Professional Documents
Culture Documents
PAPP PERSPECTIVE
Updates
in the
PAPP Officers
Olivia C. Go, MD FPPS FPAPP.President
Arnel Gerald Q. Jiao, MD FPPS FPAPP....Vice-President
Cesar M. Ong, MD FPPS FPAPP...Secretary
Maria Nerissa A. de Leon, MD FPPS FPAPP....Treasurer
Mary Therese M. Leopando, MD FPPS FPAPP.Director
Clara R. Rivera, MD FPPS FPAPP.Director
Mary Ann F. Aison, MD FPPS FPAPP...Director
PAPP Task Force on pCAP
Cristan Q. Cabanilla, MD FPPS FPAPP
Chair
Regina M. Canonizado, MD FPPS FPAPP
Anjanette R. de Leon, MD DPPS DPAPP
Roslyn Marie K. Dychiao, MD FPPS DPAPP
Beatriz Praxedes Apolla I. Mandanas-Paz, MD DPPS DPAPP
Anna Marie S. Putulin, MD FPPS FPAPP
Emily Dolores G. Resurreccion, MD FPPS FPAPP
Ana Maria A. Reyes, MD FPPS FPAPP
Marion O. Sanchez, MD DPPS DPAPP
Rita Marie Lourdes S. Vergara, MD FPPS FPAPP
Rozaida R. Villon, MD FPPS FPAPP
Members
Gerardo L. Beltran, MD FPCR
Guest Radiologist
Gladys L. Gillera, MD DPPS DPAPP
Secretary!
CONTENTS
Foreword
Appendix
Bibliography
FOREWORD
In the past years, we witnessed a major revolution in the science and practice of pediatric
pulmonary medicine, more particularly in our concept and management of pneumonia in children.
We are challenged to adopt and apply these newer insights about the disease in dealing with our
patients.
Despite the inadequate and limited advancement in medical technology among
developing countries, we are able to establish the diagnosis of pneumonia and manage it
comprehensively largely based on good clinical acumen. Furthermore, our knowledge in clinical
epidemiology is imperative to facilitate its holistic management, while the rational use of
antimicrobial agents increases our awareness on the emergence of drug resistance in specific
localities.
This clinical update on pneumonia contains a comprehensive evidence-based review of
national as well as international researches that depicts the current clinical practice and
management strategies adopted to contain the disease. The Academy maintains its primary
purpose to apprise our pediatric practitioners of the many medical investigations on pneumonia
and propose practical treatment options to combat the disease.
This current issue does not intend to replace the 2004 PPS Clinical Practice Guideline in
the Management of Pediatric Community-Acquired Pneumonia. This is simply presented to
clarify some gaps in the knowledge stated therein. We look forward that this understanding
bridges the small differences in our daily practice to bring forth a worthy clinical outcome.
Allow me to take this good opportunity to congratulate the Task Force on PCAP for such
an excellent job.
Olivia C. Go, MD
President
Philippine Academy of Pediatric Pulmonologists, Inc.
One of the issues that was raised regarding the 2004 Clinical Practice Guideline in the
Evaluation and Management of Pediatric Community-Acquired Pneumonia is the gap in
knowledge underscored in each recommendation. To address this concern, the Task Force on
pCAP has reviewed data available from local and foreign literature. As this manuscript is merely
an update consisting of recent literature, it is not intended to be a standard of care much more a
revision of the current guideline.
This update is available in two formats. The abbreviated format consists of update
highlights and summary of recent evidence. This is made available as a limited service item in the
form of hard copy during the 2008 16th PAPP Annual Convention. The complete version which
includes not only similar highlights but detailed description of each update can be downloaded
from the Philippine Academy of Pediatric Pulmonologists, Inc. through the website of the
Philippine Pediatric Society www.pps.org.ph. The reader is encouraged to access the complete
version for a more thorough discussion.
Cristan Q Cabanilla, MD
Chair
Task Force on pCAP
Acknowledgement
This manuscript is the result of a concerted effort by the Task Force on pCAP
under the leadership and guidance of the PAPP officers headed by Olivia C. Go.
Special gratitude is due to Luis M. Rivera Sr., Alexander O. Tuazon, Milagros S.
Bautista and Agnes R. Mendoza for reviewing the document.
Evaluation
1.
2.
3.
4.
Treatment
5. When is antibiotic recommended?
6. What empiric treatment should be administered if a bacterial etiology
is strongly considered?
7. What treatment should be initially given if a viral etiology
is strongly considered?
8. When can a patient be considered as responding to the current
antibiotic?
9. What should be done if a patient is not responding to current
antibiotic therapy?
10. When can switch therapy in bacterial pneumonia be started?
11. What ancillary treatment can be given?
Prevention
12. How can pneumonia be prevented?
INTRODUCTION
The world incidence of lower respiratory tract infection that includes pneumonia
in developing countries has been recently estimated to be 150.7 million cases, 95% of
whom are under five years of age, and 13% severe enough to require hospital admission
[Rudan I,2004]. In the Philippines, it continues to be a leading cause of morbidity in
children accounting to about 828.8 per 100,000 population [Department of Health Field Health
Service Information System, 2006].
Estimates of treatment cost highlight the economic burden that childhood
pneumonia places on health care systems. An average cost of treatment for acute
respiratory infection per episode from the perspective of developing economies in Asia
ranged from USD 1.70 in a primary health care setting to USD 155.30 for hospitalized
care [Toan NV,2001; Rattanadilok N,2002]. Outpatient and hospitalized care of a child with
pneumonia have been estimated to be USD 13.44 and USD 71.0 per episode, respectively
[Hussain H, 2006]. An average parents total household expenses for a childs admission
because of pneumonia have been found to be 5 to 11% of an average net income per
family in Israel [Shoham Y,2005]. In the local setting as provided by the National Health
Insurance Program, the 2006 total payment claims for pneumonia [ICD-10 Code J18.9]
below 19 years of age amounted to PhP 324.688 M [Philippine Health Insurance Corporation,
Claims Payment Summary for CY 2006 Ages 0-19 for Pneumonia,2007].
One public health strategy to address this continuing concern is the
implementation of a clinical practice guideline. In 2004, the Philippine Pediatric Society,
the Philippine Academy of Pediatric Pulmonologists and the Pediatric Infectious Disease
Society of the Philippines came out with a clinical practice guideline in the evaluation
and management of pediatric community-acquired pneumonia. In 2006, the Philippine
Health Insurance Corporation has adopted the document as one of the guidelines that can
serve as a basis for quality assurance and accreditation [PhilHealth Health Technology
Assessment Unit, Quality Assurance Research and Policy Development Group,2006]. Its acceptability
and utilization have been subsequently assessed. Of the 166 respondents to a random
sampling questionnaire survey conducted during the 2006 43rd PPS Annual Convention,
82% acknowledged applying the recommendation in their practice [Cabanilla C, Santos J,
2006]. In another survey among 61 pediatric consultants and residents from MetroManila,
about 96% confirmed that such guideline was being followed [de Jesus-Oabel BA and Atienzade Leon MN, 2007].
This update presents evidences based on recent local and foreign literature dealing
with the recognition of community-acquired pneumonia in an immunocompetent patient
aged 2 months to 19 years, identification of appropriate and practical diagnostic
procedures, and initiation of rational management and preventive measures
UPDATE HIGHLIGHTS
1. A patient presenting with a history of cough and/or respiratory difficulty
should be evaluated for the possible presence of pneumonia. However, the lack of
cough does not necessarily imply the absence of the disease as it may not be
present as an initial presentation in 24% of cases with radiographic pneumonia.
This is particularly true in the younger age group.
2. There are physical signs that are useful to predict the presence of pneumonia
using chest x ray as reference standard.
In four studies involving children below 5 years old, age-specific tachypnea
as defined by the World Health Organization [WHO] remains to be the best single
predictor. Another useful single physical sign is the presence of chest indrawing.
A combination of tachypnea and chest indrawing provides a higher probability as
to the presence of pneumonia. In one study, the combination of tachypnea, low
oxygen saturation on admission and nasal flaring gave the highest predictive
value among all other signs and symptoms.
In two studies dealing with patients older than 5 years, tachypnea alone, or
in combination with fever and crackles are reliable predictors.
3. The absence of either age-specific tachypnea as defined by WHO or chest
indrawing does not rule out the presence of pneumonia.
b. There is one [1] study dealing with identifying patients with radiographic
pneumonia in the combined out-patient department and emergency room
Among 510 patients aged 2-59 months of age with cough and with any
one of the following [Mahabee-Gittens EM, 2005 ]:
!
!
!
!
Among 570 patients aged 1-16 years of age, tachypnea has +LR of 2.6
and -LR of 0.90; and combination of fever, decreased breath sounds,
crackles and tachypnea has +LR of 1.04 and LR of 0.20 [Lynch T, 2004 ].
___________________________________________
*
Likelihood ratio [LR] of around 1 indicate that no useful information for ruling the diagnosis in or out has
been produced from the clinical findings. A LR that is further away from 1 increases reliability. A high
likelihood ratio (e.g. LR>10) indicate that the sign or symptom [or any diagnostic test] can be used to rule
in the disease, while a low likelihood ratios (e.g. LR<0.1) can rule out the disease. Please see Appendix B.
10
UPDATE HIGHLIGHTS
1. Single evidence supports the current recommendation on risk classification scheme.
2. A single clinical index that suggests the need for admission because of possible
hypoxemia is chest indrawing.
3. Indices that predict mortality include young age, malnutrition, lack of Hib/measles
vaccination, and high oxygen requirement on admission.
Annotation 2A. Risk classification scheme
Among 221 patients with an impression of pCAP, none of the 61 and 80 patients
classified as pCAP A and B respectively were admitted within 48 hours. Similarly, none
of the 84 patients admitted as pCAP C were discharged or admitted to ICU within 48
hours after admission [Pocsidio C, 2007]. See Appendix C for the table showing the risk
classification.
Annotation 2B. Individual indices predicting the need for admission
1. Physical examination of the chest in predicting hypoxemia
Among 150 patients aged 2-60 months, chest indrawing has a +LR of 5.7
and -LR of 0.39 in predicting the presence and absence respectively of hypoxemia
[Basnet S, 2006].
2. Age and nutrition in predicting mortality
Among 30 mortalities because of pneumonia, young age [2-5 months] and weight
for age z-score less than -2 SD have an OR of 2.20 (95% CI 1.06-4.54) and
1.86 (95% CI 0.89-3.87), respectively [Lupisan SP, 2007].
3. Hib/measles vaccination on admission in predicting mortality
Among 102 mortalities because of pneumonia, the absence of measles/HIb
vaccination has an OR of 15.89 (95% CI 3.473-72.784), and
8.31(95% CI 3.5-19.3), respectively [Sadang-Saguinsin S, 2006].
Annotation 2C. Day care management of pCAP C
Among 251 patients aged 2-59 months with severe and very severe pneumonia without
any associated co-morbidities, successful management was possible in a day care setting
among 93.2% (95% CI, 89-96) of patients [Ashraf H, 2007].
11
CQ 3. What diagnostic aids are initially requested for a patient classified as either
PCAP A or PCAP B being managed in an ambulatory setting?
No diagnostic aids are initially requested for a patient classified as either PCAP A or
PCAP B who is being managed in an ambulatory setting [Grade D].
UPDATE HIGHLIGHT
The low risk of bacteremia does not warrant blood culture determination in
nonsevere pneumonia.
12
UPDATE HIGHLIGHTS
1. Chest radiographic evaluation is primarily utilized as an integral part of a
clinical prediction rule in identifying the presence of a bacterial pathogen. As an
individual tool, it can be used to assess severity and presence of complications,
and to predict subsequent course of illness.
2. WBC and CRP have a limited value as an individual test in differentiating
bacterial from viral pneumonia. A CRP level [ 12 mg/dl] is associated with
necrotizing pneumonia and/or empyema.
3. Single evidence suggests a 63 mm/h value for ESR in predicting the presence
of a bacterial pathogen.
4. The microbiologic yield for blood culture ranged from 1.2% to 6.2%.
5. High oxygen requirement on admission is one of the variables associated
with mortality.
13
1. Chest x-ray has been used as a tool to predict the type of pathogen
Chest x-ray is an integral part of the clinical prediction rule
[see Clinical Question 5 and Appendix D] in initiating antibiotic
therapy [Moreno L, 2006]. However, its value as an individual tool in
differentiating bacterial from other types of infection is
insignificant as shown in one report [Michelow IC, 2004]. In this
study of 154 patients aged 2 months17 years, the presence of
lobar or segmental consolidation with or without effusion can be
seen among different pathogens such as bacterial, viral and
atypical organisms (p value = 0.06).
A compounding variable is the presence of mixed causative agents
in about a third of cases of pneumonia in which the radiographic
pattern has been shown to be similar to that seen in single pathogen
[Tsolia MN, 2004; Taina Juve n, 2004; Michelow IC, 2003; Don M, 2005;
Tajima T,2006; Lehtinen P,2006; Huang HH,2006; Chiang WC,2007].
14
b. Predictor of mortality
Among 102 mortalities because of pneumonia, multilobar
(2 lobes) involvement has an OR of 2.55 (95% CI 1.56.5.64) of mortality [Sadang-Saguinsin S, 2006].
In 30 mortalities because of pneumonia, the presence of
dense infiltrates has an OR of 3.89 (95% CI 1.75-8.67)
[Lupisan SP, 2007].
c. Predictor of treatment failure
Among 20% of 218 patients, bilateral consolidation has an
OR of 3.10 of having treatment failure on the 72nd hour of
admission [Victor R, 2007].
15
In one study, a CRP level 12 mg/dl has an OR of 3.51 (95% CI 1.717.66) to predict the presence of necrotizing pneumonia and/or empyema
[Lin K, 2006].
3. Serum procalcitonin
In two studies, there is evidence that serum procalcitonin may predict the
presence of a bacterial pathogen. This test however is not currently
available locally
a. Among 132 patients aged <11 months to >5 y old, a
procalcitonin level of > 0.84 ng/L has a +LR of 2.05 and a -LR
0.76 [Korppi M, 2004].
b. Among 57 patients less than 15 years old with Streptococcus
pneumoniae, procalcitonin > 1 ng/L found in only 14 patients had
+LR of 2.40 [Korppi M,2003].
16
17
UPDATE HIGHLIGHTS
1. Epidemiology
a. Recent epidemiologic trend shows that more than 50% of hospitalized
cases of pCAP will require antibiotic.
b. The importance of mixed infection as causative agents should be clarified
as it is responsible for about one-third of all identified causes of hospitalized
pCAP.
2. Microbiologic tests
The yield in detecting bacteremia in pCAP remains to be low at 1.2% to 26%.
3. Predictors of bacterial pathogen.
a. A clinical prediction rule that makes use of a bacterial pneumonia score
[BPS] of > 4 can predict the presence of a bacterial pathogen in hospitalized
patients aged one month to five years.
b. Other individual parameters include the following.
Increasing age generally correlates with the presence of
antibiotic-requiring pathogen. Identifying a specific age as to
when an antibiotic should be started is difficult.
There is single evidence in the use of ESR with a value of 63
mm/h in predicting the presence of a bacterial pathogen.
There is weak evidence in the use of clinical symptomatology,
chest x-ray, WBC and CRP as predictors of bacterial pathogen.
18
A. Microbiology
There are five [5] studies that have looked simultaneously into viral, bacterial,
atypical organisms and mixed infection [Michelow I, 2004,; Don M, 2005; Tsolia MN,
2005; Tajima T, 2006; Chang WC, 2007]. Etiology was determined through different
methodologies using culture, serology, and pneumolysin-based polymerase chain
reaction assays. It is important to note that all patients in these studies are
hospitalized [except in one study dealing with both ambulatory and hospitalized
patients], and are from developed economies where the rate of vaccination is
higher than in the third world. As the table below indicates, organisms requiring
antibiotic coverage accounts for more than 50% across all ages. The importance
of mixed infection needs to be further studied as there is an observational
evidence of a high morbidity from 2% to 35%.
Author
Year
Bacteriaa
%
Atypical
Pathogena
%
Mixed
Infection
%
5.5%
10.3%
20.3%
2.0%
126 [80.2%]
44.0%
80.1%
25.3%
18.0% b
101
66 [65.3%]
42.0%
30.3%
53.0%
30.0%
75
58 [77.3%]
65.0%
7.0%
48.2%
35.0%
154
122 [79.2%]
45.0%
60.0%
33.6%
23.0%
23.6%
26.5%
26.0%
10.7%
2189
1018 [46.5%]
Age
[Years]
Subjects
N
Known
Etiology
N [%]
Chiang
2007
0.1-16
1702
646 [37.9%]
Tajima
2006
0.1-13
157
Don
2005
0.3-16
Tsolia
2005
5-14
Michelow
2004
0.2-17
Virusa
%
MEAN
TOTAL
a
b
19
20
Author
Year
Age
[Years]
Subjects
[N]
Chiang
2007
0.1-16
<2
2-5
>5
1702
Tajima
2006
0.1-13
<2
2-5
>5
157
126
Don
2005
0.3-16
<2
2-5
>5
101
66
Michelow
2004
0.2-17
<2
2-5
>5
154
Known
Etiology
[N]
653
122
Virus a
[%]
Bacteria a
[%]
Atypical
Pathogena
[%]
5.5
6.6
6.9
0.9
10.3
20.3
Mixed
Infection
[%]
2.0
5.2
13.2
8.5
5.0
16.5
31.0
40.0
52.7
47.3
0
43.0
69.6
32.8
4.2
18.0
3.5
42.8
64.2
19.0; [2.0b]
83.0
17.0
0
18.8a
31.6
57.8
10.5
17.5
22.2
38.8
38.8
34.6
29.7
36.8
22.7
34.2
19.0
55.0c
48.0c
38.0c
26.0
55.0c
68.0c
55.0c
11.0
5.7
22.8
71.4
23.0
47.0 d
53.0
21
Prevalence
[%]
Author
Year
Age
[Years]
Butun
2006
0.3-12
100
<5
Bamba
2006
<4-13
141
<4
Othman
2005
0.5-15
76
<5
36.8
Garcia
2005
1-10
142
<5
63.4
Tsai
2004
1-14
26
<5
53.8
53.0
20.0
2. Clinical symptomatology
Among 254 inpatients [mean age of 3.8 years] with radiographic
pneumonia and proven etiology, the presence of decreased breath sounds
is the only single clinical sign noted among patients with bacterial
pathogen as compared with viral infection (p<0.05) [Juven T, 2003].
22
23
UPDATE HIGHLIGHTS
1 Epidemiology
a. Epidemiologic trend in developed economies suggests that
Streptococcus pneumoniae and Mycoplasma pneumoniae appear
to be the most common pathogens causing community-acquired
pneumonia across all ages.
b. An important emerging pathogen is community-acquired methicillin
resistant Staphylococcus aureus [CA-MRSA].
2. Antibiotic resistance
Data on 2006 Antimicrobial Resistance Surveillance Program showed
resistance rate of less than 10% for penicillin and chloramphenicol with
Streptococcus pneumoniae infection, and for ampicillin with Haemophilus
influenzae.
3. Empiric antibiotic therapy
a. For pCAP A and B [nonsevere pneumonia], there is evidence for the use
of amoxicillin [45 mg/kg/day in three divided doses for a minimum
duration of three days]. For those with known hypersensitivity to
amoxicillin, a macrolide may be considered. The use of cotrimoxazole is
discouraged because of high failure and resistance rates.
b. For pCAP C [severe pneumonia], equal efficacies were noted between
oral amoxicillin and parenteral penicillin among patients who can tolerate
feeding; and between monotherapy and combination therapy for those
who cannot tolerate feeding. Among monotherapy available for use,
parenteral ampicillin is the best choice considering its cost.
24
Author
Year
Age
[Years]
Chiang
2007
0.1-16
17.4%
0.4%
28.6%
0%
Tajima
2006
0.1-13
35.7%
26.1%
17.4%
0%
Huang
2006
2.0-14
8.9%
1.2%
7.1%
1.8%
Don
2005
0.3-16
17.8%
4.5%
26.7%
7.9%
Tsolia
2005
5.0-14
7.0%
0%
35.0%
3.0%
Michelow
2004
0.2-17
73.0%
0%
14.0%
9.0%
Streptococcus pneumoniae is more common above 5 years of age[Chiang, 2007; Michelow 2004].
25
Penicillin a
Chloramphenicol
Cotrimoxazole
Ampicillin
2003
04
05
06
2003
04
05
06
2003
04
05
06
2003
04
05
06
Streptococcus
Pneumoniae
9%
5%
11%
6%
3%
5%
4%
5%
9%
15%
16%
14%
No
data
No
data
No
data
No
data
Haemophilus
Influenzae
No
data
No
data
No
data
No
data
13%
10%
20%
14%
18%
36%
15%
16%
13%
10%
10%
9%
A. Oral Amoxicillin
1. Comparative trial
27
2. Treatment regimen
c. Three-day versus five-day duration using clinical cure rate and relapse
rate as outcome measures
Among 2188 patients aged 2-59 months, clinical cure rates with
three days and five days treatment were 89.5% and 89.9%,
respectively (absolute difference 0.4, 95% CI 2.1-3.0). There was
no difference in relapse rate between the two groups after 5 days
(RR = 1.22; absolute difference 1.0, 95% CI 1-3). Limitations such
as the study was performed in patients with clinical suspicion of
pneumonia without radiographic evidence and insufficient
detailing of patients history were noted [Agarwal, 2004].
28
1. Cotrimoxazole
a. Comparative trial using cure rate as outcome measure
There is one Cochrane systematic review dealing with antibiotic treatment
of pCAP showing procaine penicillin having better cure rate compared
with co-trimoxazole (OR 2.64; 95% CI 1.57 - 4.45) [Kabra SK;2006].
b. Treatment regimen using treatment failure rate as an outcome measure
Among 1134 patients aged 2-59 months, treatment failure occurred in
112 (19.4%) on standard dose [4 mg trimethoprim plus 20 mg
sulfamethoxazole/kg of body weight] group and in 118 (21.2%) on
double-dose (RR 1.10; 95% CI 0.871.37) [Zeba A,2005].
29
A. Monotherapy
Parenteral penicillin vs oral amoxicillin
A Cochrane systematic review using failure rate as an outcome
measure showed no difference between injectable penicillin and oral
amoxicillin (OR 1.03; 95% CI 0.81 to 1.31) [Kabra SK;2006]. Included in
this review is a study among 1702 patients aged 3-59 months who
received either oral amoxicillin or parenteral penicillin. Results showed
that treatment failure was 19% in either group (risk difference 0.4%,
95% CI -4.2 - 3.3) [Addo-Yobo, 2004].
Among 246 patients aged 6 months to 16 years with radiologically
confirmed pneumonia, no significant difference exists between the group
on oral amoxicillin versus IV benzylpenicillin using time for
temperature to settle <38C for 24 continuous hours (p value = 0.001) as
the outcome measure. Using another outcome measure, the median time
to complete resolution of symptoms was 9 days in both groups
[Atkinson M, 2007].
B. Combination therapy
1. Parenteral penicillin plus chloramphenicol versus ampicillin using cure rate
and duration of hospitalization as outcome measures
In a Cochrane systematic review, the cure rates (OR 0.48; 95% CI 0.15 to
1.51), and duration of hospitalization were similar in the two groups
(weighted mean difference (WMD) 0.1; 95% CI -1.13 to 0.93)
[Kabra SK; 2006].
2. Parenteral penicillin plus chloramphenicol versus ceftriaxone using cure rate as
outcome measure
In a Cochrane systematic review using cure rate as outcome measure, the
use of parenteral penicillin plus chloramphenicol was as efficacious
compared with ceftriaxone alone (OR 1.36; 95% CI 0.47 to 3.93)
[Kabra SK; 2006].
30
31
b. Chloramphenicol
Among 250 children treated with chloramphenicol, 98%
had a favorable treatment outcome [Ayap J, 2006]
C. Community-acquired MRSA
For suspected cases of community-acquired MRSA, immediate referral to an appropriate
specialist is necessary. The following information serves to provide basic knowledge in
the therapeutic options dealing with MRSA [Strategies for Clinical Management of MRSA in the
community: Summary of an Experts meeting,2006; Shelburne S, 2004].
32
UPDATE HIGHLIGHT
Oseltamivir remains to be the drug of choice for laboratory confirmed cases of
influenza.
Influenza
33
UPDATE HIGHLIGHTS
1. In children with nonsevere pneumonia, clinical index suggestive of good
therapeutic response is a respiratory rate >5 breaths/min slower than baseline
recording at the 72nd hour.
2. In children with severe pneumonia, clinical indices suggestive of good
therapeutic response are defervescense, decrease in tachypnea and chest
indrawing, increase in oxygen saturation, and ability to feed within 48 hours.
34
B. Response to treatment
1. Ambulatory patients
Respiratory rate
Among 876 patients aged 2-59 months with nonsevere pneumonia,
clinical improvement on the 72nd hour is respiratory rate >5
breaths/min slower than baseline recording [Hazir T,2006].
2. Hospitalized patients
Duration of fever
Among 153 children aged 1 month to 16 years, 91% became
afebrile within 48 hours. Children with bacteremic pneumococcal
pneumonia have become afebrile within an average of 22 hours
after onset of antimicrobial therapy [Juve n T, 2006].
Respiratory rate
Average time of recovery from tachypnea among 71 children aged
2-59 months is 38-40 hours [Bansal A, 2006].
Oxygen saturation
Average time of recovery from SpO2 (<90%) among 71 children
aged 2-59 months is 32-33 hours [Bansal A,2006].
Chest indrawing
Average time of recovery from chest indrawing among 71 children
aged 2-59 months is 33-36 hours [Bansal A,2006].
Inability to feed
Average time of recovery from inability to feed among 71 children
aged 2-59 months is 33-36 hours [Bansal A,2006].
35
UPDATE HIGHLIGHTS
1. There are no studies dealing with therapeutic interventions following
treatment failure among children having community-acquired pneumonia.
2. A definition of treatment failure for nonsevere pneumonia is as follows:
a. Same status. This is defined as respiratory rate > age-specific range but
+ 5 breaths/min to the baseline reading and without lower chest indrawing
or any danger signs;
b. Worse status. This is defined as developing lower chest indrawing or
with any of the danger signs.
3. The causes of treatment failure include coinfection with respiratory syncytial
virus or mixed infection, non-adherence to treatment for nonsevere pneumonia,
resistance to antibiotics, clinical sepsis, and progressive pneumonia.
36
A. Background
The clinical outcome definitions of same and worse status provided by the
World Health Organization in 1990 are as follows [WHO 1990] :
Same : Respiratory rate > age-specific range without lower chest
indrawing or any danger signs (central cyanosis, inability to drink,
abnormally sleepy or convulsions)
Worse : Developed lower chest indrawing or any of the danger signs
(central cyanosis, inability to drink, abnormally sleepy,
or convulsions)
B. Treatment failure
1. pCAP A and B [Nonsevere pneumonia]
Among 876 patients aged 2-59 months with nonsevere pneumonia,
treatment failure has been redefined on the 72nd hour after initiating
antibiotic as either [a] same status : respiratory rate > age-specific range
but + 5 breaths/min to the baseline reading without lower chest indrawing
or danger signs (central cyanosis, inability to drink, abnormally sleepy or
convulsions), or [b] worse status : developed lower chest indrawing or any
of the danger signs (central cyanosis, inability to drink, abnormally sleepy
or convulsions) [Hazir T,2006].
2. pCAP C [Severe pneumonia]
There are no studies in hospitalized patients.
37
38
Switch from intravenous antibiotic administration to oral form 2-3 days after I
nitiation of antibiotic is recommended in a patient [Grade D] who
[a] is responding to the initial antibiotic therapy,
[b] is able to feed with intact gastrointestinal absorption; and
[c] does not have any pulmonary or extrapulmonary complications.
UPDATE HIGHLIGHTS
Switch therapy from three [3] days of IV ampicillin to four [4] days of either
amoxicillin or cotrimoxazole may be used among patients admitted because of
community-acquired pneumonia. Amoxicillin is preferred because of high failure
and resistance rates reported in the use of cotrimoxazole.
39
1. Among inpatients, oxygen and hydration should be given if needed [Grade D].
2. Cough preparations, chest physiotherapy, bronchial hygiene, nebulization using
normal saline solution, steam inhalation, topical solution, bronchodilators and
herbal medicines are not routinely given in community-acquired pneumonia
[Grade D].
UPDATE HIGHLIGHTS
1. There is no evidence to support the use of hydration or fluid restriction and cough
preparation in the management of pneumonia.
2. The value of elemental zinc or vitamin A is inconclusive.
3. Single study demonstrated benefit for either virgin coconut oil or probiotic as
adjunct therapy in pneumonia.
Annotation 11A. Fluid management
A. Increase fluid intake
In a Cochrane systematic review among ambulatory patients with acute
respiratory infection, no randomized controlled trials assessing the effect of
increasing fluid intake in acute respiratory infections were found
[Guppy MPB,2005].
B. Fluid restriction
There are no controlled studies assessing the effect of restricting fluid intake
among patients hospitalized with pneumonia.
In a Cochrane systematic review among hospitalized patients, the rate of
hyponatremia has been reported to be 31%-45% for nondehydrated children with
moderate to severe pneumonia [Guppy MPB, 2005].
Among 50 children aged 259 months with severe, and very severe pneumonia,
extracellular water [ECW] and plasma volume [PV] were moderately increased
[ECW 318 (45) vs 308 (49) ml/kg, PV 53.2 (2.3) vs 52.1 (2.3) ml/kg, p,0.05].
The SpO2 showed a significant linear relationship with ECW and PV (0.46 and
0.42 respectively, p =0.05) [Singhi S, 2005].
40
41
C. In a randomized controlled trial involving 287 children aged 259 months, with
pneumonia, no overall differences were observed between the group who received
vitamin A 50 000 IU (aged 212 mo) or 100 000 IU (aged 1259 mo) and those who
received placebo [Rodriguez A,2005].
D. Among 187 children aged < 11 years hospitalized with 215 ALRI episodes, there was
no clinical benefit of supplementation with vitamin A, elemental zinc or the two
combined, compared with placebo in time to resolution of fever or tachypnea, or duration
of hospitalization. Children given elemental zinc had an increased risk of readmission for
ALRI within 120 days (relative risk [RR] 2.4; 95% CI 1.0036.1) [Chang AB, 2006].
E. In a randomized controlled trial of patients aged 2-35 months admitted with severe
LRI, there is no difference between the groups who receive alpha-tocopherol 200 mg and
ascorbic acid 100 mg twice daily or placebo for 5 days as to time taken to recover from a
very ill status, fever, tachypnoea, and feeding difficulty [Mahalanabis D, 2006].
F. In a randomized trial of 299 patients aged 2-23 months, there were no clinical or
statistically significant differences in the duration of tachypnea, hypoxia, chest
indrawing, inability to feed, lethargy, severe illness, or hospitalization between those who
received 10-mg tablets of zinc sulfate versus placebo twice a day (p value = 0.015)
[Bose A, 2006].
G. In a randomized controlled trial 153 children aged 224 months who were hospitalized
with severe ALRI, recovery rates from very ill status and from fever in zinc treated boys
were 2.6 times (p= 0.004) and 3 times (p= 0.003) those in non-zinc-treated children;
feeding difficulty and tachypnea were not significantly different between groups after an
adjusted analysis. Recovery rates were not significantly different between groups on the
basis of vitamin A treatment [Mahalanabis D,2004].
42
B. Probiotic
Among 76 infants, probiotic OMX capsules had shorter duration of cough and
hospital stay with mean 2.4 + 1 days compared to control mean 4.3 + 1 day (p
value <0.007); resolution of tachypnea and retractions 1.5 + 0.5 days compared
to control 4.3+ 1 days (p value < 0.001); and tachypnea on day 3 as outcome
measure (RR 0.11; NNT 2) [Bayer-Mulsid,2006].
43
UPDATE HIGHLIGHTS
1. A meta-analysis on immunomodulators showed a general reduction of rates in
acute respiratory tract infection through the use of immunostimulants.
2. There are evidences to suggest that handwashing using antibacterial soaps,
pneumococcal and Hib vaccination, elemental zinc, and breastfeeding are
effective in preventing pneumonia.
3. Single study showed that patients on gastric acid inhibitors are at an increase
risk to have pneumonia
44
B. Hib vaccine
In 1293 children (431 cases, 862 controls) below 2 years, the risk for radiologic
pneumonia is OR 0.69; 95% CI 0.43 to 1.09 [Sampaio AL,2004]
45
Annotation 12 D. Micronutrients
In a randomized controlled trial of 1665 children aged 60 days to 12 months old, 70 mg
elemental zinc given orally once a week for 1 year compared with placebo led to a
significantly lower incidence of pneumonia in the zinc group than in the placebo group
(RR 0.83 95% CI 0.73-0.95) [Brooks WA,2005].
Annotation 12 E. Breastfeeding
15,890 infants who were exclusively breastfed had a large and statistically significant
reduction in risk for hospitalization for lower respiratory tract infection (adjusted OR:
0.66; 95% CI: 0.470.92) compared with those who were not breastfed [Quigley MA, 2007].
46
External Review.
The update has been reviewed by pediatric pulmonologists who are not involved in the
development process, and subsequently approved by the PAPP Board of Directors.
Funding.
PAPP has exclusively funded the formulation of this update.
Disclaimer.
As the update merely serves to inform the physician of recent evidence, it is not intended
to be a standard of care. Due to specific requirements imposed by individual children, the
physician is advised to exercise personal clinical judgment to the best interest of the
patient.
47
48
49
PCAP B
PCAP C
PCAP D
Minimal risk
Low risk
Moderate risk
High risk
VARIABLES
None
Present
Present
Present
Yes
Yes
No
No
Possible
Possible
Not possible
Not possible
None
Mild
Moderate
Severe
Able
>11 mo
Able
>11 mo
Unable
<11 mo
Unable
< 11 mo
>50/min
>40/min
>30/min
>50/min
>40/min
>30/min
>60/min
>50/min
>35/min
>70/min
>50/min
>35/min
a. Retraction
None
None
b. Head bobbing
c. Cyanosis
d. Grunting
e. Apnea
f. Sensorium
None
None
None
None
Awake
None
None
None
None
Awake
Intercostal /
subcostal
Present
Present
None
None
Irritable
9. Complications
None
None
Present
Supraclavicular/
intercostal/subcostal
Present
Present
Present
Present
Lethargic/stuporous/
comatose
Present
1. Co-morbid
illnessb
2. Compliant
caregiverc
3. Ability to
follow-upc
4 Presence of
dehydrationd
5. Ability to feed
6. Age
7. Respiratory ratee
2-12 months
1-5 years
> 5 years
8. Signs of resp failure
[effusion, pneumothorax]
ACTION PLAN
OPDf
Follow-up
at end of
treatment
OPDf
Follow-up
after 3
days
Admit to
regular ward
Admit to a critical
care unit
Refer to specialist
In the presence of overlapping parameters, assume the next severe classification even with only one
parameter present.
Comorbid illness includes malnutrition, asthma, congenital heart disease and other clinical conditions
that can directly affect respiratory function.
Nonavailability of these external factors necessitates admission even if accompanied by less severe
parameters
Grading of dehydration adapted from Nelsons Textbook of Pediatrics1: MILD [thirsty, normal or
increased pulse rate, decreased urine output and normal physical examination]; MODERATE
[tachycardia, little or no urine output, irritable/lethargic, sunken eyes and fontanel, decreased tears,
dry mucus membranes, mild tenting of the skin, delayed capillary refill, cool and pale]; SEVERE
[rapid and weak pulse, decreased blood pressure, no urine output, very sunken eyes and fontanel, no
tears, parched mucous membranes, tenting of the skin, very delayed capillary refill, cold and mottled]
Parents should be advised that if patient is rapidly deteriorating, immediate follow-up is necessary
50
Predictor
Points
3
Location
2 points
1 point
-1 point
1 point
1 point
-1 point
1 point
2 points
Abscess, bullae or
pneumotocoele
Equivocal
Obvious
1 point
2 points
Atelectasis
-1 point
-1 point
0 point
Moreno L, Krishnan JA, Duran P, and Ferrero F: Development and Validation of a Clinical Prediction Rule
to Distinguish Bacterial From Viral Pneumonia in Children. Pediatr Pulmonol 2006; 41:331-337
51
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