to AOM via dysfunction of
the eustachian tube, leading to negative pressure and accumulation of middle ear
secretions and impairment in host defenses such as normal mucociliary action of the
respiratory mucosa. Microbial growth in the middle ear secretions may result in
suppuration and clinical signs of AOM. (See 'Pathogenesis' above.)
Streptococcus pneumoniae, nontypeable Haemophilus influenzae (NTHi),
and Moraxella catarrhalis account for most of the bacterial isolates from middle ear
fluid. The most common viral pathogens include respiratory syncytial virus,
rhinoviruses, influenza viruses, and adenoviruses. (See 'Microbiology' above.)
Children with AOM, particularly infants, may present with nonspecific symptoms and
signs (eg, fever, fussiness, headache, anorexia, vomiting, and diarrhea). Specific
findings of AOM or complications/sequelae of AOM include ear pain, otorrhea, bulging
of the tympanic membrane (TM) (picture 1), hearing loss, vertigo, nystagmus, tinnitus,
swelling about the ear, and facial paralysis. (See 'Symptoms and signs' above.)
AOM may occur in conjunction with conjunctivitis; this symptom complex is usually
caused by NTHi. AOM also may occur with bullae on the TM (bullous myringitis
(picture 2A)); the distribution of viral and bacterial pathogens in cases of bullous
myringitis is similar to that in cases of AOM without bullae. (See 'Clinical
syndromes' above.)
The diagnosis of AOM requires evidence of middle ear inflammation (eg, bulging)
and middle ear effusion. (See "Acute otitis media in children: Diagnosis", section on
'Diagnosis'.)
Complications of AOM include mild conductive hearing loss; vestibular, balance, and
motor dysfunctions; TM perforation; inflammation of the mastoid and/or mastoiditis;
petrositis; and labyrinthitis. Intracranial complications are rare in developed countries;
they include meningitis, epidural abscess, brain abscess, lateral sinus thrombosis,
cavernous sinus thrombosis, subdural empyema, and carotid artery thrombosis.
(See 'Complications and sequelae' above.)
Author:
Ellen R Wald, MD
Section Editors:
Morven S Edwards, MD
Glenn C Isaacson, MD, FAAP
Deputy Editor:
Mary M Torchia, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Sep 27, 2016.
INTRODUCTION Acute otitis media (AOM), also called suppurative otitis media, is one
of the most frequent diagnoses for children seeking acute medical care [1]. It accounts for
a large proportion of pediatric antibiotic prescriptions and is associated with considerable
medical expenditures [2,3].
The diagnosis of AOM will be reviewed here. The epidemiology, pathogenesis, treatment,
and prevention of AOM are discussed separately. (See "Acute otitis media in children:
Epidemiology, microbiology, clinical manifestations, and complications" and "Acute otitis
media in children: Treatment" and "Acute otitis media in children: Prevention of
recurrence".)
TERMINOLOGY
Middle ear effusion Middle ear effusion (MEE) refers to fluid in the middle ear cavity.
MEE occurs in both otitis media with effusion and AOM.
Acute otitis media AOM refers to acute infection of middle ear fluid. (See "Acute otitis
media in children: Epidemiology, microbiology, clinical manifestations, and complications",
section on 'Definition'.)
Otitis media with effusion Otitis media with effusion (OME) refers to middle ear fluid
that is not infected. OME is also called serous, secretory, or nonsuppurative otitis media.
OME frequently precedes the development of AOM or follows its resolution. (See "Otitis
media with effusion (serous otitis media) in children: Clinical features and diagnosis",
section on 'Clinical features'.)
The distinction between OME and AOM may be difficult, since they are part of a
continuous spectrum. (See "Acute otitis media in children: Treatment", section on 'Clinical
course' and 'Otitis media with effusion' below.)
ANATOMY The anatomic features of the right tympanic membrane are depicted in the
figure (figure 1). The normal middle ear is aerated, and the tympanic membrane is slightly
convex, translucent, mobile, and intact (picture 1). In contrast, in established AOM, the
middle ear is fluid-filled, and the tympanic membrane is usually bulging, yellow or white in
color, opaque, and immobile (picture 2). In some cases, the tympanic membrane may be
erythematous, but erythema of the tympanic membrane is a nonspecific finding; it is only
helpful in making a diagnosis of AOM if there is concomitant bulging. Increased pressure in
the middle ear may lead to central ischemia, necrosis, and perforation of the tympanic
membrane.
Establishing the diagnosis of AOM in infants and young children can be difficult. The child
may not cooperate with the examination, and the tympanic membrane may be obscured
by cerumen. In addition, symptoms of AOM may overlap with those of upper respiratory
tract infection or may be subtle or absent [7-11]. (See "Acute otitis media in children:
Epidemiology, microbiology, clinical manifestations, and complications", section on
'Symptoms and signs'.)
A pneumatic otoscope with a round head is preferred because it has the best seal (picture
3). The magnifying glass can be moved aside if and when cerumen removal is necessary.
The nipple on the metal head is the site of attachment for the insufflator bulb, which is
used to assess mobility of the tympanic membrane. (See 'Mobility' below.)
Cerumen must be removed from the external canal under direct vision in order to be sure
that the view of the tympanic membrane is unobstructed. Once cerumen has been
removed, systematic assessment of the entire tympanic membrane is undertaken, as
described below. (See "Cerumen", section on 'Cerumen removal'.)
Overview The diagnosis of AOM requires middle ear effusion (MEE) and acute signs of
middle ear inflammation (bulging of the tympanic membrane is the most specific and
reproducible sign of middle ear inflammation) [15,16]. The classic examination findings
include a tympanic membrane that is white or pale yellow, bulges into the external auditory
canal, and has decreased or absent mobility (picture 4) [17-19]. However, this constellation
of findings is not always present. (See 'Diagnosis' below.)
Accurate diagnosis of AOM requires systematic evaluation of the tympanic membrane for
position, translucency, mobility, color, and other findings (eg, fluid level, perforation).
Systematic assessment of the tympanic membrane is facilitated by the use of the
COMPLETES mnemonic [20]:
Color (eg, gray, white, pale yellow, amber, pink, red, blue)
Other conditions (eg, fluid level, bubbles, perforation, otorrhea, bullae,
tympanosclerosis [scars], atrophic areas, retraction pockets, cholesteatoma)
Mobility
Position (eg, neutral, retracted, full, or bulging)
Lighting (a halogen light source and fully charged battery should be used)
Entire surface (the four quadrants of the tympanic membrane should be examined)
(figure 1)
Translucency
External auditory canal and auricle (eg, deformed, displaced, inflamed, foreign body)
Seal (a good seal requires an airtight pneumatic system and a speculum that is
large enough to prevent air leak)
Although the cases of AOM, OME, and no MEEs that were used to develop and validate
the classification scheme were not microbiologically confirmed, the otoscopists had
completed a training program in which their diagnoses were validated against
myringotomy findings. Expert otoscopists from other centers concurred in the relative
importance of the findings of otoscopy [19]. We agree that bulging of the tympanic
membrane is the crucial finding that differentiates AOM from OME.
(See 'Diagnosis' below.)
A bulging tympanic membrane is the single most important sign of acute inflammation
[10,15,17,19]. In a large study correlating examination findings with a diagnosis of AOM,
the triad of bulging tympanic membrane, impaired mobility, and redness or cloudiness of
the tympanic membrane predicted myringotomy diagnosis of AOM in 83 to 99 percent of
cases [17]. In another study correlating examination findings with a diagnosis of AOM, 92
percent of children with AOM had a bulging tympanic membrane compared with none of
the children with OME or no effusion [15]. In a systematic review, the adjusted likelihood
ratio (LR) for bulging tympanic membrane was 51 (95% CI 36-73) [10].
An air-fluid level is present when the tympanic membrane appears translucent above and
opaque below the line of demarcation (picture 6). Air fluid levels are more suggestive of
OME than AOM [15]. Air-fluid levels fluctuate with pneumatic otoscopy, a technique that
helps distinguish fluid levels from tympanosclerosis, which, being part of the tympanic
membrane, moves with it. (See 'Mobility' below.)
Bulging of the tympanic membrane remains the single most important sign of AOM and
precludes the necessity of pneumatic otoscopy because all bulging membranes have
decreased or absent mobility. In addition, pneumatic otoscopy can be extremely painful in
children with AOM.
To ensure an airtight seal, the largest speculum that fits comfortably into the cartilaginous
portion of the external auditory canal should be used (a 4 mm speculum will work for most
children) [20]. The outer diameter of the speculum may be increased by putting a small
piece of rubber tubing around the tip of the speculum [21,24].
A leak in the pneumatic system is another reason for a poor seal. The pneumatic system
should be checked for leaks periodically by occluding the tip of the speculum with a finger
and squeezing the rubber bulb to see if resistance is felt [20].
When there is high negative pressure in the middle ear cavity, the tympanic membrane
may be maximally retracted and unable to move away from the observer with positive
pressure (movie 2). Mobility of a retracted tympanic membrane can be assessed by
creating negative pressure in the external auditory canal. The otoscope should be
removed from the external canal and the bulb compressed. After the bulb is compressed,
the otoscope is reinserted into the external canal. When the seal is secured, the bulb is
released, creating negative pressure, which allows the retracted tympanic membrane to
move toward the observer into a neutral position.
Interpretation Mobility is described as normal (movie 1), increased, absent (movie 2),
or decreased.
The finding of decreased or absent mobility of the tympanic membrane can confirm a
diagnosis of MEE. When using this criterion to establish MEE, it is essential that the
adequacy of the seal be assured; if it is not, the diagnosis of MEE may be faulty.
Decreased or absent mobility should not be used as the sole criterion for AOM since it
provides no information regarding whether the fluid is infected or uninfected.
(See 'Diagnosis' below.)
In a study correlating examination findings with a diagnosis of AOM by experienced
otoscopists, decreased mobility of the tympanic membrane was present in 50 of 50 cases
of AOM and 23 of 34 cases of OME [15].
Color Assessment of the color of the tympanic membrane is another important aspect
of the otoscopic examination.
Under normal conditions, the color of the tympanic membrane is pearly gray or pink
(picture 1).
When there is uninfected fluid in the middle ear (ie, OME), the color is usually
amber, gray, or blue.
A white or pale yellow tympanic membrane usually indicates pus in the middle ear
cavity, which is a sign of AOM (picture 4).
Asymptomatic whitish plaques of calcium and phosphate crystals that move with the
tympanic membrane are known as tympanosclerosis or myringosclerosis (picture 7).
(See 'Other findings' below.)
A red or hemorrhagic-appearing tympanic membrane may indicate acute
inflammation, but a hyperemic tympanic membrane also may be caused by
vasodilatation related to manipulation of the canal (as occurs during removal of
cerumen), crying, or high fever. In the crying child, vascular engorgement is limited to
the periphery and handle of the malleus [25]. Vessels crossing the tympanic
membrane suggest inflammation.
Other findings In addition to position, translucency, mobility, and color, the tympanic
membrane should be assessed for the following other findings [20]:
Bubbles or fluid levels (picture 6), which indicate MEE. (See 'Translucency' above.)
Acute perforation with purulent otorrhea, which satisfies the criteria for diagnosis of
AOM provided that otitis externa is excluded. (See "External otitis: Pathogenesis,
clinical features, and diagnosis".)
Bullae, which are caused by inflammation of the tympanic membrane that occurs in
association with AOM (picture 8). (See "Acute otitis media in children: Epidemiology,
microbiology, clinical manifestations, and complications", section on 'Bullous
myringitis'.)
Tympanosclerosis of the tympanic membrane (asymptomatic whitish plaques of
calcium and phosphate crystals) (picture 7), which may be the result of chronic middle
ear inflammation, perforation, myringotomy with or without tympanostomy tube
placement, or trauma. Tympanosclerosis moves with the tympanic membrane during
otoscopy. (See "Otitis media with effusion (serous otitis media) in children: Clinical
features and diagnosis", section on 'Complications and sequelae'.)
Atrophic areas, which may be the sequelae of otitis media or its treatment; atrophic
areas may have increased mobility. (See 'Mobility' above.)
Retraction pockets (picture 9), which may be sequelae of otitis media. Retraction
pockets can predispose to the development of cholesteatoma (a benign growth of
desquamated, stratified, squamous epithelium). A cholesteatoma may appear as a
cyst within the tympanic membrane, greasy white debris, or as a mass (picture 10). If
not treated, the cholesteatoma may gradually enlarge, with eventual erosion of the
ossicular chain, mastoid air cells, and external auditory canal. Patients with
cholesteatoma or suspected cholesteatoma should be referred to an otolaryngologist.
(See "Cholesteatoma in children".)
The light reflex is a cone of light in the anterior inferior portion of the tympanic
membrane that may be seen during otoscopy. Neither its presence nor absence is a
helpful sign in distinguishing AOM from OME. When present, the light reflex can be
observed for change during the assessment of mobility.
DIAGNOSIS
A diagnosis of AOM also can be established if there is acute purulent otorrhea and otitis
externa has been excluded [22]. (See "External otitis: Pathogenesis, clinical features, and
diagnosis", section on 'Diagnosis'.)
Bulging of the tympanic membrane The best and most reproducible sign of
acute inflammation is distinct fullness or bulging of the tympanic membrane (picture
4) [10,15,17,19]. Experienced otoscopists rarely make the diagnosis of AOM in the
absence of bulging of the tympanic membrane [15,19]. (See 'Position' above.)
Other signs of inflammation Signs of acute inflammation are necessary to
differentiate AOM from otitis media with effusion (OME). Marked redness of the
tympanic membrane is another sign of acute inflammation [22]. However, marked
redness of the tympanic membrane without bulging is unusual in AOM [15]. A
distinctly red tympanic membrane in the absence of bulging or impaired mobility has a
positive predictive value of only 15 percent for AOM [17].
Nonotoscopic signs and symptoms such as fever, ear tugging, or otalgia must be
accompanied by abnormal otoscopic findings to make a diagnosis of AOM. As an
example, a child who complains of ear pain may be diagnosed with AOM when he or
she also has a bulging tympanic membrane.
MEE MEE can be confirmed by one or both of the following findings on otoscopy
[22]:
Bubbles or an air-fluid level (picture 6)
Two or more of the following:
-Abnormal color (white, yellow, amber, or blue)
-Opacity (involving part or all of the tympanic membrane) not due to
scarring
-Impairment of mobility (movie 2)
MEE also can be confirmed by myringotomy/tympanocentesis, but this procedure is
rarely performed in the primary care setting [5,10].
MEE is necessary but not sufficient for a diagnosis of AOM; there also must be
bulging of the tympanic membrane or other signs of acute inflammation. If a child has
MEE but no evidence of acute inflammation, he or she has OME.
Etiologic diagnosis Tympanocentesis (aspiration of the middle ear fluid) for culture is
required for etiologic diagnosis. Etiologic diagnosis is not necessary in most cases of AOM
since the antimicrobial agent can be chosen empirically. However, tympanocentesis is
warranted if the patient with AOM appears toxic, has immune deficits, or has failed
previous courses of antibiotic therapy. (See "Acute otitis media in children: Treatment",
section on 'Treatment failure'.)
Otitis media with effusion Middle ear effusion (MEE) with decreased mobility and
opacification or cloudiness of the tympanic membrane occurs in both AOM and OME.
However, careful evaluation of the position, color, and other findings of the tympanic
membrane can help to distinguish AOM from OME [20]. (See 'Otoscopy' above.)
In AOM, the tympanic membrane is usually bulging (picture 4); in OME, it is usually
retracted (picture 7) or in the neutral position.
In AOM, the tympanic membrane is typically white or pale yellow; in OME, it is
typically amber or blue.
In AOM, pus may be visualized behind the tympanic membrane (picture 4); the
tympanic membrane may be perforated with acute purulent otorrhea, or bullae may
be present. In OME, a fluid level (picture 6) or bubbles may be seen.
Other conditions Other conditions share some of the otoscopic and nonotoscopic
features of AOM, but the history and physical examination should readily distinguish these
conditions from AOM. (See "External otitis: Pathogenesis, clinical features, and
diagnosis".)
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)
Basics topic (see "Patient education: Ear infections (otitis media) (The Basics)")
Beyond the Basics topic (see "Patient education: Ear infections (otitis media) in
children (Beyond the Basics)")
Authors:
Jerome O Klein, MD
Stephen Pelton, MD
Section Editors:
Morven S Edwards, MD
Glenn C Isaacson, MD, FAAP
Deputy Editor:
Mary M Torchia, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Jan 24, 2017.
INTRODUCTION Acute otitis media (AOM), also called purulent otitis media and
suppurative otitis media, occurs frequently in children. It is the most common diagnosis for
which they receive antibiotics [1,2].
DIAGNOSIS OF AOM The clinical diagnosis of acute otitis media (AOM) requires
bulging of the tympanic membrane or other signs of acute inflammation and middle ear
effusion (picture 1) [3,4]. (See "Acute otitis media in children: Diagnosis", section on
'Diagnosis'.)
CLINICAL COURSE With appropriate antibiotic therapy, the systemic and local signs
and symptoms of acute otitis media (AOM) usually resolve in 24 to 72 hours [5,6].
Symptoms and signs resolve more slowly in children who are managed with analgesia and
observation initially. In a 2013 meta-analysis of seven randomized trials and three
observational studies (1409 children), ear pain resolved within three days in 50 percent of
children and within seven to eight days in 90 percent of children who did not receive
antibiotic therapy [7].
Whether initially treated with antibiotics or not, persistence of middle ear effusion after the
resolution of acute symptoms is common. In a prospective study of 2565 children followed
from birth, middle ear effusion (diagnosed via pneumatic otoscopy) persisted for weeks to
months after the onset of AOM [8]. At two weeks, 70 percent still had effusion; at one
month, 40 percent still had effusion; at two months, 20 percent still had effusion; and at
three months, 10 percent still had effusion (figure 1).
The clinical features, complications, and management of persistent middle ear effusion are
discussed separately. (See "Otitis media with effusion (serous otitis media) in children:
Clinical features and diagnosis" and "Otitis media with effusion (serous otitis media) in
children: Management".)
SYMPTOMATIC THERAPY
Systemic and topical analgesics Pain is a common feature of acute otitis media
(AOM) and may be severe [5]. We recommend treatment to reduce ear pain in children
with AOM whether or not they are treated with antibiotics [3].
We suggest oral ibuprofen or acetaminophen for pain control in children with AOM.
Topical benzocaine, procaine, or lidocaine preparations (if available) are an alternative for
children 2 years but should not be used in children with tympanic membrane perforation.
Topical benzocaine is avoided in children <2 years because of the risk of
methemoglobinemia [9]. Topical benzocaine products have been withdrawn from the
market in the United States because they have not been evaluated by the US Food and
Drug Administration (FDA) for safety, effectiveness, and quality [10]. (See "Topical
anesthetics in children", section on 'Benzocaine'.)
The efficacy of topical benzocaine and lidocaine in reducing AOM-associated ear pain has
also been evaluated in randomized trials [12]. In a trial in which 54 children (5 to 19 years)
who presented to an emergency department with ear pain and AOM were randomly
assigned to treatment with a topical benzocaine preparation or olive oil placebo, more
children in the treatment group reported a 25 percent reduction in ear pain score 30
minutes after treatment (96 versus 70 percent) [13].
Studies of the efficacy of antihistamines and decongestants in treating AOM suggest a lack
of benefit and a potential for delayed resolution of middle ear fluid. A 2007 systematic
review found that decongestants and antihistamines alone or in combination were
associated with increased medication side effects and did not improve healing or prevent
surgery or other complications in AOM [15]. In addition, treatment with antihistamines may
prolong the duration of middle ear effusion [16].
In children with AOM and known or suspected nasal allergy, an oral decongestant or
antihistamine may provide symptomatic relief of nasal congestion. When treating such
children, practitioners should weigh the potential symptomatic benefit against the reported
adverse events and potential for prolongation of middle ear effusion.
(See "Pharmacotherapy of allergic rhinitis", section on 'Approach to specific patient
groups'.)
The American Academy of Pediatrics (AAP) recommends that over-the-counter cough and
cold medications not be given to infants and children <6 years of age because of the risk
of life-threatening side effects [17,18]. (See "The common cold in children: Management
and prevention", section on 'Over-the-counter medications'.)
The choice of strategy depends upon the age of the child and the severity of illness:
We recommend that children <6 months with AOM be treated immediately with an
appropriate antibiotic. (See 'Initial antimicrobial therapy' below.)
Febrile infants younger than 60 days who are diagnosed with AOM may require
additional evaluation before initiation of antimicrobial therapy to avoid masking an
invasive bacterial infection. (See "Febrile infant (younger than 90 days of age):
Outpatient evaluation", section on 'Ancillary studies'.)
We suggest that children six months to two years with bilateral AOM be treated
immediately with an appropriate antibiotic. We also suggest antibiotic treatment for
children six months to two years with unilateral AOM.
For children six months to two years with unilateral AOM and mild symptoms, the
American Academy of Pediatrics (AAP) guideline (2013) permits initial observation
after joint decision-making with the parent(s)/caregiver [3]. However, given the high
rate of treatment failure among children <24 months with unilateral nonsevere AOM
who are initially managed with observation and analgesia [20], we suggest that such
children be treated with antimicrobial therapy. (See 'Initial antimicrobial
therapy' below.)
We suggest that children 2 years who appear toxic; have persistent otalgia for
more than 48 hours; have temperature 102.2F (39C) in the past 48 hours; have
bilateral AOM or otorrhea; or have uncertain access to follow-up be immediately
treated with an appropriate antibiotic. (See 'Initial antimicrobial therapy' below.)
For children 2 years who are normal hosts (eg, immune competent, without
craniofacial abnormalities) with mild symptoms and signs and no otorrhea, initial
observation may be appropriate if the caretakers understand the risks and benefits of
such an approach. (See 'Initial observation' below.)
In a 2006 meta-analysis of individual data from six high-quality randomized trials (1643
children age 6 months to 12 years), children who were younger than two years who had
bilateral AOM and children with otorrhea benefited most from antibiotic therapy [5]. Among
children younger than two years with bilateral AOM, 25 percent (95% CI 14-36 percent)
fewer children treated with antibiotics than with symptomatic care continued to have
pain and/or fever on days three to seven of illness. Among children with otorrhea, 36
percent (95% CI 19-53 percent) fewer children treated with antibiotics than with
symptomatic care continued to have pain and/or fever on days three to seven of illness.
Antibiotics reduced pain at two to three days (seven trials, 2320 patients): 11.6
versus 15.9 percent (relative risk [RR] 0.70 95% CI 0.57-0.86)
Antibiotics reduced tympanic membrane perforations (five trials, 1075 patients): 1.9
versus 4.8 percent (RR 0.37 95% CI 0.18-0.76)
Antibiotics reduced contralateral episodes of AOM (four trials, 906 patients): 10.6
versus 18.8 percent (RR 0.49 95% CI 0.25-0.95)
Antibiotics did not affect the rate of late recurrence (six trials, 2200 patients):
approximately 20 percent
Antibiotics increased adverse events (vomiting, diarrhea, or rash): 27.1 versus 19.6
percent (RR 1.38 95% CI 1.19-1.59)
Serious complications (eg, mastoiditis, meningitis) were rare in both the treatment
and placebo groups
Randomized trials comparing immediate versus delayed antibiotics have used different
outcome measures (eg, parental satisfaction, rate of filled prescriptions, etc) and types of
follow-up (eg, telephone versus office examination), but also document earlier resolution of
symptoms and signs of tympanic membrane inflammation among children who receive
immediate treatment [21-26].
Systematic reviews and meta-analyses suggest that many children with AOM do well with
initial observation and analgesia only, and that the benefits of antibiotics are modest [6,27-
30]. However, many of the studies included in the meta-analyses had increased risk of
bias (related to nonstringent diagnostic criteria, inclusion of children with mild disease,
exclusion of patients <2 years of age, use of an inappropriate antibiotic or inappropriate
dose, etc), making the results difficult to interpret [31-34]. Exclusion of children with severe
symptoms biases toward the null hypothesis (ie, no difference between early antimicrobial
treatment and observation).
Individual randomized trials that used stringent diagnostic criteria and experienced
otoscopists to make the diagnosis of AOM and appropriate antibiotic regimens to treat
AOM indicate that children younger than two years benefit from antibiotic therapy [35,36].
Pooled data from these trials indicate increased rates of treatment failure among placebo
recipients <24 months with unilateral nonsevere AOM (40 versus 14 percent among
antibiotic recipients; relative risk 0.34, 95% CI (0.18-0.65) [20]. These and other
randomized trials suggest that children with "severe" (defined by fever and ear pain score)
or bilateral AOM also benefit from antibiotic therapy [20,37,38].
The 2013 AAP and American Academy of Family Physicians (AAFP) guideline
recommends immediate antimicrobial treatment for children <6 months, children with
severe signs or symptoms (defined by moderate or severe ear pain, ear pain for 48
hours, or temperature 39C [102.2F]) and bilateral AOM in children <24 months of age
[3]. The 2013 AAP/AAFP guideline recommends either immediate treatment or
observation (with pain control) for children between 6 and 24 months with unilateral
nonsevere AOM and for children 24 months with unilateral or bilateral nonsevere AOM.
However, given the additional analysis now available showing a high rate of treatment
failure among children <24 months with unilateral nonsevere AOM [20], we suggest that
such children be treated at the time of diagnosis with antimicrobial therapy.
Guidelines from many other countries (eg, the Dutch College of General Practitioners)
recommend a no or delayed antibiotic strategy for most children 6 months of age with
AOM.
INITIAL ANTIMICROBIAL THERAPY When the decision is made to treat acute otitis
media (AOM) with antimicrobial agents, the selection among available drugs (table 1) is
based upon:
First-line therapy
Initial antimicrobial therapy for children with penicillin allergy are discussed below.
(See 'Penicillin allergy' below.)
Increasing the dose of amoxicillin from 40 mg/kg per day to 90 mg/kg per day increases
the concentration of amoxicillin in the middle ear [44]. The increased concentrations
provide activity against most intermediate strains of Streptococcus pneumoniae, as well as
many of the resistant strains. Only S. pneumoniae that are highly resistant to penicillin,
approximately 2 percent of pneumococcal isolates using a breakpoint of 8 mcg/mL for
highly resistant, will not respond to high-dose amoxicillin [3,45].
In a 2013 meta-analysis of five trials (1601 children <12 years), once or twice daily dosing
with amoxicillin or amoxicillin-clavulanate was similar to three times daily dosing in clinical
cure of AOM, recurrence of AOM, and adverse effects [47]. We suggest twice daily dosing
based on pharmacokinetic and pharmacodynamic principles, results of double
tympanocentesis (ie, before and after treatment) studies demonstrating middle ear
sterilization with twice daily regimens, and the lack of any substantial data with once daily
regimens (only 33 patients in the meta-analysis received once daily therapy) [48,49].
Delayed reaction For children who report penicillin allergy but who did not experience
an immediate type 1 hypersensitivity reaction (anaphylaxis, angioedema, bronchospasm,
or urticaria), we suggest one of the following:
Cefdinir 14 mg/kg per day orally in one or two doses (maximum 600 mg/day)
Cefpodoxime 10 mg/kg orally in two doses (maximum 400 mg/day)
Cefuroxime suspension 30 mg/kg per day orally divided in two doses (maximum
1 g/day)
Cefuroxime tablets 250 mg orally every 12 hours
Ceftriaxone 50 mg/kg intramuscularly once per day (maximum 1 g/day) for one to
three doses (if there is symptomatic improvement within 48 hours of the first dose,
additional doses are not necessary; if symptoms persist, a second, and if necessary,
a third dose are administered [50])
The oral regimens do not achieve sufficient concentration in the middle ear to eradicate
penicillin-resistant S. pneumoniae.
Immediate reaction Macrolide or lincosamide antibiotics can be used to treat AOM in
children who have had an immediate type 1 hypersensitivity reaction (anaphylaxis,
angioedema, bronchospasm, or urticaria) to amoxicillin or other beta-lactam antimicrobial
agents. However, macrolide or lincosamide resistance is common (approximately 25 to 35
percent) among isolates of S. pneumoniae, and macrolides and lincosamides generally
are not effective for eradication of H. influenzae [46,51,52].
Azithromycin 10 mg/kg per day orally (maximum 500 mg/day) as a single dose on
day one and 5 mg/kg per day (maximum 250 mg/day) for days two through five
Clarithromycin 15 mg/kg per day orally divided into two doses (maximum 1 g/day)
Erythromycin-sulfisoxazole 50 mg/kg per day orally of the erythromycin component
divided into three to four doses (maximum 2 g/day erythromycin or
6 g/day sulfisoxazole); erythromycin plus sulfisoxazole is often rejected by patients
based upon taste and frequency of dosing [53]
The optimal dose for clindamycin therapy for AOM is uncertain; the American
Academy of Pediatrics (AAP) suggests a dose of 10 to 25 mg/kg per day orally
divided in three doses (maximum 1.8 g/day) for mild to moderate infections and 30 to
40 mg/kg per day orally divided in three doses (maximum 1.8 g/day) [3,54]
Increasing the dose of macrolide antibiotics does not overcome macrolide resistance
among pneumococcal isolates (as with beta-lactam drugs) [43].
AOM with perforation For children with AOM and tympanic membrane perforation, we
suggest oral rather than topical antibiotic therapy. We suggest amoxicillin 90 mg/kg per
day orally divided in two doses (we suggest a maximum of 3 g/day) as the preferred first-
line oral therapy. Because of the possibility of group A streptococcus, an agent other than
TMP-SMX should be used. For patients with acute otorrhea, 10 days of oral therapy is
more effective than a shorter course [55].
Although topical therapy with quinolone otic drops (ofloxacin or ciprofloxacin) is equivalent
to oral therapy for treatment of otorrhea in children with tympanostomy tubes or chronic
suppurative otitis media, topical therapy has not been studied in children with AOM and
acute perforation [56,57]. Nonantimicrobial topical agents, such as benzocaine or olive oil,
should not be used in patients with perforation of the tympanic membrane.
(See "Tympanostomy tube otorrhea in children: Causes, prevention, and management",
section on 'Treatment'.)
Duration of therapy The duration of treatment varies with age, associated clinical
features, and antimicrobial agent:
Most clinical trials and standard pediatric practice provide a 10-day course of an oral
antimicrobial agent for the treatment of AOM [58-61]. However, some data suggest that a
shorter course (ie, seven days) may be adequate for older children [62].
Many of the studies comparing short- and long-term antibiotic therapy had limitations that
precluded definitive conclusions (eg, lack of blinding, failure to use strict diagnostic criteria
or directly compare the same antibiotic agent) [63]. These limitations were addressed in a
trial that randomly assigned 520 children 6 through 23 months of age with strictly defined
AOM to treatment with amoxicillin-clavulanate for 10 days or for five days followed by five
days of placebo [61]. The rate of clinical failure (defined as worsening of symptoms or
otoscopic signs of AOM during treatment or lack of complete/near complete resolution of
symptoms and signs at the end of treatment) was lower among those assigned to 10 days
of treatment (16 versus 34 percent; difference of 17 percentage points [before rounding]
95% CI 9-25). The rate of adverse events did not differ between groups. The trial did not
address duration of treatment in children older than two years.
When the initial observation strategy is chosen, caretakers must understand the risks and
benefits, and appropriate follow-up must be ensured so that antibiotic therapy can be
initiated if symptoms worsen or persist after 48 to 72 hours [3]. Unilateral AOM at first
observation may rapidly progress to bilateral disease during the early hours of illness.
Adequate follow-up may include a parent-initiated visit or phone contact if symptoms
worsen or do not improve at 48 to 72 hours, a scheduled follow-up appointment in 48 to 72
hours, or giving parents an antibiotic prescription that can be filled if illness does not
improve in this time frame [22,23,64-67]. (See 'Follow-up' below.)
The 2013 American Academy of Pediatrics (AAP) and American Academy of Family
Physicians (AAFP) guideline suggests initial observation (with pain control) as an option
for healthy children (ie, without conditions that predispose to AOM) between 6 and 24
months with unilateral nonsevere AOM and for children 24 months with unilateral or
bilateral nonsevere AOM [3]. This is a change from the 2004 guidelines, which suggested
initial observation as an option for children 6 months with "uncertain" diagnosis and
children 2 years with non-severe illness [68].
Guidelines from many other countries (eg, the Dutch College of General Practitioners)
recommend no antibiotics or delayed antibiotics for most children 6 months of age with
AOM.
FOLLOW-UP
Children who worsen or fail to improve after 48 to 72 hours of initial observation and
symptomatic treatment without antibiotics should be started on antibiotics. (See 'Initial
antimicrobial therapy' above.)
Resolved symptoms Follow-up for children whose symptoms have resolved depends
upon the child's age and underlying medical problems, particularly language delay or
learning problems.
We suggest that:
Children <2 years be seen 8 to 12 weeks after diagnosis (by which time middle ear
effusion will have resolved in 80 to 90 percent (figure 1)); many such children will
already have a routine healthcare visit scheduled within this time frame
Children 2 years who have language or learning problems be seen 8 to 12 weeks
after diagnosis AOM
Children 2 years who are without language or learning problems be followed up at
their next health maintenance visit, or sooner if there are concerns regarding
persistent hearing loss
The main reason for follow-up of children with resolved symptoms is to monitor the
resolution of middle ear effusion which is associated with conductive hearing loss.
Persistent middle ear effusion is common after the resolution of acute symptoms. In a
large prospective study, middle ear effusion persisted for weeks to months after the onset
of AOM in children (figure 1) [8]. (See 'Clinical course' above.)
The management of persistent middle ear effusion is discussed separately. (See "Otitis
media with effusion (serous otitis media) in children: Clinical features and diagnosis",
section on 'Hearing loss' and "Otitis media with effusion (serous otitis media) in children:
Management", section on 'Overview of management'.)
If pain occurs or persists in a child with AOM and tympanic membrane perforation, causes
other than AOM must be considered. The pain is unlikely to be due to AOM because the
pressure of middle ear fluid is relieved when the tympanic membrane is perforated. Other
possible causes include:
Nonantimicrobial topical agents, such as benzocaine or olive oil, should not be used to
treat pain in patients with perforation of the tympanic membrane.
Patients with perforation that persists for three months or longer (with or without
suppurative drainage) should be referred to an otolaryngologist for further management
[69]. Prevention of chronic suppurative otitis media entails prompt and appropriate
treatment of AOM [70]. Chemoprophylaxis is not warranted. (See "Chronic suppurative
otitis media (CSOM): Clinical features and diagnosis" and "Chronic suppurative otitis
media (CSOM): Treatment, complications, and prevention".)
TREATMENT FAILURE
Fluid may persist in the middle ear for prolonged periods, even when the antimicrobial
agents have sterilized the effusion and the acute signs and symptoms are no longer
present. Persistent middle ear effusion after the resolution of acute symptoms is not an
indication of treatment failure or an indication for additional antibiotic therapy [71].
(See 'Clinical course' above.)
Treatment failure suggests either the initial therapy was not adequate or another disease is
present. (See 'Approach' below and "Acute otitis media in children: Diagnosis", section on
'Differential diagnosis'.)
Approach
Patients initially treated with amoxicillin We suggest that patients who fail
treatment with high-dose amoxicillin be treated with amoxicillin-clavulanate [3]. The
dose is 90 mg/kg per day amoxicillin and 6.4 mg/kg per day of clavulanate divided in
two doses (we suggest a maximum of 3 g/day). Adolescents 16 years who can take
large tablets can use extended-release amoxicillin-clavulanate 1 to 2 g of the
amoxicillin component and 62.5 to 125 mg of the clavulanate component every 12
hours.
We prefer amoxicillin-clavulanate for children who fail treatment
with amoxicillin because of its efficacy against beta-lactamase-producing H.
influenzae and Moraxella catarrhalis; for S. pneumoniae, amoxicillin and amoxicillin-
clavulanate have equivalent efficacy.
Patients initially treated with amoxicillin-clavulanate and without immediate
reaction to amoxicillin Alternatives to high-dose amoxicillin-clavulanate for patients
without immediate reaction to penicillin include cephalosporins or quinolones.
However, with the exception of ceftriaxone, the alternative cephalosporins are less
potent against penicillin-resistant S. pneumoniae:
Cefdinir 14 mg/kg per day orally in one or two doses (maximum
600 mg/day) [75].
Cefpodoxime 10 mg/kg orally in two doses (maximum 400 mg/day).
Cefuroxime suspension 30 mg/kg per day orally divided in two doses (maximum
1 g/day); the spectrum of activity of cefuroxime is excellent for AOM; however,
because children may find it unpalatable [53,76], its usefulness as a second-line
agent may be limited [50].
Cefuroxime tablets 250 mg orally every 12 hours.
Ceftriaxone 50 mg/kg intramuscularly or intravenously once per day
(maximum 1g/day) for one to three doses (if there is symptomatic improvement
within 48 hours of first dose, additional doses are not necessary; if symptoms
persist, a second, and if necessary, a third dose are administered [50]).
Parenteral ceftriaxone 50 mg/kg achieves high levels in the middle ear and is
effective for the treatment of AOM in children who fail amoxicillin [3]; although the
US Food and Drug Administration (FDA) has approved a single dose of
parenteral ceftriaxone for the treatment of AOM in children, an open-label
prospective study suggested that three doses were superior in eradicating
penicillin-resistant S. pneumoniae from the middle ear [77].
Levofloxacin 10 mg/kg orally every 12 hours for 10 days for children six months
to five years or 10 mg/kg per orally once daily for 10 days for children 5 years
(maximum 500 to 750 mg/day) [78].
Levofloxacin should be reserved for children with AOM refractory to other drugs
(ideally it should only be used in children who have had serotype 19A isolated
from the middle ear that is susceptible to levofloxacin) [74]; levofloxacin is not
approved by the FDA for the treatment of AOM, and levofloxacin resistance
among S. pneumoniae respiratory isolates has been described in adults and
rarely in children [79].
Trimethoprim-sulfamethoxazole (TMP-SMX), macrolides (eg, erythromycin-
sulfisoxazole, azithromycin, clarithromycin), and lincosamides (eg, clindamycin) are
not recommended for AOM that fails to respond to treatment with high-
dose amoxicillin or amoxicillin-clavulanate. Pneumococcal surveillance studies
indicate that resistance to these agents is substantial [45,80]. Macrolides and
lincosamides have limited activity against nontypeable H. influenzae, which is a more
likely pathogen among children who have failed initial amoxicillin therapy.
Patients initially treated with macrolides or clindamycin The management of
treatment failure in children with AOM and immediate hypersensitivity reactions to
penicillin who were initially treated with macrolides or clindamycin is challenging. The
pathogens most likely in this scenario are nontypeable H. influenzae (either beta
lactamase-positive or beta lactamase negative) or multidrug resistant S. pneumoniae.
Consultation with a pediatric infectious diseases expert and/or pediatric
otolaryngologist may be warranted.
Our suggested approach is as follows:
Tympanocentesis (if available), which will provide relief of ear pain and permit
culture and susceptibility testing to guide antimicrobial selection. Concomitant
placement of a tympanostomy tube may be warranted. A discussion of the
tympanocentesis procedure is beyond the scope of this topic review, but is
available in reference [81].
If tympanocentesis is not available, we suggest levofloxacin 10 mg/kg orally
every 12 hours for 10 days for children six months to five years or 10 mg/kg per
orally once daily for 10 days for children 5 years (maximum 500 to
750 mg/day) [78]. Levofloxacin is not approved by the FDA for the treatment of
AOM and should be reserved for AOM refractory to other drugs.
Most nontypeable H. influenzae are susceptible to TMP-SMX, but susceptibility of S.
pneumoniae varies geographically. TMP-SMX may be an option in areas with high
rates of susceptibility.
RECURRENT AOM Recurrent acute otitis media (AOM) is defined by the development
of signs and symptoms of AOM soon after completion of successful treatment. It is
particularly important to establish the diagnosis of recurrent AOM with bulging of the
tympanic membrane and signs of inflammation. Otherwise, persistent middle ear effusion
in a child with a febrile upper respiratory infection may be misinterpreted as a recurrent
episode and the child may receive antibiotics unnecessarily.
There are no randomized trials to guide treatment of recurrent AOM in children. The
approach varies depending upon the therapy that was used for recent episodes. Treatment
of recurrent AOM must include coverage for resistant pathogens, particularly S.
pneumoniae.
When recurrence occurs within 15 days of completion of antimicrobial treatment for the
previous episode, we suggest:
Ceftriaxone 50 mg/kg per day intramuscularly (IM) or intravenously (IV) for three
days, or
Ceftriaxone 50 mg/kg per dose IM or IV every 36 hours for a total of two doses, or
Levofloxacin 10 mg/kg every 12 hours orally for 10 days for children six months to
five years or 10 mg/kg per once daily for 10 days for children 5 years (maximum 500
to 750 mg/day) [78]
When the recurrence occurs more than 15 days after completion of the treatment for the
previous episode, it is most often due to a different pathogen than the previous episode.
Although the child is at higher risk for a nonsusceptible pathogen, we suggest high
dose amoxicillin-clavulanate as initial therapy, even if the child received amoxicillin-
clavulanate for the previous episode.
Tympanostomy tube insertion may be warranted for children with 3 distinct and well-
documented episodes of AOM within six months or 4 episodes within 12 months if middle
ear fluid is also present [82]. (See "Acute otitis media in children: Prevention of
recurrence", section on 'Tympanostomy tubes'.)
AIRPLANE TRAVEL Children with Eustachian tube dysfunction, including those with
acute otitis media (AOM), may have pain during airplane descent [83,84]. Most
commercial airplanes have pressurized cabins, with the pressure equal to that at 7000 to
10,000 feet. During the flight, middle ear pressure gradually equilibrates through
swallowing or absorption of air by the middle ear mucosa. With airplane descent, the
pressure in the cabin increases to that at landing altitude. If middle ear pressure does not
increase accordingly (ie, if the Eustachian tube "locks in" the reduced pressure, due to
obstruction of the nasopharyngeal orifice), the tympanic membrane may be forced
medially and stretched, which can lead to painful barotrauma: bleeding into the tympanic
membrane (picture 2), formation of fluid exudates in the middle ear, and occasionally to
tympanic membrane rupture [85]. Upper respiratory infection appears to be a predisposing
condition for aerotitis (inflammation of the ear caused by changes in atmospheric pressure,
also known as barotitis). (See "Ear barotrauma", section on 'Etiology'.)
Interventions to equalize middle ear and atmospheric pressure have not been well studied
in controlled trials. We suggest that children be awake during descent and chewing gum or
food (or sucking on a pacifier or bottle if they are too young to chew gum or food) to open
the Eustachian tube and facilitate equalization of middle ear pressure [86]. Autoinflation via
the Valsalva maneuver (forced exhalation with the mouth and nose closed) or a purpose-
manufactured nasal balloon also may be helpful in older children [87]. In younger children,
nasal bulb suction may be helpful. We do not suggest preflight treatment with
antihistamines or decongestants. In a randomized trial, predeparture administration
of pseudoephedrine did not decrease ear pain, but was associated with increased
drowsiness [88].
There is little published information describing other adverse effects of airplane travel in
children with AOM. However, there are no reports of extratemporal extension of AOM
related to flying.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
Basics topics (see "Patient education: Ear infections (otitis media) (The
Basics)" and "Patient education: Ruptured eardrum (The Basics)")
Beyond the Basics topic (see "Patient education: Ear infections (otitis media) in
children (Beyond the Basics)")
The diagnosis of acute otitis media (AOM) requires bulging of the tympanic
membrane or other signs of acute inflammation and middle ear effusion (picture 1).
The importance of accurate diagnosis is crucial to avoidance of unnecessary
treatment. (See 'Diagnosis of AOM' above and "Acute otitis media in children:
Diagnosis", section on 'Diagnosis'.)
We suggest oral ibuprofen or acetaminophen to treat ear pain in children with AOM
(Grade 2B). Topical benzocaine, procaine, or lidocaine preparations (if available) are
an alternative for children 2 years, but should not be used in children with tympanic
membrane perforation. We recommend NOT using
decongestants and/or antihistamines (Grade 1A). (See 'Symptomatic
therapy' above.)
The choice of initial treatment with antibiotics or observation depends upon the age
of the child and the laterality and severity of illness (see 'Antibiotic therapy versus
observation' above):
We recommend that children with AOM who are <6 months be treated with
antibiotics (Grade 1A).
We suggest that children with AOM who are between six months and two years
be treated with antibiotics (Grade 2A).
We suggest that children 2 years who appear toxic; have persistent otalgia for
more than 48 hours; have temperature 102.2F (39C) in the past 48 hours;
have bilateral AOM or otorrhea; or have uncertain access to follow-up be
immediately treated with an appropriate antibiotic (Grade 2A). (See 'Initial
antimicrobial therapy' above.)
For children 2 years who are normal hosts (eg, immune competent, without
craniofacial abnormalities) and have unilateral AOM with mild symptoms and
signs and no otorrhea, initial observation may be appropriate if the caretakers
understand the risks and benefits of such an approach.
When antibiotic treatment is warranted, we suggest amoxicillin as the first-line
therapy for AOM in most children (Grade 2B). The dose is 90 mg/kg per day (we use
a maximum of 3 g/day) divided in two doses. We suggest amoxicillin-clavulanate as
the first-line therapy for children with AOM who have received a beta-lactam antibiotic
in the previous 30 days or have concomitant purulent conjunctivitis (Grade 2A). The
dose is 90 mg/kg per day of amoxicillin and 6.4 mg/kg per day of clavulanate divided
in two doses. (See 'First-line therapy' above.)
Macrolides or clindamycin are an alternative for patients who have had immediate
hypersensitivity reactions (eg, anaphylaxis, angioedema, bronchospasm, urticaria) to
penicillin (table 1). However, macrolides and clindamycin lack activity against
most Haemophilus influenzae isolates and approximately one-third of pneumococcal
isolates. Patients with other types of allergic reactions may be treated safely
with cefdinir, cefpodoxime, cefuroxime, or intramuscular ceftriaxone. (See 'Penicillin
allergy' above.)
We generally treat children <2 years, children with tympanic membrane perforation,
and children with recurrent AOM for 10 days. We generally treat children 2 years
without a history of recurrent AOM for five to seven days. (See 'Duration of
therapy' above.)
Treatment failure is defined by lack of symptomatic improvement 48 to 72 hours
after initiation of antimicrobial therapy. We suggest that patients who fail first-line
therapy be treated with amoxicillin-clavulanate (Grade 2B). Alternatives
include cefdinir, cefpodoxime, cefuroxime, and ceftriaxone. (See 'Initial treatment
failure' above.)
Acute otitis media in children: Prevention of recurrence
Authors:
Jerome O Klein, MD
Stephen Pelton, MD
Section Editors:
Sheldon L Kaplan, MD
Glenn C Isaacson, MD, FAAP
Deputy Editor:
Mary M Torchia, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Oct 18, 2016.
The prevention of AOM will be reviewed here. Other topics related to otitis media are
presented separately:
Infants who have their first episode before six months of age or who have siblings with
severe and recurrent AOM are at highest risk for severe and recurrent AOM. It remains
unresolved as to whether early disease damages the Eustachian tube or middle ear
leading to recurrent disease or selects those with anatomic or genetic predisposition to
recurrent disease or both.
PREVALENCE In a claims data study of AOM and recurrent AOM in the United States
between 2001 and 2011, the prevalence of recurrent AOM in children <6 years declined
from 17 to 11 percent after introduction of the 13-valent pneumococcal conjugate
vaccine [5]. In a prospective, longitudinal study in the postpneumococcal conjugate
vaccine era (2006-2016), the reported prevalence of recurrent AOM in children <2 years in
the Rochester community varied depending on how the diagnosis was made and who
made the diagnosis [4]. Among children seen by community clinicians, 27 percent were
diagnosed with recurrent AOM, whereas 14 percent of children seen by validated
otoscopists from a single practice met criteria for recurrent AOM, and only 6 percent when
tympanocentesis was employed for diagnosis of AOM.
OVERVIEW OF APPROACH
Age of the child Children younger than two years appear to receive the most
benefit from antibiotic prophylaxis.
Age at first episode Infants who have their first episode of AOM before six months
of age are at risk for severe and recurrent AOM [11], and early initiation of prevention
strategies may be warranted.
Time of year The child who has already had several episodes of AOM by late fall
(ie, November in the northern hemisphere) is likely to have many more before the end
of the winter, whereas the child who has recurrent episodes by late spring (ie, May in
the northern hemisphere) could be expected to have fewer additional infections
during the late spring and summer.
Attendance in large-group day care Children in this setting are likely to have more
respiratory infections, some of which will be accompanied by AOM.
Siblings Children with siblings younger than five years or who attend day care are
at increased risk for recurrent OM [12-15].
Family history The risk of AOM is increased in children whose other family
members have AOM.
The developmental status of the child, particularly language development. Children
with permanent hearing loss, suspected or confirmed speech or language delay or
disorder, developmental delay, autism spectrum disorder, or blindness or
uncorrectable visual impairment are at increased risk for speech, language, or
learning problems [16].
Underlying medical conditions that predispose to AOM (eg, cleft palate, immotile
cilia syndrome, immunoglobulin G [IgG] deficiency, Down syndrome).
The effects of recurrent AOM on the quality of life for the child and family.
Choice of intervention(s) When all factors are considered, the balance of risks and
benefits will favor less aggressive interventions for some children and more aggressive
interventions for others.
Age <2 years (when optimal hearing is necessary for acquisition of language skills),
particularly in children with early onset disease
Multiple risk factors, especially if the risk factor cannot be modified (eg, time of year,
size of day care) (see "Acute otitis media in children: Epidemiology, microbiology,
clinical manifestations, and complications", section on 'Risk factors')
Underlying medical conditions that predispose to recurrent AOM
Comorbid conditions associated with developmental or language delays (the
conductive hearing loss associated with middle ear effusion may persist for weeks to
months after the acute signs of AOM have resolved and may add additional burden in
children with existing delays or deficits)
However, the ultimate decision about whether to use a more aggressive intervention and
which intervention to use is made on a case-by-case basis after discussion of the potential
benefits and risks with the caregivers.
The 2013 American Academy of Pediatrics (AAP) and American Academy of Family
Physicians (AAFP) clinical practice guideline for the diagnosis and management of AOM in
children 6 months through 12 years of age recommends that clinicians not prescribe
prophylactic antibiotics but "may offer" tympanostomy tubes to prevent recurrent AOM [8].
The 2013 AAP/AAFP guideline does not apply to children with underlying conditions that
may alter the natural course of AOM (eg, anatomic abnormalities, genetic conditions with
craniofacial abnormalities, immune deficiencies, or cochlear implants), whereas this topic
review does not make such exclusions.
Children who have had suppurative infections at multiple sites, including recurrent AOM,
may have immunologic deficiencies. The most commonly identified immune abnormality in
children with recurrent AOM is an immunoglobulin G (IgG) subclass deficiency. Children
with recurrent AOM as their only manifestation of recurrent infection rarely have severe
immunologic abnormalities. However, hypogammaglobulinemia, granulocyte defects,
defective cell-mediated immunity, or HIV infection may present with recurrent AOM as part
of the spectrum of either increased infections or infections that resolve more slowly than
expected [17]. (See "Approach to the child with recurrent infections" and "IgG subclass
deficiency", section on 'Clinical manifestations' and "Primary humoral immunodeficiencies:
An overview", section on 'Presentation of humoral immunodeficiency'.)
Children with palatal clefts also are predisposed to the development of recurrent AOM.
This includes children with craniofacial abnormalities that are associated with submucous
palatal clefts, such as micrognathia and glossoptosis (seen in Robin sequence and similar
syndromes). (See "Congenital anomalies of the jaw, mouth, oral cavity, and pharynx",
section on 'Jaw anomalies'.)
EDUCATION Educating parents about ways to decrease exposure to risk factors (eg,
cigarette smoke) and increase exposure to protective factors (eg, breast feeding) is an
appropriate prevention strategy for all children with recurrent AOM [8]. Although the
effectiveness of parental education in preventing recurrent AOM has not been proven,
there is little risk of harm. The risk factors for AOM are discussed in detail separately.
(See "Acute otitis media in children: Epidemiology, microbiology, clinical manifestations,
and complications", section on 'Risk factors'.)
Day care The fewer children in the day care group, the lower the exposure to
respiratory pathogens and risk for AOM.
Exposure to smoke Children exposed to cigarette smoke in the home have more
episodes of AOM than children in smoke-free homes; methods of home heating, such
as wood or coal burning stoves, also may be a risk factor. A suggested mechanism is
increased colonization with bacterial otopathogens leading to greater risk for
development of bacterial OM following viral respiratory tract infection. (See "Control of
secondhand smoke exposure".)
Breastfeeding Breastfeeding for at least three months protects against AOM
during the first year of life. Although this knowledge may not prevent recurrent AOM in
the index case, when family history suggests an increased risk of recurrent AOM,
breastfeeding may help prevent recurrent AOM in subsequent children.
Pacifiers The use of pacifiers after six months of age increases the risk of
recurrent AOM [18].
Randomized trials and systematic reviews have not found administration of pneumococcal
conjugate vaccines after the development of recurrent otitis media to be beneficial [21-24].
This is primarily because the importance of pneumococcal disease decreases as children
with recurrent otitis media get older. PCV13 has not been specifically studied in children
with recurrent otitis media. Despite the lack of evidence, we suggest PCV13 for children
younger than six years who continue to have recurrent episodes of AOM and have not
previously received PCV13. (See "Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children".)
In randomized trials, administration of the PCV7 beginning at age two months was
associated with a modest reduction in AOM (6 to 8 percent) [25-27]. However, the efficacy
of prevention of culture-confirmed pneumococcal AOM caused by a vaccine serotype was
57 to 65 percent. In these and other randomized and observational studies, receipt of
PCV7 was associated with fewer medical visits for AOM and fewer tympanostomy tube
placements [19,25,26,28-33]. Several studies have noted an increase in AOM caused by
pneumococcal serotypes not included in the vaccine (ie, "replacement" serotypes)
[25,34,35].
The additional serotypes (particularly serotype 19A) in PCV13 provide additional protection
against AOM and recurrent AOM (table 1) [36]. In prospective surveillance from eight
childrens hospitals in the United States, the proportion of pneumococcal isolates from the
middle ear or mastoid of children that were PCV13 serotypes decreased from 50 percent
in 2011 to 29 percent in 2013 [37]; 19A isolates decreased from 34 to 10 percent. Initial
reports from Israel have also demonstrated declines in OM due to PCV13 vaccine
serotypes and overall otitis media [38]. Continued monitoring is necessary to characterize
the efficacy for prevention of vaccine serotype AOM and monitor for "replacement"
serotypes.
In countries where the pneumococcal conjugate vaccine is not part of the routine
immunization schedule, we suggest pneumococcal conjugate vaccine for infants and
young children at high-risk for recurrent AOM (ie, first episode of AOM at <6 months of
age, older siblings with severe and recurrent AOM). In a randomized trial, 96 infants with
AOM onset at <6 months of age were assigned to receive or not receive PCV7 [39].
Receipt of PCV7 was associated with a 26 percent reduction in AOM, a 36 percent
reduction in emergency department visits for suspected AOM, and a 50 percent reduction
in placement of ventilation tubes.
Pneumococcal polysaccharide vaccine For children older than two years who
continue to have recurrent episodes of AOM, we suggest administration of the 23-valent
pneumococcal polysaccharide (PPSV23) after completion of immunization with PCV13 to
provide coverage for as broad a range of pneumococcal serotypes as possible (table 1).
PPSV23 should be administered at least eight weeks after PCV13 [20].
In a 2015 meta-analysis of five randomized trials including 4736 children age six months to
six years, influenza vaccine slightly reduced the risk of at least one episode of AOM over
six months of follow-up (risk difference [RD] 4 percent [95% CI 2 to 7]; risk ratio [RR] 0.80,
95% CI 0.67 to 0.96) [42]. In meta-analysis of two trials (1223 children), influenza vaccine
also appeared to reduce the number of antibiotic prescriptions (RD 15 percent, 95% CI [0-
30]; RR 0.70, 95% CI 0.59-0.83), but it is unclear whether this reduction was due to
influenza vaccine or increased frequency of "watchful waiting" for AOM to avoid overuse of
antibiotics. It is not surprising that influenza vaccine has only a modest impact on AOM
episodes, because infection with other respiratory viruses, such as respiratory syncytial
virus, parainfluenzae, and human metapneumovirus, appear to have a much greater
association with AOM. (See "Acute otitis media in children: Epidemiology, microbiology,
clinical manifestations, and complications", section on 'Viruses'.)
Indications Antibiotic prophylaxis may be warranted for children who have had 3
distinct and well-documented episodes within six months or 4 episodes within 12 months
[3,46]. It also may be warranted for children with early onset of AOM (ie, at less than six
months of age) who have additional risk factors such as day care attendance, family
history of recurrent OM, or large number of siblings. However, decisions regarding the use
of antibiotic prophylaxis should be made on a case-by-case basis. The potential benefits
(20 to 50 percent fewer episodes) must be balanced with the risk of development of
nasopharyngeal colonization with antibiotic-resistant organisms [44,47]. Additional factors
that influence the decision to use antibiotic prophylaxis are discussed above. (See 'Factors
influencing choice' above.)
The findings of the meta-analysis must be interpreted with caution because the studies
that were included had different entry criteria, used different drugs for different durations,
and observed patients for various lengths of time. Most were conducted before the era of
widespread penicillin-resistant pneumococci and the recommendation for routine
immunization of infants with the pneumococcal conjugate vaccine.
Antibiotic prophylaxis compared with tubes In the only trial comparing antibiotic
prophylaxis and tympanostomy tube placement that excluded children with otitis media
with effusion, antibiotic prophylaxis was more effective [2]. In this trial, 264 children 7 to 35
months of age with recurrent AOM (3 episodes within six months or 4 episodes within 12
months) were randomly assigned to three groups, amoxicillin prophylaxis, myringotomy
and tympanostomy tube placement, or placebo, and followed for two years [2]. The
average rate of new episodes of AOM was decreased in the amoxicillin group compared
with the tympanostomy and placebo groups (0.6, 1.02, and 1.08 new episodes of AOM or
otorrhea per child per year, respectively).
Adverse effects Prolonged use of antibiotic prophylaxis for AOM may result in the
selection of resistant bacteria in the nasopharynx and subsequent respiratory tract
infection with resistant pathogens [44,47]. The treatment of AOM and other upper
respiratory infections caused by antibiotic-resistant organisms is discussed separately.
(See "Acute otitis media in children: Treatment", section on 'Initial antimicrobial
therapy' and "Acute bacterial rhinosinusitis in children: Microbiology and treatment",
section on 'Empiric antibiotic therapy'.)
Additional risks of prolonged antibiotic use include allergic reactions and diarrhea, as well
as Clostridium difficile-associated diarrhea (on rare occasions). (See "Clostridium difficile
infection in children: Microbiology, pathogenesis, and epidemiology", section on 'Risk
factors'.)
Antibiotic choice and regimen When the decision is made to use antibiotic
prophylaxis, we typically use amoxicillin 40 mg/kg orally once per day unless the child has
a penicillin allergy (see "Penicillin allergy: Immediate reactions"). Sulfisoxazole
50 mg/kg orally once per day is an alternative. Cephalosporins usually are not used for
prophylaxis because they have a broader spectrum and are more expensive.
Antibiotic prophylaxis should be provided during the fall, winter, and early spring months,
when respiratory infections are most prevalent, but for no longer than six months [46]. In a
small randomized trial, administration every day was more effective than administration
only during upper respiratory infections [48].
Children without signs of AOM should be examined approximately every two months to
determine the presence and duration of middle ear effusion [7]. The management of
persistent middle ear effusion is discussed separately. (See "Otitis media with effusion
(serous otitis media) in children: Management", section on 'Overview of management'.)
SURGERY
The use of tympanostomy tubes in the prevention of recurrent AOM in otherwise healthy
children has increased as the popularity of chemoprophylaxis has decreased due to
concerns about antibiotic resistance among otopathogens. (See 'Adverse effects' above.)
Indications Tympanostomy tube placement may be warranted for children who have
had 3 distinct and well-documented episodes within six months or 4 episodes within 12
months. Decisions regarding the placement of tympanostomy tubes for recurrent AOM
must be individualized after consideration of the risks and benefits. (See 'Factors
influencing choice' above.)
We suggest tympanostomy tube placement for children who warrant more aggressive
prevention strategies and:
A subsequent systematic review [52] that included only two trials (both of which included
children with OME) [53,54] found that insertion of tympanostomy tubes was associated
with a mean of 1.5 fewer episodes of AOM in the six months after surgery.
In a randomized trial published after the systematic review, 300 children (10 months to 2
years of age) with recurrent AOM (3 episodes in the previous six months) were randomly
assigned to tympanostomy tubes, tympanostomy tubes plus adenoidectomy, or neither
[55]. Treatment failure (defined as two episodes of AOM in two months, three episodes in
six months, or effusion for longer than two months) occurred in fewer patients in the
tympanostomy tube groups (21 and 16 percent in the tympanostomy tube and
tympanostomy tube/adenoidectomy groups, respectively, versus 34 percent in controls).
More children in the tympanostomy tube groups were AOM-free during the one year of
follow-up (48 and 49 percent in the tympanostomy tube and
tympanostomy tube/adenoidectomy groups, respectively, versus 34 percent in controls).
As discussed below, the combination of adenoidectomy and tympanostomy tubes did not
provide any advantage over tympanostomy tubes alone. (See 'Adenoidectomy or
adenotonsillectomy' below.)
Two trials included in the first meta-analysis compared tympanostomy tube placement with
chemoprophylaxis and placebo [2,56]. However, only one excluded children with OME [2].
This study, which is described in greater detail above, found antibiotic prophylaxis
with amoxicillin to be more effective than tympanostomy tube placement or placebo.
(See 'Antibiotic prophylaxis compared with tubes' above.)
OTHER INTERVENTIONS
Xylitol We do not suggest the use of xylitol to prevent recurrent AOM in children.
Although there is some evidence to suggest that xylitol may be beneficial, additional
information is necessary before it can be routinely recommended [63].
Xylitol is a five-carbon sugar alcohol that is used in place of sucrose as a sweetener. It has
been shown to prevent dental caries by inhibiting the growth of Streptococcus mutans and
has been studied as a means of preventing AOM in children attending day care [64-66].
In a 2016 meta-analysis of three randomized trials [67-69], two to three months of xylitol
chewing gum, syrup, or lozenges prevented recurrent AOM among healthy children (mean
age two to five years) attending day care (risk ratio 0.75, 95% CI 0.65-0.88) [66]. In
individual studies, administration of xylitol five times per day was effective [67,68], but
three times per day was not [69]. In a separate randomized trial, xylitol syrup administered
only during respiratory infections did not prevent AOM among children attending day care
[70].
Although the results of the meta-analysis are promising, it has several limitations. The
mean ages in the study populations were older than the age of peak incidence of AOM (2
to 5 years versus 6 to 18 months). In addition, it is not clear that the study conditions (eg,
administration of xylitol five times per day) could be replicated in "the real world." A
subsequent randomized trial in children six months to five years (mean age approximately
22 months) found no benefit of a three-times-daily dosing regimen of xylitol in preventing
recurrent otitis media [71].
The optimal dose, dosing regimen, long-term benefits, and full range of adverse effects
must be determined before xylitol can be recommended to prevent AOM [63].
Two randomized trials, each including >200 children, found no benefit of oral probiotics in
the prevention of recurrent AOM [77,78]. In another randomized trial, more children who
received alpha-streptococcal nasal spray than placebo nasal spray remained AOM-free for
three months (42 versus 22 percent) [79]. Alpha-streptococcal nasal spray is not
commercially available.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)
FARINGOAMIGDALITIS
Author:
Gary R Fleisher, MD
Section Editors:
George A Woodward, MD
Jan E Drutz, MD
Deputy Editor:
James F Wiley, II, MD, MPH
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Aug 14, 2015.
INTRODUCTION Sore throat refers to any painful sensation localized to the pharynx or
surrounding anatomy. The developmental ability of young children to identify and define
their symptoms varies and the physician must pay careful attention to the patient and the
caretaker in order to clarify the exact nature of the complaint.
Sore throat can be the symptom of a disease process that does not directly affect the
pharynx. Occasionally, young patients with dysphagia that results from disease in the area
of the esophagus or with difficulty swallowing because of a neuromuscular disorder may
verbalize these sensations as a sore throat or their symptoms may be interpreted by a
caretaker as a sore throat.
This topic will review conditions that can cause the symptom of sore throat. The discussion
will include pertinent features of the history and physical examination and an algorithmic
approach to common and life threatening conditions. The approach to the child with
infectious pharyngitis is discussed in more detail elsewhere. (See "Group A streptococcal
tonsillopharyngitis in children and adolescents: Clinical features and diagnosis".)
CAUSES
Life-threatening conditions
Common conditions
Viral pharyngitis Infection is the most common cause of sore throat and the etiologic
agents are usually respiratory viruses, including adenoviruses, coxsackie A viruses,
influenza, or parainfluenza virus (table 1). Some of these viruses produce easily
identifiable syndromes, including herpangina or hand, foot, and mouth disease (coxsackie
virus) and pharyngoconjunctival fever (adenovirus). Herpangina is common in infants and
young children and decreases in frequency as age increases. Herpes simplex virus usually
causes stomatitis (discussed below). However, it may cause pharyngitis in the
immunocompromised child, and rarely in the immunocompetent child. (See "Clinical
manifestations and diagnosis of enterovirus and parechovirus
infections" and "Epidemiology and clinical manifestations of adenovirus infection".)
Other conditions
HISTORY Key historical variables that may assist in the diagnosis of a specific cause of
sore throat include respiratory distress, fever, fatigue, and the rapidity of the onset of
symptoms.
Sore throat and respiratory distress The combination of sore throat and
respiratory distress suggests conditions in or near the pharynx that are producing an
obstruction, including epiglottitis, retropharyngeal or lateral pharyngeal abscess,
peritonsillar abscess, massive tonsillar hypertrophy secondary to infectious
mononucleosis, and rarely diphtheria.
Fever Fever points to one of the many infectious causes (table 1) but may also
occur with inflammatory conditions.
Fatigue Fatigue, particularly when prolonged, characterizes infectious
mononucleosis.
Abrupt onset Among the diseases causing pharyngitis, epiglottitis has a
particularly abrupt onset, in a matter of hours, while infectious mononucleosis
manifests over a period of days or weeks.
Other factors in the history that may be important in selected cases include
immunocompromising conditions, immunizations, travel, sexual activity, and frequent
recurrences. The patient with a compromised immune system is susceptible to a number
of infections, including Candida albicans. Diphtheria rarely merits consideration, except in
unimmunized children and those from underdeveloped nations. With a history of oral
sexual activity, pharyngeal gonorrhea may be a concern. Frequently recurring episodes of
pharyngitis are usually secondary to respiratory viruses and/or GABHS infections but may
indicate PFAPA.
Viral pharyngitis that results from Coxsackie virus will be self-evident in a few cases
on the basis of vesicular formation in the posterior pharynx alone (herpangina) or in
combination with involvement of the extremities (hand, foot, and mouth disease).
(See "Clinical manifestations and diagnosis of enterovirus and parechovirus
infections" and "Clinical manifestations and diagnosis of herpes simplex virus type 1
infection".)
The typical appearance of streptococcal pharyngitis includes fever, exudative
pharyngitis, palatal petechiae, and swollen anterior cervical lymph nodes. Strategies
for improving the clinical diagnosis of streptococcal pharyngitis, including a scoring
system, are discussed elsewhere. In general, scoring systems do not replace the
need for rapid streptococcal antigen testing.
Diphtheria causes a particularly thick exudate (diphtheritic membrane), often in
association with tremendous enlargement of the cervical lymph nodes ("bull neck").
(See "Epidemiology and pathophysiology of diphtheria".)
In infectious mononucleosis, the examination may show large, mildly tender
posterior cervical lymph nodes, diffuse lymphadenopathy outside the cervical region,
and splenomegaly or, less commonly, hepatomegaly. Although some young children
with EBV infection do not always develop this typical pattern of signs and symptoms,
many will have fever, pharyngitis, and cervical lymphadenopathy [17]. (See "Clinical
manifestations and treatment of Epstein-Barr virus infection".)
ANCILLARY STUDIES The history and physical examination will often suffice for
diagnosis. Ancillary studies that may be useful include testing for streptococcal disease by
antigen detection or culture and a heterophile test and white blood cell count with
differential for infectious mononucleosis [18]. (See "Group A streptococcal
tonsillopharyngitis in children and adolescents: Clinical features and diagnosis", section on
'Diagnosis'.) Children can have symptomatic primary EBV infection without the production
of heterophile antibodies and EBV specific serology may be necessary to make the
diagnosis [19]. (See "Clinical manifestations and treatment of Epstein-Barr virus
infection".)
A soft-tissue radiographic examination of the lateral neck may be useful in the child who is
ill appearing, has significant difficulty swallowing, or who will not move his neck. An
abnormal epiglottis and a retropharyngeal abscess can be identified on this view (image
1).
In order to diagnose a retropharyngeal abscess, the radiograph should be a true lateral,
and the child must keep the neck in extension during inspiration to avoid a false thickening
of the retropharyngeal space. Findings consistent with a retropharyngeal abscess include
a prevertebral space that is increased in depth compared with the anteroposterior
measurement of the adjacent vertebral body, or a retropharyngeal space that is greater
than 7 mm at C2 or 14 mm at C6 (image 2). Another method for interpreting the width of
the prevertebral space is that it should normally measure no more than half the thickness
of the vertebral body from C1-C4, or the full thickness from C5-C7. If the diagnosis
remains uncertain despite adequate radiographs, a computed tomography (CT) scan
should be obtained. A CT scan will confirm the diagnosis of a lateral abscess (image 3).
If radiographs are normal and a lateral pharyngeal abscess is suspected on the basis of
torticollis or asymmetrically enlarged anterior cervical lymph nodes, then a CT scan is
indicated.
Acutely ill patients Conditions that have immediate life-threatening potential include
epiglottitis, retropharyngeal and lateral pharyngeal abscesses, peritonsillar abscess,
severe tonsillar hypertrophy (usually as an exaggerated manifestation of infectious
mononucleosis), diphtheria, and Lemierre's syndrome.
Generally, stridor and signs of respiratory distress accompany the complaint of sore throat
in epiglottitis and retropharyngeal abscess. Drooling occurs commonly in children with
these two conditions. Patients with epiglottitis, peritonsillar abscess, or severe infectious
tonsillar hypertrophy often experience a change in their voice. In cases of epiglottitis or
retropharyngeal abscess that are not clinically obvious, a lateral neck radiograph, obtained
under appropriate supervision, is confirmatory.
Peritonsillar abscess and tonsillar hypertrophy are diagnosed by visual examination of the
pharynx. Diphtheria, which produces a thick pharyngeal exudate and markedly enlarged
cervical lymph nodes, is rarely a consideration except in unimmunized children, particularly
those from underdeveloped nations.
The next phase of the evaluation of the child with a complaint of sore throat hinges on a
careful physical examination, particularly of the pharynx. The appearance of vesicles on
the buccal mucosa anterior to the tonsillar pillars points to a herpetic stomatitis or
noninfectious syndromes, such as Behets or Stevens-Johnson syndrome (erythema
multiforme), and generalized inflammation of the oral mucosa in a persistently febrile child
suggests Kawasaki disease.
Uncommonly, a small, pointed foreign body, perhaps a fish bone, becomes lodged in the
mucosal folds of the tonsils or pharynx; usually, the history suggests the diagnosis, but an
unanticipated sighting may occur in the younger child. Significant asymmetry of the tonsils
indicates a peritonsillar cellulitis or, if extensive, an abscess. Clinically, the diagnosis of an
abscess is reserved for the tonsil that protrudes beyond the midline, causing the uvula to
deviate to the uninvolved side.
A pharynx that is not inflamed suggests a source of referred pain or irritative pharyngitis.
Sources of referred pain (otitis media, dental abscess, and cervical adenitis) usually are
identified during the examination. Irritative pharyngitis, seen most commonly during the
winter among older children who live in homes with forced hot-air heating, produces
minimal or no pharyngeal inflammation. It often is transient, appearing on arising and
resolving by midday.
Suspected infectious pharyngitis Patients who do not have one of the life threatening
conditions discussed above and do not have another easily identifiable cause of sore
throat (eg, foreign body) are likely to have infectious pharyngitis.
For patients without pharyngeal vesicles who have significant symptoms with pharyngeal
erythema and/or exudate, it is prudent to obtain a rapid test for group A streptococcus,
followed by a throat culture if the rapid test is negative. Back up culture for a rapid antigen
diagnostic test is recommended. However back up testing (either culture or rapid DNA
probe) may not be necessary in older adolescents similar to the approach in adult patients.
(See "Evaluation of acute pharyngitis in adults", section on 'Rapid antigen detection test'.)
In settings where a rapid test is not routinely performed or available, a throat culture for
group A streptococcus should be obtained.
In the rare child with an unusual history, the physician must pursue diagnoses such as
gonococcal pharyngitis (sexual abuse, oral sex) or diphtheria (immigration from an
underdeveloped country, lack of immunization). If no diagnosis has yet been made in a
child who has persistent sore throat and fever, infectious mononucleosis merits
consideration even in the absence of lymphadenopathy and splenomegaly. (See "Clinical
manifestations and treatment of Epstein-Barr virus infection".)
Some authorities find it acceptable not to perform either culture or rapid antigen diagnostic
testing if all clinical features point towards a viral etiology (no exudate, no palatal
petechiae, no cervical lymphadenopathy, URI symptoms present) in a developed country
with a low risk of non-suppurative post-streptococcal complications, such as rheumatic
fever [20].
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SUMMARY
Author:
Michael E Pichichero, MD
Section Editors:
Daniel J Sexton, MD
Morven S Edwards, MD
Deputy Editor:
Elinor L Baron, MD, DTMH
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Feb 16, 2017.
The efficacy of penicillin for primary prevention of ARF was established in the early 1950s
when military recruits with GAS tonsillopharyngitis received injectable penicillin G mixed in
peanut oil or sesame oil with 2% aluminum monostearate [12,13]. GAS eradication and
ARF primary prevention were optimized with injection schedules that provided at least 9 to
11 days of penicillin.
Subsequently, evaluation of GAS tonsillopharyngitis therapies has been based upon GAS
eradication from the upper respiratory tract; it is assumed that such eradication is an
adequate surrogate marker for efficacy in primary prevention of rheumatic fever. Antibiotic
therapy can be helpful for prevention of rheumatic fever if initiated up to nine days
following onset of symptoms [12].
Reducing transmission The rate of GAS transmission from an infectious case to close
contacts (such as a family or school setting) is approximately 35 percent. Antibiotic
treatment does have a role for preventing transmission of GAS. In one study including 47
children with pharyngitis and positive throat culture for GAS, subsequent throat culture
after 24 hours of treatment with penicillin was negative in about 80 percent of cases [14].
In another study including 111 children with positive rapid antigen detection test (RADT)
treated with amoxicillin (50 mg/kg) by 5:00 pm on day 1, negative follow-up RADT the
following morning was observed in 91 percent of patients [15].
Data on the duration of contagion for alternative antibiotics are not available. In untreated
patients, GAS is eliminated from the upper respiratory tract by host immune factors in 50
percent of cases at one month following acute infection [16].
Additional issues related to antibiotic therapy for reducing transmission are discussed
further below. (See 'Follow-up' below.)
TREATMENT Antimicrobial therapy is warranted for patients with symptomatic
pharyngitis if the presence of group A streptococci (GAS) in the pharynx is confirmed by
culture or rapid antigen detection testing (RADT) [17]. The approach to establishing the
diagnosis of acute streptococcal pharyngitis is discussed in detail separately.
(See "Evaluation of acute pharyngitis in adults", section on 'Identifying patients with GAS'.)
In the natural history of GAS pharyngitis, the incubation period is two to four days. Fever
and constitutional symptoms usually resolve within three to four days, even in the absence
of antimicrobial therapy [16]. Clinical improvement has been observed up to 48 hours
sooner in patients receiving penicillin versus placebo within the first two days of illness [5-
9].
Treatment is warranted for patients with negative rapid antigen detection testing but
subsequent positive culture results whose symptoms are resolving, in order to reduce the
likelihood of transmission.
There is some concern that early therapy may suppress host antibody response and
thereby increase risk for recurrent pharyngitis. In a study of 142 children with presumed
GAS pharyngitis, those treated with penicillin at the initial office visit had a higher incidence
of recurrent infection than those for whom treatment was delayed at least 48 hours
(recurrent infection occurred eight times more frequently) [6].
Intramuscular penicillin is the only therapy that has been shown to prevent initial attacks of
rheumatic fever in controlled studies [13,21]. These studies were performed with penicillin
G procaine in oil containing aluminum monostearate; this preparation has since been
supplanted by penicillin G benzathine. There are data suggesting that penicillin G
benzathine is effective for primary prevention of rheumatic fever, although they are not
definitive [22]. Other antimicrobials have been shown to effectively eradicate GAS from the
upper respiratory tract, and it is assumed that such eradication is a surrogate for efficacy in
primary prevention of rheumatic fever.
Resistance Antimicrobial resistance has not been a significant issue in the treatment of
GAS. No clinical isolate of GAS has demonstrated penicillin resistance, likely due to the
organism's lack of altered penicillin-binding proteins and/or inefficient gene transfer
mechanisms for resistance [23,24]. However, streptococcal strains tolerant to penicillin
(eg, strains inhibited but not killed by penicillin in vitro, with ratio of minimum bactericidal
concentration to minimum inhibitory concentration [MIC] of 32) have been described [25-
28]. The clinical significance of such strains is not clear; they have been isolated in the
setting of outbreaks in which penicillin treatment failure was observed, but there was no
difference in failure rates among tolerant and susceptible strains. (See "Antibiotic failure in
the treatment of streptococcal tonsillopharyngitis".)
There have been reports of relatively high levels of resistance to macrolide antibiotics in
some regions of the United States and Asia; given the increasing use of macrolides for
treatment of upper and lower respiratory tract infections, clinicians should be cognizant of
local patterns of antimicrobial resistance [29-39].
Selection Oral penicillin V is the agent of choice for treatment of GAS pharyngitis given
its proven efficacy, safety, narrow spectrum, and low cost [2,40-44]. The appropriate
duration is 10 days of therapy; dosing is outlined in the Table (table 3). This approach is
extrapolated from studies performed in the 1950s demonstrating that treatment of
streptococcal pharyngitis with intramuscular penicillin prevents acute rheumatic fever
[13,21]. (See "Acute rheumatic fever: Treatment and prevention".)
Amoxicillin is often used in place of oral penicillin in children, since the taste of the
amoxicillin suspension is more palatable than that of penicillin. Some data suggest that
oral amoxicillin may be marginally superior to penicillin, most likely due to better
gastrointestinal (GI) absorption [45,46]. In addition, amoxicillin has activity against one-
third of the common pathogens that cause otitis media (which presents concurrently with
GAS tonsillopharyngitis in up to 15 percent of children, particularly those under four years
of age). Dosing is outlined in the Table (table 3). (See "Acute otitis media in children:
Treatment", section on 'Initial antimicrobial therapy'.)
Cephalosporins are acceptable alternatives in patients with recurrent GAS infection but are
not recommended as first-line therapy in national guidelines [47-54]. Cephalosporins have
demonstrated better microbiologic and clinical cure rates than penicillin; these differences
appear to be greater among children than adults, and some favor use of first-generation
cephalosporins as first-line therapy in this group [55-57]. However, second- and third-
generation cephalosporins may facilitate development of antibiotic resistance and are not
favored as first-line therapy [48,49]. (See 'Recurrent infection' below.)
There are a number of acceptable dosing regimens for azithromycin (table 3); these
include the following:
Five-day course
12 mg/kg (not to exceed 500 mg) on day 1, followed by 6 mg/kg (not to exceed
250 mg) on days 2 through 5 [36,43,63]
12 mg/kg (not to exceed 500 mg) on days 1 through 5 [2,64,66]
Three-day course: 20 mg/kg (not to exceed 500 mg) on days 1 through 3 [37,65,66]
Data from studies in adults form the basis for the five-day course of 12 mg/kg on day 1
followed by 6 mg/kg on days 2 through 5; data from studies in children form the basis for
the five-day course of 12 mg/kg and the three-day course of 20 mg/kg.
For the rare patient with an erythromycin-resistant strain of GAS who is unable to tolerate
beta-lactam agents, clindamycin is an appropriate choice [29,33,67]. (See "Penicillin-
allergic patients: Use of cephalosporins, carbapenems, and monobactams".)
Attempts to treat GAS pharyngitis with a single daily dose of penicillin have been
unsuccessful. Although some data suggest that once-daily amoxicillin may be sufficient for
treatment of GAS pharyngitis, others have shown that this approach is not adequate for
effective eradication; further investigation is needed [83-86]. Among the alternative
agents, azithromycin and some cephalosporins
(including cefixime, cefpodoxime, cefadroxil, and cefdinir) are effective for eradication of
pharyngeal streptococci with once-daily dosing [75,87-90].
The approach to treatment of infection due to Streptococcus other than group A, influenza,
infectious mononucleosis, primary HIV infection, N. gonorrhoeae, Mycoplasma
pneumoniae, Chlamydia pneumoniae, and Corynebacterium diphtheriae is discussed
separately. (See related topics.)
In general, test of cure is not necessary for asymptomatic patients or their close contacts
following completion of a course of antimicrobial therapy. The majority of patients with GAS
remaining in their upper respiratory tracts after completing a course of antimicrobial
therapy are asymptomatic Streptococcus carriers [96,97].
However, follow-up test of cure is appropriate testing for asymptomatic index patients and
their asymptomatic household contacts in the following circumstances:
Recurrent infection In the setting of recurrent acute pharyngitis with positive repeat
diagnostic testing, there are several possible explanations [96,98,99]:
In the setting of a second episode of acute pharyngitis with positive repeat diagnostic
testing, a repeat course of treatment is appropriate (table 3). Repeat treatment should be
administered with an agent with greater beta-lactamase stability than the previous agent
[58].
It is not necessary to perform follow-up testing after the second course of therapy unless
the patient remains or becomes symptomatic or unless special circumstances as outlined
above are present. (See 'Antibiotics for group A Streptococcus' above and 'Follow-
up' above.)
In the setting of multiple recurrent episodes, it may be difficult to distinguish true GAS
pharyngitis from viral pharyngitis in the setting of streptococcal carriage. It is likely that
most of these patients are carriers experiencing nonstreptococcal infections. This may be
discernible by evaluating for the presence of GAS during asymptomatic intervals and/or by
typing streptococcal isolates obtained during distinct episodes (with the expertise of a
specialized laboratory). In these circumstances, treatment with clindamycin or amoxicillin-
clavulanate may be beneficial since these agents have demonstrated high eradication
rates for pharyngeal streptococci carriage (table 3) [58,67,100]. (See 'Carriers' below.)
For patients with as many as six GAS infections in a single year or three to four episodes
in two consecutive years, tonsillectomy may be an appropriate therapeutic consideration
[101,102]. This was illustrated in a randomized trial including 187 children with recurrent
pharyngitis, of whom 95 were managed with tonsillectomy [101]. The incidence of
pharyngitis during the first two years of follow-up was significantly lower among the
tonsillectomy group. (See "Tonsillectomy and/or adenoidectomy in children: Indications
and contraindications", section on 'Recurrent throat infection'.)
PREVENTION
Carriers may demonstrate evidence of GAS in the upper respiratory tract during an
episode of viral pharyngitis, suggesting acute streptococcal pharyngitis. In these
circumstances, clinically distinguishing viral from streptococcal pharyngitis can be difficult.
Useful clues may include patient age, season, local epidemiology, and the nature of
presenting signs and symptoms. In addition, pharyngeal strep carriers tend to have low
antistreptolysin O (ASO) titers; they may be just above detectable. (See "Evaluation of
acute pharyngitis in adults".)
Streptococcus carriers are unlikely to spread the organism to close contacts and are at
very low risk for developing suppurative complications or acute rheumatic fever [103].
Moreover, eradication of GAS from the upper respiratory tract of carriers is much more
difficult than eradication of GAS from patients with acute infection [52,96,104]. In general,
except for the circumstances described above, Streptococcus carriers do not require
antimicrobial therapy. (See 'Follow-up' above.)
Vaccination There is no vaccine against GAS available for clinical use, although
development of this preventive measure is under investigation [113,114]. An important area
of uncertainty is whether vaccine-induced antibodies may cross-react with host tissue to
produce nonsuppurative sequelae in the absence of clinical infection.
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Author:
Jan E Drutz, MD
Section Editor:
Teresa K Duryea, MD
Deputy Editor:
Mary M Torchia, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Sep 16, 2016.
GENERAL MEASURES
Expected course of illness Throat pain caused by infections usually lasts a few
days and should improve steadily without worsening.
In a 2013 meta-analysis of six randomized trials and one observational study (344
children), sore throat lasted between two to seven days among children who received
control, placebo, or over-the-counter treatment; sore throat resolved by day 3 in
approximately 60 to 70 percent of cases [1]. The duration of symptoms was similar in
children with and without group A streptococcal (GAS) tonsillopharyngitis.
Indications for reevaluation Indications for reevaluation in children and
adolescents with sore throat include:
Difficulty breathing or drooling (may indicate upper airway obstruction)
(see "Emergency evaluation of acute upper airway obstruction in children",
section on 'Infectious etiologies')
Inability to maintain hydration (see "Clinical assessment and diagnosis of
hypovolemia (dehydration) in children", section on 'Clinical assessment')
Worsening pain or pain that persists for >3 days without improvement
(see 'Worsening or persistent pain' below)
Indications for antibiotics and potential harms of inappropriate use
Antibiotics generally are indicated for laboratory-documented bacterial pharyngitis.
They are not helpful in viral pharyngitis and may be associated with adverse effects
including diarrhea, allergy, increased bacterial resistance, unnecessary expense, etc.
(See "Patient education: What you should know about antibiotics (The Basics)".)
Pain management Management of throat pain is discussed below. (See 'Systemic
analgesia' below.)
Safety and efficacy of over-the-counter medications versus complementary
and alternative therapies Over-the-counter medications for the treatment of sore
throat or other inflammatory conditions (not limited to sore throat) must demonstrate
safety and efficacy in clinical studies before approval by the US Food and Drug
Administration (FDA). In contrast, manufacturers of alternative products can claim
efficacy and safety without providing the rigorous documentation of safety and
efficacy.
Viral infections Viral causes of sore throat that may require antiviral therapy
include:
Influenza A or B viruses (see "Seasonal influenza in children: Prevention and
treatment with antiviral drugs", section on 'Antiviral therapy')
Herpes simplex virus type 1 (herpetic gingivostomatitis) (see "Herpetic
gingivostomatitis in young children", section on 'Oral acyclovir')
Human immunodeficiency virus (see "Selecting antiretroviral regimens for the
treatment-nave HIV-infected patient")
Other viruses that cause pharyngitis generally do not require antiviral therapy in
immunocompetent children and adolescents. These include adenoviruses,
enteroviruses, rhinoviruses, coronaviruses, and parainfluenza viruses 1, 2, and 3 [2].
(See "Diagnosis, treatment, and prevention of adenovirus infection", section on
'Treatment' and "Hand, foot, and mouth disease and herpangina: An overview",
section on 'Management' and "Parainfluenza viruses in children", section on
'Treatment' and "The common cold in children: Management and prevention", section
on 'Sore throat'.)
Bacterial infections Antimicrobial therapy should be provided for patients with
laboratory-documented bacterial pharyngitis/tonsillitis. Antibiotic therapy helps to
prevent complications and the spread of infection [3].
Antimicrobial treatment of bacterial sore throat is discussed separately:
Group A streptococcal pharyngitis (see "Treatment and prevention of
streptococcal tonsillopharyngitis")
For patients with GAS tonsillopharyngitis, early initiation of antibiotic therapy
appears to modestly reduce the duration of symptoms, but antibiotics are less
effective in reducing pain than other interventions (eg, systemic analgesic
agents) [3-6] (see 'Systemic analgesia' below)
Group C and G streptococcal pharyngitis (see "Group C and group G
streptococcal infection", section on 'Treatment')
Arcanobacterium hemolyticum (see "Group A streptococcal tonsillopharyngitis in
children and adolescents: Clinical features and diagnosis", section on 'Other
bacterial infections')
Neisseria gonorrhoeae (see "Treatment of uncomplicated gonococcal
infections", section on 'Pharyngeal infection')
Treponema pallidum (secondary syphilis) (see "Syphilis: Treatment and
monitoring", section on 'Treatment of early syphilis')
Oral anaerobes (acute necrotizing ulcerative gingivitis, also called Vincent
angina and trench mouth) (see "Gingivitis and periodontitis in children and
adolescents: An overview", section on 'Acute necrotizing ulcerative gingivitis')
Yersinia enterocolitica or Y. pestis (see "Treatment and prevention of Yersinia
enterocolitica and Yersinia pseudotuberculosis infection", section on 'Treatment')
Francisella tularensis (see "Clinical manifestations, diagnosis, and treatment of
tularemia", section on 'Treatment')
Corynebacterium diphtheriae (see "Clinical manifestations, diagnosis, and
treatment of diphtheria", section on 'Treatment')
Fungal infections Although oropharyngeal candidiasis usually occurs in infants, it
may occur in older children and adolescents (eg, after a course of systemic
antibiotics) (see "Candida infections in children: An overview", section on
'Oropharyngeal candidiasis')
Allergic rhinitis (see "Pharmacotherapy of allergic rhinitis")
Postoperative tonsillectomy (see "Tonsillectomy (with or without adenoidectomy)
in children: Postoperative care and complications", section on 'Pain')
Behet syndrome (see "Treatment of Behets syndrome", section on
'Mucocutaneous manifestations')
Caustic ingestion (see "Caustic esophageal injury in children", section on 'Initial
management')
Supportive care General supportive measures that can be suggested for most patients
with infectious pharyngitis include [7-10]:
SYMPTOMATIC TREATMENT
Our approach
Soothing measures We offer one or more of the following topical soothing measures
to patients with throat pain. The interventions may be tried in any sequence or combination
at patient/caregiver discretion. Although most of the interventions have not been studied in
clinical trials, they may provide short term-relief and are unlikely to be harmful [7,9].
Adjunctive systemic therapy also may be warranted. (See 'Systemic analgesia' below.)
Sipping cold or warm beverages (eg, tea with honey or lemon) Honey should be
avoided in children <12 months because of the possible contamination of honey
with Clostridium botulinum spores, potentially leading to infantile botulism.
(See "Botulism", section on 'Infant botulism'.)
Eating cold or frozen desserts (eg, ice cream, popsicles)
Sucking on ice
Sucking on hard candy For children 5 years and adolescents, we suggest
sucking on hard candy rather than medicated throat lozenges (eg, cough drops,
troches, or pastilles) or medicated sprays. Hard candy and lozenges should not be
used in children 4 years of age because they are a choking hazard.
Hard candy is probably as effective as medicated lozenges, less expensive, and less
likely to have adverse effects [8,11-13]. (See 'Medicated lozenges and sprays' below.)
Gargling with warm salt water For children 6 years of age and adolescents, we
suggest gargling with warm salt water rather than other medicated oral rinses. Most
recipes call for to teaspoon of salt per 8 ounces (approximately 240 mL) of warm
water. Children <6 years generally cannot gargle properly.
Medicated oral rinses have not been proven to be superior to placebo and have
potential adverse effects (eg, toxicity from systemic absorption, allergic reaction) [14-
17]. (See 'Medicated oral rinses' below.)
Worsening or persistent pain Children and adolescents with sore throat that worsens
or persists for >3 days without improvement should be instructed to return for reevaluation
[9]. Worsening throat pain or throat pain that persists for >3 days without improvement
may indicate the development of a complication (eg, tonsillopharyngeal cellulitis or
abscess, jugular vein septic thrombophlebitis) or the need to consider a different diagnosis
[10]. (See "Peritonsillar cellulitis and abscess" and "Retropharyngeal infections in
children" and "Suppurative (septic) thrombophlebitis", section on 'Jugular
vein' and "Evaluation of sore throat in children".)
Other therapies
Medicated lozenges and sprays We suggest not using medicated lozenges or throat
sprays for relief of throat pain in children and adolescents. Although there is some
evidence from randomized trials that medicated lozenges and sprays provide symptomatic
relief [7,25-28], it is not clear that they work any better than hard candy and have greater
potential for adverse effects [8,11-13]. A 2010 systematic review found no good quality
evidence on the effectiveness of nonprescription lozenges or throat sprays [17].
Medicated lozenges usually are designed to relieve dryness or pain. They commonly
contain menthol (a cooling agent), antiseptics (hexylresorcinol, chlorhexidine), topical
anesthetics (eg, phenol, benzocaine,
hexylresorcinol, benzydamine), and/or antiinflammatory agents (flurbiprofen). Medicated
throat sprays usually contain topical anesthetics (eg, benzocaine, phenol, benzydamine).
Medicated throat lozenges and sprays have the potential to cause allergic reactions, and
those that contain benzocaine may cause methemoglobinemia. Lozenges that contain
benzocaine should not be used in children younger than four years (they are a choking
hazard); sprays that contain benzocaine should not be used in children younger than two
years [14]. (See "Clinical features, diagnosis, and treatment of methemoglobinemia",
section on 'Acquired methemoglobinemia'.)
Medicated oral rinses We suggest not routinely using topical oral therapies
containing lidocaine or other topical therapies (eg, diphenhydramine, Kaolin pectin,
magnesia-alumina [eg, Maalox]) to coat oral lesions and/or soothe pain in children with
throat pain due to oral ulcers (eg, herpetic gingivostomatitis; hand, foot, and mouth
disease) given the lack of evidence of benefit from clinical trials [15], the potential for harm
(eg, toxicity from systemic absorption, allergic reaction) [14,16], and difficulty of application
in young children [29].
We also suggest not using medicated oral rinses for symptomatic relief of throat pain
caused by infectious pharyngitis. A 2010 systematic review found no good quality evidence
on the effectiveness of nonprescription oral rinses [17].
A 2015 systematic review of randomized trials comparing glucocorticoids with placebo for
relief of symptoms of infectious mononucleosis found insufficient evidence to recommend
glucocorticoids for symptom relief and lack of research addressing adverse effects and
long-term complications [35]. The use of glucocorticoids for symptomatic relief in infectious
mononucleosis, including relief of upper-airway obstruction is discussed separately.
(See "Infectious mononucleosis in adults and adolescents", section on 'Symptomatic
treatment' and "Infectious mononucleosis in adults and adolescents", section on
'Complications including airway obstruction'.)
Although some of these agents have been studied in randomized trials [36-41], high
quality studies are lacking [42,43], and most have not been studied in children. In addition,
the US Food and Drug Administration (FDA) does not regulate the safety, purity, or
potency of herbal products or dietary supplements (which may vary from lot to lot or
capsule to capsule). These therapies may contain potentially harmful unlabeled
ingredients (pesticides, herbicides, pharmaceuticals, allergens) [44-48]; this is particularly
problematic if the child is taking these nonprescription preparations in addition to
prescribed medications.
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Children and adolescents with sore throat that worsens or persists for >3 days
without improvement should be instructed to return for reevaluation. Worsening or
persistent pain may indicate the development of a complication or the need to
consider a different diagnosis. (See 'Worsening or persistent pain' above
and "Evaluation of sore throat in children".)
We suggest not using systemic glucocorticoids for the symptomatic relief of throat
pain in children and adolescents (Grade 2B). The use of glucocorticoids for upper
airway obstruction in infectious mononucleosis is discussed separately.
(See 'Glucocorticoids' above and "Clinical manifestations and treatment of Epstein-
Barr virus infection", section on 'Treatment and prevention'.)
We suggest not using herbal therapies, homeopathic therapies, dietary
supplements, or other complementary/alternative therapies in the treatment of sore
throat in children and adolescents (Grade 2C). (See 'Alternative therapies' above.)
roup A streptococcal tonsillopharyngitis in children and adolescents: Clinical
features and diagnosis
Author:
Ellen R Wald, MD
Section Editors:
Morven S Edwards, MD
Anna H Messner, MD
Deputy Editor:
Mary M Torchia, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Sep 29, 2016.
In temperate climates, the incidence of GAS pharyngitis peaks during the winter and early
spring [5]. During these seasons, as many as 35 to 40 percent of cases of pharyngitis in
children and adolescents are caused by GAS.
GAS pharyngitis is most common in school-age children but may occur in younger
children, especially if they have contact with school-age children [5,6]. In a meta-analysis,
the pooled prevalence of GAS among children (<18 years) who presented to an outpatient
clinic or emergency department with sore throat was 37 percent (95% CI 32-43 percent)
[7]. The prevalence among children <5 years was 24 percent (95% CI 21-26 percent).
CLINICAL FEATURES
Children 3 years In children 3 years, GAS pharyngitis typically has an abrupt onset.
Fever, headache, abdominal pain, nausea, and vomiting may accompany the sore throat,
which can lead to poor oral intake [3,8,9]. Additional features may include exudative
tonsillopharyngitis, with enlarged erythematous tonsils, enlarged tender anterior cervical
lymph nodes, palatal petechiae, inflamed uvula, and scarlatiniform rash (erythematous,
finely papular rash which characteristically starts in the groin and axilla and then spreads
to the trunk and extremities, followed by desquamation) (picture 1A-B) [3,8,10]. Symptoms
usually resolve spontaneously in three to five days. (See "Complications of streptococcal
tonsillopharyngitis", section on 'Scarlet fever'.)
Constellations of symptoms and epidemiologic features have been used to develop clinical
scores in an attempt to predict the likelihood that a throat culture will be positive for GAS
[11-14]. None is sufficiently sensitive and specific to eliminate the need for microbiologic
testing in children and adolescents [3,10,15,16]. However, they may be helpful in
determining a testing strategy. (See 'Choice of test' below.)
Children <3 years Symptoms of streptococcal infections usually are atypical in children
<3 years of age [17]. Instead of a well-defined episode of pharyngitis, they may have
protracted symptoms of nasal congestion and discharge, low-grade fever (eg, <38.3C
[101F]), and tender anterior cervical adenopathy [18]. This GAS symptom complex is
called "streptococcosis."
Infants <1 year of age may present with fussiness, decreased appetite, and low-grade
fever. They often have older siblings or day care contacts with GAS infection.
DIAGNOSIS
However, between 5 and 21 percent of children between 3 and 15 years of age are
pharyngeal carriers of GAS [7,19,20]. Neither throat culture nor RADT for GAS can
differentiate patients with acute GAS pharyngitis from GAS carriage with intercurrent viral
illness [3]. Such patients may fail to respond to appropriate therapy for GAS infection.
(See "Treatment and prevention of streptococcal tonsillopharyngitis", section on
'Carriers' and "Antibiotic failure in the treatment of streptococcal tonsillopharyngitis",
section on 'Streptococcal carriage'.)
Whom to test We suggest microbiologic testing for GAS in children and adolescents
with [3,8,21]:
Whom not to test We recommend not performing microbiologic testing for GAS in
children and adolescents with manifestations suggestive of viral illness (eg, coryza,
conjunctivitis, cough, hoarseness, anterior stomatitis, discrete ulcerative lesions or
vesicles, diarrhea) [3,21]. (See 'Viral infections' below.)
For children and adolescents in whom microbiologic testing for GAS is necessary:
The strategy of initial testing with throat culture is more cost effective than initial testing
with RADT. Most children who require microbiologic testing for pharyngitis do not have
GAS pharyngitis and will have a negative RADT. Given that negative RADT in children and
adolescents must be confirmed with throat culture, if RADT is used as the initial test, the
majority of children and adolescents who are tested will require both RADT and throat
culture. Limiting RADT to children in whom it is likely to be positive and performing throat
cultures in the remainder minimizes the number of children who require both tests [24].
Microbiologic tests
Throat culture Throat culture is the reference standard for the diagnosis of acute
pharyngitis due to GAS [8,31]. When performed properly, the sensitivity of throat culture is
90 to 95 percent for GAS [3,21,32]. (See 'Specimen collection and processing' above.)
Throat culture is usually performed on 5 percent sheep blood agar [31]. After incubation for
18 to 24 hours at 35 to 37C, the plate is inspected for a small gray colony that gives rise
to an area of beta hemolysis. If no beta hemolytic colonies are seen after 18 to 24 hours,
the plate should be reincubated for an additional 24 hours before being interpreted as
negative [3,33]. Twenty-five to 40 percent of throat cultures that are ultimately positive for
GAS become positive after 24 hours [34].
Throat culture also can identify other bacteria that cause pharyngitis less commonly than
GAS (eg, group C and group G streptococci, Arcanobacterium haemolyticum). However,
most laboratories do not routinely identify these pathogens in throat cultures unless
specifically requested to do so.
RADT for GAS RADT for GAS, sometimes referred to as rapid streptococcal antigen
tests (RSAT), are based upon enzyme or acid extraction of antigen from throat swabs [35-
38]. RADT results are available at the point of care in the office or emergency department
and, if positive, permit early institution of therapy for GAS pharyngitis. Early institution of
therapy enables earlier resolution of symptoms and return to school. However, early
therapy also predisposes to more frequent recurrences of GAS within 30 days [39,40].
RADT have a specificity of 95 percent and a sensitivity that varies between 70 and 90
percent for GAS [3,32,35-38,41-46]. In a 2016 meta-analysis of studies in which 58,244
children underwent both RADT and throat culture, the pooled sensitivity and specificity of
RADT were 85.6 percent (95% CI 83.3-87.6) and 95.4 percent (95% CI 94.5-96.2),
respectively [46]. Given the high specificity and limited sensitivity of the available tests, a
positive RADT is useful in establishing the diagnosis of GAS pharyngitis, but a negative
RADT does not rule out GAS; back-up throat culture should be performed in children and
adolescents with a negative RADT [3,21,25,26].
Molecular assays We do not routinely use molecular assays (ie, nucleic acid
amplification tests [NAAT], polymerase chain reaction assays [PCR]) for the evaluation of
GAS pharyngitis. Additional evaluation is necessary to confirm the sensitivity and
specificity results in initial studies.
NAAT are used extensively for the diagnosis of infectious diseases [47]. Although they are
highly sensitive for GAS [48], the complexity of these tests frequently requires
performance in a laboratory setting, which increases the turn-around time for results.
However, two PCR assays for GAS pharyngitis that can be performed at the point of care
and provide results in 15 minutes are now available (Cobas Strep A test of the Liat
system, Alere i strep A test) [49,50]. Initial evaluation suggests that these PCR assays
have sensitivity and specificity >98 percent [50], thereby potentially eliminating the need
for follow-up throat culture in children with negative PCR results. Additional evaluation is
necessary before these tests are routinely recommended.
GAS serology Serologic testing for GAS may be necessary to confirm previous
infection in patients who are being evaluated for acute rheumatic fever or
poststreptococcal glomerulonephritis, but it is not helpful in managing patients at the time
of clinical presentation with pharyngitis.
Other bacterial infections Other bacterial causes of pharyngitis that may require
treatment include:
Viral infections Viruses are the most common cause of acute pharyngitis (table 1)
[31,63,64]. Clinical features suggestive of viral etiology include concurrent conjunctivitis,
coryza, cough, hoarseness, anterior stomatitis, discrete ulcerative lesions, viral
exanthems, and/or diarrhea [3].
Viral infections in the differential diagnosis of GAS pharyngitis in children and adolescents
that have important management or infection control implications include:
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
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View in English
Redactado por los mdicos y editores de UpToDate
Pida una ambulancia (en EE. UU. y Canad, marque 9-1-1) o lleve a su hijo a la sala de
emergencia si el nio:
Los nios que tienen un dolor de garganta causado por un virus por lo general no tienen
que consultar a un mdico o enfermero, pero si el dolor aparece debido a una bacteria
entonces podran tener que hacerlo, ya que es posible que tengan un tipo de infeccin
llamada infeccin por estreptococo. (Ver "Educacin para el paciente: Infeccin en la
garganta por estreptococo en nios (Conceptos Bsicos)").
Cmo puedo saber si el dolor de garganta de mi hijo fue causado por un virus o
por un estreptococo? Es difcil detectar la diferencia, pero se pueden buscar algunos
indicios (figura 1).
En general, las personas que tienen un dolor de garganta causado por un virus tambin
tienen otros sntomas, como por ejemplo:
Escurrimiento nasal
Pecho congestionado
Comezn en los ojos u ojos rojos
Tos
Voz spera (ronca)
Dolor en el paladar
Las personas que tienen infeccin por estreptococo no suelen tener tos, escurrimiento
nasal, comezn en los ojos ni ojos enrojecidos.
Si cree que su hijo puede tener una infeccin por estreptococo, llame al mdico. l puede
hacer una prueba para detectar la bacteria que causa la infeccin por estreptococo.
Qu puedo hacer para ayudar a mi hijo a sentirse mejor? Hay varias maneras de
aliviar el dolor de garganta:
Cmo puedo evitar que mi hijo vuelva a tener dolor de garganta? Lave las manos
de su hijo frecuentemente con agua y jabn. Esa es una de las mejores maneras de
prevenir el contagio de la infeccin. Tambin puede usar alcohol en gel, pero debe
asegurarse de que el gel cubra toda la superficie de la mano de su hijo.
Todos los artculos se actualizan a medida que se descubre nueva evidencia y culmina
nuestro proceso de evaluacin por homlogos
LARINGOTRAQUEITIS
Croup: Clinical features, evaluation, and diagnosis
Author:
Charles R Woods, MD, MS
Section Editors:
Gregory Redding, MD
Anna H Messner, MD
Sheldon L Kaplan, MD
Deputy Editor:
Carrie Armsby, MD, MPH
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: May 10, 2016.
The clinical features, evaluation, and diagnosis of croup will be discussed here. The
management of croup is discussed separately. (See "Croup: Approach to
management" and "Croup: Pharmacologic and supportive interventions".)
DEFINITIONS The term croup has been used to describe a variety of upper respiratory
conditions in children, including laryngitis, laryngotracheitis, laryngotracheobronchitis,
bacterial tracheitis, or spasmodic croup [1]. These terms are defined below. In the past, the
term croup also has been applied to laryngeal diphtheria (diphtheritic or membranous
croup), which is discussed separately. (See "Epidemiology and pathophysiology of
diphtheria" and "Clinical manifestations, diagnosis, and treatment of diphtheria".)
Throughout this review, the term croup will be used to refer to laryngotracheitis.
Laryngotracheobronchitis, laryngotracheobronchopneumonitis, bacterial tracheitis, and
spasmodic croup are designated specifically as such.
Parainfluenza virus type 1 is the most common cause of acute laryngotracheitis, especially
the fall and winter epidemics [5-7]. Parainfluenza type 2 sometimes causes croup
outbreaks, but usually with milder disease than type 1. Parainfluenza type 3 causes
sporadic cases of croup that often are more severe than those due to types 1 and 2. In
multicenter surveillance of children <5 years who were hospitalized with febrile or acute
respiratory illnesses, 43 percent of children with confirmed parainfluenza infection were
diagnosed with croup [8]. Croup was the most common discharge diagnosis for children
with confirmed parainfluenza 1 (42 percent) and parainfluenza 2 (48 percent) infections but
was only diagnosed in 11 percent of children with confirmed parainfluenza 3 infections.
Compared with types 1 to 3, infection caused by parainfluenza virus type 4 is less likely to
be associated with stridor and croup in children [9].
A number of other viruses that typically cause lower respiratory tract disease also can
cause upper respiratory tract symptoms, including croup, as described below [7].
Respiratory syncytial virus and adenoviruses are relatively frequent causes of croup.
The laryngotracheal component of disease is usually less significant than that of the
lower airways. (See "Respiratory syncytial virus infection: Clinical features and
diagnosis", section on 'Clinical manifestations' and "Epidemiology and clinical
manifestations of adenovirus infection", section on 'Clinical presentation'.)
Human coronavirus NL63 (HCoV-NL63), first identified in 2004, has been implicated
in croup and other respiratory illnesses [10-12]. The prevalence of HCoV-NL63 varies
geographically. (See "Coronaviruses", section on 'Respiratory'.)
Measles is an important cause of croup in areas where measles remains prevalent.
(See "Measles: Clinical manifestations, diagnosis, treatment, and prevention".)
Influenza virus is a relatively uncommon cause of croup. However, children
hospitalized with influenzal croup tend to have longer hospitalization and greater risk
of readmission for relapse of laryngeal symptoms than those with parainfluenzal
croup. (See "Seasonal influenza in children: Clinical features and diagnosis", section
on 'Pneumonia and respiratory tract complications'.)
Rhinoviruses, enteroviruses (especially Coxsackie types A9, B4, and B5, and
echovirus types 4, 11, and 21), and herpes simplex virus are occasional causes of
sporadic cases of croup that are usually mild. (See "Clinical manifestations and
diagnosis of enterovirus and parechovirus infections" and "Epidemiology, clinical
manifestations, and pathogenesis of rhinovirus infections".)
Metapneumoviruses cause primarily lower respiratory tract disease similar to RSV,
but upper respiratory tract symptoms have been described in some patients [13].
(See "Human metapneumovirus infections".)
Croup also may be caused by bacteria. Mycoplasma pneumoniae has been associated
with mild cases of croup. In addition, secondary bacterial infection may occur in children
with laryngotracheitis, laryngotracheobronchitis, or laryngotracheobronchopneumonitis.
The most common secondary bacterial pathogens include Staphylococcus
aureus, Streptococcus pyogenes, and Streptococcus pneumoniae [1].
Family history of croup is a risk factor for croup and recurrent croup. In a case-control
study, children whose parents had a history of croup were 3.2 times as likely to have an
episode of croup and 4.1 times as likely to have recurrent croup as children with no
parental history of croup [17]. Parental smoking, a well-recognized risk factor for
respiratory tract infections in children, does not appear to increase the risk of croup
[17,18]. (See "Secondhand smoke exposure: Effects in children", section on 'Respiratory
symptoms and illness'.)
Most cases of croup occur in the fall or early winter, with the major incidence peaks
coinciding with parainfluenza type 1 activity (often in October) and minor peaks occurring
during periods of respiratory syncytial virus or influenza virus activity. (See "Respiratory
syncytial virus infection: Clinical features and diagnosis", section on
'Seasonality' and "Seasonal influenza in children: Clinical features and diagnosis", section
on 'Influenza activity'.)
Emergency department (ED) visits for croup are most frequent between 10:00 PM and
4:00 AM [19]. However, children seen for croup between noon and 6:00 PM are more likely
to be admitted to the hospital [5,20]. A morning peak between 7:00 AM and 11:00 AM in ED
visits for croup also has been noted [16].
Hospital admissions for croup have declined steadily since the late 1970s. In an analysis
of data from the National Hospital Discharge Surveys from 1979 through 1997, the
estimated number of annual hospitalizations for croup decreased from 48,900 to 33,500
[6]. Estimates of annual hospitalization rates for croup caused by parainfluenza virus types
1 to 3 from 1994 to 1997 were 0.4 to 1.1 per 1000 children for children younger than one
year and 0.24 to 0.61 per 1000 children for children between one and four years.
Approximately one-half of these hospitalizations were attributed to parainfluenza type 1.
PATHOGENESIS The viruses that cause croup typically infect the nasal and
pharyngeal mucosal epithelia initially and then spread locally along the respiratory
epithelium to the larynx and trachea.
The anatomic hallmark of croup is narrowing of the subglottic airway, the portion of the
larynx immediately below the vocal folds. The cricoid cartilage of the subglottis is a
complete cartilaginous ring, unlike the tracheal rings which are horseshoe shaped.
Because it is a complete ring, the cricoid cannot expand, causing significant airway
narrowing whenever the subglottic mucosa becomes inflamed. In addition to this "fixed"
obstruction, dynamic obstruction of the extrathoracic trachea below the cartilaginous ring
may occur when the child struggles, cries, or becomes agitated. The dynamic obstruction
occurs as a result of the combination of high negative pressure in the distal extrathoracic
trachea and the floppiness of the tracheal wall in children.
Patients with bacterial tracheitis have a bacterial superinfection that causes thick pus to
develop within the lumen of the subglottic trachea (picture 1). Ulcerations,
pseudomembranes, and microabscesses of the mucosal surface occur. The supraglottic
tissues usually are normal. (See "Bacterial tracheitis in children: Clinical features and
diagnosis", section on 'Pathogenesis and pathology'.)
Host factors Only a small fraction of children with a parainfluenza viral infection
develop overt croup. This suggests that host (or genetic) factors play a role in the
pathogenesis. Host factors that may contribute to the development of croup include
functional or anatomic upper airway narrowing, variations in immune response, and
predisposition to atopy [16].
Underlying host factors that predispose to clinically significant narrowing of the upper
airway include:
Congenital anatomic narrowing of the airway, such as subglottic stenosis due to an
elliptical cricoid cartilage [4]. (See "Congenital anomalies of the larynx", section on
'Laryngeal atresia'.)
Hyperactive airways, perhaps aggravated by atopy or gastroesophageal reflux, as
suggested in some children with spasmodic croup or recurrent croup [28-30].
Acquired airway narrowing from a post-intubation subglottic cyst or stenosis, or
rarely from respiratory tract papillomas (human papillomavirus). Subglottic
hemangiomas (picture 2 and picture 3) grow in the first few months of life and the
patients will typically present with symptoms mimicking croup (ie, stridor and a
barking cough). (See "Congenital anomalies of the larynx", section on
'Cysts' and "Congenital anomalies of the larynx", section on 'Subglottic
hemangiomas'.)
The potential role of the immune response was demonstrated in studies that demonstrated
increased production of parainfluenza virus-specific immunoglobulin E (IgE) and increased
lymphoproliferative response to parainfluenza virus antigen, and diminished histamine-
induced suppression of lymphocyte transformation responses to parainfluenza virus in
children with parainfluenza virus and croup compared with those with parainfluenza virus
without croup [31,32].
Hypoxia and cyanosis can develop, as can respiratory fatigue from sustained increased
respiratory effort. High respiratory rates also tend to correlate with the presence of
hypoxia. Without intervention, the hypoxia or fatigue can rarely lead to death.
Spasmodic croup Spasmodic croup also occurs in children three months to three
years of age [2]. In contrast to laryngotracheitis, spasmodic croup always occurs at night;
the duration of symptoms is short, often with symptoms subsiding by the time of
presentation for medical attention; and the onset and cessation of symptoms are abrupt.
Fever is typically absent, but mild upper respiratory tract symptoms (eg, coryza) may be
present. Episodes can recur within the same night and for two to four successive evenings
[34]. A striking feature of spasmodic croup is its recurrent nature, hence the alternate
descriptive term, "frequently recurrent croup." There may be a familial predisposition to
spasmodic croup, and it may be more common in children with a family history of allergies
[28].
Early in the clinical course, spasmodic croup may be difficult to distinguish from
laryngotracheitis. As the course progresses, the episodic nature of spasmodic croup and
relative wellness of the child between attacks differentiate it from classic croup, in which
the symptoms are continuous.
Although the initial presentation can be dramatic, the clinical course is usually benign.
Symptoms are almost always relieved by comforting the anxious child and administering
humidified air. Rarely, children may benefit from treatment with
corticosteroids and/or nebulized epinephrine [35]. Other therapies generally are not
indicated. (See "Croup: Approach to management".)
Recurrent croup A child who has had recurrent episodes of classic viral croup may
have an underlying condition that predisposes him or her to develop clinically significant
narrowing of the upper airway. Recurrent episodes of croup-like symptoms occurring
outside the typical age range for "viral croup" (ie, six months to three years) and recurrent
episodes that do not appear to be simple "spasmodic croup" should raise suspicion for
airway lesions, gastroesophageal reflux or eosinophilic esophagitis, or atopic conditions
[3,4,27,36-39]. (See 'Differential diagnosis' below.)
In children who have recurrent croup without clear predisposing factors as noted above,
radiographic evaluation, laryngoscopy, bronchoscopy, and/or esophagoscopy may be
warranted. (See 'Host factors' above and 'Imaging' below.)
Bacterial tracheitis Bacterial tracheitis may present as a primary or secondary
infection [40]. In primary infection, there is acute onset of symptoms of upper airway
obstruction with fever and toxic appearance. In secondary infection, there is marked
worsening during the clinical course of viral laryngotracheitis, with high fever, toxic
appearance, and increasing respiratory distress secondary to tracheal obstruction from
purulent secretions. In both of these presentations, signs of lower airway disease, such as
crackles and wheezes, may be present. However, the upper airway obstruction is the more
clinically significant manifestation [2,41]. (See "Bacterial tracheitis in children: Clinical
features and diagnosis", section on 'Clinical features'.)
EVALUATION
Overview The evaluation of children with suspected croup has several objectives,
including prompt identification of patients with significant upper airway obstruction or at risk
for rapid progression of upper airway obstruction. In addition, there are some conditions
with presentations similar to that of croup that require specific
evaluations and/or interventions; these too must be promptly identified. (See 'Differential
diagnosis' below.)
During the evaluation, efforts should be made to make the child as comfortable as
possible. The increased inspiratory effort that accompanies anxiety and fear in young
children can exacerbate subglottic narrowing, further diminishing air exchange and
oxygenation. (See 'Pathogenesis' above.)
Once treatment is under way and the child is more stable, the remainder of the evaluation
can proceed.
History The history should include a description of the onset, duration, and progression
of symptoms. Factors that are associated with increased severity of illness include:
Aspects of the history that are helpful in distinguishing croup from other causes of acute
upper airway obstruction include [1,42]:
Fever The absence of fever from onset of symptoms to the time of presentation is
suggestive of spasmodic croup or a noninfectious etiology (eg, subglottic cyst,
subglottic hemangioma).
Barking cough The classic physical finding in a patient with subglottic narrowing is
a barky seal-like cough.
Hoarseness Hoarseness may be present in croup, particularly in older children,
whereas hoarseness is not a typical finding in epiglottitis or foreign body aspiration.
Difficulty swallowing Difficulty swallowing may occur in acute epiglottitis. Rarely, a
large, ingested foreign body may lodge in the upper esophagus, where it distorts and
narrows the upper trachea, thus mimicking the croup syndrome (including barking
cough and inspiratory stridor).
Drooling Drooling may occur in children with peritonsillar or retropharyngeal
abscesses, retropharyngeal cellulitis, and epiglottitis. In an observational study,
drooling was present in approximately 80 percent of children with epiglottitis, but only
10 percent of those with croup [42].
Throat pain Complaints of dysphagia and sore throat are more common in children
with epiglottitis than croup (approximately 60 to 70 percent versus <10 percent) [42].
The differential diagnosis of croup is discussed in greater detail below. (See 'Differential
diagnosis' below.)
Examination The objectives of the examination of the child with croup include
assessment of severity of upper airway obstruction and exclusion of other infectious and
non-infectious causes of acute upper airway obstruction, both of which are necessary in
making management decisions.
The initial examination often can be accomplished by observing the child in a comfortable
position with the caretaker. Every effort should be made to measure the child's weight and
vital signs.
Aspects of the examination that are helpful in assessing the degree of upper airway
obstruction and severity of illness include:
Overall appearance Is the child comfortable and interactive, anxious and quiet, or
obtunded? Is there stridor at rest? Stridor at rest is a sign of significant upper airway
obstruction. Children with significant upper airway obstruction may prefer to sit up and
lean forward in a "sniffing" position (neck is mildly flexed, and head is mildly
extended). This position tends to improve the patency of the upper airway.
Quality of the voice Does the child have a hoarse or diminished cry? Is the voice
muffled? A muffled "hot potato" voice is suggestive of epiglottitis, retropharyngeal
abscess, or peritonsillar abscess.
Degree of respiratory distress Signs of respiratory distress include tachypnea,
hypoxemia, and increased work of breathing (intercostal, subcostal, or suprasternal
retractions; nasal flaring; grunting; use of accessory muscles)
Tidal volume Does there appear to be good chest expansion with inspiration,
indicating adequate air entry?
Lung examination Are there abnormal respiratory sounds during inspiration or
expiration? Inspiratory stridor indicates upper airway obstruction, whereas expiratory
wheezing is a sign of lower airway obstruction. If there is stridor, is it present at rest or
only with agitation? As discussed above, stridor at rest is a sign of significant upper
airway obstruction. Stridor will be more obvious on auscultation, since the inspiratory
noise is transmitted through the chest. The presence of crackles (rales) also suggests
lower respiratory tract involvement (eg, laryngotracheobronchitis,
laryngotracheobronchopneumonitis, or bacterial tracheitis).
Assessment of hydration status Decreased oral intake and increased insensible
losses from fever and tachypnea may result in dehydration. (See "Clinical
assessment and diagnosis of hypovolemia (dehydration) in children".)
These aspects of the examination are often used in clinical scoring systems to evaluate
the severity of illness and/or in making decisions regarding the need for hospital
admission. (See 'Severity assessment' below and "Croup: Approach to management",
section on 'Observation and disposition'.)
Components of the examination that are useful in distinguishing croup from other causes
of acute upper airway obstruction include [42,43]:
Preferred posture Children with epiglottitis usually prefer to sit up in the "tripod" or
"sniffing position" (picture 4A-B).
Examination of the oropharynx for the following signs:
Cherry red, swollen epiglottis, suggestive of epiglottitis.
Pharyngitis, typically minimal in laryngotracheitis, may be more pronounced in
epiglottitis or laryngitis.
Excessive salivation, suggestive of acute epiglottitis, peritonsillar abscess,
parapharyngeal abscess or retropharyngeal abscess.
Diphtheritic membrane.
Tonsillar asymmetry or deviation of the uvula suggestive of peritonsillar
abscess.
Midline or unilateral swelling of the posterior pharyngeal wall suggestive of
retropharyngeal abscess.
Concerns have been raised about safety of examining the pharynx in children
with upper airway obstruction and possible epiglottitis since such efforts have
been reported to precipitate cardiorespiratory arrest. However, in two series,
each including more than 200 patients with epiglottitis or viral croup, direct
examination of the oropharynx was not associated with sudden clinical
deterioration [40,44].
Examination of the cervical lymph nodes, which can be enlarged in patients with
retropharyngeal or peritonsillar abscesses.
Other physical findings may be present, depending on the particular inciting virus.
As an example, rash, conjunctivitis, exudative pharyngitis, and adenopathy are
suggestive of adenovirus infection.
Otitis media (acute or with effusion) may be present as a primary viral or secondary
bacterial process.
The differential diagnosis of croup is discussed in greater detail below. (See 'Differential
diagnosis' below.)
Mild croup (Westley croup score of 2) Children with mild croup have no stridor
at rest (although stridor may be present when upset or crying), a barking cough,
hoarse cry, and either no, or only mild, chest wall/subcostal retractions [1,43,46].
Moderate croup (Westley croup score of 3 to 7) Children with moderate croup
have stridor at rest, have at least mild retractions, and may have other symptoms or
signs of respiratory distress, but little or no agitation [1,43,46].
Severe croup (Westley croup score of 8) Children with severe croup have
significant stridor at rest, although the loudness of the stridor may decrease with
worsening upper airway obstruction and decreased air entry [1,43,46]. Retractions
are severe (including indrawing of the sternum) and the child may appear anxious,
agitated, or pale and fatigued.
Impending respiratory failure (Westley croup score of 12) Croup occasionally
results in significant upper airway obstruction with impending respiratory failure,
heralded by the following signs [1,43,46]:
Fatigue and listlessness
Marked retractions (although retractions may decrease with increased
obstruction and decreased air entry)
Decreased or absent breath sounds
Depressed level of consciousness
Tachycardia out of proportion to fever
Cyanosis or pallor
Prompt recognition and treatment of children with severe croup are paramount.
(See "Croup: Approach to management", section on 'Moderate to severe croup'.)
Imaging
In contrast, the lateral radiograph in virtually all children with epiglottitis demonstrates
swelling of the epiglottis, sometimes called the "thumb sign" (image 3). (See "Epiglottitis
(supraglottitis): Clinical features and diagnosis", section on 'Radiographic features'.)
The lateral radiograph in children with bacterial tracheitis may demonstrate only
nonspecific edema or intraluminal membranes and irregularities of the tracheal wall (image
4) [48].
Laboratory studies Laboratory studies, which are rarely indicated in children with
croup, are of limited diagnostic utility, but may help guide management in more severe
cases.
Blood tests The white blood cell (WBC) count can be low, normal, or elevated; WBC
counts >10,000 cells/microL are common. Neutrophil or lymphocyte predominance may be
present on the differential [49,50]. The presence of a large number of band-form
neutrophils is suggestive of primary or secondary bacterial infection. Croup is not
associated with any specific alterations in serum chemistries.
DIAGNOSIS
Clinical diagnosis The diagnosis of croup is clinical, based on the presence of a
barking cough and stridor, especially during a typical community epidemic of one of the
causative viruses. (See 'Etiology' above.)
Neither radiographs nor laboratory tests are necessary to make the diagnosis. However,
radiographs may be helpful in excluding other causes if the diagnosis is in question.
(See 'Differential diagnosis' below.)
Diagnosis of a specific viral etiology can be made by viral culture of secretions from the
nasopharynx or throat. Rapid tests that detect viral antigens in these secretions are
commercially available for many respiratory viruses. The diagnosis of specific viral
infections is discussed in detail in individual topic reviews:
In addition, multiplex tests, which assess the presence of multiple agents at the same time,
and polymerase chain reaction-based tests are becoming more widely available [51].
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
The term croup has been used to describe a variety of upper respiratory conditions
in children, including laryngitis, laryngotracheitis, laryngotracheobronchitis, bacterial
tracheitis, or spasmodic croup. (See 'Definitions' above.)
Croup is usually caused by viruses. Bacterial infection may occur secondarily.
Parainfluenza virus type 1 is the most common cause of croup; other causes include
respiratory syncytial virus and influenza virus. (See 'Etiology' above.)
Croup most commonly occurs in children 6 to 36 months of age. Most cases occur
in the fall or early winter. (See 'Epidemiology' above.)
Host factors that may contribute to the development of croup include functional or
anatomic susceptibility to upper airway narrowing. (See 'Pathogenesis' above.)
The clinical presentation of croup depends upon the specific croup syndrome and
the degree of upper airway obstruction. (See 'Clinical presentation' above.)
The onset of symptoms in laryngotracheitis is gradual, beginning with nasal irritation,
congestion, and coryza. Fever, hoarseness, barking cough, and stridor usually
develop during the next 12 to 48 hours. Rapid progression or signs of lower airway
involvement suggest a more serious illness. (See 'Laryngotracheitis' above.)
The onset of symptoms in spasmodic croup is sudden and always occurs at night.
Fever is typically absent, but mild upper respiratory tract symptoms may be present.
(See 'Spasmodic croup' above.)
Bacterial tracheitis (picture 1 and image 4) may present acutely or as marked
worsening during the course of an antecedent viral upper respiratory infection.
Clinical manifestations of bacterial tracheitis include fever, toxic appearance, and
severe respiratory distress. (See 'Bacterial tracheitis' above and "Bacterial tracheitis
in children: Clinical features and diagnosis".)
The objectives of the evaluation of the child with croup include assessment of
severity (table 1) (calculator 1) and exclusion of other causes of upper airway
obstruction. (See 'Overview' above and 'Severity assessment' above.)
Rapid assessment of general appearance, vital signs, pulse oximetry, airway
stability, and mental status are necessary to identify children with severe respiratory
distress and/or impending respiratory failure. (See 'Rapid assessment and initial
management' above.)
The history should include a description of the onset, duration, and progression of
symptoms, and ascertain whether there are any underlying conditions that predispose
to a more severe course. (See 'History' above.)
Aspects of the examination that are useful in assessing the severity of upper airway
obstruction include overall appearance (including the presence of stridor at rest or
only with agitation), quality of voice, work of breathing, tidal volume and air entry, and
the presence of wheezing. (See 'Examination' above.)
The diagnosis of croup is clinical, based upon the presence of a barking cough and
stridor. Neither radiographs nor laboratory tests are necessary to make the diagnosis.
However, radiographs may be helpful in excluding other causes if the diagnosis is in
question. (See 'Diagnosis' above.)
The differential diagnosis of croup includes other causes of stridor and/or respiratory
distress. The primary considerations are those with acute onset, particularly those
that may rapidly progress to complete upper airway obstruction, and those that
require specific therapy. Important considerations include acute epiglottitis,
peritonsillar and retropharyngeal abscesses, foreign body aspiration, acute
angioneurotic edema, upper airway injury, and congenital anomalies of the upper
airway. (See 'Differential diagnosis' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
Author:
Charles R Woods, MD, MS
Section Editors:
Sheldon L Kaplan, MD
Anna H Messner, MD
Deputy Editor:
Carrie Armsby, MD, MPH
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Aug 02, 2016.
Most children with croup who seek medical attention have a mild, self-limited illness and
can be successfully managed as outpatients. The clinician must be able to identify children
with mild symptoms, who can be safely managed at home, and those with moderate to
severe croup or rapidly progressing symptoms, who require full evaluation and possible
treatment in the office or emergency department setting. (See 'Severity assessment' below
and 'Outpatient treatment' below.)
There is no definitive treatment for the viruses that cause croup. Pharmacologic therapy is
directed toward decreasing airway edema, and supportive care is directed toward the
provision of respiratory support and the maintenance of hydration. Corticosteroids and
nebulized epinephrine are the cornerstones of therapy; their use is supported by
substantial clinical evidence. (See 'Initial treatment' below and "Croup: Pharmacologic and
supportive interventions".)
The approach to the management of croup will be discussed below. The clinical features
and evaluation of croup, and the evidence supporting the use of the pharmacologic and
supportive interventions included below are discussed separately. (See "Croup: Clinical
features, evaluation, and diagnosis" and "Croup: Pharmacologic and supportive
interventions".)
SEVERITY ASSESSMENT This initial step in the management of a child with croup is
assessing severity of illness. The first contact with the healthcare system may occur by
phone and the healthcare provider must be able to distinguish children with more severe
symptoms who need immediate medical attention from those who can be managed at
home. (See 'Telephone triage' below.)
When the child is seen in the office or emergency department, croup severity is assessed
by examining the child and using a clinical scoring system. (See 'Croup severity
score' below.)
Telephone triage When assessing patients by phone, the healthcare provider must
distinguish children who need immediate medical attention or further evaluation from those
who can be managed at home. Children who need further evaluation include those who
have:
Stridor at rest
Rapid progression of symptoms (ie, symptoms of upper airway obstruction after less
than 12 hours of illness)
Inability to tolerate oral fluids
Underlying known airway abnormality (eg, subglottic stenosis, subglottic
hemangioma, previous intubation)
Previous episodes of moderate to severe croup
Medical conditions that predispose to respiratory failure (eg, neuromuscular
disorders or bronchopulmonary dysplasia)
Parental concern that cannot be relieved by reassurance
Prolonged symptoms (more than three to seven days) or an atypical course
(perhaps indicating an alternative diagnosis) (see "Croup: Clinical features,
evaluation, and diagnosis", section on 'Differential diagnosis')
Patients who are assessed by phone and determined to have mild symptoms and none of
the above indications for further evaluation can be managed at home. (See 'Home
treatment' below.)
Croup severity score There are a number of validated croup scoring systems. The
Westley croup score has been the most extensively studied (table 1) (calculator 1) [1].
Severity is determined by the presence or absence of stridor at rest, the degree of chest
wall retractions, air entry, the presence or absence of pallor or cyanosis, and the mental
status:
Mild croup (Westley croup score of 2) Children with mild croup have no stridor at
rest (although stridor may be present when upset or crying), a barking cough, hoarse
cry, and either no, or only mild, chest wall/subcostal retractions [2-4]. (See 'Mild
croup' below.)
Moderate croup (Westley croup score of 3 to 7) Children with moderate croup
have stridor at rest, have at least mild retractions, and may have other symptoms or
signs of respiratory distress, but little or no agitation [2-4]. (See 'Moderate to severe
croup' below.)
Severe croup (Westley croup score of 8) Children with severe croup have
significant stridor at rest, although the loudness of the stridor may decrease with
worsening upper airway obstruction and decreased air entry [2-4]. Retractions are
severe (including indrawing of the sternum) and the child may appear anxious,
agitated, or pale and fatigued. Prompt recognition and treatment of children with
severe croup are paramount. (See 'Moderate to severe croup' below.)
Impending respiratory failure (Westley croup score of 12) Croup occasionally
results in significant upper airway obstruction with impending respiratory failure,
heralded by the following signs [2,4,5]:
Fatigue and listlessness
Marked retractions (although retractions may decrease with increased
obstruction and decreased air entry)
Decreased or absent breath sounds
Depressed level of consciousness
Tachycardia out of proportion to fever
Cyanosis or pallor
Patients who present to an office clinic with severe croup or signs and symptoms of
impending respiratory failure should be transported via emergency medical services
to an emergency department for management. (See 'Moderate to severe
croup' below.)
MILD CROUP Children with mild symptoms (Westley croup score of 2 (table 1)
(calculator 1)) should be treated symptomatically with humidity, fever reduction, and oral
fluids. Many such children can be managed by phone, provided that none of the criteria for
further evaluation described above are present. (See 'Telephone triage' above.)
Home treatment The caregivers of children with mild croup who are managed at home
should be instructed in provision of supportive care including mist, antipyretics, and
encouragement of fluid intake.
In acute situations and for short periods of time, caregivers may try sitting with the child in
a bathroom filled with steam generated by running hot water from the shower to improve
symptoms. This may help reassure parents that "something" is being done to reverse the
symptoms, and anecdotal evidence supports some benefit with this measure.
Exposure to cold night air also may lessen symptoms of mild croup, although this has
never been systematically studied. If parents or caregivers wish to use humidifiers at
home, only those that produce mist at room temperature should be used to avoid the risk
of burns from steam or the heating element.
Instructions should be provided to the caregivers regarding when to seek medical
attention, including watching for [2]:
Stridor at rest
Difficulty breathing
Pallor or cyanosis
Severe coughing spells
Drooling or difficulty swallowing
Fatigue
Worsening course
Fever (>38.5C)
Prolonged symptoms (longer than seven days)
Suprasternal retractions
Caregivers also should be provided with some guidance regarding when it is safe for them
to drive the child to the emergency department; emergency medical services should
provide transportation for children who are severely agitated, pale or cyanotic, struggling to
breathe, or lethargic [2].
Patients who are managed at home should receive a follow-up phone call within 24 hours.
Outpatient treatment We suggest that children with mild croup who are seen in the
outpatient setting be treated with a single dose of oral dexamethasone (0.15 to
0.6 mg/kg, maximum dose 10 mg) (algorithm 1). Randomized controlled trials in children
with mild croup have demonstrated that treatment with a single dose of oral
dexamethasone reduces the need for reevaluation, shortens the duration of symptoms,
improves the child's sleep, and reduces parental stress [6,7]. (See "Croup: Pharmacologic
and supportive interventions", section on 'Dexamethasone'.)
Treatment with nebulized epinephrine is not typically necessary for management of mild
croup.
Children with mild croup who are tolerating fluids and have not received
nebulized epinephrine can be sent home after specific follow-up (which may occur by
phone) has been arranged and the caregiver has received instructions regarding home
care and indications to seek medical attention as described above. (See 'Home
treatment' above.)
Children with moderate croup (Westley croup score 3 to 7; stridor at rest and mild to
moderate retractions, but no or little distress or agitation (table 1) (calculator 1))
should be evaluated in the emergency department or office (provided the office is
equipped to handle acute upper airway obstruction).
Children with severe croup (Westley croup score 8; stridor at rest and marked
retractions with agitation, lethargy, or cyanosis (table 1) (calculator 1)) should be
evaluated in the emergency department as they require aggressive therapy,
monitoring, and supportive care.
The child with severe croup must be approached cautiously, as any increase in anxiety
may worsen airway obstruction. The parent or caregiver should be instructed to hold and
comfort the child. Nebulized epinephrine should be added as quickly as possible, as
described below. In the meantime, healthcare providers should continuously observe the
child and be prepared to provide bag-mask ventilation and advanced airway techniques if
the condition worsens (algorithm 1). (See 'Initial treatment' below and 'Respiratory
care' below.)
The benefit of corticosteroids for moderate to severe croup have been demonstrated in a
meta-analysis of 24 trials that found improvement in croup scores six hours after
treatment, fewer return visits or readmissions, decreased length of stay in the emergency
department or hospital, and decreased epinephrine use [7]. (See "Croup: Pharmacologic
and supportive interventions", section on 'Glucocorticoids'.)
Observation and disposition Patients should be observed for three to four hours after
initial treatment. The need for additional intervention and/or admission to the hospital is
determined chiefly by the response to therapy with corticosteroids and
nebulized epinephrine. The majority of children with moderate croup have symptomatic
improvement after treatment with nebulized epinephrine and corticosteroids and can be
discharged home, whereas those with severe symptoms on presentation are more likely to
require hospitalization.
Discharge to home Patients who have a good response to initial treatment should be
observed for three to four hours after pharmacologic intervention (algorithm 1) [13-16].
Croup symptoms usually improve within 30 minutes of administration of
nebulized epinephrine, but may recur as the effects of epinephrine wear off (usually by two
hours) [17,18]. Children who have recurrence or worsening of moderate to severe
symptoms during the observation period should receive additional racemic epinephrine
and should be admitted to the hospital. (See 'Indications for hospital admission' below.)
After three to four hours of observation, children who remain comfortable may be
discharged home if they meet the following criteria [13-16]:
No stridor at rest
Normal pulse oximetry
Good air exchange
Normal color
Normal level of consciousness
Demonstrated ability to tolerate fluids by mouth
Caregivers understand the indications for return to care and would be able to return
if necessary
Before discharge, follow-up with the primary care provider should be arranged within the
next 24 hours. Instructions regarding home treatment should be provided. (See 'Home
treatment' above.)
Approximately 5 percent of children well enough for discharge from the emergency
department after receiving corticosteroids and nebulized epinephrine treatments are
expected to return for care [19]. Relapse within 24 hours is unlikely in those who have
minimal symptoms at the time of discharge [20].
Indications for hospital admission Patients with ongoing severe symptoms after
initial treatment should receive additional nebulized epinephrine and should be admitted to
the hospital. Nebulized epinephrine can be repeated every 15 to 20 minutes. The
administration of three or more doses within a two- to three-hour time period should
prompt initiation of close cardiac monitoring if this is not already underway.
Children with persistent moderate symptoms can be observed for at least four hours
before deciding whether they require hospital admission as the effect
of dexamethasone may not be apparent for several hours [2].
Severe croup with poor air entry, altered consciousness, or impending respiratory
failure
Moderate/severe croup with persistent or deteriorating respiratory distress after
treatment with nebulized epinephrine and corticosteroids
"Toxic" appearance or clinical picture suggesting serious secondary bacterial
infection
Need for supplemental oxygen
Severe dehydration
Additional factors that influence the decision regarding admission include [2,21]:
Admission to the pediatric intensive care unit (PICU) is warranted if any of the following
are present:
Supportive care Supportive care for children hospitalized with moderate to severe
croup includes:
Respiratory care Respiratory support for children hospitalized with croup may include
the following:
Infection control Children who are admitted to the hospital with croup should be
managed with contact precautions (ie, gown and gloves for contact), particularly if
parainfluenza or respiratory syncytial virus is the suspected etiology. If influenza is
suspected, droplet isolation measures (ie, respiratory mask within three feet) also should
be followed. (See "Infection prevention: Precautions for preventing transmission of
infection".)
Discharge criteria Children who require hospital admission may be discharged when
they meet the following criteria:
No stridor at rest
Normal pulse oximetry in room air
Good air exchange
Normal color
Normal level of consciousness
Demonstrated ability to tolerate fluids by mouth
Atypical course Children admitted for croup typically remain in the hospital for less
than 36 hours [23]. The child who does not show improvement as expected (over the
course of one to two days) may have an underlying airway abnormality or may be
developing a complication of croup. Further evaluation with radiographs of the soft tissues
of the neck, or consultation with otolaryngology, may be warranted. A biphasic illness with
poor response to nebulized epinephrine in conjunction with high fever and toxic
appearance should prompt consideration of bacterial tracheitis (picture 1) [2]. (See "Croup:
Clinical features, evaluation, and diagnosis", section on 'Differential
diagnosis' and "Bacterial tracheitis in children: Clinical features and diagnosis".)
Follow-up should continue until the child's symptoms have begun to resolve. The child
whose symptoms do not resolve over the course of approximately seven days may have
an underlying airway abnormality or may be developing a complication of croup.
(See 'Atypical course' above.)
PROGNOSIS Symptoms of croup resolve in most children within three days, but may
persist for up to one week [26,27]. Approximately 8 to 15 percent of children with croup
require hospital admission [19,28], and among those, less than 1 percent require
intubation [22]. Mortality is rare, occurring in <0.5 percent of intubated children [29].
Here are the patient education articles that are relevant to this topic. We encourage you to
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on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
Author:
Charles R Woods, MD, MS
Section Editors:
Sheldon L Kaplan, MD
Anna H Messner, MD
Deputy Editor:
Carrie Armsby, MD, MPH
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Aug 02, 2016.
The treatment of croup has changed significantly since the 1980s. Glucocorticoids and
nebulized epinephrine have become the cornerstones of therapy. Substantial clinical
evidence supports the efficacy of these interventions [1-5]. The impact also is evident in
the decrease in annual hospital admissions for croup in children in the United States
between 1979 to 1982 and 1994 to 1997 (from 2.8 to 2.1 per 1000 for children <1 year and
from 1.8 to 1.2 per 1000 children for children 1 to 4 years) [6].
Treatment with glucocorticoids at various doses and by various routes has been shown to
improve croup scores and to decrease unscheduled medical visits, length of stay in the
emergency department (ED) or hospital, and the use of epinephrine [7]. Among the
available glucocorticoids, dexamethasone has been used most frequently, is the least
expensive, has the longest duration of action, and is the easiest to administer.
Efficacy Intramuscular (IM), intravenous (IV), oral, and inhaled routes of administration
of glucocorticoids have been shown to be effective in croup of all levels of severity
[7,8]. Dexamethasone (oral or IM) and budesonide (inhaled) were the agents used in the
majority of studies. A systematic review included 24 trials (with collective enrollment of
2878 children) that objectively measured the effectiveness of glucocorticoid treatment for
croup compared with placebo [7]. Fourteen other trials compared different glucocorticoid
agents or different routes or dosages of the same agent [7]. Compared with treatment with
placebo, treatment with glucocorticoid was associated with:
Improvement in the croup score at six hours with a weighted mean difference of -1.2
(95% CI -1.6 to -0.8) and at 12 hours -1.9 (95% CI -2.4 to -1.3); at 24 hours this
improvement was no longer significant (-1.3, 95% CI -2.7 to 0.2).
Fewer return visits and/or (re)admissions (relative risk [RR] 0.50, 95% CI 0.3-0.7).
Decreased length of time spent in ED or hospital (weighted mean difference 12
hours, 95% CI 5-19 hours).
Decreased use of epinephrine (risk difference 10 percent; 95% CI 1-20 percent).
There were no significant differences in clinical efficacy between the routes or
agents, and the combination of oral or IM dexamethasone with
inhaled budesonide was not superior to either agent alone [11,12].
Another systematic review of eight randomized controlled trials compared the
administration of nebulized glucocorticoids with placebo. Children treated with nebulized
glucocorticoids were significantly more likely to show improvement in croup score at five
hours (combined RR 1.48, 95% CI 1.27-1.74) and significantly less likely to need hospital
admission (combined RR 0.56, 95% CI 0.42-0.75) [13].
The primary concern is potential risk of progressive viral infection or secondary bacterial
infection, which have been reported in patients who received glucocorticoid treatment over
several days [17], or received nebulized dexamethasone and had neutropenia [18]. These
complications have not been described in children who have received single doses of oral,
IM, or IV glucocorticoids for croup.
Glucocorticoid use may exacerbate active varicella and tuberculosis and should be
avoided in children with these infections and in those recently exposed to, and possibly
incubating, varicella [19,20]. (See "Clinical features of varicella-zoster virus infection:
Chickenpox".)
Agents
Dexamethasone Dexamethasone can be given IM, IV, or orally and should generally
be administered via the least invasive route possible (orally if oral intake is tolerated, IV if
IV access has been established, or IM if oral intake is not tolerated and IV access has not
been established). Based on the available evidence, there do not appear to be clinically
significant differences in croup outcomes between IM and orally administered
dexamethasone [7].
The optimal dose of dexamethasone in children with croup is uncertain. In clinical trials,
doses ranging from 0.15 to 0.6 mg/kg have been shown to be effective [7]. For children
with moderate to severe croup (ie, Westley croup score of 3 (table 1)), we recommend a
single dose of 0.6 mg/kg (maximum 10 mg) [22]. Dexamethasone at this dose has proven
efficacy in croup as demonstrated in numerous clinical trials, including several high-quality
placebo-controlled trials [4,7,9,23]. Based on these data, we also suggest a dose of
0.6 mg/kg (maximum 10mg) for children with mild croup (ie, Westley croup score of 2
(table 1)); however, limited data suggest that lower doses (0.15 mg/kg to 0.4 mg/kg) may
be equally effective in patients with mild croup [7,24-27]. Nonpharmacologic management
is another reasonable alternative for patients with mild croup. (See "Croup: Approach to
management", section on 'Mild croup'.)
The oral liquid preparation of dexamethasone (1 mg per mL) has a foul taste. The IV
preparation is more concentrated (4 mg per mL) and can be given orally mixed with syrup
[11,28,29].
Studies of nebulized dexamethasone in children with croup have mixed results. One study
found nebulized dexamethasone to be less effective than oral dexamethasone in
preventing the need for subsequent treatment with glucocorticoid or epinephrine in
children with mild croup [23]. Another study found that treatment with nebulized
dexamethasone in children with moderate croup improved croup scores at four hours but
did not affect the rate of hospitalization [18]. In addition, two patients with neutropenia who
were treated with dexamethasone developed bacterial tracheitis.
Budesonide Nebulized budesonide has been shown to be more effective than placebo
and as effective as IM or oral dexamethasone for the treatment of croup [7,30]. However,
nebulized budesonide is more expensive and more difficult to administer than IM or oral
dexamethasone and is not routinely indicated in the treatment of croup. However,
nebulized budesonide may provide an alternative to IM or IV dexamethasone for children
with vomiting or severe respiratory distress [22]. In children with severe respiratory
distress, a single dose of budesonide may be mixed with epinephrine and administered
simultaneously. (See "Croup: Approach to management", section on 'Moderate to severe
croup'.)
Prednisolone Some authorities suggest that for children who are treated as
outpatients, oral prednisolone (2 mg/kg per day for three days) is an alternative to
oral dexamethasone [31]. The use of prednisolone in the treatment of croup has been
evaluated in a limited number of studies.
A subsequent randomized trial compared oral dexamethasone (0.6 mg/kg on the first day
followed by placebo on the next two days) with oral prednisolone (2 mg/kg per day for
three days) in 87 children with mild or moderate croup who were treated as outpatients
[31]. There were no differences between groups in additional health care visits (2 versus 7
percent [not significant]), duration of symptoms (2.8 versus 2.2 days), duration of nonbarky
cough (6.1 versus 5.9 days), nights with disturbed parental sleep (0.7 versus 1.2), or days
with stress (1.6 versus 1.4).
Prednisone The use of prednisone in the management of croup has not been
evaluated in clinical trials. However, it has equivalent potency to prednisolone and, in
theory, should have similar effects. Despite its lack of proven benefit, prednisone is widely
used in the outpatient management of croup [33].
Repeated dosing The majority of clinical trials of oral and IM glucocorticoids in croup
have used a single dose. Repeat doses are not necessary on a routine basis. Although
repeat doses may be reasonable in the occasional child who has persistent symptoms,
they should be used with caution. The anecdotal cases of progression of viral illness and
secondary bacterial infection that have been reported with use of glucocorticoids for croup
occurred with repeated dosing over several days [35], or in neutropenic patients [18].
(See 'Adverse effects' above.)
Moderate to severe symptoms that persist for more than a few days should prompt
investigation for other causes of airway obstruction. (See "Croup: Clinical features,
evaluation, and diagnosis", section on 'Differential diagnosis'.)
NEBULIZED EPINEPHRINE The administration of nebulized epinephrine to patients
with moderate to severe croup often results in rapid improvement of upper airway
obstruction. Epinephrine constricts precapillary arterioles in the upper airway mucosa and
decreases capillary hydrostatic pressure, leading to fluid resorption and improvement in
airway edema [19]. Even a small increase in airway diameter can lead to significant clinical
improvement.
Administration of epinephrine does not alter the natural history of croup in the short (>2
hours) or longer term (24 to 36 hours) [1,37,40].
Dose
Racemic epinephrine is administered as 0.05 mL/kg per dose (maximum of 0.5 mL)
of a 2.25 percent solution diluted to 3 mL total volume with normal saline. It is given
via nebulizer over 15 minutes.
L-epinephrine is administered as 0.5 mL/kg per dose (maximum of 5 mL) of a
1:1000 dilution [41]. It is given via nebulizer over 15 minutes.
Nebulized epinephrine treatments may be repeated every 15 to 20 minutes if warranted by
the clinical course. Children who require repeated frequent dosing (eg, three or more
doses within two to three hours) to achieve stabilization of their respiratory function
generally should be admitted to an ICU or intermediate care setting (depending on the
severity of persisting signs).
Precautions The clinical effects of nebulized epinephrine last for no more than two
hours. After the effects have worn off, symptoms may return to baseline (an apparent
worsening, sometimes referred to as the "rebound phenomenon"). Children who receive
even a single dose of nebulized epinephrine should be observed in the ED or hospital
setting for at least three to four hours after administration to ensure that symptoms do not
return to baseline.
Serious adverse effects from nebulized epinephrine are exceedingly rare. However, a case
of myocardial infarction in a child with croup who received three doses of racemic
epinephrine within 60 minutes has been reported [42]. Thus, it seems prudent to place
children who require ongoing epinephrine treatments more frequently than every one to
two hours on cardiac monitors (both because of the severity of illness and the potential
systemic impact of nebulized epinephrine). Continuous electrocardiographic monitoring (or
equivalent cardiac monitoring) also should be considered in these cases.
OXYGEN Oxygen is not known to have any direct impact on the subglottic edema or
airway narrowing, but should be administered to children who are hypoxemic (oxygen
saturation of <92 percent in room air) and/or in moderate to severe respiratory distress
[15,22]. Supplemental oxygen should be humidified to decrease drying effects on the
airways, since drying may impede the physiologic removal of airway secretions via
mucociliary and cough mechanisms. (See "Continuous oxygen delivery systems for
infants, children, and adults".)
Heliox Helium is inert, nontoxic, and of very low density. Heliox is a mixture of helium
(70 to 80 percent) and oxygen (20 to 30 percent). It can flow through airways with less
turbulence and resistance than pure oxygen. (See "Physiology and clinical use of heliox".)
Heliox decreases the work of respiration in children with croup and theoretically could be
used as a temporizing measure, to prevent the need for intubation while waiting for
glucocorticoids to decrease airway edema [43]. However, in clinical trials, heliox has not
definitively been shown to be more effective than humidified oxygen or
racemic epinephrine in reducing croup scores [44-46]. A 2013 systematic review found
only three methodologically limited trials (91 patients) evaluating heliox in children with
croup and concluded that a larger trial is needed before recommendations regarding the
use of heliox in children with croup can be made [46].
MIST THERAPY Humidified air is frequently used in the treatment of croup, although
there have been no studies supporting its efficacy in reducing symptoms [47]. Two
randomized trials (one comparing mist versus no mist and the other comparing no mist,
low humidity, and 100 percent humidity) among children brought to an emergency
department for croup demonstrated no significant change in croup scores from baseline
between the groups [48,49].
Although humidified air does not reduce subglottic edema, it may provide other benefits.
Inhalation of moist air, relative to dry air, may decrease drying of inflamed mucosal
surfaces and reduce inspissation of secretions [50]. In addition, a mist source may provide
a sense of comfort and reassurance to both the child and family [51-53]. In medical
settings, mist therapy may be provided by blow-by or saline nebulization treatments. Croup
tents should be avoided, since they can aggravate a child's anxiety and make vital signs
and other visual assessments of the child more difficult. Some guidelines recommend
against the use of mist therapy for children who are hospitalized with croup [22]. Certainly
if the child is agitated by the provision of mist, mist therapy should be discontinued.
OTHER THERAPIES
Antitussives Nonprescription antitussive agents are of unproven benefit for croup (or
other respiratory tract infections). Codeine, which is a more potent cough suppressant, can
alter the child's sensorium, making it difficult to follow the clinical course.
Sedatives The routine use of sedative agents in effort to improve airway obstruction by
relieving anxiety and apprehension is not recommended. Sedatives may treat the
symptom of agitation while masking the underlying causes of air hunger and hypoxia. They
also may decrease respiratory effort (and therefore croup scores), without improving
ventilation [15,54].
Here are the patient education articles that are relevant to this topic. We encourage you to
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on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
SUMMARY
BRONQUIOLITIS
Bronchiolitis in infants and children: Treatment, outcome, and prevention
Authors:
Pedro A Piedra, MD
Ann R Stark, MD
Section Editors:
George B Mallory, MD
Morven S Edwards, MD
Deputy Editor:
Mary M Torchia, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Feb 23, 2017.
DEFINITION For the purposes of this topic review, bronchiolitis is broadly defined as a
clinical syndrome that occurs in children <2 years of age and is characterized by upper
respiratory symptoms (eg, rhinorrhea) followed by lower respiratory (eg,
small airway/bronchiole) infection with inflammation, which results in wheezing and or
crackles (rales). Bronchiolitis typically occurs with primary infection or reinfection with a
viral pathogen, but occasionally is caused by bacteria (eg, Mycoplasma pneumoniae). In
young children, the clinical syndrome of bronchiolitis may overlap with recurrent virus-
induced wheezing and acute viral-triggered asthma. The diagnosis of bronchiolitis, virus-
induced wheezing, and acute viral-triggered asthma are discussed separately.
(See "Bronchiolitis in infants and children: Clinical features and diagnosis", section on
'Diagnosis' and "Virus-induced wheezing and asthma: An overview" and "Asthma in
children younger than 12 years: Initial evaluation and diagnosis" and "Asthma in children
younger than 12 years: Initial evaluation and diagnosis", section on 'Respiratory tract
infections'.)
Although age <12 weeks is a risk factor for severe or complicated disease, young age in
and of itself is not an indication for hospitalization. (See "Bronchiolitis in infants and
children: Clinical features and diagnosis", section on 'Risk factors for severe disease'.)
Hypoxemia is often used as a criterion for admission in infants without comorbid conditions
for severe disease. However, it should not be the only criterion. Observational studies
suggest that episodes of desaturation with mild to moderate respiratory distress are
common in infants with bronchiolitis and that detection of hypoxemia may be associated
with increased health care utilization (eg, supplemental oxygen, admission, increased
length of stay) but little or no acute benefit [4,10-12]. The effect of brief periods of
hypoxemia caused by bronchiolitis on the developing brain has not been adequately
addressed.
NONSEVERE BRONCHIOLITIS
Overview of approach Infants and children with nonsevere bronchiolitis usually can be
managed in the outpatient setting, unless there are concerns about the caregivers' ability
to care for them at home. (See 'Indications for hospitalization' above.)
Supportive care and anticipatory guidance are the mainstays of management of nonsevere
bronchiolitis. Supportive care includes maintenance of adequate hydration, relief of
nasal congestion/obstruction, and monitoring for disease progression. (See 'Anticipatory
guidance' below and 'Follow-up' below.)
For immune competent infants and children with nonsevere bronchiolitis who are treated in
the office or emergency department, we do not routinely recommend pharmacologic
interventions because they lack proven benefit, increase the cost of care, and may have
adverse effects. Randomized trials, systematic reviews, and meta-analyses do not support
the benefits of bronchodilators (inhaled or oral) [13-18], glucocorticoids (inhaled or
systemic) [1,19-24], or leukotriene inhibitors [25]. Antibiotics are indicated only if there is
evidence of a coexisting bacterial infection. This approach is consistent with that of the
American Academy of Pediatrics, the National Institute for Care Excellence, and other
professional organizations [1,5,7,26]. (See 'Interventions that are not routinely
recommended' below.)
For infants and children with nonsevere bronchiolitis who are treated in the office or
emergency department, we suggest not routinely treating with nebulized hypertonic saline.
In a 2015 systematic review of randomized trials evaluating administration of hypertonic
saline in the emergency department, hypertonic saline reduced the rate of hospitalization
among children with bronchiolitis, but the evidence was of low quality [26].
Follow-up Children with bronchiolitis who are not hospitalized should be monitored by
their clinician for progression and resolution of disease. Follow-up, usually within one to
two days, may occur by phone or at the office. The timing and method of follow-up depend
upon initial severity and duration of symptoms; patients who are seen in the first one to two
day of symptoms may worsen before they improve. Repeated clinical assessments of the
respiratory system (eg, respiratory rate, nasal flaring, retractions, grunting) may be
necessary to determine the course of the illness and to identify deteriorating respiratory
status. (See 'Anticipatory guidance' above.)
In children who do not improve as expected, chest radiographs may be helpful in excluding
other conditions in the differential diagnosis (eg, foreign body aspiration, heart failure,
vascular ring) [1]. (See "Bronchiolitis in infants and children: Clinical features and
diagnosis", section on 'Differential diagnosis' and 'Anticipatory guidance' above.)
SEVERE BRONCHIOLITIS Infants and children severe bronchiolitis usually require
treatment in the emergency department or inpatient setting. Supportive care and
anticipatory guidance are the mainstays of management of severe bronchiolitis. Supportive
care includes maintenance of adequate hydration, respiratory support, and monitoring for
disease progression. (See 'Severity assessment' above and 'Indications for
hospitalization' above.)
Fluid management The fluid intake and output of infants and children with bronchiolitis
should be assessed regularly. Children with bronchiolitis may have difficulty maintaining
adequate hydration because of increased needs (related to fever and tachypnea) and
decreased intake (related to tachypnea and respiratory distress).
It is also important to monitor urine output. Plasma antidiuretic hormone levels rarely may
be elevated, leading to fluid retention and hyponatremia [36-38]. Fluid overload should be
avoided, since it may lead to pulmonary congestion. (See "Pathophysiology and etiology of
the syndrome of inappropriate antidiuretic hormone secretion (SIADH)", section on
'Pulmonary disease' and "Maintenance fluid therapy in children", section on 'Hospitalized
children'.)
Respiratory support Respiratory support for infants and young children with
bronchiolitis generally is provided in a stepwise fashion. Most children require nasal
suctioning. Supplemental oxygen is provided as necessary to maintain SpO2 >90 to 92
percent. Infants who are at risk for progression to respiratory failure often receive a trial of
heated humidified high-flow nasal cannula (HFNC) therapy and/or continuous positive
airway pressure (CPAP) before endotracheal intubation. However, initial endotracheal
intubation is more appropriate than HFNC or CPAP for children with hemodynamic
instability, intractable apnea, or loss of protective airway reflexes.
Data are lacking to support the use of a specific SpO2 cutoff value. The American Academy
of Pediatrics practice guideline suggests SpO2 <90 percent as the threshold to start
supplemental oxygen [1]. However, variability in the accuracy of oximeters, and
concomitant fever, acidosis, or hemoglobinopathy favor the use of a higher cutoff value. In
a multicenter study comparing oxygen saturation simultaneously measured with pulse
oximetry (SpO2) and arterial blood gas (SaO2), the accuracy of pulse oximetry varied with
the range of oxygen saturation [41]. In the SpO2 range of 76 to 90 percent, pulse oximetry
tended to overestimate SaO2 (by a median of approximately 5 percent); in the SpO2 range
of 91 to 97 percent, SpO2 and SaO2 values were similar (median difference of 1 percent).
HFNC and CPAP Heated humidified high-flow nasal cannula (HFNC, also called high-
flow warm humidified oxygen) therapy and/or continuous positive airway pressure (CPAP)
are used to reduce the work of breathing, improve gas exchange, and avoid the need for
endotracheal intubation in children with bronchiolitis who are at risk for progression to
respiratory failure [42-44]. Successful therapy with HFNC or CPAP avoids the adverse
effects of endotracheal intubation (eg, laryngeal injury, ventilator-induced lung injury,
ventilator-associated pneumonia, narcotic dependence and withdrawal) [45].
HFNC and CPAP typically require care in an intensive or immediate care unit. However,
some institutions initiate HFNC in the emergency department or on the general ward [44].
A detailed discussion of critical care respiratory interventions for infants and young children
with bronchiolitis is beyond the scope of this review. General discussions of invasive and
noninvasive ventilation strategies for infants and children with respiratory failure are
provided separately. (See "Continuous oxygen delivery systems for infants, children, and
adults", section on 'High flow' and "Noninvasive ventilation for acute and impending
respiratory failure in children".)
Clinical course Although discharge criteria vary from center to center, in multicenter-
studies of children younger than two years hospitalized with bronchiolitis, the median
length of stay was two days [88,89]. Length of stay may be shorter in children with
bronchiolitis due to rhinovirus and longer in children with respiratory syncytial virus-
rhinovirus coinfection [88-90]. The respiratory status typically improves over two to five
days [84,91-95]. However, wheezing persists in some infants for a week or longer. The
course may be prolonged in younger infants and those with comorbid conditions (eg,
bronchopulmonary dysplasia) [8,96].
Discharge criteria Minimal clinical criteria for discharge from the hospital or
emergency department include [5,6,26]:
Respiratory rate <60 breaths per minute for age <6 months, <55 breaths per minute
for age 6 to 11 months, and <45 breaths per minute for age 12 months
Caretaker knows how to clear the infant's airway using bulb suctioning
Patient is stable while breathing ambient air; discharge from the hospital requires
that the patient remain stable for at least 12 hours prior to discharge
Patient has adequate oral intake to prevent dehydration
Resources at home are adequate to support the use of any necessary home
therapies (eg, bronchodilator therapy if the trial was successful and this therapy is to
be continued)
Caretakers are confident they can provide care at home
Education of the family is complete (see 'Anticipatory guidance' above)
The overall mortality rate in children hospitalized with respiratory syncytial virus (RSV)
bronchiolitis in developed countries is less than 0.1 percent [99]. Mortality is increased in
young infants (6 to 12 weeks), those with low birth weight, and those with underlying
medical conditions (eg, underlying cardiopulmonary disease, immune deficiency)
[84,100,101].
Infants hospitalized for lower respiratory tract infection (LRTI), especially RSV and
rhinovirus, are at increased risk for recurrent wheezing and reduced pulmonary function,
particularly during the first decade of life [102-107]. In a prospective cohort, LRTI with RSV
increased the risk for subsequent frequent and infrequent wheezing (odds ratio 4.3 and
3.2, respectively) and was associated with reduced forced expiratory volume in children up
to 11 years of age [108]. However, this association was lost by age 13 years, perhaps due
to inadequate sample size. Similar findings have been observed for infants infected with
rhinovirus [106,109].
Whether bronchiolitis in early childhood, especially that caused by RSV and rhinovirus, is
associated with the development of asthma is uncertain. In some studies, a correlation
exists between infection with RSV and the later development of reversible airways
disease. However, this may reflect the multifactorial nature of risk for asthma, including a
genetic predisposition to airway reactivity, exposure to environmental pollutants such as
smoke, immunologic mechanisms, and disruption of the growth and development of the
lungs due to viral infection in early childhood. (See "Risk factors for asthma", section on
'Respiratory infections' and "Respiratory syncytial virus infection: Clinical features and
diagnosis", section on 'Airway reactivity'.)
PREVENTION
Bronchodilators
Glucocorticoids
For infants and children admitted to the hospital with bronchiolitis, we suggest not routinely
treating with nebulized hypertonic saline. Although two meta-analyses found low-quality
evidence that nebulized hypertonic saline reduces length of stay (by approximately one-
half day) [118,119], a subsequent meta-analysis found no effect when the data were
reanalyzed to control for heterogeneity (eg, imbalance between mean day of illness at
presentation between treatment groups, divergent outcome definition) [120].
Most of the trials included in the systematic reviews administered hypertonic saline with
bronchodilators. A subsequent randomized, comparator-controlled trial found that,
compared with normal saline, 3 percent hypertonic saline administered every four hours
without bronchodilators did not reduce length of stay in infants younger than 12 months of
age who were hospitalized with bronchiolitis and had no significant comorbidities [121].
Well-designed randomized, comparator-controlled studies suggest no benefit from
hypertonic saline for the treatment of infants hospitalized with bronchiolitis [121-124]. Until
additional high quality studies show otherwise, nebulized hypertonic saline cannot be
routinely recommended for hospitalized children with bronchiolitis [125].
The 2015 NICE bronchiolitis guideline recommends against the use of hypertonic saline in
children with bronchiolitis [26]. The 2014 AAP clinical practice guideline on the
management of bronchiolitis indicated that clinicians "may administer hypertonic saline to
infants and children hospitalized for bronchiolitis" [1].
Chest physiotherapy We suggest that chest physiotherapy not be used routinely in the
management of bronchiolitis. A systematic review of 12 randomized trials concluded that
chest physiotherapy did not reduce severity of disease or time to recovery [126]. The use
of chest physiotherapy is discouraged because it may increase the distress and irritability
of ill infants.
Heliox We do not suggest the routine use of heliox (a 70/30 or 80/20 mixture of helium
and oxygen, respectively) in the treatment of bronchiolitis in infants and children. The
administration of heliox is cumbersome and results in a relatively small benefit in a limited
group of infants. A 2015 systematic review of seven heterogeneous randomized trials of
heliox for the treatment of moderate or severe bronchiolitis concluded that heliox did not
reduce the rate of intubation, rate of discharge from the emergency department, or the
length of treatment for respiratory distress [132]. (See "Physiology and clinical use of
heliox", section on 'Technical issues'.)
Here are the patient education articles that are relevant to this topic. We encourage you to
print or email these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
Basics topics (see "Patient education: Bronchiolitis (and RSV) (The Basics)")
Beyond the Basics topics (see "Patient education: Bronchiolitis (and RSV) in infants
and children (Beyond the Basics)")
Authors:
Pedro A Piedra, MD
Ann R Stark, MD
Section Editors:
Gregory Redding, MD
Morven S Edwards, MD
Deputy Editor:
Mary M Torchia, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Nov 03, 2016.
For clinical research, bronchiolitis is typically defined as the first episode of wheezing in a
child younger than 12 to 24 months who has physical findings of a viral lower respiratory
infection and no other explanation for the wheezing [4,5].
RSV RSV is the most common cause of bronchiolitis and the virus most often
detected as the sole pathogen. RSV is ubiquitous throughout the world and causes
seasonal outbreaks. In temperate climates, late fall and winter epidemics of
bronchiolitis usually are linked to RSV. In tropical and semitropical climates, the
seasonal outbreaks usually are associated with the rainy season. (See "Respiratory
syncytial virus infection: Clinical features and diagnosis".)
Rhinovirus Human rhinoviruses are the main cause of the common cold. There
are more than 170 serotypes. Rhinovirus is associated with lower respiratory tract
infection in young children and in individuals with chronic pulmonary disease [19].
Dual viral infections are often detected. Rhinovirus is often associated with
bronchiolitis in the spring and fall [20]. (See "Epidemiology, clinical manifestations,
and pathogenesis of rhinovirus infections".)
Parainfluenza virus Parainfluenza virus type 3, which is associated with epidemics
in early spring and fall, is another cause of bronchiolitis. Parainfluenza virus types 1
and 2 also can cause bronchiolitis although croup is the more common presentation
[21]. (See "Parainfluenza viruses in children", section on 'Clinical presentation'.)
Human metapneumovirus Human metapneumovirus sometimes occurs in
conjunction with other viral infections and has been identified as an etiology of
bronchiolitis and pneumonia in children [22,23]. (See "Human metapneumovirus
infections".)
Influenza virus The lower respiratory tract manifestations of influenza are clinically
indistinguishable from those due to RSV or parainfluenza viral infections.
(See "Seasonal influenza in children: Clinical features and diagnosis", section on
'Clinical features'.)
Adenovirus Adenovirus may cause lower respiratory tract infections, including
bronchiolitis, bronchiolitis obliterans, and pneumonia, though it more typically causes
pharyngitis and coryza. Adenovirus can also infect other organs causing disseminated
disease. (See "Epidemiology and clinical manifestations of adenovirus infection",
section on 'Clinical presentation'.)
Coronavirus Human coronaviruses are another important cause of the common
cold, which can also cause lower respiratory tract infection, including bronchiolitis
[24,25]. Severe acute respiratory syndrome (SARS) was caused by a coronavirus that
likely originated from the Chinese horseshoe bat [26]. Middle East respiratory
syndrome (MERS) is also caused by a coronavirus that was first detected in the
Arabian Peninsula in 2012. (See "Coronaviruses".)
Human bocavirus Human bocavirus 1 causes upper and lower respiratory
infections during the fall and winter months [14,27-29]. Bronchiolitis and pertussis-like
illness can occur. Human bocavirus 2 through 4 are primarily enteric viruses [30].
EPIDEMIOLOGY Bronchiolitis typically affects infants and children younger than two
years, principally during the fall and winter [31,32]. Bronchiolitis hospitalization has a peak
incidence between two and six months of age and remains a significant cause of
respiratory disease during the first two years of life [33]. It is a leading cause of
hospitalization in infants and young children [32-34].
RISK FACTORS FOR SEVERE DISEASE Risk factors for severe or complicated
bronchiolitis include [35-41]:
Environmental and other risk factors, such as passive smoking, crowded household,
daycare attendance, being born approximately two months before or after the start of the
epidemic, concurrent birth siblings, older siblings, and high altitude (>2500 meters) can
also contribute to more severe disease [40,42-45].
CLINICAL FEATURES
Clinical course The duration of the illness due to bronchiolitis depends upon age,
severity of illness, associated high-risk conditions (eg, prematurity, chronic pulmonary
disease), and the causative agent [9]. Bronchiolitis usually is a self-limited disease. Most
children who do not require hospitalization recover by 28 days [47-49].
Typical illness with bronchiolitis begins with upper respiratory tract symptoms, followed by
lower respiratory tract signs and symptoms on days two to three, which peak on days
three to five and then gradually resolve. In a systematic review of four studies including
590 children with bronchiolitis who were seen in outpatient settings and not treated with
bronchodilators [5,48-50], the mean time to resolution of cough ranged from 8 to 15 days
[51]. Cough resolved in 50 percent of patients within 13 days and in 90 percent within 21
days. In a cohort of 181 children (not included in the systematic review), the median
duration of caretaker-reported symptoms was 12 days; approximately 20 percent
continued to have symptoms for at least three weeks, and 10 percent had symptoms for at
least four weeks [47].
Although discharge criteria vary from center to center, in multicenter studies of children
younger than two years hospitalized with bronchiolitis, the median length of stay was two
days [9,52]. Length of stay may be shorter in children with bronchiolitis due to rhinovirus
and longer in children with bronchiolitis due to respiratory syncytial virus (RSV)-rhinovirus
co-infection. The respiratory status typically improves over two to five days [36,53-56].
However, wheezing persists in some infants for a week or longer.
The course may be prolonged in infants younger than six months (particularly those
younger than 12 weeks) and those with comorbid conditions (eg, bronchopulmonary
dysplasia); these children often are severely affected and may require assisted ventilation
[35,57]. (See 'Risk factors for severe disease' above and 'Respiratory failure' below.)
In a three-year multicenter prospective study (2007 to 2010) that included 2156 children <2
years hospitalized with bronchiolitis, apnea was documented in 5 percent [64]. The study
focused on sicker patients by aiming to enroll 20 percent of patients from the intensive
care unit. Independent risk factors for apnea included age <8 weeks (age was corrected
for gestational age if born preterm), caretaker report of previous apnea during the illness,
high or low respiratory rate at presentation (ie, respiratory rate <30 or
>70 breaths/minute), and room air oxygen saturation <90 percent at presentation. Similar
risk factors for apnea were identified in large prospective and retrospective cohorts [63,66].
The risk of apnea was not increased with RSV compared with other viral pathogens [64].
These findings suggest that low respiratory (ie, <30 breaths/minute) rate in children with
bronchiolitis is not necessarily reassuring and that results of virologic studies are not
helpful in determining the risk for apnea among hospitalized infants.
Hypoxemia, associated with mucus plugging and atelectasis, is common in children with
bronchiolitis. It may respond to supplemental oxygen alone, although sometimes it
requires additional respiratory support. Hypercapnic respiratory failure, associated with
fatigue, usually requires additional respiratory support (eg, intubation and mechanical
ventilation).
Between 2000 and 2009, approximately 2 percent of children younger than two years
hospitalized with bronchiolitis in the Kids Inpatient Database required mechanical
ventilation [32]. Requirement for mechanical ventilation was increased in infants younger
than 12 months and high-risk medical conditions.
Secondary bacterial infection With the exception of otitis media, secondary bacterial
infection is uncommon among infants and young children with bronchiolitis or RSV
infection. In a nine-year prospective study of 565 children (<3 years) hospitalized with
documented RSV infection, subsequent bacterial infection developed in only 1.2 percent
and subsequent bacterial pneumonia in 0.9 percent [67]. The risk of secondary bacterial
pneumonia is increased among children who require admission to the intensive care unit,
particularly those who require intubation [68,69].
In infants and young children with mild disease, radiographs are unlikely to alter treatment
and may lead to inappropriate use of antibiotics [2,71,73]. However, in infants and young
children with moderate or severe respiratory distress (eg, nasal flaring, retractions,
grunting, respiratory rate >70 breaths/minute, dyspnea, or cyanosis), radiographs may be
warranted, particularly if there are focal findings on examination, the infant has a cardiac
murmur, or it is necessary to exclude alternate diagnoses [2]. Radiographs also may be
indicated to exclude alternate diagnoses in children who fail to improve at the expected
rate [3]. (See 'Severity assessment' below and 'Differential diagnosis' below and 'Clinical
course' above.)
EVALUATION The evaluation of infants and young children with suspected bronchiolitis
generally requires only history and physical examination, including pulse oximetry.
Laboratory studies and radiographs usually are not necessary for diagnosis but may be
warranted to evaluate complications, comorbid infections, or other conditions in the
differential diagnosis. The evaluation outlined below is largely consistent with that
suggested in the American Academy of Pediatrics 2014 clinical practice guideline for the
diagnosis, management, and prevention of bronchiolitis [3].
History Infants with moderate to severe bronchiolitis typically present for medical
attention three to six days after illness onset. Bronchiolitis often is preceded by a one- to
three-day history of upper respiratory tract symptoms, such as nasal
congestion and/or discharge and mild cough [46]. It typically presents with fever (usually
38.3C [101F), cough, and respiratory distress (eg, increased respiratory rate,
retractions).
Compared with other viruses that cause bronchiolitis, fever tends to be lower with
respiratory syncytial virus (RSV) and higher with adenovirus [74]. (See "Respiratory
syncytial virus infection: Clinical features and diagnosis", section on 'Clinical
manifestations' and "Epidemiology and clinical manifestations of adenovirus infection",
section on 'Clinical presentation'.)
Aspects of the history of present illness that help in determining the severity of
illness and/or need for hospitalization include (see 'Severity assessment' below
and "Bronchiolitis in infants and children: Treatment, outcome, and prevention", section on
'Indications for hospitalization') [3,75]:
Aspects of the past medical history associated with severe disease include prematurity,
chronic pulmonary disease, anatomic abnormalities of the airways, hemodynamically
significant congenital heart disease, immunodeficiency, and neurologic disease. (See 'Risk
factors for severe disease' above.)
Severely affected patients have increased work of breathing (subcostal, intercostal, and
supraclavicular retractions; nasal flaring; and expiratory grunting). They may appear
cyanotic and have poor peripheral perfusion. Wheezing may not be audible if the airways
are profoundly narrowed or when increased work of breathing results in exhaustion.
Labs and imaging for select patients Laboratory tests are not routinely indicated in
the evaluation of infants and young children with bronchiolitis. However,
laboratory and/or radiographic evaluation may be necessary to evaluate the possibility of:
DIAGNOSIS
Clinical diagnosis Bronchiolitis is diagnosed clinically. Characteristic features include a
viral upper respiratory prodrome followed by increased respiratory effort (eg, tachypnea,
nasal flaring, chest retractions) and wheezing and/or rales in children younger than two
years of age [1-3]. (See 'History' above and 'Examination' above.)
Chest radiographs and laboratory studies are not necessary to make the diagnosis of
bronchiolitis and should not be routinely performed [3]. However, they may be necessary
to evaluate the possibility of secondary or comorbid bacterial infection, complications, or
other conditions in the differential diagnosis, particularly in children who have pre-existing
cardiopulmonary disease [1,3,80]. (See 'Complications' above and 'Differential
diagnosis' below and 'Labs and imaging for select patients' above.)
Virology We do not routinely suggest testing for specific viral agents in children with
bronchiolitis unless the results of such testing will alter management of the patient or
patient's contacts (eg, discontinuation of palivizumab prophylaxis, initiation
or continuation/discontinuation of antibiotic therapy, anti-influenza therapy, or isolation or
cohorting of hospitalized patients or caregivers) [1,85]. (See "Seasonal influenza in
children: Prevention and treatment with antiviral drugs", section on 'Antiviral therapy'.)
There is debate about whether testing for specific viral agents alters clinical management
or outcome, particularly in the outpatient setting [1,80,85-89]. However, the identification of
a viral etiologic agent during emergency department evaluation or in hospitalized patients
has been associated with a decreased utilization of antibiotic treatment in some studies
[87,90-94].
Identification of the responsible virus in hospitalized patients may help to avoid health
care-associated transmission by permitting cohorting of patients and/or caregivers.
However, direct evidence that this strategy prevents transmission of respiratory viruses in
children is lacking, and it may be more logical to isolate all infants with bronchiolitis [1,95].
Cohorting has the potential to increase the risk of infection with other respiratory viruses
leading to prolonged hospitalization [9]. (See "Respiratory syncytial virus infection:
Prevention", section on 'Health care-associated infection'.)
The laboratory diagnosis depends upon the quality and proper handling of the specimen.
Virologic testing should be performed on respiratory specimens obtained by nasal wash or
nasal aspirate; midturbinate nasal swab is also acceptable [97,98].
Nasal wash specimens are obtained by holding the infant or child upright at a 45 angle. A
bulb syringe or a soft plastic catheter attached to suction is used to aspirate nasal
secretions after a small amount of normal saline (1 to 3 mL) is instilled in each nostril.
Other factors that have been associated with increased illness severity include toxic or ill
appearance, oxygen saturation <90 percent by pulse oximetry while breathing room air,
respiratory rate 70 breaths/minute, and atelectasis on chest radiograph [35,36,100].
However, there is limited and/or conflicting evidence relating these clinical findings to
clinical outcomes [3,35,36,53,72,101,102].
Several scoring instruments have been developed to assess the clinical severity of
bronchiolitis in research settings [103-107]. The use of these measures in clinical practice
is limited by lack of sufficient validation [108].
Here are the patient education articles that are relevant to this topic. We encourage you to
print or email these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)
Basics topic (see "Patient education: Bronchiolitis (and RSV) (The Basics)")
Beyond the Basics topic (see "Patient education: Bronchiolitis (and RSV) in infants
and children (Beyond the Basics)")
Neumona bacteriana
Author:
William J Barson, MD
Section Editors:
Morven S Edwards, MD
George B Mallory, MD
Deputy Editor:
Mary M Torchia, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Jan 13, 2016.
The Pediatric Infectious Diseases Society/Infectious Diseases Society of America and the
British Thoracic Society have developed clinical practice guidelines for the evaluation and
treatment of CAP in children [1,2].
The outpatient treatment of CAP in infants and children will be reviewed here. Neonatal
pneumonia and inpatient treatment of pneumonia are discussed separately, as are the
epidemiology, etiology, clinical features, and diagnosis. (See "Neonatal
pneumonia" and "Pneumonia in children: Inpatient treatment" and "Pneumonia in children:
Epidemiology, pathogenesis, and etiology" and "Community-acquired pneumonia in
children: Clinical features and diagnosis".)
EMPIRIC THERAPY
Overview Children with CAP who are treated in the outpatient setting typically are
treated empirically; tests to identify a microbiologic etiology are not recommended for most
children who are well enough to be treated in the outpatient setting [1,2]. Decisions
regarding empiric therapy are complicated by the substantial overlap in the clinical
presentation of bacterial and nonbacterial pneumonias [2,5,6]. Treatment decisions are
usually based upon algorithms that include patient age, epidemiologic and clinical
information, and diagnostic laboratory and imaging studies (if such studies were obtained)
(table 2 and table 3) [4]. Consultation with a specialist in infectious disease may be helpful
in children with medication allergies or comorbid conditions. (See "Community-acquired
pneumonia in children: Clinical features and diagnosis" and "Pneumonia in children:
Epidemiology, pathogenesis, and etiology", section on 'Etiologic agents'.)
There are few randomized controlled trials to guide the choice of empiric antibiotics in
children with CAP. Factors that must be considered include the spectrum of likely
pathogens, antimicrobial susceptibility, simplicity, tolerability, palatability, safety, and cost
[7]. The recommendations of most guidelines are based upon observations regarding the
susceptibility of the most likely pathogen or pathogens, rather than on evidence of the
superiority of one antibiotic over another [1,2]. The clinical response to the most commonly
used antimicrobials appears to be similar, regardless of etiology [8-10]. The response
within the first 48 to 72 hours of empiric therapy (or lack of therapy if a viral etiology is
most likely) helps to determine whether additional evaluation or changes in therapy are
necessary. (See 'Monitoring response' below.)
One to six months Infants younger than three to six months of age with suspected
bacterial CAP or who are hypoxemic (oxygen saturation <90 percent in room air at sea
level) should be admitted to the hospital for empiric therapy. (See "Pneumonia in children:
Inpatient treatment", section on 'Empiric therapy'.)
In afebrile infants one to four months of age with CAP, the most likely bacterial pathogen
is C. trachomatis (ie, "afebrile pneumonia of infancy") [4,11]. Infants who are thought to
have afebrile pneumonia of infancy can be treated in the outpatient setting if they are not
hypoxemic and remain afebrile [4]. (See "Chlamydia trachomatis infections in the
newborn", section on 'Treatment'.)
Bordetella pertussis is a less common, but more severe, cause of pneumonia in young
infants; fever may or may not be present. Like C. trachomatis, B. pertussis is susceptible
to the macrolides [4]. However, young infants who are thought to have B. pertussis-
associated pneumonia should be admitted to the hospital because they are at risk for
complications (eg, hypoxia, apnea, pulmonary hypertension, etc). (See "Pertussis infection
in infants and children: Clinical features and diagnosis", section on 'Infants' and "Pertussis
infection in infants and children: Treatment and prevention", section on 'Hospitalization'.)
Suspected viral etiology Viral etiologies predominate during early childhood. Viral
pneumonia (suggested by gradual onset, preceding upper respiratory tract symptoms,
diffuse findings on auscultation, lack of toxic appearance (table 3)) should not be treated
with antibiotics. Antiviral agents generally are not used for viral pneumonia in the
outpatient setting, with the exception of neuraminidase inhibitors for influenza pneumonia.
(See "Community-acquired pneumonia in children: Clinical features and diagnosis",
section on 'Clues to etiology' and "Pneumonia in children: Epidemiology, pathogenesis,
and etiology", section on 'Etiologic agents' and "Seasonal influenza in children: Prevention
and treatment with antiviral drugs", section on 'Antiviral therapy'.)
Infants and young children with known or suspected chronic disease (eg, cardiopulmonary
disease, neuromuscular disease, etc) are at increased risk for severe or complicated viral
lower respiratory tract infection (LRTI). If such children are not admitted to the hospital,
they merit close monitoring in the outpatient setting.
Although there are prospective, comparative data supporting the efficacy of twice daily
dosing of amoxicillin for the treatment of acute otitis media [16-18], similar data are not
available for documented pneumococcal pneumonia in children. Unless the etiologic agent
is identified as a S. pneumoniae isolate with a minimum inhibitory concentration (MIC) of
<2 mcg/mL, dividing the total daily 90 to 100 mg/kg dose of amoxicillin into three doses
may be warranted. Twice daily dosing for pneumonia due to a S. pneumoniae isolate with
an MIC of 2 mcg/mL is predicted to achieve a clinical and microbiologic cure in only 65
percent of children, whereas the same total daily dose divided in three equal portions is
predicted to achieve a cure in 90 percent [19].
For children with non-type 1 hypersensitivity reactions to penicillin (table 5), a second- or
third-generation cephalosporin (eg, cefdinir) is an acceptable alternative to amoxicillin [1].
For children with type 1 hypersensitivity reactions (table 5) to penicillin, clindamycin or a
macrolide may be used [1,2]. However, if local resistance rates are high for clindamycin
and macrolides, levofloxacin or linezolid may be preferable. Doses are provided in the
table (table 2).
For the infant or child who is suspected to have bacterial CAP and is unable to tolerate
liquids at the time of presentation, a single initial dose of ceftriaxone (50 to 75 mg/kg) may
be administered intramuscularly or intravenously before starting oral antibiotics [20,21].
Administration of intramuscular ceftriaxone to children with uncomplicated CAP who are
able to tolerate liquids is expensive and provides no benefit over oral antibiotics.
Children 5 years
We suggest macrolide antibiotics for initial empiric therapy for CAP in children older than
five years who are treated as outpatients [1,4]. However, the prevalence of macrolide-
resistant M. pneumoniae is increasing in some geographic regions, including Asia, Europe,
Israel, and the United States [23-31]. The reported prevalence of resistance among M.
pneumoniae isolates ranges from approximately 10 percent in the United States to 90
percent in China and some parts of Japan [25,28,32,33]. Alternative agents
include levofloxacin and doxycycline [1]. The long-held concern for enamel staining
associated with doxycycline in children younger than eight years use is unfounded [34].
The British Thoracic Society clinical practice guideline suggests amoxicillin as the first-line
therapy for children of all ages [2]. Doses are provided in the table (table 2).
Among the macrolide antibiotics, clarithromycin and azithromycin have a more convenient
dosing schedule and fewer side effects than erythromycin, but erythromycin is less
expensive [8,35,36]. Macrolide antibiotics may provide coverage for S. pneumoniae, which
is the most frequent typical bacterial pathogen for all age groups [37-39]. However,
approximately 40 to 50 percent of S. pneumoniae isolates are resistant to macrolides.
Failure to respond to macrolide therapy may indicate the development of a complication, a
macrolide-resistant pathogen, and/or the need to alter therapy to provide better
pneumococcal coverage. (See 'Treatment failure' below.)
Given the significant resistance of S. pneumoniae to macrolides, fluoroquinolones
(eg, levofloxacin, moxifloxacin) are another reasonable alternative for the outpatient
treatment of CAP. In addition to their excellent gram-negative spectrum, the
fluoroquinolones are active against a number of the pathogens responsible for CAP,
including beta-lactam-susceptible and non-susceptible S. pneumoniae, M. pneumoniae,
and C. pneumoniae [40]. However, S. pneumoniae resistant to levofloxacin has been
identified [41].
Duration Few randomized controlled trials have been performed to determine the
appropriate duration of antimicrobial therapy in radiographically confirmed childhood
pneumonia [2]. Current practice in the developed world determines the duration of therapy
based upon the age of the host, likely causative agent, and severity of disease:
Monitoring response Children with CAP who are treated as outpatients (including
those who were not initially treated with antibiotics) should have follow-up within 24 to 48
hours [1,2]. Follow-up may be performed by phone. Children with CAP who are
appropriately treated generally show signs of improvement within 48 to 72 hours.
Treatment failure Among patients who do not improve as anticipated, the following
possibilities must be considered [1,2,14,46]:
Failure to improve In patients who fail to improve, but have not worsened, it may be
reasonable to add or strengthen coverage for S. pneumoniae or atypical bacteria if these
organisms were not covered in the initial therapy (table 2) [1,4]. It is also important to
consider underlying or comorbid conditions (eg, immunodeficiency, anatomic abnormality).
(See "Community-acquired pneumonia in children: Clinical features and diagnosis",
section on 'Differential diagnosis'.)
SUPPORTIVE CARE The families of children who are managed as outpatients should
be instructed regarding management of fever and pain, maintaining adequate hydration,
and identification of deterioration (eg, persistent fever, increased retractions, use of
accessory muscles, grunting, inability to feed) [2].
Children with pneumonia usually have fever and may have pleuritic chest pain,
which can lead to shallow breathing and impaired ability to cough [2]. Administration
of antipyretics and/or analgesics can be used to keep the child comfortable. Adequate
pain control may promote coughing, which facilitates airway clearance. Antitussives
should be avoided as none have been found to be effective in pneumonia [49].
Symptomatic treatment of cough is discussed separately. (See "The common cold in
children: Management and prevention", section on 'Cough'.)
Infants and young children with respiratory distress may be better able to maintain
hydration if fluids are provided in small volumes more frequently than in large
volumes less often.
Gentle suction of the nares may be helpful in infants and children whose nares are
blocked by nasal secretions.
FOLLOW-UP
Clinical course Children who are appropriately treated for CAP gradually improve with
time [50]. The symptoms associated with viral lower respiratory tract infections, particularly
cough, usually resolve in less than one month in healthy infants and children, but may
rarely last for up to three to four months. Cough may persist for as long as three to four
months after viral pneumonia or pertussis. Children who are recovering from typical or
atypical bacterial pneumonia may continue to cough for several weeks and have moderate
dyspnea on exertion for two to three months [50].
Several studies have evaluated the utility of follow-up radiographs in cohorts of children
with acute radiologically proven CAP [56-61]. Three of the studies included clinical as well
as radiologic follow-up at three to seven weeks after initial diagnosis [56-59]. In each of
these studies, follow-up radiographs were normal or improved in asymptomatic children.
Residual findings, even when present, did not result in additional therapy.
PROGNOSIS Most otherwise healthy children who develop pneumonia recover without
any long-term sequelae [39]. Although some prospective studies suggest that pneumonia
in childhood is associated with subsequent symptoms of asthma that may persist into
adulthood, it is not clear whether this is related to unrecognized asthma at the time of
presentation with pneumonia or a tendency to develop asthma after CAP [62,63].
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
Author:
William J Barson, MD
Section Editors:
Morven S Edwards, MD
George B Mallory, MD
Deputy Editor:
Mary M Torchia, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Dec 02, 2016.
The recommendations provided below are largely consistent with practice guidelines
provided by The Pediatric Infectious Diseases Society/Infectious Diseases Society of
America and the British Thoracic Society [1,2].
HOSPITALIZATION
Hypoxemia (oxygen saturation [SpO2] <90 percent in room air at sea level)
Dehydration, or inability to maintain hydration orally; inability to feed in an infant
Moderate to severe respiratory distress: Respiratory rate >70 breaths/minute for
infants <12 months of age and >50 breaths per minute for older children; retractions;
nasal flaring; difficulty breathing; apnea; grunting
Toxic appearance (more common in bacterial pneumonia and may suggest a more
severe course) [4]
Underlying conditions that may predispose to a more serious course of pneumonia
(eg, cardiopulmonary disease, genetic syndromes, neurocognitive disorders), may be
worsened by pneumonia (eg, metabolic disorder) or may adversely affect response to
treatment (eg, immunocompromised host)
Complications (eg, effusion/empyema)
Suspicion or confirmation that CAP is due to a pathogen with increased virulence,
such as Staphylococcus aureus or group A Streptococcus
Failure of outpatient therapy (worsening or no response in 48 to 72 hours)
Indications for intensive care The decision to treat a child with pneumonia in an
intensive care setting is individualized, based upon clinical, laboratory, and radiologic
findings. Treatment in an intensive care setting generally is warranted for children who
manifest [1,2]:
The need for ventilatory support beyond that which can be provided outside the
intensive care unit (eg, mechanical ventilation, noninvasive positive pressure
ventilation, failure to maintain oxygen saturation [SpO2] >92 percent in FiO2 >0.5)
Signs of impending respiratory failure (lethargy, increasing work of
breathing, and/or exhaustion with or without hypercarbia)
Recurrent apnea or slow irregular respirations
Cardiovascular compromise with progressive tachycardia and/or hypotension that
requires or is refractory to fluid management
Care in the intensive care unit also may be warranted for children with two or more of the
following [1]:
Respiratory rate >70 breaths/minute for infants <12 months of age and
>50 breaths/minute for older children
Apnea
Increased work of breathing (retractions, dyspnea, nasal flaring, grunting)
PaO2/FiO2 ratio <250
Multilobar infiltrates
Altered mental status
Hypotension
Pleural effusion
Comorbid condition (eg, sickle cell disease, immune deficiency,
immunosuppression)
Unexplained metabolic acidosis
Pediatric Early Warning Score >6 [5]
Hand washing is the single most important procedure to prevent the spread of infection.
Additional infection control measures depend upon the likely pathogen(s), as follows [6,7]:
Respiratory syncytial and parainfluenza viruses Gown and gloves (ie, contact
precautions)
Influenza virus, group A Streptococcus (for the first 24 hours of treatment),
methicillin-susceptible S. aureus, Bordetella pertussis (until patient has received five
days of effective therapy), and Mycoplasma pneumoniae Mask within 3 feet (ie,
droplet precautions)
Adenovirus Contact and droplet precautions
Methicillin-resistant S. aureus and other multidrug resistant organisms Special
organism precautions; contact and droplet precautions and dedicated patient
equipment
These precautions are discussed separately (see "Infection prevention: Precautions for
preventing transmission of infection"). Guidelines for hand hygiene in healthcare settings
can be accessed through the Centers for Disease Control and Prevention.
Antipyresis and analgesia Children hospitalized with pneumonia usually have fever
and may have pleuritic chest pain, which can lead to shallow breathing and impaired ability
to cough. Administration of antipyretics and/or analgesics (eg, acetaminophen, ibuprofen)
can be used to keep the child comfortable; opioid analgesia is rarely necessary in children
without a chest tube in place. Adequate pain control may promote coughing, which
facilitates airway clearance. Antitussives should be avoided as none have been found to
be effective in pneumonia [8]. Symptomatic treatment of cough is discussed separately.
(See "The common cold in children: Management and prevention", section on 'Cough'.)
We suggest that children with oxygen saturation [SpO2] <95 percent in room air be treated
with supplemental oxygen to maintain oxygen saturation 95 percent while they are in
respiratory distress. Different thresholds for supplemental oxygen are suggested by other
experts (eg, the British Thoracic Society guidelines suggest supplemental oxygenation to
maintain oxygenation saturation >92 percent) [2]. Gentle bulb suction of the nares may be
helpful in infants and children whose nares are blocked with secretions. Minimal handling
seems to reduce oxygen requirements. (See "Continuous oxygen delivery systems for
infants, children, and adults".)
In children who are severely ill, it may be necessary to monitor carbon dioxide tension via
blood gas analysis in addition to oxygen saturation (SpO2) by oximetry. Hypercarbia is an
important sign of impending respiratory failure, particularly in the young infant who is tiring
but may have preserved oxygenation.
Fluid management Children who cannot maintain adequate fluid intake because of
breathlessness, fatigue, or risk of aspiration [9] may require intravenous fluid therapy.
Nasogastric (NG) tubes should be avoided if possible because they may compromise
breathing; if necessary, the smallest NG tube possible should be used [2].
(See "Maintenance fluid therapy in children".)
Children with pneumonia are at risk for inappropriate secretion of antidiuretic hormone
(SIADH) [10,11]. Serum electrolytes, fluid balance, and urine specific gravity should be
monitored if there is clinical suspicion of SIADH [11]. Confirmation of SIADH is discussed
separately. Isotonic, rather than hypotonic, intravenous fluids should be provided if SIADH
is suspected. (See "Pathophysiology and etiology of the syndrome of inappropriate
antidiuretic hormone secretion (SIADH)", section on 'Pulmonary
disease' and "Maintenance fluid therapy in children", section on 'Hospitalized children'.)
EMPIRIC THERAPY
The recommendations of most guidelines are based on in vitro susceptibilities of the most
likely pathogen or pathogens, rather than evidence of the superiority of one antibiotic over
another. Clinical response to empiric therapy and results of microbiologic studies, when
available, help to determine whether additional evaluation or changes in therapy are
necessary [1,2]. (See "Community-acquired pneumonia in children: Clinical features and
diagnosis", section on 'Microbiology' and 'Specific therapy' below and 'Response to
therapy' below.)
There are few randomized controlled trials to guide the choice of empiric antibiotics in
children with CAP. Decisions regarding empiric therapy are complicated by the substantial
overlap in the clinical presentation of bacterial and nonbacterial pneumonias [21-23].
Treatment decisions usually are based upon algorithms that include patient age,
epidemiologic and clinical information, and diagnostic laboratory and imaging studies
(table 2) [4]. The scope of empiric therapy (ie, narrow or broad) depends upon the severity
of illness and presence of complications. Agents other than those suggested in the table
may be more appropriate if there are clinical or epidemiologic features strongly suggestive
of a specific cause (eg, mediastinal or hilar lymphadenopathy, residence in the central
United States, and exposure to caves and/or bat guano suggestive of pulmonary
histoplasmosis) [24].
Etiologic clues Certain clinical and epidemiologic features can be used to determine
the most likely pathogen(s) to aid in decisions regarding empiric therapy. Because these
features often overlap, they cannot be used with complete confidence, but are helpful in
guiding empiric therapy until results of microbiologic tests are available (table 3). These
features are discussed in greater detail separately. (See "Community-acquired pneumonia
in children: Clinical features and diagnosis", section on 'Clues to etiology' and "Community-
acquired pneumonia in children: Clinical features and diagnosis", section on 'Etiologic
clues'.)
Viral pneumonia Most children younger than three to five years of age who are
admitted to the hospital with pneumonia have viral pneumonia (eg, respiratory syncytial
virus) [25]. This is particularly true in the absence of lobar (or lobular) infiltrate and pleural
effusion [4]. Viral pneumonia does not require antibiotic therapy, unless a mixed infection
or secondary bacterial infection is suspected. (See "Respiratory syncytial virus infection:
Treatment", section on 'Overview' and "Respiratory syncytial virus infection: Clinical
features and diagnosis", section on 'Clinical manifestations'.)
No effective antivirals are available for most viral pneumonias, with a few important
exceptions, described below.
Other viral pneumonias Acyclovir can be used in the treatment of pneumonia due to
herpes simplex virus (HSV) or varicella zoster virus (VZV). Ganciclovir be used in the
treatment of pneumonia due to cytomegalovirus (CMV). (See "Treatment of varicella
(chickenpox) infection", section on 'Individuals with complications'.)
Ampicillin or penicillin G generally provides adequate coverage for the fully immunized
child (table 4) in communities without substantial prevalence of penicillin-resistant S.
pneumoniae [1,34,35]. We suggest a third-generation cephalosporin
(eg, cefotaxime, ceftriaxone) for children younger than 12 months and those who are not
fully immunized because third-generation cephalosporins provide coverage for the beta-
lactamase producing pathogens (eg, H. influenzae and M. catarrhalis) that may occur in
these children. We also suggest third-generation cephalosporins for children with more
severe illness (table 1) because third-generation cephalosporins provide coverage for a
broader range of pathogens, including penicillin-resistant S. pneumoniae, than ampicillin
[1,36,37]. The fifth-generation parenteral cephalosporin, ceftaroline, is approved by the US
Food and Drug Administration (FDA) for treatment of community-acquired bacterial
pneumonia due to S. pneumoniae, methicillin-susceptible S. aureus (MSSA), and H.
influenzae in children 2 months of age. Although ceftaroline exhibits in vitro activity
against MRSA, clinical experience is insufficient to suggest its use when MRSA is a
consideration. In a randomized trial in children between 2 months and <18 years who were
hospitalized with CAP, ceftaroline and ceftriaxone had similar cure rates [38]. Three
children with S. aureus infection (two with MSSA recovered from sputum and one with
MRSA recovered from blood) were successfully treated with ceftaroline. However, patients
considered at risk for MRSA infection or those with sputum demonstrating a predominance
of gram-positive cocci in clusters were excluded from the trial, precluding conclusions
about efficacy in this population.
We suggest that children who require hospitalization for treatment of CAP be treated
initially with parenteral antibiotics. However, oral amoxicillin may be an alternative for
infants and children fully immunized against Hib and S. pneumoniae with uncomplicated
pneumonia that is not thought to be due to S. aureus. In a multicenter randomized trial,
treatment with amoxicillin was equivalent to treatment with penicillin G in children with CAP
who required hospital admission but did not have wheezing, hypotension, chronic
pulmonary conditions (other than asthma), immunodeficiency, pleural effusion requiring
drainage, or oxygen saturations <85 percent in room air [39]. The British Thoracic Society
guidelines suggest that oral antibiotics are safe and effective even for children with severe
pneumonia as long as they are able to tolerate oral fluids, are not vomiting, and do not
have signs of septicemia or complicated pneumonia [2].
For children older than four years, coverage for typical bacterial pathogens
(eg, ampicillin or a third-generation cephalosporin) may be added to empiric coverage for
atypical pathogens if there is strong evidence of a bacterial cause. Strong evidence of a
bacterial cause includes white blood cell count >15,000/microL, C-reactive protein (CRP)
>35 to 60 mg/L (3.5 to 6 mg/dL), chills, or no response to outpatient therapy with a
macrolide or doxycycline [4,40].
Severe CAP
Severe CAP not requiring ICU admission Children with severe community-acquired
pneumonia (CAP) that does not require admission to the intensive care unit (ICU) (table 1)
may benefit from combination empiric therapy with a macrolide and a beta-lactam
antibiotic (eg, penicillin or third-generation cephalosporin) (table 2). Combination therapy
improves coverage for resistant organisms and mixed bacterial/atypical bacterial
infections. Antimicrobial therapy can be adjusted as necessary when results of
microbiologic testing become available. Invasive diagnostic testing, including
bronchoscopy with bronchoalveolar lavage, may be necessary for specific microbiologic
diagnosis. (See 'Uncomplicated bacterial pneumonia' above and 'Atypical
pneumonia' above and "Community-acquired pneumonia in children: Clinical features and
diagnosis", section on 'Invasive studies'.)
Severe CAP requiring ICU admission Children who are admitted to the intensive care
unit for serious or life-threatening infections require broad-spectrum empiric coverage that
addresses potential beta-lactam resistance and community-associated methicillin-
resistant S. aureus (CA-MRSA). (See 'Indications for intensive care' above.)
When treating with vancomycin, renal function and serum trough levels or dosing to
achieve an area under the curve/minimum inhibitory concentration (AUC/MIC) ratio >400
should be monitored in an attempt to assure therapeutic efficacy and limit toxicity. In
adults, vancomycin trough levels between 15 and 20 microgram/mL have been suggested
to improve clinical outcomes for complicated infections due to S. aureus [45-47]. Similar
trough levels may not be needed in children to achieve an AUC/MIC >400 and further
studies are needed to evaluate the clinical effectiveness and safety of these dosing
recommendations in children [47-52].
Patients with true beta-lactam hypersensitivity (ie, type 1 hypersensitivity reaction) (table
5) can be treated with a combination of clindamycin and an aminoglycoside.
DURATION OF TREATMENT
Parenteral therapy There are few data to guide decisions about the duration of
parenteral therapy for community-acquired pneumonia (CAP) [2]. It is common to switch to
oral therapy in patients who have received parenteral antibiotics when the patient has
become afebrile for 24 to 48 hours and is not having emesis [65].
Total duration There are few randomized controlled trials to guide decisions about the
appropriate duration of antimicrobial therapy for radiographically confirmed childhood
pneumonia [2]. Current practice assigns duration of therapy according to the host,
causative agent, and severity.
Uncomplicated cases The usual duration of combined parenteral and oral therapy for
uncomplicated pneumonia is 7 to 10 days [1,2]. Some authorities suggest continuing oral
therapy at least one week beyond resolution of fever; others suggest treating until the
erythrocyte sedimentation rate falls below 20 mm/hour. Some data from trials in adults
suggest that a shorter course may be equivalent to a 7- to 10-day course, but additional
controlled studies are necessary before this practice can be recommended routinely for
children [53,66-68].
Temperature
Respiratory rate
Heart rate
Oxygen saturation (SpO2)
Work of breathing (eg, retractions, nasal flaring, grunting)
Chest examination (extent of abnormal or absent breath sounds; extent of dullness
to percussion)
Mental status
Ability to maintain oral intake and hydration
The frequency of monitoring depends upon the severity of illness. In patients who are
receiving oxygen supplementation, oxygen saturation should be evaluated regularly.
Evaluation for hypercarbia may be necessary in children with severe respiratory distress,
as oxygenation may be preserved.
The respiratory status of children with community-acquired pneumonia (CAP) who are
appropriately treated should improve within 48 to 72 hours [1]. However, fevers may
persist for several days after initiation of appropriate therapy [53].
The history should be reviewed with special attention to the possibility of foreign body
aspiration and geographic or environmental exposures associated with pathogens not
treated by the empiric regimen (table 7).
Changes in laboratory parameters (eg, peripheral white blood cell count, inflammatory
markers [if obtained initially]) may provide information about disease progression. Repeat
radiographs or additional imaging studies can help to assess the degree of parenchymal
involvement and evaluate for complications or anatomic abnormalities [1].
(See "Community-acquired pneumonia in children: Clinical features and diagnosis",
section on 'Complications' and "Pneumonia in children: Epidemiology, pathogenesis, and
etiology", section on 'Etiologic agents'.)
Depending upon the severity of illness, more aggressive attempts may need to be made to
establish a microbiologic diagnosis (eg, induced sputum [71], bronchoscopy with
bronchoalveolar lavage, percutaneous needle aspiration, or lung biopsy). In children with
lung abscess whose condition fails to improve or worsens after 72 hours of antibiotic
therapy, needle aspiration or percutaneous catheter drainage may provide diagnostic
information and therapeutic benefit [53,54,58,59]. (See "Community-acquired pneumonia
in children: Clinical features and diagnosis", section on 'Invasive studies'.)
DISCHARGE CRITERIA Discharge criteria for children who have been admitted to the
hospital with community-acquired pneumonia (CAP) have not been standardized, but
typically include [1,53]:
FOLLOW-UP
Clinical course Children with pneumonia should be seen by their primary care provider
soon after discharge to ensure that clinical improvement continues and antibiotic therapy is
being taken as prescribed [53]. Decisions regarding the timing of clinical follow-up should
involve the child's primary care provider and the clinical status of the child at the time of
discharge.
Children who are appropriately treated for pneumonia should gradually improve with time.
Cough may persist for as long as three to four months after viral pneumonia or pertussis.
Children who are recovering from typical or atypical bacterial pneumonia may continue to
cough for several weeks and have moderate dyspnea on exertion for two to three months
[75]. Symptomatic treatment of cough is discussed separately. (See "The common cold in
children: Management and prevention", section on 'Cough'.)
Several studies have evaluated the utility of follow-up radiographs in cohorts of children
with acute radiologically proven CAP [83-88]. Three of the studies included clinical as well
as radiologic follow-up at three to seven weeks after initial diagnosis [83-86]. In each of
these studies, follow-up radiographs were normal or improved in asymptomatic children.
Residual findings, even when present, did not result in additional therapy.
Although some data suggest that nearly one-half of children who are hospitalized for viral
pneumonia have symptoms of asthma five years after hospitalization, it is not clear
whether this is related to unrecognized asthma at the time of presentation with pneumonia
or a tendency to develop asthma after community-acquired viral pneumonia [91,92].
The overall pneumonia mortality rate in developed countries is <1 per 1000 per year
[25,93]. Pneumococcal pneumonia case fatality rates (not adjusted for comorbid
conditions) for children in the United States were estimated to be 4 percent in children
younger than two years and 2 percent in children 2 to 17 years before the introduction of
pneumococcal conjugate vaccines [94].
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
Author:
William J Barson, MD
Section Editor:
Sheldon L Kaplan, MD
Deputy Editor:
Mary M Torchia, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Jan 17, 2017.
EPIDEMIOLOGY
Incidence The World Health Organization (WHO) estimates there are 156 million cases
of pneumonia each year in children younger than five years, with as many as 20 million
cases severe enough to require hospital admission [1]. In the developed world, the annual
incidence of pneumonia is estimated to be 33 per 10,000 in children younger than five
years and 14.5 per 10,000 in children 0 to 16 years [2].
Approximately one-half of children younger than five years of age with community-
acquired pneumonia (CAP) require hospitalization [3]. Hospitalization rates for pneumonia
(all causes) among children younger than two years in the United States decreased after
introduction of the pneumococcal conjugate vaccine to the routine childhood immunization
schedule in 2000 (from 12 to 14 per 1000 population to 8 to 10 per 1000 population)
(figure 1) [4].
Mortality The mortality rate in developed countries is low (<1 per 1000 per year) [5,6].
In developing countries, respiratory tract infections are not only more prevalent but more
severe, accounting for more than 2 million deaths annually; pneumonia is the number one
killer of children in these societies [1,7].
Seasonality Although both viral and bacterial pneumonia occur throughout the year,
they are more prevalent during the colder months, presumably because direct
transmission of infected droplets is enhanced by indoor crowding. For reasons that are
unknown, different viruses cause peaks of infection at different times during the respiratory
virus season and these peaks seldom occur simultaneously [8]. In tropical regions, peaks
of infection follow no common pattern and can occur during either the wet or dry seasons.
Risk factors Lower socioeconomic groups have a higher prevalence of LRTIs, which
correlates best with family size, a reflection of environmental crowding. School-age
children often introduce respiratory viral agents into households, resulting in secondary
infections in their parents and siblings [8].
The use of cigarettes, alcohol, and other substances of abuse in adolescents may
increase the risk of pneumonia by increasing the risk of aspiration through impairment of
the cough and epiglottic reflexes. In addition, the use of alcohol has been associated with
increased colonization of the oropharynx with aerobic gram-negative bacilli [11].
Effect of vaccines Immunization with the Haemophilus influenzae type b (Hib) and
pneumococcal conjugate vaccines protects children from invasive disease caused by
these organisms. Hib was once a common cause of pneumonia in young children in the
United States. However, it has been virtually eliminated as a result of routine immunization
with Hib conjugate vaccines. (See "Prevention of Haemophilus influenzae type b infection",
section on 'Efficacy/effectiveness'.)
The universal immunization of infants in the United States with the 7-valent pneumococcal
conjugate vaccine has effectively decreased the incidence of pneumonia requiring
hospitalization and other invasive Streptococcus pneumoniae infections in children
younger than two years (figure 1) [12-15]. Rates of ambulatory visits for pneumonia in
children younger than two years also declined after the introduction of pneumococcal
conjugate vaccine [16], but the rates for children aged 1 to 18 years remained stable [17].
(See "Pneumococcal (Streptococcus pneumoniae) conjugate vaccines in children", section
on 'Pneumonia'.)
It is anticipated that the 13-valent pneumococcal conjugate vaccine that replaced the 7-
valent pneumococcal conjugate vaccine in 2010, and affords additional coverage against
serotypes 1, 3, 5, 6A, 7F, and 19A, will further decrease the incidence of pneumonia
requiring hospitalization because these serotypes are responsible for the majority of
pneumococcal pneumonia cases among children worldwide [18,19]. Early data from the
United States Pediatric Multicenter Pneumococcal Surveillance Group demonstrate a 53
percent reduction in cases of pneumonia compared with the average number of cases for
2007 to 2009 [20]. (See "Pneumococcal (Streptococcus pneumoniae) conjugate vaccines
in children", section on '13-valent vaccine'.)
Pneumococcal vaccination also protects against viral pneumonia. This was shown in a
double-blind, randomized, placebo-controlled trial in which full immunization with a nine-
valent pneumococcal conjugate vaccine was associated with a 31 percent reduction (95%
CI 15-43) in the incidence of pneumonia associated with any of seven respiratory viruses
(influenza A/B, parainfluenza types 1 to 3, respiratory syncytial virus [RSV], adenovirus) in
hospitalized children [21]. This observation suggests that the pneumonias associated with
these viruses in hospitalized children are often because of concurrent pneumococcal
infection.
In the typical scenario, pneumonia follows an upper respiratory tract illness that permits
invasion of the lower respiratory tract by bacteria, viruses, or other pathogens that trigger
the immune response and produce inflammation [3,22]. The lower respiratory tract air
spaces fill with white blood cells (WBC), fluid, and cellular debris. This process reduces
lung compliance, increases resistance, obstructs smaller airways, and may result in
collapse of distal air spaces, air trapping, and altered ventilation-perfusion relationships [3].
Severe infection is associated with necrosis of bronchial or bronchiolar epithelium
[23], and/or pulmonary parenchyma [24].
Acquisition The agents that cause lower respiratory tract infection (LRTI) are most
often transmitted by droplet spread resulting from close contact with a source case.
Contact with contaminated fomites also may be important in the acquisition of viral agents,
especially respiratory syncytial virus (RSV).
Most typical bacterial pneumonias are the result of initial colonization of the nasopharynx
followed by aspiration or inhalation of organisms. Invasive disease most commonly occurs
upon acquisition of a new serotype of the organism with which the patient has not had
previous experience, typically after an incubation period of one to three days. Occasionally,
a primary bacteremia may precede the pneumonia. Atypical bacterial pathogens attach to
respiratory epithelial membranes through which they enter cells for replication.
The viral agents that cause pneumonia proliferate and spread by contiguity to involve
lower and more distal portions of the respiratory tract.
Normal host defense The pulmonary host defense system is complex and includes
anatomic and mechanical barriers, humoral immunity, phagocytic activity, and cell-
mediated immunity [25,26], as discussed below, with a focus on bacterial infection. The
host response to respiratory viral infection is beyond the scope of this review; more
information can be obtained from reference [27].
Anatomic and mechanical barriers Anatomic and mechanical barriers in the upper
airway form an important part of the host defense. Particles greater than 10 microns
are efficiently filtered by the hairs in the anterior nares or impact onto mucosal
surfaces. The nasal mucosa contains ciliated epithelium and mucus-producing cells.
The cilia beat synchronously, clearing the entrapped organisms through the
nasopharynx via expulsion or swallowing. In the oropharynx, salivary flow, sloughing
of epithelial cells, local production of complement and immunoglobulin A (IgA), and
bacterial interference from the resident flora serve as important factors in local host
defense.
An intact epiglottic reflex helps to prevent aspiration of infected secretions, and the
cough reflex helps to expel materials that may be aspirated. The sharp angles at
which the central airways branch cause 5 to 10 micron particles to impact on mucosal
surfaces, where they are entrapped in endobronchial mucus. Once entrapped, the
ciliary system moves the particles upward out of the airways into the throat, where
they are normally swallowed.
Humoral immunity Secretory IgA is the major immunoglobulin produced in the
upper airways and accounts for 10 percent of the total protein concentration of nasal
secretions. Although it is not a very good opsonizing agent, it does possess
antibacterial and antiviral activity. IgG and IgM enter the airways and alveolar spaces
predominantly via transudation from the blood and act to opsonize bacteria, activate
complement, and neutralize toxin. Immunoglobulins, surfactant, fibronectin, and
complement act as effective opsonins to help eliminate microorganisms (0.5 to 1
micron particles) that reach the terminal airways and alveoli. Free fatty acids,
lysozyme, and iron-binding proteins also are present and may be microbicidal.
Phagocytic cells There are two populations of phagocytic cells in the lung:
polymorphonuclear leukocytes (PMNs) from the blood and macrophages. There are
several distinct populations of macrophages, which vary in their location and function:
The alveolar macrophage is located in the alveolar fluid and is the first
phagocyte encountered by inert particles and potential pathogens entering the
lung. If this cell is overwhelmed, it has the capacity to become a mediator of
inflammation and produce cytokines that recruit neutrophils.
Interstitial macrophages are located in the lung connective tissue and serve
both as phagocytic cells and antigen-processing cells.
The intravascular macrophage is located in capillary endothelial cells and
phagocytizes and removes foreign material entering the lungs via the
bloodstream.
Cell-mediated immunity Cell-mediated immunity is especially important against
certain pathogens, including viruses and intracellular microorganisms that can survive
within pulmonary macrophages. Although relatively few in number (5 to 10 percent of
the total lung parenchyma cell population), lymphocytes play three critical roles: the
production of antibody, cytotoxic activity, and the production of cytokines.
Examination findings The examination findings vary depending on the site of infection
as follows [3]:
Inspiratory crackles, also called rales and crepitations [28], are more common in
lobar pneumonia and bronchiolitis/pneumonia
Decreased breath sounds may be noted in areas of consolidation
Coarse, low-pitched continuous breath sounds (rhonchi) are more common in
bronchopneumonia
Expiratory wheezes, high-pitched breath sounds, are caused by oscillation of air
through a narrowed airway; they are more common in bronchiolitis and interstitial
pneumonitis
ETIOLOGIC AGENTS A large number of microorganisms have been implicated as
etiologic agents of pneumonia in children (table 1A-B). The agents commonly responsible
vary according to the age of the child and the setting in which the infection is acquired.
Community-acquired pneumonia
Despite these problems, systematic reviews have identified some consistent trends and
conclusions regarding the etiology of CAP in children, which are listed below [2,29]:
In infants As described below, viruses are the most common etiology of CAP in
children younger than five years, including infants. However, infants younger than one year
also may develop "afebrile pneumonia of infancy." Afebrile pneumonia of infancy is a
syndrome generally seen between two weeks and three to four months of life. It is
classically caused by Chlamydia trachomatis, but other agents, such as cytomegalovirus
(CMV), Mycoplasma hominis, and Ureaplasma urealyticum, also are implicated.
(See "Chlamydia trachomatis infections in the newborn", section on 'Pneumonia'.)
Infants with severe Bordetella pertussis infection also may develop pneumonia.
(See "Pertussis infection in infants and children: Clinical features and diagnosis", section
on 'Complications'.)
Viruses Viruses are the most common etiology of CAP in older infants and children
younger than five years of age [2,6,29]. However, bacterial pathogens, including S.
pneumoniae, S. aureus, and S. pyogenes, also are important because they are
associated with increased morbidity and mortality [47,48,50].
Respiratory syncytial virus (RSV), a member of the Paramyxoviridae virus family, is
the most common viral pathogen responsible for pneumonia in children younger than
five years [6,36,51]. RSV pneumonia frequently represents an extension of
bronchiolitis. (See "Bronchiolitis in infants and children: Clinical features and
diagnosis", section on 'Clinical features' and "Respiratory syncytial virus infection:
Clinical features and diagnosis", section on 'Clinical manifestations'.)
Other viral causes of pneumonia in children younger than five years include [6]:
Influenza A and B viruses.
Parainfluenza viruses, usually type 3. (See "Parainfluenza viruses in children",
section on 'Clinical presentation'.)
A number of adenovirus serotypes (1, 2, 3, 4, 5, 7, 14, 21, and 35) have been
reported to cause pneumonia; serotypes 3, 7, and 21 have been associated with
severe and complicated pneumonia [52]. (See "Epidemiology and clinical
manifestations of adenovirus infection", section on 'Clinical presentation'.)
Human metapneumovirus, identified in 2001, is a common cause of lower
respiratory tract infections in children; most children have been infected by five
years of age. (See "Human metapneumovirus infections".)
Rhinovirus has been implicated as a cause of pneumonia using PCR assays
[53], but its etiologic role is questioned [51,54,55].
Coronaviruses, including the severe acute respiratory syndrome (SARS), the
Middle East respiratory syndrome (MERS), and the New Haven coronaviruses,
also cause respiratory tract infections in children younger than five years [56,57].
However, their clinical impact has yet to be fully determined [51,58].
(See "Coronaviruses", section on 'Respiratory' and "Severe acute respiratory
syndrome (SARS)", section on 'Clinical manifestations' and "Middle East
respiratory syndrome coronavirus: Clinical manifestations and diagnosis",
section on 'Clinical manifestations'.)
Human bocavirus and human parechovirus types 1, 2, and 3 also have been
implicated as a cause of lower respiratory tract infections in children [59-61].
Enterovirus D68 emerged as a significant pathogen of lower respiratory tract
disease among United States children in 2014 [62]. (See "Epidemiology,
pathogenesis, treatment, and prevention of enterovirus and parechovirus
infections", section on 'Serotypes and disease' and "Clinical manifestations and
diagnosis of enterovirus and parechovirus infections", section on 'Respiratory
disease'.)
Bacteria Important bacterial causes of pneumonia in preschool children include S.
pneumoniae, H. influenzae type b, nontypeable H. influenzae, Moraxella
catarrhalis, S. aureus, S. pyogenes, and atypical bacteria.
S. pneumoniae is the single most common bacterial pathogen causing
pneumonia in all patients beyond the first few weeks of life [9,43].
(See "Pneumococcal pneumonia in children", section on 'Epidemiology'.)
H. influenzae type b is a rare cause of pneumonia in countries with universal
childhood immunization.
S. aureus (particularly community-associated MRSA, CA-MRSA) and S.
pyogenes are becoming increasingly frequent causes of CAP, particularly those
complicated by necrosis and empyema [47,63]. In addition, these organisms
occasionally cause pneumonia following influenza and chickenpox, respectively
[48,49]. (See "Clinical features of varicella-zoster virus infection: Chickenpox".)
The prevalence of M. pneumoniae and C. pneumoniae may be increasing in
preschool children with CAP [29,64]. (See "Pneumonia caused by Chlamydia
species in children" and "Mycoplasma pneumoniae infection in children", section
on 'Epidemiology'.)
In children 5 years
In addition, during the winter respiratory viral season, all patients in a medical care
environment are at risk for healthcare-associated pneumonia caused by RSV,
parainfluenza, and influenza viruses. (See "Seasonal influenza in children: Clinical
features and diagnosis" and "Parainfluenza viruses in children", section on 'Clinical
presentation' and "Respiratory syncytial virus infection: Clinical features and diagnosis",
section on 'Transmission'.)
Special populations
Opportunistic fungi, such as Aspergillus spp and Fusarium spp, also are a concern in
neutropenic patients and in those receiving immunosuppressive therapies that impair the
cell-mediated response. One of the more common pneumonia pathogens diagnosed in
HIV-infected patients is Pneumocystis jirovecii, which was formerly called Pneumocystis
carinii [69]. (See "Epidemiology and clinical manifestations of invasive
aspergillosis" and "Mycology, pathogenesis, and epidemiology of Fusarium
infection" and "Pediatric HIV infection: Classification, clinical manifestations, and
outcome", section on 'Pneumocystis jirovecii pneumonia'.)
Cystic fibrosis Young children with cystic fibrosis frequently are infected with S.
aureus, P. aeruginosa, and H. influenzae (mostly nontypeable strains). Later in the course
of the disease, multiple drug-resistant gram-negative organisms, such as Burkholderia
cepacia, Stenotrophomonas maltophilia, and Achromobacter xylosoxidans, can be
recovered. Aspergillus spp and nontuberculous mycobacteria also may cause disease in
this population. Cystic fibrosis lung disease is discussed in detail separately. (See "Cystic
fibrosis: Clinical manifestations of pulmonary disease" and "Cystic fibrosis: Overview of the
treatment of lung disease" and "Cystic fibrosis: Antibiotic therapy for lung disease".)
Sickle cell anemia The prevalence of pneumonia is increased in children with sickle
cell anemia [72]. Atypical bacterial pathogens appear to be most frequent and are more
commonly associated with the acute chest syndrome. Other bacterial causes of
pneumonia in children with sickle cell anemia include S. pneumoniae, S. aureus, and H.
influenzae [9]. (See "The acute chest syndrome in children and adolescents with sickle cell
disease", section on 'Infection'.)
Environmental considerations
Other exposures Exposure to individuals at high risk for tuberculosis is a risk factor for
the development of tuberculosis in children. High-risk individuals include the homeless,
recent immigrants from endemic regions (figure 2), incarcerated individuals, and HIV-
infected patients. (See "Epidemiology of tuberculosis".)
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SUMMARY Pneumonia is more common in children younger than five years of age
than in older children and adolescents. Risk factors for pneumonia include environmental
crowding, having school-aged siblings, and underlying cardiopulmonary and other medical
disorders. (See 'Epidemiology' above.)
Pneumonia can be caused by a large number of microorganisms (table 1A-B). The agents
commonly responsible vary according to the age of the child and the setting in which the
infection is acquired. (See 'Etiologic agents' above.)
In children younger than five years, viruses are most common. However, bacterial
pathogens, including Streptococcus pneumoniae, Staphylococcus aureus, and S.
pyogenes, also are important. (See 'In children <5 years' above.)
In otherwise healthy children older than five years, S. pneumoniae, M. pneumoniae,
and Chlamydophila pneumoniae are most common. (See 'In children 5
years' above.)
Community-associated methicillin-resistant S. aureus (CA-MRSA) is an increasingly
important pathogen in children of all ages, particularly in those with necrotizing
pneumonia. S. pneumoniae is another frequent cause of necrotizing pneumonia.
(See 'Overview' above.)
Aspiration pneumonia is usually caused by anaerobic oral flora. (See 'Aspiration
pneumonia' above.)
Healthcare-associated pneumonia is usually caused by gram-negative bacilli
or Staphylococcus aureus. (See 'Healthcare-associated pneumonia' above.)
Vitral
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Jul 06, 2016.
MICROBIOLOGY
The virions are pleomorphic and range in diameter from 150 to 200 nm. The single strand
of negative-sense RNA is 15,462 nucleotides in length and encodes six common viral
proteins: the nucleocapsid protein (NP), the phosphoprotein (P), the matrix protein (M), the
fusion glycoprotein (F), the hemagglutinin-neuraminidase glycoprotein (HN), and the RNA
polymerase (L) [10].
The HN and F proteins project through the lipid envelope and form the major
antigenic targets for neutralizing antibody [11]. Their hydrophobic tails project into the
virion, where they interact with the M protein to aid in virus assembly [12].
The nucleocapsid core is composed of NP, P, and L proteins in association with viral
RNA. NP proteins bind tightly to the viral genome, creating a template for the RNA-
dependent RNA polymerase composed of the P and L proteins [13].
The HN glycoproteins are involved in attachment of the virus to the host cell via
interactions with sialic acid residues on the cell surface [14]. This interaction allows the F
protein to mediate virus-cell membrane fusion, which is required for nucleocapsid entry
and infection of the host cell. The neuraminidase portion of the HN protein [14] mediates
budding of progeny virions from the surface of infected cells [15].
In addition, each parainfluenza virus expresses at least one non-essential protein: PIV1
and PIV3 RNA encode short C proteins, PIV2 RNA encodes a V protein, and PIV 3 also
expresses a D protein. The C and V proteins inhibit the host innate immune response (host
cell antiviral responses) by suppressing the activity of type I interferons; the function of the
D protein is unknown [16,17].
Viral serotypes Four major serotypes of human PIV (PIV-1, 2, 3, 4) have been
described based upon complement fixation and hemagglutinating antigens [18].
Parainfluenza virus 5 (PIV-5) causes disease in animals (dogs, cats, pigs) but its role in
human disease remains controversial [19].
PIV-3 is the most prevalent serotype, with 90 to 100 percent of children demonstrating
antibody responses by age five [20]. In contrast, PIV-1 and PIV-2 infections are less
common, with only 50 to 74 percent of five-year-olds demonstrating seropositivity. Fifty
percent of six-year-old children and 70 to 90 percent of young adults have antibodies to
PIV-4, despite the fact that infection is infrequently recognized [21,22]. PIV-1 particularly
and PIV-2 are associated with croup in children, whereas PIV-3 is frequently associated
with pneumonia and bronchiolitis in young infants. PIV-4 typically causes mild upper
respiratory infection (URI) in both adults and children, but pneumonia and bronchiolitis
have been described in infants and in children with underlying conditions [22-25].
(See 'Pathogenesis' below.)
PATHOGENESIS Parainfluenza viruses (PIV) initially infect epithelial cells of the nose
and oropharynx [26] and then spread distally to the ciliated and alveolar cells of the
bronchial epithelium of large and small airways [27]. Significant viral replication is seen in
the nose and lungs 24 hours after infection, with viral replication peaking after two to five
days [28]. Viral antigen can be detected in the apical portion of respiratory epithelial cells
from days one to six of infection, with a decrease on day seven [29].
The extent of infection correlates well with disease: mild upper respiratory infections
(URIs) are associated with limited infection of the nasopharynx, whereas more severe
disease involves spread of infection to the large and small airways [30]. PIV-1 and PIV-2,
which are associated with croup, tend to infect the larynx and upper trachea, whereas PIV-
3, which is associated with bronchiolitis and pneumonia, infects the distal airways [28].
Progression to the lower respiratory tract and severity of disease depend upon factors
such as virus titer in the upper respiratory tract, previous exposure to the specific virus,
and genetic susceptibility [9,31,32].
Pathologic examination of infected tissues in animal models of PIV infection suggests that
minimal cellular or tissue damage is caused by direct viral effects [29]. Similarly, PIV
infection does not result in extensive cytopathic effect in in vitro models of respiratory
airway epithelium [16,27,33]. As is the case with other respiratory viruses, the host
immune response plays an important role in the pathogenesis of PIV infection. PIV
induces innate immune responses, CD8+ and CD4+ T cell responses, interferon
production, and local and systemic immunoglobulin A (IgA) and IgG responses, which
contribute to the clearing of the virus [28,34]. The increase in airway responsiveness that
often is associated with PIV-3 infection (and other respiratory viruses, such as respiratory
syncytial virus [RSV]) may result from IgE, increased stromal interleukin-11 production and
enhanced acetylcholine release [35-37]. Preliminary experiments in animal models of
infection suggest that a "two-pronged" approach to therapy, antiviral and anti-inflammatory,
may be useful in PIV-related illness [38].
EPIDEMIOLOGY
Incubation period The incubation period ranges from two to six days [41].
Prevalence Human PIV are recovered most commonly in children younger than five
years of age with upper respiratory infections (URIs) [3,42]. Serologic studies have shown
that as many as 50 percent of children have been infected with PIV-3 by their first birthday,
whereas PIV-1 and PIV-2 most often affect preschool-aged children three to five years of
age [43].
PIV infections account for 20 to 40 percent of lower respiratory tract illnesses (eg,
bronchiolitis, pneumonia) in children from which a virus is recoverable, and 2.8 per 1000
children with such infections require hospitalization [44]. PIV is responsible for
approximately 30,000 (range 7600 to 48,000) pediatric hospitalizations annually in the
United States [45]. A study based upon the National Hospital Discharge survey from 1994
through 1997 estimated hospitalization rates due to PIV-1 to 3 to range from 1.9 to 12 per
1000 children younger than one year and from 0.5 to 2.0 per 1000 children ages one to
four years [46]. The highest overall hospitalization rates were for PIV-3, estimated at 0.48
to 2.6 per 1000 children. A population-based study in the United States (2000 to 2004)
estimated that PIV accounts for up to 7 percent of all hospitalizations for fever, acute
respiratory illness, or both in children younger than five years of age [3]; PIV3 is the cause
of one-half of these hospitalizations. Data from the National Respiratory and Enteric Virus
Surveillance System (NREVSS, 1998-2010) indicate an annual estimated PIV-associated
hospitalization rate of 0.2 per 1000 children for bronchiolitis, 0.4 per 1000 children for
croup, and 0.5 per 1000 children for pneumonia [47].The majority of PIV-associated
hospitalizations occurred in children younger than two years.
PIV infections occur throughout the world and throughout the year, with certain serotypes
predominating during the spring or fall. PIV-1 usually causes outbreaks biennially during
the fall of odd-numbered years (figure 1) [48,49]. In contrast, PIV-2 and PIV-3 occur in
annual epidemics in the fall and spring, respectively [48]. During years in which PIV-1 is
not circulating, there is an increase in PIV-3 activity, manifested either as a longer spring
PIV-3 season or as a second smaller peak in the fall. Seasonal patterns of PIV-4 infections
have not been established, since the disease is usually mild, and the virus is difficult to
detect. However, it is diagnosed more frequently between October and January [23]. In
tropical countries, parainfluenza viruses do not exhibit seasonal variation [50].
Ethnicity and sex may play roles in the severity of PIV infection. Bronchiolitis occurs most
commonly in non-Caucasian males [30]. Breast-fed infants have a reduced risk of serious
infection. Spread within families is extensive, requiring only direct person-to-person
contact or large droplet inhalation [51].
Otitis media and sinusitis can result from either primary viral infections or secondary
bacterial superinfection. Nonrespiratory complications of PIV are rare but include
meningitis [54], myocarditis and pericarditis [55], Guillain-Barr syndrome [56], and acute
disseminated encephalomyelitis [57]. (See "Clinical manifestations and diagnosis of
myocarditis in children" and "Guillain-Barr syndrome in adults: Treatment and
prognosis" and "Viral meningitis: Clinical features and diagnosis in children", section on
'Clinical features'.)
Although most PIV infections are mild, severe disease can occur, particularly in
immunocompromised patients. Immunocompromised children and adults, including those
with human immunodeficiency virus (HIV) infection can progress from mild URI symptoms
to severe pneumonia with prolonged viral shedding and dissemination [58-61]. Children
with severe T cell deficiencies can succumb to fatal giant cell pneumonia after infection
with PIV [62].
In a study of children with hematologic malignancies at a pediatric cancer center, PIV was
the second most common respiratory viral infection after influenza, detected in 10 percent
of children tested [63]. Ninety percent of PIV infections were community acquired. PIV 3
accounted for 61 percent of PIV infections. PIV infections were approximately four times
more common in children with acute lymphoblastic leukemia than in those with other
hematologic malignancies. Although most (80 percent) of children had upper respiratory
tract illness, children who were young (median age 27 months) and presented with fever,
severe neutropenia, or lymphopenia were at increased risk for lower respiratory tract
infection.
In one report, 2.2 percent of 1253 children and adults who underwent bone marrow
transplantation developed symptomatic PIV infection [64]. These patients are at particular
risk of severe PIV-associated pneumonia, with prolonged shedding and mortality rates of
up to 30 percent [62,64-70].
Solid organ transplant recipients are at an increased risk for pulmonary complications.
Complications such as bronchiolitis obliterans, and acute and chronic rejection have been
reported in lung transplant patients with PIV and other respiratory viral infections [6,71].
DIAGNOSIS The diagnosis of parainfluenza virus (PIV) infection can be made clinically
with a compatible presentation during an outbreak of PIV in the community. Laboratory
confirmation may be useful in determining if a community outbreak exists or in excluding
other infections in seriously ill patients.
PCR assays permit the detection of PIV and a number of respiratory viruses in
nasopharyngeal and oropharyngeal secretions with reported sensitivities of 95 to 100
percent and excellent specificity [72-75]. Collection of paired oropharyngeal and
nasopharyngeal samples may increase the sensitivity [76,77]. PCR increases the yield of
detection of PIV-3 by 1.5-fold, compared with viral culture [78].
PIV also can be identified by culture from the nasopharynx (nasopharyngeal swabs,
aspirates, or washes). Specimens should be placed in viral transport media and kept at
4C because the virus loses infectivity at room temperature [79]. Hemadsorption and
immunofluorescence typing are routinely used for identification, as observed cytopathic
effects can be variable.
Serologic testing also can be performed but is time-consuming and can be confounded by
the presence of heterologous antibodies [21].
TREATMENT There are no antiviral agents with proven efficacy for parainfluenza virus
(PIV) infections, which are self-limited in most cases. Glucocorticoids and
nebulized epinephrine may be used to treat croup (see "Croup: Approach to
management"). The management of bronchiolitis is supportive. (See "Bronchiolitis in
infants and children: Treatment, outcome, and prevention".)
Ribavirin and other agents that have been used to treat PIV in immunocompromised hosts
are discussed separately. (See "Parainfluenza viruses in adults", section on 'Treatment'.)
DAS181 is a sialidase fusion protein that cleaves the sialic acid containing receptors of
PIV in respiratory cells. It has antiviral activity against influenza and parainfluenza viruses
and has been reported to successfully treat PIV in patients with hematopoietic stem cell
and lung transplantation [84-92]. In one report, four severely immunocompromised
children who had received hematopoietic cell transplantation were treated with DAS181 for
lower respiratory tract infection. Inhaled DAS181 was administered for 5 to 10 days. All
patients tolerated the treatment well and had clinical improvement, with decreased oxygen
requirement. Improvement in viral load was also documented [90]. DAS181 treatment of
PIV in immunocompetent patients is being evaluated in a phase II clinical trial [93].
Vaccine development began in the 1960s with the production of an inactivated mixture of
PIV-1, -2, and -3. This vaccine produced variable antibody responses and did not protect
against challenge [10]. Subunit vaccines containing purified HN and F glycoproteins of PIV
were later shown to induce functional antibodies in animal models [10]. Using a different
approach, a modified vaccinia recombinant, Ankara (MVA), expressing the HN or F protein
of PIV-3 tested in non-human primates showed significant protection of the lower
respiratory tract but failed to demonstrate significant upper respiratory tract protection
against challenge with PIV-3 [95].
Several live attenuated intranasal vaccine candidates have been developed using cell
culture passage or chemical mutagenesis for viral attenuation and reverse genetics
technology:
Bovine PIV-3 (BPIV-3), a virus that is antigenically related to human PIV-3 (hPIV-3),
has been evaluated in clinical trials as a vaccine candidate to protect against PIV-3 in
children and infants. However, seroconversion rates to hPIV-3 have been modest
[94,96,97].
Murine PIV (Sendai virus), another virus that is antigenically related to human PIV,
has been evaluated in clinical trials as a nasally administered live attenuated
xenotropic vaccine against human PIV-1, similar to the use of bovine PIV-3 [98].
A live attenuated, cold-adapted PIV-3 vaccine candidate, hPIV-3-cp45, the cp45
derivative of the JS strain of wild-type human PIV-3, was developed in the 1990s.
When administered intranasally, it provided almost complete protection against
challenge with wild-type PIV-3 in both the upper and lower respiratory tracts in non-
human primates [10]. HPIV-3-cp45 was found to be appropriately attenuated and
immunogenic in children and infants as young as one month of age [99-101].
Similarly, this vaccine was found to be safe and immunogenic in a phase 2 trial of
healthy seropositive and seronegative infants and children, with two or three doses
needed to induce durable immunity [102]. A combined hPIV-3-
cp45/respiratory syncytial virus (RSV) experimental vaccine has been studied in 6- to
18-month-old seronegative children, showing antibody responses similar to the
monovalent vaccine components [103].
Through reverse genetics, several PIV-1 and PIV-2 candidate vaccines also have been
developed and some are undergoing clinical testing [16,94,108-110]. A live-attenuated
human PIV-1 vaccine (rHPIV-1/84/del 170/942A) was studied in a phase I clinical trial, but
insufficiently immunogenic in PIV-seronegative children [111]. A live attenuated
recombinant bivalent PIV-1/RSV vaccine (rHPIV1-RSV-F) is undergoing preclinical
evaluation [112].
Authors:
Phyllis Flomenberg, MD
Tsoline Kojaoghlanian, MD
Section Editors:
Martin S Hirsch, MD
Sheldon L Kaplan, MD
Deputy Editor:
Anna R Thorner, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Apr 27, 2016.
The major surface protein of the virion is the trimeric polypeptide hexon. Group-reactive
antigenic determinants are present on the hexon proteins from all human adenoviruses.
Type-specific neutralizing epitopes are present both on the fiber and hexon proteins with
minor sites on the penton base. In addition, many adenoviruses hemagglutinate rat or
rhesus red blood cells; this property is related to the fiber protein.
Most adenoviruses readily infect human epithelial cell lines, exhibiting a characteristic
cytopathic effect. This property is often used to isolate adenoviruses from clinical
specimens in diagnostic virology laboratories.
Adenovirus infections are prevalent in daycare centers and in households with young
children. Nosocomial transmission also has been documented.
Transmission Transmission of adenovirus can occur via aerosol droplets, the fecal-oral
route, and by contact with contaminated fomites. Adenoviruses can survive for long
periods on environmental surfaces; they are resistant to lipid disinfectants because they
are nonenveloped, but they are inactivated by heat, formaldehyde, or bleach (sodium
hypochlorite).
There are several other modes of adenovirus transmission:
Serotype prevalence
Overview Over 50 human adenovirus serotypes have been identified based upon
antigenic determinants detected by viral neutralization assay. Serotypes are further
classified into six subgroups, A to F, based upon differences in patterns of
hemagglutination. Serotypes within each subgroup are closely related at the DNA level
and frequently share similar biologic properties. As examples, subgroup B types 11, 34,
and 35 cause hemorrhagic cystitis, whereas subgroup D types 8, 19, and 37 are
associated with keratoconjunctivitis (table 1).
The prevalence of the different serotypes cannot be determined with confidence since the
vast majority of patients with adenovirus infection are not cultured. This issue was
addressed in a study in which 1653 clinical adenovirus isolates were collected from 22
hospital laboratories between 2004 and 2006 [16]. The following distribution was noted:
These serotypes are primarily associated with upper respiratory tract diseases (table 1).
However, the distribution of adenovirus serotypes is different in military recruits.
Military recruits Beginning in 1971, military recruits in the United States received a
highly effective, enteric-coated, oral live vaccine with adenovirus types 4 (subgroup E) and
7 (subgroup B); manufacture of this vaccine was discontinued in 1996 [17]. Since that
time, both susceptibility and clinical infection due to adenovirus have increased in military
recruits. Rare fatalities have been reported in recruits due to probable adenovirus
pneumonia with or without accompanying encephalitis [17].
A study of 341 military recruits in 2004 found that more than three-quarters were
susceptible to either adenovirus type 4 or type 7 infection and, during active
surveillance, one-quarter developed a febrile respiratory illness attributable to
adenovirus serotype 4 [18]. Furthermore, the percentage of recruits seropositive for
this strain increased from 34 percent at enrollment to 97 percent by the end of the
study. Potential sources of transmission included environmental contamination and
extended pharyngeal shedding of virus.
Among 584 clinical adenovirus isolates from military recruits collected between 2004
and 2006, 93 percent were serotype 4 [16]. However, the distribution appears to be
changing. In a series of 1867 military recruits with adenovirus respiratory infections,
serotype 4 was the most prevalent serotype between 2002 and 2005 [19], while in
2006 subgroup B adenoviruses became more prevalent, including types 3, 7, 21, and
14. The emergence of adenovirus 14 is discussed in detail below. (See 'Adenovirus
14' below.)
Adenovirus 14 was detected in the United States in 2006 when it was associated with a
fatal respiratory illness in a 12-day-old infant in New York [23]. Clusters of severe acute
adenovirus 14 respiratory disease have been subsequently identified in Oregon,
Washington, Texas, and Alaska [23-25]. In a report that included 140 patients, 38 percent
were hospitalized, 17 percent were admitted to intensive care units, and 5 percent died
[23]. In a retrospective review published subsequently, it was shown that adenovirus 14
had emerged in Oregon in 2005 and became the prevalent serotype in 2006 and 2007,
causing over 50 percent of adenovirus infections [26].
The cluster in Texas involved military recruits at an Air Force base [27]. Preexisting
antibodies against adenovirus 7 were detected in 7 of 19 individuals with mild illness but in
none of 16 individuals with pneumonia caused by adenovirus 14, suggesting that
adenovirus 7specific antibodies might provide some degree of cross-protection against
adenovirus 14. Among military recruits in Texas hospitalized with pneumonia during the
outbreak, adenovirus 14 was not associated with excess morbidity or mortality compared
with other causes of pneumonia [28]. However, women with adenovirus 14 infection had
higher rates of hospitalization than men (83 versus 40 percent).
Adenovirus 14 has also been identified in military recruits at a number of other bases
[19,29], in healthcare workers (HCW) and a household contact of a HCW [30,31], and in
two children and an adult in California with severe pneumonia superimposed upon chronic
pulmonary disease [32]. It also caused an outbreak of pneumonia among a group of
individuals who socialized and smoked together in Alaska [25]. A study of healthcare
personnel at a military hospital where 15 trainees were hospitalized with pneumonia
caused by adenovirus 14 suggested likely nosocomial transmission [31].
An analysis of 99 isolates from military and civilian cases of adenovirus 14 infection in the
United States showed that all isolates were identical and suggested that they arose from
recombination among adenovirus 11 and adenovirus 14 ancestral strains [33].
Adenoviruses can cause persistent infections, with the virus being shed in the feces for
months to years after acute infection [5].
Respiratory tract Adenoviruses are among the most common viruses isolated from
young children with febrile respiratory illnesses. The usual duration of illness is five to
seven days, although symptoms may persist for up to two weeks. Bacterial superinfections
can occur.
Otitis media and less common presentations Otitis media is another common
presentation, especially in children under age 1 [40,41]. However, the presence of
adenovirus in middle ear fluid has only been documented in a few cases [43]. Less
frequently, adenoviruses cause a pertussis-like syndrome, bronchiolitis, coryza without
fever, or an exanthem.
Pneumonia A number of adenovirus serotypes (1, 2, 3, 4, 5, 7, 14, 21, and 35) have
been reported to cause pneumonia [23,32,44-46]. Subgroup B types 3, 7, 14, and 21 have
been associated with severe and complicated pneumonia [23,32,47-50]. In a study of 2638
hospitalized children with pneumonia, adenoviruses were detected in 15 percent of
children younger than five years of age compared with 3 percent of older children [51]. In a
prospective study that compared the prevalence of viruses in the upper respiratory tracts
of children and adults with community-acquired pneumonia with the prevalence in
asymptomatic controls, detection of adenovirus was associated with pneumonia only in
children <2 years of age [52]. This suggests that adenovirus may not be the causative
pathogen of pneumonia in all patients in whom it is detected (especially in those 2 years
of age).
Pneumonia is more severe in infants than older children and may be associated with
lethargy, diarrhea, and vomiting. Extrapulmonary complications occasionally occur,
including meningoencephalitis, hepatitis, myocarditis, nephritis, neutropenia, and
disseminated intravascular coagulation [53,54].
Neonates and infants with underlying diseases are at high risk for fatal adenoviral
pneumonia. On the other hand, pneumococcal vaccination has been associated with a
reduction in the incidence of pneumonia in infants with adenovirus and other respiratory
virus infections [55]. This observation suggests that the pneumococcus is an important
pathogen in virus-associated pneumonia. (See "Pneumococcal (Streptococcus
pneumoniae) conjugate vaccines in children", section on 'Pneumonia'.)
EKC may be transmitted in medical offices and hospitals by the ophthalmologist's hands
and contaminated instruments or eye drops [7,8,60]. In one report of EKC due to
adenovirus type 8 in a neonatal intensive care unit where premature infants underwent
repetitive eye exams, the outbreak spread from neonates to the staff and then to their
families [7]. In another review of an adenovirus type 8 epidemic, the authors demonstrated
that almost 50 percent of patients diagnosed with EKC carried virus on their hands and
that the virus remained viable on inanimate surfaces for up to 35 days [61].
In one study of over 400 cases of acute infantile gastroenteritis, enteric adenoviruses were
the sole recognizable cause of diarrhea in 7.2 percent of cases; no isolates were found
among 200 controls [62]. Diarrhea was prolonged, lasting from 8 to 12 days. A review of
another outbreak in several daycare centers found that 38 percent of 249 young children
had positive stool specimens, although only one-half were symptomatic [63].
Unlike types 40 and 41, epidemiologic studies have not shown a clear correlation between
most other serotypes and gastroenteritis. However, the subgroup A type 31 has been
associated with infantile diarrhea in some reports [65]. In addition, lower serotype
adenoviruses have been associated with mesenteric adenitis, which may mimic
appendicitis and occasionally cause intussusception [66].
Adenoviruses may be excreted in feces for months after a primary infection. Thus, a
positive stool culture for adenovirus is not usually clinically significant as a cause of
diarrhea. However, in immunocompromised hosts, symptomatic gastroenteritis has been
associated with a range of adenovirus serotypes.
In adults, adenovirus subgroup D types 19 and 37 have been occasionally associated with
urethritis [70,71]. In immunocompromised patients, adenovirus subgroup B types 11, 34,
and 35 can cause hemorrhagic cystitis and tubulointerstitial nephritis [72,73].
Myocarditis In two series of acute myocarditis in children, adenovirus was the most
common cause of viral myocarditis, occurring in 60 percent of PCR-proven cases of viral
myocarditis [77,78].
Other Adenovirus has occasionally been associated with viral myositis accompanied by
rhabdomyolysis [79,80] (see "Viral myositis"). Fewer than 10 cases of adenovirus-
associated arthritis have also been reported [81,82] (see "Specific viruses that cause
arthritis").
INFECTIONS IN IMMUNOCOMPROMISED HOSTS A variety of clinical syndromes can
occur in immunocompromised individuals with adenovirus infection [83]. Reactivation of
endogenous virus plays a role in adenoviral diseases in these patients. The major
reservoirs for persistent adenovirus infections and the mechanisms of viral persistence are
unknown; however, CD4 lymphocytes found in tonsils can harbor adenoviruses for a
prolonged period [84].
In one study of 1050 adult HCT recipients, 51 (4.8 percent) shed adenoviruses and 10 (0.9
percent) had invasive adenoviral disease [86]. Another report documented a higher
incidence of adenoviral infection and disease in a HCT patient population (both children
and adults) treated with T celldepleted bone marrow grafts and more intensive
immunosuppressive regimens; 42 of 210 patients (20.9 percent) had evidence of infection,
while 13 (6.5 percent) developed invasive disease [87]. Adenoviral infections occurred
more frequently and appeared earlier post-transplant in pediatric patients. Treatment and
outcomes of adenovirus infections in adult HCT recipients are discussed separately.
(See "Diagnosis, treatment, and prevention of adenovirus infection", section on
'Treatment'.)
Adenoviruses cause more frequent disease in pediatric HCT recipients compared with
adults [88,90]. In one study of 204 pediatric HCT recipients, 31 had adenovirus infections
(15.1 percent) and 18 (8.8 percent) developed severe disease [90]. Allogeneic recipients
and, in particular, recipients of unrelated or mismatched related grafts had an increased
risk of infection. In a study of 123 pediatric allogeneic recipients, adenovirus infection was
a major independent risk factor for treatment-related mortality [91].
Solid organ transplantation Adenovirus infections in solid organ transplant recipients
may range from asymptomatic to severe and disseminated, with prolonged viral shedding
and significant morbidity and mortality, including associated graft dysfunction and rejection
[92]. Adenovirus more frequently affects pediatric than adult solid organ transplant
recipients. Infection after transplant may be associated with reactivation of a prior latent
infection in the recipient or the graft or with a newly acquired infection.
In contrast to the HCT population, adenoviral disease typically involves the donor organ in
solid organ transplant recipients. As an example, the primary clinical manifestation in those
who have undergone renal transplantation is acute hemorrhagic cystitis, sometimes
complicated by interstitial nephritis [72]. This syndrome is almost exclusively associated
with subgroup B types 11, 34, and 35. The incidence has not been well defined but is low.
The prognosis is generally good, although infection occasionally results in fatal
disseminated disease [94].
AIDS A number of unusual adenovirus serotypes have been isolated from HIV-infected
patients. The most common urine isolates are subgroup B types 11, 34, and 35, with
several intermediate strains [101,102]. The subgroup D adenoviruses are the predominant
isolates from stool samples, including eight new serotypes, 43 through 49 and 51
[102,103].
Despite the frequency with which they are found in stool or urine specimens, adenoviruses
are an uncommon cause of morbidity or mortality in HIV-infected patients. The viruses
have been documented by histopathology or electron microscopy in colonic biopsies in
some patients with chronic diarrhea [104]. However, the diarrhea may improve with
treatment of other pathogens.
Fatal cases of adenovirus infection in AIDS patients have been reported. For example,
fatal hepatic necrosis has been documented in pediatric AIDS patients due to adenovirus
types 1, 2, and 5 [105]. In the same review, a case of fatal adenovirus type 3 pneumonia
complicated by hepatitis and encephalitis was described in an adult AIDS patient. Other
reports include cases of adenoviral encephalitis [106] and necrotizing tubulointerstitial
nephritis [107].
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SUMMARY
Adenoviruses are a family of viruses that are an important cause of febrile illnesses
in young children. They are most frequently associated with upper respiratory tract
syndromes, such as pharyngitis or coryza, but can also cause pneumonia. Less
commonly, adenoviruses cause gastrointestinal, ophthalmologic, genitourinary, and
neurologic diseases. Most adenoviral diseases are self-limiting, although fatal
infections can occur in immunocompromised hosts and occasionally in healthy
children and adults. (See 'Introduction' above and 'Clinical presentation' above.)
Adenoviruses have a double-stranded DNA genome of approximately 35 kb
surrounded by a nonenveloped icosahedron with fiber-like projections. (See 'Virion
structure' above.)
Adenoviruses have a worldwide distribution, and infections occur throughout the
year. Most individuals have serologic evidence of prior adenoviral infection by the age
of 10. Adenovirus infections are prevalent in daycare centers and in households with
young children. (See 'Epidemiology' above.)
Many epidemics of adenoviral disease have been described, including
pharyngoconjunctival fever in summer camps and in association with public
swimming pools, keratoconjunctivitis in medical facilities, and serious acute
respiratory disease in military recruits. (See 'Epidemiology' above.)
Over 50 human adenovirus serotypes have been identified based upon antigenic
determinants detected by viral neutralization assay. Serotypes are further classified
into six subgroups, A to F. Serotypes within each subgroup frequently share similar
biologic properties. As examples, subgroup B types 11, 34, and 35 cause
hemorrhagic cystitis, whereas subgroup D types 8, 19, and 37 are associated with
keratoconjunctivitis (table 1). (See 'Overview' above.)
Adenovirus 14 is a subgroup B serotype that was first identified in military recruits in
the Netherlands in 1955. It subsequently emerged in the United States in 2005 as a
cause of outbreaks of severe respiratory illness in military recruits and civilians.
(See 'Adenovirus 14' above.)
The clinical manifestations of adenoviral disease vary according to the age and
immunocompetence of the host (table 2). Severe disease has been associated
primarily with subgroups B and C serotypes. (See 'Clinical presentation' above.)
A wide range of clinical syndromes has been reported in hematopoietic cell
transplant (HCT) recipients, including pneumonia, colitis, hepatitis, hemorrhagic
cystitis, tubulointerstitial nephritis, encephalitis, and disseminated disease.
(See 'Hematopoietic cell transplantation' above.)
In contrast to the HCT population, adenoviral disease typically involves the donor
organ in solid organ transplant recipients. (See 'Solid organ transplantation' above.)
Authors:
Flor M Munoz, MD, MSc
Phyllis Flomenberg, MD
Section Editors:
Martin S Hirsch, MD
Morven S Edwards, MD
Deputy Editors:
Anna R Thorner, MD
Mary M Torchia, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Apr 15, 2016.
INTRODUCTION Adenoviruses are a family of DNA viruses that are an important cause
of febrile illnesses in young children. They are most frequently associated with upper
respiratory tract syndromes such as pharyngitis or coryza but can also cause pneumonia.
Less commonly, adenoviruses cause gastrointestinal, ophthalmologic, genitourinary,
neurologic, and disseminated disease. Most adenoviral diseases are self-limiting, although
fatal infections can occur in immunocompromised hosts and occasionally in healthy
children and adults.
The available diagnostic tests and strategies for treatment and prevention of adenovirus
infection will be reviewed here. The virology, epidemiology, and clinical manifestations of
adenovirus infection are discussed separately. (See "Epidemiology and clinical
manifestations of adenovirus infection".)
OVERVIEW Since adenoviruses are associated with a variety of clinical syndromes and
nonspecific manifestations, diagnosis based upon clinical criteria alone is challenging. The
diagnosis of adenovirus disease should be confirmed in outbreaks of infection and in
individual patients with serious disease manifestations. Confirmation of adenovirus
infection is important in order to decide on the use of antiviral agents, exclude other
treatable infections, establish a prognosis, and initiate infection control measures when
appropriate.
DIAGNOSTIC TESTS A number of different approaches are available for the specific
diagnosis of adenovirus infection (table 1). Viral culture, adenovirus-specific viral antigen
assays, and polymerase chain reaction (PCR) assays are used most frequently.
Viral culture All adenovirus serotypes except types 40 and 41 cause a characteristic
cytopathic effect (CPE) in human epithelial cell lines such as HeLa, A549, or HEp2 and in
primary human embryonic kidney (HEK) cells. CPE generally occurs within 2 to 7 days
with the common lower serotypes, but some others, especially subgroup D serotypes
(which cause epidemic keratoconjunctivitis), can require up to 28 days.
Adenoviruses are relatively stable and can be readily recovered from clinical samples early
in the course of the disease. Appropriate samples include nasopharyngeal swabs or
aspirates, throat swabs or washes, sputum, tracheal aspirates, bronchoalveolar lavage
(BAL) fluid, conjunctival swabs or scrapings, stool or rectal swabs, urine, blood,
cerebrospinal fluid (CSF), and tissue samples. Swabs and tissue biopsies should be
placed in a viral transport medium to prevent drying and to inhibit bacterial overgrowth.
Specimens should be transported to the laboratory on ice. The duration of viral excretion at
the time of acute disease is approximately one to three days from throat in adults with
upper respiratory infection; three to five days from nose, throat, and eye in patients with
pharyngoconjunctival fever; and two weeks from eye cultures in patients with
keratoconjunctivitis. Viral excretion may be prolonged (for weeks) in young children [1-4].
After acute infection, adenoviruses may be intermittently excreted in stool (or upper
respiratory tract, less commonly) for months in some patients. In immunocompromised
hosts, adenoviruses may be continuously shed from stool or urine for months without
symptoms. Therefore, a positive culture result needs to be interpreted based upon the
current clinical manifestations. (See "Epidemiology and clinical manifestations of
adenovirus infection".)
Viral antigen assay Direct detection of adenovirus antigens in clinical samples may be
performed by an adenovirus-specific enzyme immunoassay (EIA) or immunofluorescence
assay. These assays are more rapid but less sensitive than viral culture for the detection of
most serotypes [5]. They are insufficiently sensitive for diagnosis in immunocompromised
hosts [6].
Another potential application for direct antigen assays is in the rapid diagnosis of epidemic
keratoconjunctivitis (EKC). The Adenoclone-EIA (Cambridge Biotech) was evaluated as a
rapid diagnostic test for adenoviral ocular infection applied to conjunctival swabs from 372
culture-positive infected eyes [8]. The overall sensitivity of the EIA was only 38 percent,
but, in swabs obtained within the first week of illness, the sensitivity improved to 65
percent. Therefore, this assay may be a useful adjunct to routine viral culture early in the
course of the illness.
Direct adenovirus antigen assays can also be used to screen cell cultures before the
development of CPE, as well as to confirm the presence of adenovirus in cell cultures
positive for CPE.
Polymerase chain reactions PCR is a highly sensitive and specific assay that can be
used to detect adenovirus DNA from a variety of clinical specimens including fixed tissues.
PCR is particularly helpful in samples from normally sterile sites such as blood, CSF, and
tissues. A positive result from upper respiratory tract or stool samples is more difficult to
interpret as it may represent virus shedding rather than symptomatic infection. Therefore,
PCR results must be interpreted in the context of the clinical findings of adenovirus
disease. Because different adenovirus serotypes are heterogeneous at the DNA level,
PCR primers may be selected to detect specific serotypes or related serotypes [9].
Commercial adenovirus PCR assays use universal primers and probes that detect most or
all serotypes [10,11].
Detection of adenovirus DNA in the blood by quantitative PCR is increasingly utilized for
the evaluation of adenovirus infections in immunocompromised patients [10,12]. Studies
have demonstrated an association between rising or high-level viremia and the risk of both
invasive disease and mortality [13,14]. In addition, quantification of adenovirus DNA can
be used to assess response to antiviral treatment [15-18]. In one study, a greater than 10-
fold decrease in viral load one week after the first dose of antiviral therapy was associated
with a favorable clinical course, whereas all patients with fatal disease failed to show a
significant reduction in viral load [15]. PCR can also be used in conjunction with
sequencing in order to rapidly genotype adenovirus isolates [19]. (See 'Serotyping and
genotyping' below.)
PCR has been used to diagnose adenovirus myocarditis. Routine viral cultures and
histopathology are rarely positive in cases of presumed viral myocarditis. In one study, 38
myocardial tissue samples from 34 patients with acute myocarditis and 17 control patients
with congenital heart disease or hypertrophic cardiomyopathy were tested by PCR for
adenovirus and enterovirus [20]. Although enteroviruses have been implicated as the
major etiology of viral myocarditis, adenovirus DNA was detected more commonly (15
samples) than enterovirus DNA (8 samples). All control samples were negative. In another
report, PCR was used to make a diagnosis of intrauterine adenovirus myocarditis [21].
(See "Etiology and pathogenesis of myocarditis", section on 'Adenovirus' and "Clinical
manifestations and diagnosis of myocarditis in adults", section on 'Identifying the cause of
myocarditis' and "Clinical manifestations and diagnosis of myocarditis in children", section
on 'Endomyocardial biopsy'.)
Adenoviruses can cause characteristic intranuclear inclusions (picture 1) [23]. Early post-
infection, cells may display small eosinophilic inclusions. During the later stages of
infection, basophilic inclusions appear, which initially may be surrounded by a clear halo
within the nucleus. When these intranuclear inclusions enlarge and obscure the nuclear
membrane, the cells are referred to as "smudge" cells (picture 1). Occasionally, adenovirus
inclusions may be confused with cytomegalovirus (CMV) inclusions, but, unlike CMV,
adenoviruses cause neither intracytoplasmic inclusions nor multinucleated cells [24].
If routine histopathology is non-diagnostic and viral culture of tissue is negative (or not
done), more specialized tests may be performed on tissue samples. Electron microscopy
can be used to detect the characteristic icosahedral virions that typically form large
paracrystalline aggregates with the nuclei of infected cells [25]. Adenovirus-specific
immunohistochemical assays and in situ DNA assays are also available [26,27].
Serotyping and genotyping After recovery of a clinical isolate on tissue culture, further
evaluation can be performed by serotype analysis in a reference virology laboratory.
Certain serotypes are associated with distinct clinical manifestations (table 2).
(See "Epidemiology and clinical manifestations of adenovirus infection".)
The serotype is determined by first grouping the isolate by hemagglutination pattern with
rat and rhesus red blood cells. Then, hemagglutination inhibition and/or serum
neutralization assays can be performed using a selected panel of type-specific sera.
Genotyping can also be accomplished by PCR and sequencing, which is substantially
faster than the traditional serotyping methods, although it is not widely available.
(See 'Polymerase chain reactions' above.)
When warranted, such as during an epidemic, diagnosis can be confirmed by viral culture
of the nasopharynx or throat. If viral culture is unavailable, the specimen may be tested
with the less sensitive adenovirus-specific enzyme-linked immunosorbent assay (ELISA).
The differential diagnosis includes bacterial conjunctivitis as well as other viral pathogens
such as enteroviruses and herpes simplex virus. (See "Conjunctivitis", section on 'Bacterial
conjunctivitis' and "Clinical manifestations and diagnosis of enterovirus and parechovirus
infections", section on 'Ocular infections' and "Clinical manifestations and diagnosis of
herpes simplex virus type 1 infection", section on 'Keratitis'.)
Multiplex PCR assays that detect a panel of respiratory viruses including adenovirus from
nasopharyngeal specimens are especially useful for evaluation of hospitalized patients
with suspected respiratory viral pneumonia or other influenza-like illness [32,33]. However,
in a prospective study that compared the prevalence of viruses in the upper respiratory
tracts of children and adults with community-acquired pneumonia with the prevalence in
asymptomatic controls, detection of adenovirus was associated with pneumonia only in
children <2 years of age [34]. This suggests that adenovirus may not be the causative
pathogen of pneumonia in all patients in whom it is detected (especially in those 2 years
of age).
Diarrhea in young children Although norovirus is the more common pathogen, enteric
adenoviruses (types 40 or 41) can cause a prolonged diarrheal syndrome in infants,
especially in the setting of clusters (eg, in daycare centers or as a healthcare-associated
infection). The test of choice is an adenovirus-specific PCR or ELISA on a stool specimen
because enteric adenoviruses do not grow on routine tissue culture. Symptoms are self-
limited and treatment is supportive. Strict infection control methods in daycare centers may
help to prevent transmission.
Adenoviruses may cause severe, sometimes fatal, disease in hematopoietic stem cell
transplant recipients. After hematopoietic stem cell transplantation, recovery of T cell
function and adenovirus-specific T cells has been associated with a favorable outcome
[35,36]. Recipients of T cell-depleted grafts or those with graft-versus-host disease
(GVHD) are at highest risk for disease and mortality. (See "Overview of infections following
hematopoietic cell transplantation".)
There have been no controlled trials demonstrating benefit for any antiviral agent in human
adenoviral disease. The antiviral agent most commonly used for adenoviral infection
is cidofovir, which is currently approved for the treatment of cytomegalovirus (CMV)
infections. (See "Cidofovir: An overview".)
Cidofovir Cidofovir appears more active against adenovirus in vitro than other antiviral
drugs such as ganciclovir [41] and also appears active in vivo as demonstrated by
reductions in adenoviral load measured by real-time polymerase chain reaction (PCR)
[15,16]. Published data on the efficacy of cidofovir for adenovirus infection in humans are
limited to case reports and small nonrandomized studies [15,16,42-45]. In hematopoietic
stem cell and lung transplant recipients, cidofovir therapy has been associated with clinical
improvement and a suggestion of increased survival [16,42-44].
Prior to the use of cidofovir, the mortality in patients with invasive adenoviral disease
following allogeneic hematopoietic cell transplantation (HCT) varied from 25 to 75 percent
in different series [46,47], with the higher rates being described in patients with pneumonia
and disseminated disease [16,47,48]. In contrast, the mortality rate from adenoviral
disease was only 19 percent in a review of 70 published cases of definite or probable
adenovirus infection treated with two or more doses of cidofovir; most of these patients
were severely immunocompromised (eg, graft-versus-host disease and/or T cell-depleted
allografts) [16]. However, in a report of 11 severely immunocompromised patients with
adenovirus infection who were treated with cidofovir, five died, including all three with
pneumonia [49]. Therefore, although early diagnosis and treatment of adenovirus
infections in this patient population may improve outcomes, lymphocyte reconstitution also
appears crucial for recovery from disease [50].
Other Ganciclovir has limited activity against adenovirus in vitro [55] and in a hamster
model [56]. Neither ribavirin nor vidarabine has consistent activity against adenovirus in
vitro [57]. There are case reports of patients responding to treatment with each of these
agents, but the evidence for efficacy in vivo remains anecdotal [58-60].
T cell immunity is critical for recovery from adenovirus infection following hematopoietic
stem cell transplantation [65]. Pilot studies of adoptive transfer of T cell immunity have
been performed in children with adenovirus infection after stem cell transplantation. In one
study, virus-specific donor T cells were isolated and infused into nine children with
systemic adenovirus infection [66]. In vivo expansion of adenovirus-specific T cells was
demonstrated and viral clearance was attained in five of six evaluable patients. In one
patient, adoptive T cell transfer led to exacerbation of preexisting graft-versus-host
disease.
In a study of pediatric HCT recipients treated with donor lymphocytes stimulated in vitro
with adenovirus, reductions in viral load were documented in three of three patients with
active infection, and clinical improvement was documented in one patient with adenovirus
pneumonia [67]. In another study, treatment of two haploidentical HCT recipients who had
rising adenovirus loads with donor-derived virus-specific T cells expanded in vitro using
overlapping polypeptides in combination with interleukin-15 resulted in viral clearance in
one and reduction of >1.5 log in viral load in the other [68].
PREVENTION Vaccination and infection control measures have been applied in certain
settings to prevent adenovirus infections.
In 2011, a new live, oral adenovirus vaccine against adenovirus serotypes 4 and 7 was
approved for use in United States military personnel aged 17 through 50 years [73,74].
During the two years following reintroduction of the vaccine, United States military trainees
had a 100-fold decline in adenovirus disease burden (from 5.8 to 0.02 cases per 1000
person-weeks) [75]. There was also a marked decline in the incidence of disease caused
by adenovirus serotypes other than 4 and 7, including adenovirus serotype 14. These data
suggest that the emergence of adenovirus 14 in military recruits during the non-vaccination
period was related to the discontinuation of the adenovirus serotypes 4 and 7 vaccine
program, since heterotypic antibodies to adenovirus 14 develop following adenovirus 7
immunization [72,76,77]. (See "Epidemiology and clinical manifestations of adenovirus
infection", section on 'Adenovirus 14'.)
Infection control Adenoviruses can stay viable for prolonged periods on environmental
surfaces such as sinks and hand towels, and they are not susceptible to some commonly
used disinfectants such as alcohol and ether [78]. Therefore, decontamination of
environmental surfaces and instruments may be difficult and requires specific agents such
as chlorine, formaldehyde, or heat. Outbreaks of pharyngoconjunctival fever from
swimming pool exposure have usually been associated with inadequate water chlorination
[79].
For patients with conjunctivitis and for patients with gastroenteritis who are
incontinent or in diapers, contact precautions should be maintained for the duration of
the illness. (See "Infection prevention: Precautions for preventing transmission of
infection", section on 'Contact precautions'.)
For those with respiratory tract infections, contact and droplet precautions are
recommended for the duration of the hospitalization. (See "Infection prevention:
Precautions for preventing transmission of infection", section on 'Contact
precautions' and "Infection prevention: Precautions for preventing transmission of
infection", section on 'Droplet precautions'.)
Disposable gloves and assiduous hand washing should be used when caring for
infected patients.
Healthcare personnel with known or suspected adenoviral conjunctivitis should
avoid direct patient contact for 14 days after the onset of disease in their second eye.
Children who participate in group childcare, particularly during the first two years of life, are
at increased risk for adenoviral respiratory tract infections and gastroenteritis. Specific
preventive measures in this setting have not been established.
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Basics topic (see "Patient education: Adenovirus infections (The Basics)")