Candidiasis

Practice Essentials
Candidiasis (see the image below) is a fungal infection

caused by yeasts from the genus Candida. Candida
albicans is the predominant cause of the disease.
Soreness and cracks at

the lateral angles of the mouth (angular cheilitis) are a
frequent expression of candidiasis in elderly individuals.
Courtesy of Matthew C. Lambiase, DO.
Essential update: FDA approves marketing of first rapid
blood test for 5 Candida species
In September 2014, the FDA gave marketing approval for
the T2Candida Panel and T2Dx Instrument (T2Candida),
the
first
direct
blood
test
for
detecting
fiveCandida species that cause bloodstream infections (C
albicans and/or C
tropicalis,C
parapsilosis, C
glabrata and/or C krusei).[1, 2] T2Candida can use single blood
sample to identify these five yeasts within 3-5 hours,
whereas traditional testing methods can take up to 6 days
to detect, and even longer to identify, Candid a species.
Therefore,
this
test
potentially
allows
earlier
administration of appropriate antifungal therapy and may
reduce disease severity and/or the mortality risk from
sepsis.[1, 2] However, blood cultures should be used to
confirm T2Candida results owing to the potential for falsepositive results.
Approval was based on a study of 1500 patients, in which
T2Candida correctly categorized almost 100% of negative
specimens as negative for the presence of Candida, and
another study of 300 blood samples with specific
concentrations of yeast, in which the test correctly
identified the organism in 84%-96% of positive samples.[1, 2]
Signs and symptoms
Chronic mucocutaneous candidiasis

Findings reveal disfiguring lesions of the face, scalp, hands,
and nails. Chronic mucocutaneous candidiasis is occasionally
associated with oral thrush and vitiligo.
Oropharyngeal candidiasis
Individuals with oropharyngeal candidiasis (OPC) usually
have a history of HIV infection, wear dentures, have
diabetes mellitus, or have been exposed to broad-spectrum
antibiotics or inhaled steroids. Although patients are
frequently asymptomatic, when symptoms do occur, they
can include the following:
Sore and painful mouth
Burning mouth or tongue
Dysphagia
Thick, whitish patches on the oral mucosa
Physical examination reveals a diffuse erythema and white
patches that appear on the surfaces of the buccal mucosa,
throat, tongue, and gums.
The following are the 5 types of OPC:

Membranous candidiasis - One of the most common
types; characterized by creamy-white, curdlike patches
on the mucosal surfaces
Chronic atrophic candidiasis (denture stomatitis) Also thought to be one of the most common forms of the
disease; presenting signs and symptoms include chronic
erythema and edema of the portion of the palate that
comes into contact with dentures
Erythematous candidiasis - Associated with an
erythematous patch on the hard and soft palates
Angular
cheilitis - Inflammatory reaction
characterized by soreness, erythema, and fissuring at
the corners of the mouth
Mixed - A combination of any of the above types is
possible
Esophageal candidiasis
Patients with esophageal candidiasis may be asymptomatic
or may have 1 or more of the following symptoms:
Normal oral mucosa (>50% of patients)
Dysphagia
Odynophagia
Retrosternal pain
Epigastric pain
Nausea and vomiting
Physical examination almost always reveals oral candidiasis.
Nonesophageal gastrointestinal candidiasis
The following symptoms may be present:
Epigastric pain
Nausea and vomiting
Abdominal pain
Fever and chills
Abdominal mass (in some cases)
Genitourinary tract candidiasis
The types of genitourinary tract candidiasis are as follows:
Vulvovaginal candidiasis (VVC) - Erythematous
vagina and labia; a thick, curdlike discharge; and a normal
cervix upon speculum examination [3]
Candida balanitis - Penile pruritus and whitish
patches on the penis
Candida cystitis - Many patients are asymptomatic,
but bladder invasion may result in frequency, urgency,
dysuria, hematuria, and suprapubic pain
Asymptomatic candiduria - Most catheterized
patients with persistent candiduria are asymptomatic
Ascending pyelonephritis - Flank pain, abdominal
cramps, nausea, vomiting, fever, chills and hematuria
Fungal balls - Intermittent urinary tract
obstruction with subsequent anuria and ensuing renal
insufficiency
See Clinical Presentation for more detail.
Diagnosis
Diagnostic tests for candidiasis include the following:

Mucocutaneous candidiasis - For a wet mount,
scrapings or smears obtained from skin, nails, or oral or
vaginal mucosa are examined under the microscope; a
potassium hydroxide smear, Gram stain, or methylene
blue is useful for direct demonstration of fungal cells
Cutaneous candidiasis - Using a wet mount,

scrapings or smears obtained from skin or nails can be
examined under the microscope; potassium hydroxide
smears are also useful
Genitourinary candidiasis - A urinalysis should be

performed; evidence of white blood cells (WBCs), red
blood cells (RBCs), protein, and yeast cells is common;
urine fungal cultures are useful
Gastrointestinal candidiasis - Endoscopy with or

without biopsy
See Workup for more detail.
Management
Cutaneous candidiasis - Most localized cutaneous

candidiasis infections can be treated with any number of
topical antifungal agents (eg, clotrimazole, econazole,
ciclopirox, miconazole, ketoconazole, nystatin)
Chronic mucocutaneous candidiasis - This condition
is generally treated with oral azoles
Oropharyngeal candidiasis - This can be treated
with either topical antifungal agents or systemic oral azoles
Esophageal candidiasis - Treatment requires
systemic therapy with fluconazole
VVC - Topical antifungal agents or oral fluconazole
can be used [4]
Candida cystitis
In
noncatheterized
patients, Candida cystitis
should
be
treated
with
fluconazole; in catheterized patients, the Foley catheter
should be removed or replaced; if the candiduria persists
after the catheter change, then patients can be treated
with fluconazole
See Treatment and Medication for more detail.
Background
Candidiasis is caused by infection with species of the
genus Candida,predominantly
with Candida
albicans.Candida species are ubiquitous fungi that
represent the most common fungal pathogens that affect
humans. The growing problem of mucosal and systemic
candidiasis reflects the enormous increase in the number
of patients at risk and the increased opportunity that
exists for Candidaspecies to invade tissues normally
resistant to invasion. Candida species are true opportunistic
pathogens that exploit recent technological advances to
gain access to the circulation and deep tissues.
The increased prevalence of local and systemic disease
caused by Candida species has resulted in numerous new
clinical syndromes, the expression of which depends
primarily on the immune status of the host. Candida species
produce a wide spectrum of diseases, ranging from
superficial mucocutaneous disease to invasive illnesses,
such as hepatosplenic candidiasis, Candida peritonitis, and
systemic candidiasis. The management of serious and lifethreatening invasive candidiasis remains severely hampered
by delays in diagnosis and the lack of reliable diagnostic
methods that allow detection of both fungemia and tissue
invasion byCandida species.
Advances in medical technology, chemotherapeutics, cancer
therapy, and organ transplantation have greatly reduced
the morbidity and mortality of life-threatening disease.
Patients who are critically ill and in medical and surgical
ICUs have been the prime targets for opportunistic
nosocomial
fungal
infections,
primarily
due
toCandida species. Studies suggest that the problem is not
under control and, in fact, show it is worsening. On a daily
basis, virtually all physicians are confronted with a
positive Candida isolate obtained from one or more various
anatomical sites. High-risk areas for Candida infection
include neonatal, pediatric, and adult ICUs, both medical

and surgical.[5] Candida infections can involve any anatomical
structure.
Pathophysiology
Candida species are yeastlike fungi that can form true
hyphae
and
pseudohyphae.
For
the
most
part, Candida species are confined to human and animal
reservoirs; however, they are frequently recovered from
the hospital environment, including on foods, countertops,
air-conditioning vents, floors, respirators, and medical
personnel. They are also normal commensals of diseased
skin and mucosal membranes of the gastrointestinal,
genitourinary, and respiratory tracts.
Candida species also contain their own set of wellrecognized but not well-characterized virulence factors
that may contribute to their ability to cause infection.
[6]
The main virulence factors include the following:
Surface molecules that permit adherence of the
organism to other structures (eg, human cells,
extracellular matrix, prosthetic devices)
Acid proteases and phospholipases that involve
penetration and damage of cell envelopes
Ability to convert to a hyphal form (phenotypic
switching)
As with most fungal infections, host defects also play a
significant role in the development of candidal infections.
Host defense mechanisms against Candidainfection and
their associated defects that allow infection are as follows:
Intact mucocutaneous barriers - Wounds,
intravenous catheters, burns, ulcerations
Phagocytic cells - Granulocytopenia
Polymorphonuclear
leukocytes
Chronic
granulomatous disease
Monocytic cells - Myeloperoxidase deficiency
Complement - Hypocomplementemia
Immunoglobulins - Hypogammaglobulinemia
Cell-mediated immunity - Chronic mucocutaneous
candidiasis,
diabetes
mellitus,
cyclosporin
A,
corticosteroids, HIV infection
Mucocutaneous protective bacterial flora - Broadspectrum antibiotics
Risk factors associated with invasive or systemic
candidiasis include the following[7]:
Granulocytopenia
Bone marrow transplantation
Solid organ transplantation (liver, kidney)
Parenteral hyperalimentation
Hematologic malignancies
Foley catheters
Solid neoplasms
Recent chemotherapy or radiation therapy
Corticosteroids
Broad-spectrum antibiotics
Burns
Prolonged hospitalization
Severe trauma
Recent bacterial infection
Recent surgery
Gastrointestinal tract surgery
Central intravascular access devices
Premature birth
Hemodialysis
Acute and chronic renal failure

Mechanical ventilation for longer than 3 days
The first step in the development of a candidal infection is
colonization of the mucocutaneous surfaces. All of the
factors outlined above are associated with increased
colonization rates. The routes of candidal invasion include
(1) disruption of a colonized surface (skin or mucosa),
allowing the organisms access to the bloodstream, and (2)
persorption via the gastrointestinal wall, which may occur
following massive colonization with large numbers of
organisms that pass directly into the bloodstream.
Frequency
United States
Candida species are the most common cause of fungal

infection in immunocompromised persons. Oropharyngeal
colonization is found in 30%-55% of healthy young adults,
and Candida species may be detected in 40%-65% of
normal fecal flora.
Three of every 4 women experience at least one bout
of vulvovaginal candidiasis(VVC) during their lifetime.
More than 90% of persons infected with HIV who are not
receiving highly active antiretroviral therapy (HAART)
eventually develop oropharyngeal candidiasis (OPC), and
10% eventually develop at least one episode of esophageal
candidiasis.[8]
In persons with systemic infections, Candida species are
now the fourth most commonly isolated pathogens from
blood cultures.[9]
Clinical and autopsy studies have confirmed the marked
increase in the incidence of disseminated candidiasis,
reflecting a parallel increase in the frequency of
candidemia. This increase is multifactorial in origin and
reflects increased recognition of the fungus, a growing
population of patients at risk (eg, patients undergoing
complex surgical procedures, patients with indwelling
vascular devices), and the improved survival rates among
patients with underlying neoplasms orcollagen-vascular
disease and patients who are immunosuppressed.
International
Similar
rates
of
mucocutaneous
and
systemic
candidiasis/candidemia have been observed worldwide. [10,
11]
In fact, throughout the world, Candida species have
replaced Cryptococcus species as the most common fungal
pathogens affecting immunocompromised hosts.
Mortality/Morbidity
Mucocutaneous candidiasis: Most candidal infections are
mucocutaneous and, as such, do not cause mortality.
However, in patients with advanced immunodeficiency due
to HIV infection, these mucosal infections can become
refractory to antifungal therapy and may lead to severe
oropharyngeal and esophageal candidiasis that initiates a
vicious cycle of poor oral intake, malnutrition, wasting, and
early death.
Candidemia and disseminated candidiasis: Mortality rates
associated with these infections have not improved
markedly over the past few years and remain in the range
of 30%-40%. Systemic candidiasis causes more case
fatalities than any other systemic mycosis. More than a
decade ago, investigators reported the enormous economic
impact of systemic candidiasis in hospitalized patients.
Candidemia is associated with considerable prolongation in
hospital stays (70 d vs 40 d in comparable patients without
fungemia). Although mucocutaneous fungal infections, such

as oral thrush and Candidaesophagitis, are extremely
common in patients with AIDS, candidemia and
disseminated candidiasis are uncommon.
Sex
Neither sex is predisposed to candidal colonization;
however, VVC is the second most common cause
of vaginitis in women.
Age
Persons at the extremes of age (neonates and adults >65 y)
are
most
susceptible
to
candidal
colonization.
Mucocutaneous candidiasis is also more prevalent in
neonates and older adults. Very-low-birth-weight and
extremely-low-birth-weight infants are at high risk for
blood cultureproven late-onset candidiasis (defined as
sepsis that develops after age 72 h).[12]
History
Candidiasis can cause a wide spectrum of clinical
syndromes, as described below. The clinical presentation
can vary depending on the type of infection and the degree
of immunosuppression.
Cutaneous candidiasis syndromes
Generalized cutaneous candidiasis: This is an unusual form
of cutaneous candidiasis that manifests as a diffuse
eruption over the trunk, thorax, and extremities. The
patient has a history of generalized pruritus, with
increased severity in the genitocrural folds, anal region,
axillae, hands, and feet. Physical examination reveals a
widespread rash that begins as individual vesicles that
spread into large confluent areas.
Intertrigo: The patient has a history of intertrigo
affecting any site in which skin surfaces are in close
proximity, providing a warm and moist environment. A
pruritic red rash develops. Physical examination reveals a
rash that begins with vesiculopustules that enlarge and
rupture, causing maceration and fissuring. The area
involved has a scalloped border with a white rim consisting
of necrotic epidermis that surrounds the erythematous
macerated base. Satellite lesions are commonly found and
may coalesce and extend into larger lesions (see image
below).
Erythema, maceration,
and satellite pustules in the axilla, accompanied by soreness
and pruritus, result in a form of intertrigo. Courtesy of
Matthew C. Lambiase, DO.
Metastatic skin lesions: Characteristic skin lesions occur in
approximately 10% of patients with disseminated
candidiasis and candidemia. The lesions may be numerous or
few and are generally described as erythematous, firm,
nontender macronodular lesions with discrete borders.
Biopsy specimens of these lesions demonstrate yeast cells,

hyphae, or pseudohyphae, and cultures are positive
forCandida species in approximately 50% of cases.
Candidafolliculitis: The infection is found predominantly in
the hair follicles and, rarely, can become extensive.
Paronychia and onychomycosis:
Paronychia
and
onychomycosis are frequently associated with immersion of
the hands in water and with diabetes mellitus. The patient
has a history of a painful and erythematous area around
and underneath the nail and nail bed. Physical examination
reveals an area of inflammation that becomes warm,
glistening, tense, and erythematous and may extend
extensively under the nail. It is associated with secondary
nail thickening, ridging, discoloration, and occasional nail
loss.
Chronic mucocutaneous candidiasis
Chronic mucocutaneous candidiasis describes a group

of Candida infections of the skin, hair, nails, and mucous
membranes that tends to have a protracted and persistent
course.
History: Most infections begin in infancy or during

the first 2 decades of life; onset in people older than 30
years is rare.
o
Most patients survive for prolonged
periods and rarely experience disseminated fungal
infections. The most common cause of death is bacterial
sepsis.
o
Chronic mucocutaneous candidiasis is
frequently associated with endocrinopathies, such as
the following:
Hypoparathyroidism
Addison disease
Hypothyroidism
Diabetes mellitus
Autoimmune
antibodies
to
adrenal, thyroid, and gastric tissues (approximately
50%)
Thymomas
Dental dysplasia
Polyglandular autoimmune disease
Antibodies to melanin-producing
cells
Physical examination: Findings reveal disfiguring

lesions of the face, scalp, hands, and nails. This is
occasionally associated with oral thrush (see image below)
and vitiligo.
White
plaques are present on the buccal mucosa and the
undersurface of the tongue and represent thrush. When
wiped off, the plaques leave red erosive areas. Courtesy
of Matthew C. Lambiase, DO.
Gastrointestinal tract candidiasis
The patient usually has a history of HIV

infection, wears dentures, has diabetes mellitus, or has
been exposed to broad-spectrum antibiotics or inhaled
steroids. Patients are frequently asymptomatic. However,
some of the symptoms may include the following:
Sore and painful mouth
Burning mouth or tongue
Dysphagia
Whitish thick patches on the oral
mucosa
Physical examination reveals a diffuse
erythema and white patches that appear on the surfaces
of the buccal mucosa, throat, tongue, and gums. The
following are the 5 types of oropharyngeal candidiasis
(OPC):
Membranous candidiasis: This is
one of the most common types and is characterized by
creamy-white curdlike patches on the mucosal surfaces.
Erythematous candidiasis: This is
associated with an erythematous patch on the hard and
soft palates.
Chronic
atrophic
candidiasis
(denture stomatitis): This type is also thought to be one
of the most common forms of the disease. The
presenting signs and symptoms include chronic
erythema and edema of the portion of the palate that
comes into contact with dentures.
Angular cheilitis: An inflammatory
reaction, this type is characterized by soreness,
erythema, and fissuring at the corners of the mouth
(see image below).

Soreness and cracks at the lateral angles of the mouth
(angular cheilitis) are a frequent expression of
candidiasis in elderly individuals. Courtesy of Matthew
C. Lambiase, DO.
Mixed: A combination of any of
the above types is possible.
Esophageal candidiasis
The patient's history usually includes
chemotherapy, the use of broad-spectrum antibiotics or
inhaled steroids, the presence of HIV infection or
hematologic or solid-organ malignancy. Patients may be
asymptomatic or may have one or more of the following
symptoms:
Normal oral mucosa (>50% of
patients)
Dysphagia
Odynophagia
Retrosternal pain
Epigastric pain
Nausea and vomiting
Physical examination almost always reveals

oral candidiasis.
Nonesophageal gastrointestinal candidiasis
The patient usually has a history of

neoplastic disease of the gastrointestinal tract. The
esophagus is the most commonly infected site, followed
by the stomach. Less commonly, patients have chronic
gastric ulcerations, gastric perforations, or malignant
gastric ulcers with concomitant candidal infection. The
small bowel is the third most common site of infection
(20%). The frequency of candidal infection in the small
bowel is the same as in the large bowel. Approximately
15% of patients develop systemic candidiasis.
Physical
examination
findings
vary
depending on the site of infection. The diagnosis,
however, cannot be made solely on culture results
because approximately 20%-25% of the population is
colonized by Candida. The following symptoms may be
present:
Epigastric pain
Nausea and vomiting
Abdominal pain
Fever and chills
Abdominal mass (in some cases)

Respiratory tract candidiasis
of VVC without precipitating risk factors. Physical

examination findings include a vagina and labia that are
usually erythematous, a thick curdlike discharge, and a
normal cervix upon speculum examination.[3]
Candida balanitis: Patients report penile pruritus along with
whitish patches on the penis. Candida balanitis is acquired
through direct sexual contact with a partner who has VVC.
Physical examination initially reveals vesicles on the penis
that later develop into patches of whitish exudate. The
rash occasionally spreads to the thighs, gluteal folds,
buttocks, and scrotum (see image below).
The
respiratory
tract
is
frequently
colonized
with Candida species, especially in hospitalized patients.
Approximately 20%-25% of ambulatory patients are
colonized with Candida species.
Laryngeal candidiasis: This is an uncommon form of invasive
candidiasis that sometimes results in disseminated
infection. It is primarily seen in patients with underlying
hematologic or oncologic malignancies. The patient may
present with a sore throat and hoarseness. The physical
examination findings are generally unremarkable, and the
diagnosis is frequently made with direct or indirect
laryngoscopy.
Candida tracheobronchitis: This is also an uncommon form
of
invasive
candidiasis.
Most
patients
with Candida tracheobronchitis are HIV-positive or are
severely
immunocompromised.
Most
patients
with Candida tracheobronchitis report fever, productive
cough, and shortness of breath. Physical examination
reveals dyspnea and scattered rhonchi. The diagnosis is
generally made with bronchoscopy.
Candida pneumonia: This rarely develops alone and is
associated with disseminated candidiasis in rare cases. The
most common form of infection is multiple lung abscesses
due to the hematogenous dissemination of Candidaspecies.
The high degree of Candida colonization in the respiratory
tract
greatly
complicates
the
diagnosis
of Candida pneumonia. The history reveals risk factors
similar to those of disseminated candidiasis, along with
reports of shortness of breath, cough, and respiratory
distress. Physical examination reveals fever, dyspnea, and
variable breath sounds, ranging from clear to rhonchi or
scattered rales.
Vulvovaginal candidiasis (VVC): This is the second most
common cause of vaginitis. The patient's history includes
vulvar pruritus, vaginal discharge, dysuria, and dyspareunia.
Approximately 10% of women experience repeated attacks
Dry, red, superficially scaly,

pruritic macules and patches on the penis represent
candidal balanitis. Courtesy of Matthew C. Lambiase, DO.
Candida cystitis: Many patients are asymptomatic.
However, bladder invasion may result in frequency, urgency,
dysuria, hematuria, and suprapubic pain. Candidacystitis
may or may not be associated with the use of a Foley
catheter. Physical examination may reveal suprapubic pain;
other findings are unremarkable.
Asymptomatic candiduria: Most catheterized patients with
persistent candiduria are asymptomatic, similar to
noncatheterized patients. Most patients with candiduria
have
easily
identifiable
risk
factors
for Candida colonization. Thus, invasive disease is difficult
to differentiate from colonization based solely on culture
results because approximately 5%-10% of all urine cultures
are positive for Candida.[13]
Ascending pyelonephritis: The use of stents and indwelling
devices, along with the presence of diabetes, is the major
predisposing risk factor in ascending infection. Most
patient report flank pain, abdominal cramps, nausea,
vomiting, fever, chills and hematuria. Physical examination
reveals abdominal pain, costovertebral-angle tenderness,
and fever.
Fungal balls: This is due to the accumulation of fungal
material in the renal pelvis. The condition may produce
intermittent urinary tract obstruction with subsequent
anuria and ensuing renal insufficiency.
Hepatosplenic candidiasis (chronic systemic candidiasis)
Hepatosplenic candidiasis is a form of systemic candidiasis

in patients with an underlying hematologic malignancy and
neutropenia and develops during the recovery phase of a
neutropenic episode. The patient's history includes the
following:
Fever
unresponsive
to
broad-spectrum
antimicrobials
Right upper quadrant pain
Abdominal pain and distension
Jaundice (rare)
Physical examination findings include right upper quadrant

tenderness and hepatosplenomegaly (< 40%).
Systemic candidiasis
Systemic candidiasis can be divided into 2 primary
syndromes: candidemia and disseminated candidiasis (organ
infection by Candida species). Deep organ infections due
to Candida species are generally observed as part of the
disseminated candidiasis syndromes and may involve one or
more organs.
Candidemia
o
Candida species are currently the fourth
most commonly isolated organism in blood cultures,
and Candida infection is generally considered a
nosocomial infection.[14, 15] The patient's history
commonly reveals the following:
Several days of fever that is

unresponsive to broad-spectrum antimicrobials;
frequently the only marker of infection
Prolonged
intravenous
catheterization
A history of several key risk

factors (see Pathophysiology)
Possibly
associated
with
multiorgan infection
o
Physical examination results may include
the following:
Fever
Macronodular
skin
lesions
(approximately 10%)
Candidal
endophthalmitis
(approximately 10%-28%)
Occasionally,
septic
shock
(hypotension, tachycardia, tachypnea)
o
Other causes of candidemia without
invasive disease include the following:
Intravascular
catheter-related
candidiasis: This entity usually responds promptly to
catheter removal and antifungal treatment.
Suppurative
thrombophlebitis:
This is associated with prolonged central venous
catheterization.
Suppurative
thrombophlebitis
manifests as fever and persistent candidemia despite
appropriate antifungal therapy and catheter removal.
Sepsis and septic shock may develop.
Endocarditis: The frequency of

endocarditis
has
recently
increased.
[16]
Candida species,
primarily C
albicans andCandidaparapsilosis (>60% of cases), are
the most common cause of fungal endocarditis. The
aortic and mitral valves are most commonly involved.
The endocarditis may be exogenous (due to direct
inoculation during surgery) or endogenous (due to
hematogenous dissemination during bloodstream
invasion.Candida endocarditis is associated with 4
main risk factors, including intravenous heroin use
(frequently associated with C parapsilosis infection),
chemotherapy, prosthetic valves (approximately 50%),
and prolonged use of central venous catheters. The
physical examination reveals a broad range of
manifestations,
including
feverunresponsive
to
antimicrobials, hypotension, shock, new or changing
murmurs, and large septic emboli to major organs, a

characteristic of fungal endocarditis.
Disseminated candidiasis: This is frequently
associated with multiple deep organ infections or may
involve single organ infection. Unfortunately, blood
cultures are negative in up to 40%-60% of patients with
disseminated candidiasis. The history of a patient with
presumptive disseminated candidiasis reveals a fever
unresponsive to broad-spectrum antimicrobials and
negative results from blood culture. Physical examination
reveals fever (may be the only symptom) with an unknown
source and associated sepsis and septic shock.
Candida endophthalmitis: The two primary forms
of Candida endophthalmitis are the exogenous form and
the endogenous form. Exogenous endophthalmitis is
associated with either accidental or iatrogenic
(postoperative) injury of the eye and inoculation of the
organism
from
the
environment.
Endogenous
endophthalmitis results from hematogenous seeding of
the eye. It has been found in 10%-28% of patients with
documented candidemia. Recently, newer studies have
shown a decreasing incidence of Candida endophthalmitis,
possibly due to an increased awareness of this
complication and the initiation of early or empirical
antifungal therapy. [17] It is important to note that
hematogenous candidal endophthalmitis is a marker of
disseminated candidiasis.
o
The patient's history reveals a broad
range of manifestations, including the following.
Eye injury
Ophthalmic surgery
Underlying risk factors for

candidemia
Asymptomatic and detected upon

physical examination
Ocular pain
Photophobia
Scotomas
Floaters
o
Physical examination reveals fever.
o
Funduscopic examination reveals early
pinhead-sized off-white lesions in the posterior
vitreous with distinct margins and minimal vitreous
haze. Classic lesions are large and off-white, similar to
a cotton-ball, with indistinct borders covered by an
underlying haze. Lesions are 3-dimensional and extend
into the vitreous off the chorioretinal surface. They
may be single or multiple.
Renal candidiasis
o
This is frequently a consequence of
candidemia or disseminated candidiasis. The patients
history includes fever that is unresponsive to broadspectrum antimicrobials. Frequently, patients are
asymptomatic and lack symptoms referable to the
kidney.
o
Physical examination findings are generally
unremarkable, and the diagnosis is made with a
urinalysis and with a renal biopsy. Otherwise, this
condition is commonly diagnosed at autopsy.
CNS infections due to Candida species
o
CNS infections due to Candida species are
rare and difficult to diagnose. The two primary forms
of infection include the exogenous infection and the

endogenous infection. The exogenous infection results
from postoperative infection, trauma, lumbar puncture,
or shunt placement. The endogenous infection results
from hematogenous dissemination and thus involves the
brain parenchyma and is associated with multiple small
abscesses (eg, disseminated candidiasis).
o
As with other organ infections due
to Candida species, patients usually have underlying risk
factors for disseminated candidiasis. CNS infections
due to Candida species are frequently found in patients
hospitalized for long periods in ICUs. The spectrum of
this disease includes the following:
Meningitis
Granulomatous vasculitis
Diffuse
cerebritis
with
microabscesses
Mycotic aneurysms
Fever unresponsive to broadspectrum antimicrobials
Mental status changes

o
Physical examination reveals the following:
Fever
Nuchal rigidity
Confusion
Coma
Candida arthritis, osteomyelitis, costochondritis,

and myositis
o
Candidal musculoskeletal infections were
once uncommon; recently, they have become much more
common, possibly due to the increased frequency of
candidemia and disseminated candidiasis. The most
common sites of involvement continue to be the knee
and the vertebral column. The pattern of involvement is
similar to the pattern observed in bacterial infections.
The infection may be divided into exogenous or
endogenous forms. The exogenous infection is due to
the direct inoculation of the organisms, such as
postoperative infection or trauma. Affected sites
include the following:
Ribs and leg bones (patients < 20

y)
Vertebral column and paraspinal

abscess (adulthood)
Flat bones (any age group)
Sternum - Generally observed

postoperatively after cardiac surgery
o
The patient is frequently asymptomatic,
and the history reveals risk factors typical of
disseminated candidiasis, as well as pain localized over
the affected site. The physical examination findings are
frequently unremarkable but may reveal tenderness
over the involved area, erythema, and bone deformity,
occasionally in association with a draining fistulous
tract.
Arthritis: Candida arthritis

is
generally a complication of disseminated candidiasis
but may be caused by trauma or direct inoculation due
to surgery or steroid injections. Most cases are acute
and begin as a suppurative synovitis. A high
percentage of cases progress to osteomyelitis. In
addition, Candida arthritis after joint replacement is

not uncommon.
Osteomyelitis: Candida osteomyeli

tis originates either exogenously or endogenously. The
exogenous infection is due to direct inoculation of the
organisms via routes such as postoperative infection,
trauma, or steroid injections. The endogenous form is
a complication of candidemia or disseminated
candidiasis. In most cases due to hematogenous
seeding, the vertebral disks are involved and
frequently progress to discitis with contiguous
extension into the vertebrae body. Other bones
affected include the wrist, femur, scapula, and
proximal humerus.
Costochondritis:
This is
an
uncommon form of infection and also has two modes
of infection. Candida costochondritis is usually due to
hematogenous infection spread or direct inoculation
during surgery (median sternotomy). Costochondritis
is frequently associated with pain localized over the
involved area.
Myositis: Candida myositis

is
uncommon but is frequently associated with
disseminated
candidiasis.
Most
patients
are
neutropenic and report muscular pain.
Myocarditis-pericarditis: This infection is usually

due to direct hematogenous spread in association with
candidemia and is rarely due to the direct extension from
the sternum or the esophagus. Myocarditis-pericarditis
occurs as diffuse abscesses scattered throughout the
myocardium surrounded by normal cardiac tissue. In
patients with disseminated candidiasis, the rate
of Candidamyocarditis-pericarditis has been documented
as high as 50%. The patient history reveals serious
complications in 10-20% of cases without valvular disease.
Physical examination reveals fever, hypotension, shock,
tachycardia, and new murmurs or rubs (or recent changes
in previously detected murmurs).
Candida peritonitis [18]

o
The patient history frequently reveals an
association with gastrointestinal tract surgery, viscous
perforation, or peritoneal dialysis.Candida peritonitis
tends to remain localized, disseminating into the
bloodstream in only 15% of cases. The range of
manifestations is broad and includes fever and chills,
abdominal pain and cramping, nausea, vomiting, and
constipation. The isolation of Candida species from the
peritoneal fluid in surgical patients needs to be
carefully evaluated.
o
Physical examination may reveal the
following:
Fever
Abdominal distention
Abdominal pain
Absent bowel sounds
Rebound tenderness
Localized mass
Candida splenic abscess and hypersplenism: Both

are manifestations of disseminated candidiasis and are
usually simultaneously associated with liver involvement.
Manifestations of hypersplenism are common (see
Hepatosplenic candidiasis).
Candida cholecystitis: This is uncommon and is

generally associated with bacterial cholangitis and
ascending cholangitis. In general, Candidacholecystitis is
diagnosed at the time of surgery when a culture is
obtained.
Physical
See History for physical examination findings paired with
clinical syndromes.
Causes
Over 200 species of Candida exist in nature; thus far, only
a few species have been associated with disease in humans.
The medically significant Candida species include
the following [19] :
o
C albicans, the most common species
identified (50%-60%)
o
Candida
glabrata (previously
known
as Torulopsis glabrata) (15%-20%)
o
C parapsilosis (10%-20%)
o
Candida tropicalis (6%-12%)
o
Candida krusei (1%-3%)
o
Candida kefyr (< 5%)
o
Candida guilliermondi (< 5%)
o
Candida lusitaniae (< 5%)
o
Candida dubliniensis, primarily recovered
from patients infected with HIV
C
glabrata and C
albicans account
for
approximately 70%-80% of Candidaspecies recovered
from patients with candidemia or invasive candidiasis. C
glabrata has recently become very important because of
its increasing incidence worldwide, its association with
fluconazole resistance in up to 20% of clinical specimens,
and its overall decreased susceptibility to other azoles
and polyenes.
C krusei is important because of its intrinsic
resistance to ketoconazole and fluconazole (Diflucan); it
is also less susceptible to all other antifungals, including
itraconazole (Sporanox) and amphotericin B.
Another
important Candida species
is C
lusitaniae; although
not
as
common
as
other Candida species, C
lusitaniae is
of
clinical
significance because it may be intrinsically resistant to
amphotericin B, although it remains susceptible to azoles
and echinocandins.
C parapsilosis is also an important species to
consider in hospitalized patients. It is especially common
in infections associated with vascular catheters
prosthetic devices. Additionally, in vitro analyses have
shown that echinocandins have a higher minimum
inhibitory concentration (MIC) againstC parapsilosis than
other Candida species. The clinical relevance of this in
vitro finding has yet to be determined. [20]
C tropicalis has frequently been considered an
important cause of candidemia in patients with cancer
(leukemia) and in those who have undergone bone marrow
transplantation.
Diagnostic Considerations
Cutaneous candidiasis - Dermatitis (contact,
allergic), folliculitis
Gastrointestinal tract candidiasis - Esophagitis due
to herpes simplex virus, herpes zoster, induced by
radiation, gastroesophageal reflux disease
Respiratory candidiasis - Bacterial pneumonia, viral

pneumonia, tracheitis, Aspergillus pneumonia
Genitourinary tract candidiasis - Bacterial cystitis
or pyelonephritis
Candidemia
Bacterial
sepsis,
bacterial
endocarditis
Disseminated candidiasis - Bacterial meningitis,
bacterial sepsis, bacterial endocarditis, tuberculosis
Chronic mucocutaneous candidiasis - HIVseropositive state, chronic granulomatous disease
Hepatosplenic candidiasis - Hepatic abscess,
cholelithiasis, cholecystitis, acalculous
cholecystitis,
ascending cholangitis, graft versus host disease,
granulomatous hepatitis, relapsed malignancy
Differential Diagnoses
Abdominal Abscess
Aspergillosis
Cryptococcosis
Sepsis, Bacterial
Septic Shock
Laboratory Studies
Unfortunately, results from the routine laboratory studies
are often nonspecific and not very helpful. Clinicians are
required to act definitively and early based on a high index
of suspicion. In the past, many patients with lifethreatening candidiasis died without receiving antifungal
therapy. Systemic candidiasis should be suspected in
patients with persistent leukocytosis and either persistent
neutropenia or other risk factors and who remain febrile
despite broad-spectrum antibiotic therapy. To be
effective, antifungal therapy should be provided early and
empirically in such high-risk patients. Cultures of nonsterile
sites, although not useful for establishing a diagnosis, may
demonstrate high degrees of candidal colonization. Always
consider positive culture results from sterile sites to be
significant and evidence of infection.
Mucocutaneous candidiasis
o
For a wet mount, scrapings or smears
obtained from skin, nails, or oral or vaginal mucosa are
examined under the microscope for hyphae,
pseudohyphae, or budding yeast cells.
o
A potassium hydroxide smear, Gram stain,
or methylene blue is useful for direct demonstration of
fungal cells.
o
Cultures from affected nails may help
identify
the
etiologic
agent
responsible
for
onychomycosis versus other noninfectious causes.
Candidemia and disseminated candidiasis[21]
o
Blood cultures are helpful but yield
positive results in only 50%-60% of cases of
disseminated infection.
o
Urinalysis may be helpful and may show
either colonization or renal candidiasis.
o
The serum (1,3)-D-glucan detection assay
(Glucatell, Fungitell) is a nonculture assay that was
approved for use in the United States in May 2004.
This assay measures the level of -glucan (a fungal cell
wall component). In a large multicenter study, the assay
yielded a high specificity and positive predictive value
with highly reproducible results.[22]
o
Cultures of nonsterile sites, although not
useful for establishing a diagnosis, may be useful for
o
o
o
initiating antifungal therapy in patients with fever that

is unresponsive to broad-spectrum antimicrobials.
Therefore, appropriate interpretation is required.
Positive results from blood cultures and cultures from
other sterile sites always imply the presence of invasive
disease. Positive results from sterile sites should always
be taken as significant and should always prompt
treatment.
Gastrointestinal, respiratory, and urinary
tract cultures that are positive for Candida may not
always represent invasive disease. However, these
should be considered sites of colonization.
Cutaneous candidiasis: Using a wet mount,
scrapings or smears obtained from skin or nails can be
examined under microscopy for hyphae, pseudohyphae, or
budding yeast cells. Potassium hydroxide smears are also
useful.
Genitourinary candidiasis: A urinalysis should be
performed. Evidence of WBCs, RBCs, protein, and yeast
cells is common. Additionally, urine fungal cultures are
useful.
Respiratory tract candidiasis
Sputum Gram stain may demonstrate
WBCs and yeast cells.
Sputum
cultures
may
demonstrate Candida species.
Lung biopsy is mandatory to definitively
establish the diagnosis of respiratory tract candidiasis
because of the high frequency of yeast colonization of
the respiratory tract.
Gastrointestinal candidiasis: Endoscopy with or
without biopsy is necessary to establish the diagnosis.
Focal hepatosplenic candidiasis: Serum alkaline
phosphatase levels are commonly elevated.
Species identification
C albicans, C dubliniensis, and Candida
stellatoidea can be identified morphologically via germtube formation (hyphae are produced from yeast cells
after 2-3 h of incubation) or biochemical assays.
CHROMagar Candida allows
for
the
presumptive identification of several Candida species by
using color reactions in specialized media that
demonstrate different colony colors depending on the
species ofCandida.
API20C and API32C are biochemical
assays that allow for the identification of the
different Candida species with more precision. These
assays evaluate the assimilation of numerous carbon
substrates and generate profiles used in the
identification of different fungal species.
The C albicans peptide nucleic acid (PNA)
fluorescence in situ hybridization (FISH) test can be
used to identify C albicans in 24-48 hours when the
probe is added to smears that are made directly from
the blood culture bottle and followed by hybridization.
A newer version of this test now allows for the
simultaneous identification of either C albicans or C
glabrata.[23]
Antifungal susceptibility testing
In
vitro
susceptibility
testing
for Candida species is now standardized using the
Clinical Laboratory Standards Institute (CLSI)
microbroth dilution (CLSI M27-A2, 2002) or the disk

diffusion (CLSI M44-P, 2003) methodology. This was
formerly known as the National Committee for Clinical
Laboratory Standards (NCCLS) microbroth dilution.
o
These methods may be helpful in guiding
difficult therapeutic decisions. Most of the difficult
decisions
involve
antifungal-refractory
oral
or
esophageal candidiasis in patients with advanced HIV
disease.
Nonculture Candida detection assays

o
The Candida mannan
assay
yields
a
sensitivity of 31%-90% (less for non- albicans
Candida species).
o
The Candida heat labile antigen assay
yields a sensitivity of 10%-71%.
o
The D-arabinitol assay yields a sensitivity
of 50% but is not useful for infection with C krusei or C
glabrata.
o
The enolase assay yields a sensitivity of
55%-75%, which improves with serial testing.
o
The (1,3)-D-glucan assay is an amebocyte
lysis assay with a sensitivity of 75-100% and a
specificity of 88%-100%. It is a broad-spectrum assay
that
detects Aspergillus,
Candida,
Fusarium,
Acremonium, andSaccharomyces species. -D-glucan is a
cell wall component in a wide variety of fungi and can be
detected based on its ability to activate factor G of
the horseshoe crab coagulation cascade. The Fungitell
assay may be used in the evaluation of invasive fungal
infections caused by the fungi mentioned above. The
assay
does
not
detect
infections
caused
by Cryptococcus neoformans or Zygomycetes.
o
Molecular assays such as the polymerase
chain reaction (PCR) assay and DNA probes are still
under development and in the early investigational
phases, but they appear promising.
A new, rapid test for Candida infections of the
bloodstream may cut patient mortality from 40% to 11% by
diagnosing candidemia 25 times faster than blood culture
can and quickly identifying the Candida species that is
causing the infection. The new test, T2Candida, uses
polymerase
chain
reaction
(PCR)
assay
to
amplifyCandida DNA in blood, with the genetic material
hybridizing to superparamagnetic nanoparticles coated with
complementary DNA. The nanoparticles aggregate into
"microclusters," which greatly alter a T2 magnetic
resonance (T2MR) signal.[24, 25]
Imaging Studies
Imaging studies are not required or useful in the diagnosis
of cutaneous candidiasis, oropharyngeal candidiasis (OPC),
or vulvovaginal candidiasis (VVC).
Chest radiography may be useful in differentiating a
bacterial pneumonia as the cause of fever in patients who
are hospitalized. Patients with bronchopneumonia due to
hematogenous
candidiasis
usually
have
multilobar
involvement.
Esophagography/upper gastrointestinal studies may be
useful for detecting abnormalities in the esophagus and
stomach. Unfortunately, these studies are not helpful in
determining the microbiologic etiology of the infection.
Ultrasonography may be useful for diagnosing hepatosplenic

abscess. The classic bull's eye or target lesions are
observed in the liver and spleen.
Echogenic foci with degrees of shadowing
Intra-abdominal abscess formation
Cholelithiasis
Renal abscess
Renal fungus balls
CT scanning with contrast enhancement may be useful for
diagnosing the following:
Hepatosplenic candidiasis
Intra-abdominal abscess or peritonitis
Renal abscess
Pyelonephritis
Echocardiography may be useful for excluding or
including Candida endocarditis as a possible diagnosis. It is
extremely useful because fungal endocarditis is frequently
associated with large vegetations that are easily observed
on standard echocardiograms.
Procedures
In patients with candidemia or disseminated candidiasis,
obtaining a tissue biopsy of the involved areas is frequently
helpful in establishing the presence of Candidainfection and
invasion.
Bronchoscopy
with
bronchoalveolar
lavage
and
transbronchial biopsy provide adequate tissue for diagnosis
of pulmonary candidiasis.
Endoscopy provides direct examination of the esophagus
and stomach, one of the organ systems most commonly
infected with Candida species. It is also necessary for
excluding other causes of esophagitis.
Echocardiography may be useful for excluding or
including Candida species as a cause of endocarditis. It is
extremely useful because fungal endocarditis is frequently
associated with large vegetations that are easily observed
using standard echocardiography.
Histologic Findings
Fixed tissues can be stained with hematoxylin and eosin. In
addition, fungal hyphae may be demonstrated with Grocott
silver-methenamine, methylene blue, or periodic acidSchiff staining. The classic appearance demonstrates
the Candida species as either round or ovoid yeast cells,
hyphae, or pseudohyphae.
Medical Care
The treatments used to manage Candida infections vary
substantially and are based on the anatomic location of the
infection, the patients' underlying disease and immune
status, the patients' risk factors for infection, the specific
species ofCandida responsible for infection, and, in some
cases, the susceptibility of the Candida species to specific
antifungal drugs.
There have been significant changes in the management of
candidiasis in the last few years, particularly related to the
appropriate use of echinocandins and expanded-spectrum
azoles for candidemia, other forms of invasive candidiasis,
and mucosal candidiasis. Updated guidelines were published
in March 2009 by the Infectious Disease Society of
America (IDSA),[26] replacing a previous version from 2004.
[27]
These latest recommendations include the echinocandins
caspofungin, micafungin, and anidulafungin, along with
voriconazole and posaconazole, as well as lipid formulations
of amphotericin B in various situations.
Fluconazole is still considered a first-line agent in

nonneutropenic patients with candidemia or suspected
invasive candidiasis. However, a post-hoc analysis of clinical
trial data comparing anidulafungin with fluconazole for
treatment of invasive candidiasis found that anidulafungin
was more effective in treating severely ill patients. [28] A
revision of data outcomes on treatment of invasive
candidiasis in clinical trials appears to favor use of
echinocandins in terms of increased rate of survival. This
type of finding may have an impact on future treatment
recommendations and strategies of drug use for invasive
candidiasis in different groups of patients.[29, 30]
In August 2013, the FDA announced that clinicians should
no longer prescribe ketoconazole (Nizoral, Janssen
Pharmaceuticals) tablets as a first-line therapy for any
fungal infection, including Candida and dermatophyte
infections, because of the risk for severe liver injury,
adrenal insufficiency, and adverse drug interactions.[31,
32]
The FDA also cautioned that ketoconazole tablets should
not be prescribed for any patient with underlying liver
disease. The labeling changes do not apply to topical
formulations of ketoconazole in creams, shampoos, foams,
and gels. Oral ketoconazole is now indicated only for
endemic mycoses in patients who fail to respond to or
cannot tolerate other treatments.
Ketoconazole tablets were also withdrawn from the market
in the European Union in July 2013.[31, 32]
The therapeutic options available for the management of
invasive candidiasis and candidemia have continued to
increase with the addition of newer echinocandins[33, 34] and
triazoles.
Cutaneous candidiasis: Most localized cutaneous

candidiasis infections may be treated with any number of
topical antifungal agents (eg, clotrimazole, econazole,
ciclopirox, miconazole, ketoconazole, nystatin). If the
infection is a paronychia, the most important aspect of
therapy is drainage of the abscess, followed by oral
antifungal
therapy
with
either
fluconazole
or
itraconazole. In cases of extensive cutaneous infections,
infections in immunocompromised patients, folliculitis, or
onychomycosis,
systemic
antifungal
therapy
is
recommended.
For Candida onychomycosis,
oral
itraconazole (Sporanox) appears to be most efficacious.
Two treatment regimens are available: the daily dose of
itraconazole taken for 3-6 months or the pulsed-dose
regimen that requires a slightly higher daily dose for 7
days, followed by 3 weeks of no drug administration. The
cycle is repeated every month for 3-6 months.
Gastrointestinal candidiasis
o
Oropharyngeal candidiasis OPC

can be treated with either topical antifungal agents
(eg, nystatin, clotrimazole, amphotericin B oral
suspension) or systemic oral azoles (fluconazole,
itraconazole, or posaconazole).
Infections
in
HIV-positive
patients tend to respond more slowly and, in
approximately 60% of patients, recur within 6 months
of the initial episode. Approximately 3%-5% of
patients with advanced HIV infection (CD4 cell counts
< 50/L) may develop refractory OPC. In these
situations, in addition to attempting correction of the
immune dysfunction with HAART, higher doses of

fluconazole (up to 800 mg/d) or itraconazole (up to
600 mg/d) can be attempted. Posaconazole suspension
at 400 mg orally twice per day has also yielded
excellent results in such patients. Additionally,
caspofungin 50 mg/d IV and anidulafungin 100 mg/d
IV have also yielded excellent efficacy in such
patents. Amphotericin B is rarely necessary to treat
such cases, but, when used, low doses of amphotericin
B can be used (0.3-0.7 mg/kg) and have been shown to
be effective.
Candida esophagitis requires systemic
therapy with fluconazole for 14-21 days. Parenteral
therapy with fluconazole may be required initially if the
patient is unable to take oral medications. Daily
suppressive antifungal therapy with fluconazole 100200 mg/d is effective for preventing recurrent
episodes, but it should be used only if the recurrences
become frequent or are associated with malnutrition
due to poor oral intake and wasting syndrome.
Recommended alternatives for fluconazole-refractory
disease include itraconazole, voriconazole, caspofungin,
micafungin, anidulafungin, and amphotericin B.
Vulvovaginal candidiasis (VVC) can be
managed with either topical antifungal agents or a
single dose of oral fluconazole. [4] A single dose of oral
fluconazole (150 mg) in acute episodes of VVC has been
shown to yield clinical and microbiological efficacy as
good as or better than topical antifungal agents. A small
percentage (< 5%) of women experience chronic
recurrent VVC infections, which often require longterm or prophylactic oral azole therapy for control. In
such patients, the recommended regimen includes
fluconazole 150 mg every other day for 3 doses,
followed by weekly fluconazole 150-200 mg for 6
months.[3]This regimen prevents further recurrence in
more than 80% of women.
For asymptomatic candiduria, therapy
generally depends on the presence or absence of an
indwelling Foley catheter. Candiduria frequently
resolves by simply changing the Foley catheter (20%25% of patients). Thus, most experts agree that
asymptomatic candiduria associated with a Foley
catheter does not require treatment in most cases.
However, eradicating candiduria prior to any form of
instrumentation or urological manipulation is prudent.
Candida cystitis
in
noncatheterized
patients should be treated with fluconazole at 200
mg/d orally for at least 10-14 days.
For Candida cystitis
in
catheterized
patients, the first step is always to remove the nidus of
infection. Thus, the Foley catheter should be removed
or replaced prior to initiating antifungal therapy. If the
candiduria persists after the catheter change, then
patients can be treated with 200 mg/d of fluconazole
orally for 14 days. Alternative therapy includes
amphotericin B bladder irrigation. However, its use for
the treatment of funguria is significantly limited,
primarily because of the required maintenance of a
urinary catheter; lack of adequate studies to define the
dose, duration, and method of administration;
restriction of its use to uncomplicated lower urinary

tract infections; and the availability of more convenient
treatment options (eg, oral fluconazole therapy). The
use of amphotericin B bladder irrigation is rarely
needed. Administering intravenous amphotericin B to
treat candiduria is rarely necessary.
Renal candidiasis: Regardless of whether the

infection involves hematogenous dissemination to the
kidney or ascending infection (pyelonephritis), systemic
antifungal therapy is required. The most recent
comparative studies indicate that fluconazole at 400
mg/d intravenously or orally for a minimum of 2 weeks is
as effective as amphotericin B without the toxicities
normally
associated
with
amphotericin
B.
For
amphotericin B, the daily dose is 0.5-0.7 mg/kg
intravenously for a total dose of 1-2 g administered over
a 4- to 6-week period.
Candidemia: This requires treatment in all patient

populations. Current recommendations depend on the
presence or absence of neutropenia. [26]
o
In
patients
without
neutropenia,
fluconazole is the drug of choice in most cases of
candidemia and disseminated candidiasis. Studies
conducted by the MSG have demonstrated that
fluconazole at a dose of 400 mg/d is as efficacious as
amphotericin B. In addition, fluconazole has several
advantages, including lower nephrotoxicity rates (< 2%)
and ease of use because of the high degree of
bioavailability and the long half-life of the drug.
[35]
Thus, once the gastrointestinal tract is functional,
the parenteral antifungal may be switched to the oral
formulation with the same efficacy. Alternative options
listed below need to be considered depending on history
of previous exposure to antifungals, the probability of
fluconazole resistance according to the species
of Candida recovered, the presence of comorbid
conditions, and the clinical status of the patient.[36]
o
An echinocandin is recommended for
candidemia in most patients with neutropenia.
Fluconazole is an alternative in patients who are less
critically ill and who have no recent azole exposure.
Voriconazole can be used when additional mold coverage
is desired.
o
The standard recommended dose for
fluconazole is 800 mg as the loading dose, followed by
fluconazole at a dose of 400 mg/d for at least 2 weeks
of therapy after a demonstrated negative blood culture
result or clinical signs of improvement. This treatment
regimen can be used for infections due to C albicans, C
tropicalis, C parapsilosis, C kefyr, C dubliniensis, C
lusitaniae, and C guilliermondi.
o
A critical component in the management of
candidemia and disseminated candidiasis is the removal
of the focus of infection, such as intravenous and Foley
catheters.
o
Available echinocandins for candidemia
include the following:
Caspofungin (Cancidas) can be

initiated as a 70-mg loading dose, followed by 50 mg/d
intravenously to complete a minimum of 2 weeks of
antifungals after improvement and after blood
cultures have cleared. Caspofungin is a broad-
spectrum semisynthetic echinocandin. It is an

effective alternative for severe mucosal infections
and systemic infections due to Candida, especially
those due to non-albicans Candida species such as C
glabrata.
Anidulafungin can be initiated as

a 200-mg loading dose, followed by 100 mg
cultures have cleared. Anidulafungin is a broadspectrum echinocandin. It is an effective alternative
for severe mucosal infections and systemic infections
due to Candida, especially those due to non-albicans
Candida species such as C glabrata.[37]
Micafungin can be administered

at 100 mg/d intravenously to complete a minimum of 2
weeks of antifungals after improvement and after
blood cultures have cleared. Micafungin is a broadspectrum echinocandin. It has been shown to be an
those due to non-albicans Candidaspecies such as C
glabrata.[38]
o
Additional options for candidemia include
the following:
Voriconazole can be initiated at 6

mg/kg intravenously or orally twice per day, followed
by 3 mg/kg orally twice per day or 200 mg orally twice
per day. Based on the findings from a global
multicenter clinical trial, voriconazole has also been
approved for use in candidemia in patients who are not
neutropenic.[39]
Amphotericin B deoxycholate can

be administered at 0.7 mg/kg/d intravenously for a
total dose of 1-2 g over a 4- to 6-week period.
Liposomal
preparations
of
amphotericin B have comparable efficacy to
conventional amphotericin B, but renal toxicity is
considerably less common with the former.
Chronic mucocutaneous candidiasis: This condition
is generally treated with oral azoles, such as fluconazole
at a dose of 100-400 mg/d or itraconazole at a dose of
200-600 mg/d until the patient improves. The initial
therapy for acute infection is always followed by
maintenance therapy with the same azole for life.
Hepatosplenic candidiasis: Induction therapy is
initially started with amphotericin B deoxycholate for at
least 2 weeks, followed by consolidation therapy with
fluconazole at a dose of 400 mg/d for an additional 4-12
weeks depending on the response.
Respiratory tract candidiasis: If the diagnosis is
established based on biopsy findings, then the infection
is treated as disseminated candidiasis.
Empirical treatment options for suspected invasive
candidiasis include the following:
o
Empirical antifungal therapy should be
considered for critically ill patients with risk factors
for invasive candidiasis and no other cause of fever, and
it should be based on clinical assessment of risk
factors, serologic markers for invasive candidiasis,
and/or culture data from nonsterile sites. (Its benefits
have not been clearly determined.) [40]
This continues to be a problematic

decision since criteria for starting empirical antifungal
therapy remain poorly defined. Empirical therapy in
persistently febrile and neutropenic patients should
cover infections caused by yeasts and molds.
o
The choice of drugs in nonneutropenic
patients is similar to that for proven candidiasis.
Recommended agents include fluconazole or an
echinocandin.
o
In
neutropenic
patients,
a
lipid
formulation of amphotericin B, caspofungin, or
voriconazole is recommended. Azoles should not be used
for empirical therapy in individuals who have received
an azole for prophylaxis.
Disseminated candidiasis with end organ infection:

Disseminated candidiasis with end organ involvement
requires an individualized approach. Thus, the
manifestation of invasive candidiasis involving localized
structures, such as inCandida osteomyelitis, arthritis,
endocarditis, pericarditis, and meningitis, requires
prolonged antifungal therapy for at least 4-6 weeks. The
optimum dosage and duration of therapy for various types
of deep candidal infection have not been definitively
determined.
o
The standard recommended dose for
most Candida infections is fluconazole at 800 mg as the
loading dose, followed by fluconazole at a dose of 400
mg/d either intravenously or orally for at least 2 weeks
of therapy after a demonstrated negative blood culture
result or clinical signs of improvement.
o
The echinocandins have become first-line
therapy for this type of infection in many situations
because of their efficacy and low incidence of adverse
events and drug interactions.
Caspofungin (Cancidas)[41] can be

initiated as a 70-mg loading dose, followed by 50 mg/d
cultures have cleared. Caspofungin is a broadspectrum semisynthetic echinocandin. It is an
and systemic infections due toCandida, especially
those due to non-albicans Candida species such as C
glabrata.
Anidulafungin can be initiated as

a 200-mg loading dose, followed by 100 mg
cultures have cleared. Anidulafungin is a broadspectrum echinocandin. It is an effective alternative
for severe mucosal infections and systemic infections
due to Candida, especially those due to non-albicans
Candida species such as C glabrata.[37]
Micafungin can be administered

at 100 mg/d intravenously to complete a minimum of 2
weeks of antifungals after improvement and after
blood cultures have cleared. Micafungin is a broadspectrum echinocandin. It has been shown to be an
those due to non-albicans Candidaspecies such as C
glabrata.[38]
o
Voriconazole can be initiated at 6 mg/kg

intravenously or orally twice per day, followed by 3
mg/kg orally twice per day or 200 mg orally twice per
day. Based on the findings from a global multicenter
clinical trial, voriconazole has also been approved for
use in candidemia in patients who are not neutropenic.[39]
Amphotericin B deoxycholate has been an
alternative to fluconazole for many years. However,
with the advent of the newer azoles and the
echinocandins, its role as a primary or secondary option
needs to be reconsidered. The dose for amphotericin B
deoxycholate is 0.5-0.7 mg/kg/d intravenously to
achieve a minimum of 1- to 2-g total dose. For the
treatment of invasive candidiasis caused by lesssusceptible species, such as C glabrata and C krusei,
higher doses (up to 1 mg/kg/d) should be considered.
Liposomal preparations of amphotericin B
are recommended at doses between 3 and 5 mg/kg/d
when used for invasive candidiasis.
Special situations involving antifungal resistance:
Several of the Candidaspecies require special mention
because of their known intrinsic resistance to antifungals.
Because C glabrata is known to be
resistant to fluconazole in 15%-25% of cases and has
decreased susceptibility to most antifungals, C
glabrata infections require a change in conventional
antifungal therapy. The drugs of choice for such
infections are the echinocandins: caspofungin 70 mg
intravenously as a loading dose, followed by 50 mg/d;
anidulafungin 200-mg loading dose, followed by 100
mg/d; or micafungin 100 mg/day intravenously. An
alternative is voriconazole at 6 mg/kg administered
twice on the first day, followed by 3 mg/kg twice per
day or 200 mg twice per day orally; other options
include amphotericin B deoxycholate (1 mg/kg/d), or
lipid preparations of amphotericin B at 3-5 mg/kg/d.
If in vitro susceptibility assays are
available, it may be worthwhile to establish the in vitro
susceptibility of the C glabrata strain to fluconazole. If
the MIC is less than 8 g/mL, then fluconazole can be
used at 400 mg/d intravenously or orally.
C krusei infections necessitate the use of
an agent other than fluconazole, because this organism
is intrinsically resistant to fluconazole and has a
decreased susceptibility to itraconazole, ketoconazole,
and amphotericin B. Thus, the preferred regimen
includes echinocandins (caspofungin, anidulafungin, or
micafungin) voriconazole, or amphotericin B at 1
mg/kg/d.
Infections
due
to C
lusitaniae or C
guilliermondi necessitate the use of fluconazole,
voriconazole, or the echinocandins because these
isolates are frequently intrinsically resistant to
amphotericin B or develop resistance to amphotericin B
while the patient is on therapy.
Alternative antifungal regimens
Alternative regimens may be considered in
patients who are intolerant to the treatment regimens
or when the infection is refractory to the antifungal
regimen. The combination of amphotericin B and
flucytosine has been recommended in several special
situations. For instance, this combination has been used
in immunocompromised patients with endophthalmitis,
meningitis, or osteomyelitis. Flucytosine appears to

interact synergistically with amphotericin B in animal
models.
o
The role of other combinations of
antifungals to treat complicatedCandida infections
needs to be evaluated. A human recombinant monoclonal
antibody against heat shock protein 90 was recently
reported to significantly improve outcomes in patients
treated with lipid-associated amphotericin B for
confirmed invasive candidiasis.[42]However, larger
randomized trials need to be performed before this
drug can be used clinically.
Surgical Care
Major organ infections associated with candidal abscess
formation may require surgical drainage procedures along
with the appropriate antifungal therapy.
Prosthetic joint infection with Candida species requires the
removal of the prosthesis.
Surgical debridement is generally necessary for sternal
infections and frequently for vertebral osteomyelitis.
Splenic abscesses occasionally require splenectomy.
Valve replacement surgery is always indicated to treat
endocarditis.
In addition to medical management, vitrectomy is a
therapeutic option in fungal endophthalmitis.[43]
Consultations
In some forms of candidiasis, involving physicians of
different specialties for some of the specific infections
may be necessary. Some examples of these situations
include
endocarditis,
endophthalmitis,
peritonitis,
osteomyelitis, and other forms of invasive candidiasis that
may require surgical drainage and debridement.
Ophthalmologist
General surgeon
Cardiothoracic surgeon
Gastroenterologist
Infectious disease specialist
Orthopedic surgeon
Medication Summary
Successful therapy for serious systemic Candida infections
requires initiation of antifungal therapy as early as
possible, as soon as adequate culture results are obtained.
Different classes of antifungals are now available to
manage any type of candidal infection. Azoles, fluconazole
in particular,[35] have become the mainstay of therapy over
the past few years. These include topical and systemic
agents. Posaconazole is the most recent addition to this
group of antifungals. Polyenes include amphotericin B,
liposomal amphotericin B formulations, and topical nystatin.
Allylamines include terbinafine, which is formulated in a
topical preparation and an oral tablet. The newest group of
antifungals
is
echinocandins,
including
caspofungin,
micafungin, and anidulafungin. These drugs have shown

excellent clinical efficacy, a low incidence of adverse
events, a good safety profile, and ease of use.[44, 45]
Azole Antifungals
tissue distribution than older systemic imidazoles. Available

PO/IV and has demonstrated efficacy in topical and
Class Summary
invasive forms of candidiasis. Available in 50-, 100-, 150-,

and 200-mg tabs.
These agents are synthetic compounds that include 2

groups, imidazoles and triazoles. Triazoles have 3 atoms of
nitrogen in the azole ring. Imidazoles have only two. The
primary mechanism of action is inhibition of lanosterol 14alpha-demethylase, an enzyme required for the synthesis
of
ergosterol,
membranes.
the
main
Imidazole
component
agents
of
fungal
include
cell
Daily dose varies with indication.

View full drug information
Itraconazole (Sporanox)
miconazole,
ketoconazole, and clotrimazole.

In August 2013, the FDA announced that clinicians should
no
longer
prescribe
ketoconazole
(Nizoral,
Janssen
Pharmaceuticals) tablets as a first-line therapy for any

fungal
infection,
including Candida and
dermatophyte
infections, because of the risk for severe liver injury,

adrenal insufficiency, and adverse drug interactions.
32]
[31,
The FDA also cautioned that ketoconazole tablets should
not be prescribed for any patient with underlying liver

disease. The labeling changes do not apply to topical
formulations of ketoconazole in creams, shampoos, foams,
and gels. Oral ketoconazole is now indicated only for
endemic mycoses in patients who fail to respond to or
cannot tolerate other treatments.
in the European Union in July 2013.[31, 32]
fluconazole,
itraconazole,
econazole,
terconazole, butoconazole, and tioconazole. Newer triazoles

(ie, voriconazole, posaconazole, ravuconazole) are active
against
fluconazole-resistant
P450-dependent synthesis of ergosterol, a vital component

of fungal cell membranes. Effective against broad range of
fungi,
including Candida species,
and
is
indicated
for
treatment of cutaneous, oral, esophageal, and disseminated

candidiasis.
Available IV, 100-mg caps, and oral solution at 10 mg/mL.
Caps require gastric acidity for absorption and should be
taken with food to increase absorption. Liquid formulation
increases bioavailability and decreases need for acidity for
strains
Use of solution has been recommended in mucosal and

invasive
Triazole agents, which are now the most commonly used

include
that slows fungal cell growth by inhibiting cytochrome
proper absorption.
Ketoconazole tablets were also withdrawn from the market
azoles,
Has fungistatic activity. Synthetic triazole antifungal agent
of Candida.
candidiasis,
while
caps
can
be
used
in
onychomycosis and dermatophyte infections.

Voriconazole (Vfend)
Voriconazole and posaconazole have shown high efficacy

against candidiasis in recent clinical trials.[39, 46, 47]
Topical agents are frequently used as front-line agents to
manage localized or superficial forms of candidiasis such as
cutaneous candidiasis, oropharyngeal candidiasis (OPC), and
vulvovaginal candidiasis (VVC). These preparations are
available as a cream for topical use, as troches for OPC,
and as a vaginal suppositories or tablets for vaginitis.
Fluconazole (Diflucan)
Available as tablet, suspension and parenteral preparations.

Effective as fluconazole against esophageal candidiasis, and
as effective as amphotericin B deoxycholate in treatment
of candidemia and invasive candidiasis. In Europe, it has
been approved for "treatment of fluconazole-resistant
serious
invasive Candidainfections
not decrease cortisol and testosterone levels, as occurs

with ketoconazole. Has fewer adverse effects and better
krusei)."
Additionally, associated with fewer breakthrough fungal

infections when used as empiric therapy in febrile
neutropenic
patients.
FDA
candidiasis and candidemia.

Triazole with less effect on human sterol metabolism. Does
(including C
Posaconazole (Noxafil)
approved
for
esophageal
Novel triazole antifungal agent. Blocks ergosterol synthesis
stem
cell
transplantation,
treatment
of
esophageal
of cell membrane by inhibiting enzyme lanosterol 14-alpha-
candidiasis, candidemia, and invasive candidiasis.
demethylase and sterol precursor accumulation. Action

results in cell membrane disruption. Available as oral susp
(200 mg/5 mL). Approved for treatment of OPC, including
OPC refractory to itraconazole and/or fluconazole and for

Anidulafungin (Eraxis)
prophylaxis of infections due to Candidaand Aspergillus in

patients who are at high risk, such as those undergoing
stem cell transplants with graft versus host disease or with
prolonged neutropenia due to a hematologic malignancy or
One of the newer antifungal agents belonging to the
its treatment.
echinocandin class. Also inhibits synthesis of (1,3)- -D-
Glucan synthesis inhibitors (echinocandins)
Indicated
Class Summary
intra-abdominal abscesses, peritonitis).
These agents inhibit the formation of fungal cell wall. The
Polyenes
glucan, an essential component of fungal cell walls.
antifungal class has expanded with the approvals of

caspofungin, micafungin, and anidulafungin. Indications are
evolving but have been approved for complicated forms of
invasive candidiasis, candidemia, disease refractory to
other systemic antifungals, and intolerance to amphotericin
B. They are broad spectrum and fungicidal against
most Candida species,
except C
for
treatment
of
esophageal
candidiasis,
candidemia, and other forms of candidal infections (eg,
parapsilosis and C
Class Summary
These are broad-spectrum fungicidal agents. Mechanism of
action is by insertion into fungal cytoplasmic membrane,
causing
increases
in permeability. Membrane channel
activity is increased at lower doses, and pores are formed
guilliermondii.
at higher concentrations.
Caspofungin (Cancidas)
Amphotericin B (Fungizone, Amphocin)
FDA approved to treat candidemia, invasive candidiasis, and
One of the oldest antifungals, in use for more than 40 y,
esophageal
candidiasis.
Initially
approved
to
treat
refractory invasive aspergillosis. Also approved as empiric

therapy
for
presumed
fungal
infections
in
febrile
neutropenic patients. First of a new class of antifungal

drugs (glucan synthesis inhibitors). Inhibits synthesis of
(1,3) -D-glucan, an essential component of fungal cell wall.
This component is not found in mammalian cell walls.
of
echinocandins,
a
that
new
class
inhibit
of
cell
antifungal
wall
agents,
synthesis.
essential component of the fungal cell wall, not present in

cells.
infection being treated. Most patients receive total dose of

0.5-1.5 g.
AmBisome)
Echinocandins inhibit the synthesis of (1,3)- -D-glucan, an

mammalian
Total dose must be adjusted depending on type of candidal
Amphotericin B, lipid formulations (Amphotec, Abelcet,
Micafungin (Mycamine)
member
In recent years, lipid formulations have been developed.
and the criterion standard of antifungal therapy.
Indications
include
prophylaxis
of Candida infections in patients undergoing hematopoietic
Novel lipid formulations of amphotericin B that deliver

higher concentrations of drug with a theoretical increase in
therapeutic potential and decreased nephrotoxicity.
Formulation types include amphotericin B lipid complex
(ABLC, Abelcet), amphotericin B colloidal dispersion (ABCD,
Amphotec),
AmBisome).
and
liposomal
amphotericin
(L-AMB,
ABLC and ABCD approved for treating adults and children
Broad-spectrum antifungal agent that inhibits yeast growth
intolerant of conventional amphotericin B or with fungal
by altering cell membrane permeability, causing death of
infections refractory to conventional amphotericin B. L-
fungal cells.
AMB
is
approved
for
aspergillosis,
candidiasis,
cryptococcosis, and neutropenic patients with persistent

fever on broad-spectrum antibiotics.

Butoconazole (Femstat-3, Gynazole-1)

Nystatin (Mycostatin)
Broad-spectrum antifungal agent that inhibits yeast growth
by altering cell membrane permeability, causing death of
fungal cells.
Fungicidal
and
from Streptomyces
fungistatic
antibiotic
obtained
noursei. Effective against various
Use 2% vaginal cream. Available OTC.
yeasts and yeastlike fungi. Changes permeability of fungal

cell membrane after binding to cell membrane sterols,
causing cellular contents to leak. Membrane channel activity
is increased at lower doses, and pores are formed at higher

Miconazole vaginal (Monistat, Micatin)
concentrations.
Antimetabolite
Damages
fungal
cell
wall
membrane
by
inhibiting
Class Summary
biosynthesis of ergosterol. Membrane permeability is
Flucytosine is an antimetabolite originally developed for the
cell death. Lotion preferred in intertriginous areas. If
increased, causing nutrients to leak out, resulting in fungal
treatment of leukemia.
cream is used, apply sparingly to avoid maceration effects.
Flucytosine (Ancobon)
Tioconazole (Vagistat-1)
It is deaminated to 5-fluorouracil in the fungal cell by an
Damages
enzyme not present in mammalian cells, and inhibits RNA

and
protein
synthesis.
Active
against Candidaand Cryptococcus species and generally used

in combination with amphotericin B. It has been used in
studies in invasive candidiasis. Avoid use as single agent
because of ability to quickly develop resistance in vivo.
fungal
cell
wall
membrane
by
inhibiting

cell death.
Terconazole vaginal (Terazol-7, Terazol-3)
Topical azoles
Class Summary
These agents are used extensively to treat common
mucocutaneous uncomplicated forms of candidiasis.
Clotrimazole (Mycelex, Femizole-7)
Damages
fungal
cell
wall
membrane
by
inhibiting

cell death.
Allylamines
Class Summary
These agents cause a deficiency of ergosterol within the

fungal cell wall, causing fungal cell death.
Terbinafine (Daskil, Lamisil)
For treatment of paronychia; allylamine antifungal, which

inhibits squalene epoxidase and decreases ergosterol
synthesis, causing fungal-cell death.
Use medication until symptoms significantly improve.

Duration of treatment should be >1 wk but not >4 wk. May
not be as effective for candidal infections as azole
antifungals.
Further Inpatient Care
Inpatient care is frequently prolonged because of the
severe nature of the disseminated infections. Antifungal
therapy may be necessary for a prolonged period, either
parenterally or orally.
(1,3)-D-glucan assay is a useful nonculture method for
diagnosis of invasive candidiasis. A decrease in levels during
therapy has been associated with treatment success in
patients on echinocandin therapy with proven invasive
candidiasis. Consecutive serum measurements may be useful
as prognostic markers of response.[48]
Further Outpatient Care
Mucocutaneous candidiasis
Patients treated in the outpatient area may be discharged
home with medications. Instruct patients to follow up if
the symptoms persist or worsen.
If the infections are recurrent, perform an HIV antibody
test and rule out conditions that produce immune
suppression, such as hematologic malignancies, solid organ
malignancy, and diabetes mellitus. If no etiology is
established, refer the patients for consultation with an
infectious disease specialist to rule out an underlying
immune deficiency.
Candidemia and disseminated candidiasis
Because of the severity of the infections, some patients
may remain hospitalized for a prolonged period.
Patients on outpatient amphotericin B must be monitored 23 times weekly because of its high incidence of adverse
effects. The parameters that need to be monitored include
CBC count with differentials; electrolyte evaluations; and
serum magnesium, BUN, and serum creatinine levels.
Inpatient & Outpatient Medications
With newer treatment modalities that have been recently
instituted, de-escalation of antifungal therapy or the rapid
switch from intravenous to oral administration is
encouraged. Recent clinical studies suggest that patients
who are clinically stable and have a functional
gastrointestinal tract on day 4-5 of parenteral intravenous
antifungal administration should be switched from
intravenous to oral therapy with either fluconazole or

voriconazole.
Although relatively uncommon, patients may be discharged
home on parenteral antifungal therapy or oral azole therapy
with close monitoring for toxicity.
Transfer
Transfer patients to the service that can care for the
specific candidal infections (eg, general surgery, ICU).
Transfer patients with sepsis or altered mental status to
an appropriate critical care unit.
Deterrence/Prevention
Antifungal prophylaxis of invasive candidiasis in high-risk
patients is currently recommended for the following[26, 49] :
Stem cell transplant recipients, primarily those
with allogeneic transplants, are recommended to receive
fluconazole initiated 1 day prior to neutropenia and
continued until neutropenia resolves. Micafungin and
posaconazole are also recommended for this indication. [50]
Solid organ transplant recipients may be
considered for antifungal prophylaxis with fluconazole or
liposomal amphotericin B for the prevention of
candidiasis. This is recommended for postoperative
antifungal prophylaxis in liver, pancreas, and small bowel
transplant recipients at high risk of candidiasis.
Additional indications are being investigated. [51]
For
patients
with
chemotherapy-induced
neutropenia, fluconazole, posaconazole, or caspofungin is
recommended during induction chemotherapy for the
duration of neutropenia.
Most recent candidiasis treatment guidelines
recommend prophylaxis in high-risk ICU patients in adult
units
that
have
high
incidence
of
invasive
[26]
candidiasis.
Oral nystatin prophylaxis has been shown
to decrease colonization in ICU patients and needs to be
investigated as a potential strategy to control candidarelated infection in appropriately selected patients in
this setting. [52]
Currently, no strong indications exist for primary or
secondary prevention of oropharyngeal candidiasis (OPC) or
vaginal candidiasis in patients infected with HIV. However,
concern does exist about the potential development of
resistance or colonization by resistant species or strains
of Candida. Prophylaxis may be indicated in a select group
of patients with recurrent symptomatic candidiasis.
Control the blood glucose level in patients with diabetes
mellitus.
Eliminate or decrease risk factors such as steroids,
cyclosporin, and tacrolimus.
Nosocomial candidemia prevention should be based on hand
hygiene, optimal catheter care, and prudent antimicrobial
use.[53]
Complications
If left untreated, candidemia can lead to metastatic foci
of infection in the eyes, vertebral column, liver, spleen,
CNS, and kidneys. Initiate prompt treatment to prevent
foci of infection, abscess formation, and death.
Prognosis
Prognosis depends on several factors, such as the site of
infection, the degree and type of immunosuppression, and
the rapidity of diagnosis and treatment.
Mucocutaneous candidiasis carries an excellent prognosis,
with no mortality and only minimal morbidity.
Systemic candidiasis carries a mortality rate of 30-40%

and is generally correlated with the degree of
immunosuppression and the underlying disease. In certain
groups of patients, the presentation of Candida infection
increases the likelihood of death, lengthens hospital stays,
and increases hospitalization costs.[54, 55]
The longer the delay to initiate antifungal therapy, the
higher the morbidity and mortality associated with
candidemia and disseminated candidiasis.
Patient Education
Inform patients and their families about the risk factors
associated with mucosal and systemic candidiasis. In
addition, inform them that the systemic form of the

disease is extremely serious and is associated with high
morbidity and mortality rates unless aggressive action is
undertaken.
For
patient
education
resources,
see Infections
Center, Children's Health Center, and Skin Conditions &
Beauty
Center,
as
well
as Candidiasis
(Yeast
Infection),Yeast Infection Diaper Rash, and Yeast
Infection Skin Rash.

Candidiasis

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Candidiasis

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Practice Essentials

Candidiasis (see the image below) is a fungal infection

Soreness and cracks at

Chronic mucocutaneous candidiasis

The following are the 5 types of OPC:

Diagnostic tests for candidiasis include the following:

Cutaneous candidiasis - Using a wet mount,

Genitourinary candidiasis - A urinalysis should be

Gastrointestinal candidiasis - Endoscopy with or

Cutaneous candidiasis - Most localized cutaneous

include neonatal, pediatric, and adult ICUs, both medical

Acute and chronic renal failure

Candida species are the most common cause of fungal

fungemia). Although mucocutaneous fungal infections, such

Biopsy specimens of these lesions demonstrate yeast cells,

Chronic mucocutaneous candidiasis describes a group

History: Most infections begin in infancy or during

Polyglandular autoimmune disease

Physical examination: Findings reveal disfiguring

The patient usually has a history of HIV

(see image below).

Physical examination almost always reveals

Nonesophageal gastrointestinal candidiasis

The patient usually has a history of

Nausea and vomiting

Fever and chills

Abdominal mass (in some cases)

of VVC without precipitating risk factors. Physical

Dry, red, superficially scaly,

Hepatosplenic candidiasis is a form of systemic candidiasis

Physical examination findings include right upper quadrant

Several days of fever that is

A history of several key risk

Endocarditis: The frequency of

murmurs, and large septic emboli to major organs, a

Underlying risk factors for

Asymptomatic and detected upon

of infection include the exogenous infection and the

Fever unresponsive to broadspectrum antimicrobials

Mental status changes

Candida arthritis, osteomyelitis, costochondritis,

Ribs and leg bones (patients < 20

Vertebral column and paraspinal

Flat bones (any age group)

Sternum - Generally observed

Arthritis: Candida arthritis

addition, Candida arthritis after joint replacement is

Osteomyelitis: Candida osteomyeli

Myositis: Candida myositis

Myocarditis-pericarditis: This infection is usually

Candida peritonitis [18]

Absent bowel sounds

Candida splenic abscess and hypersplenism: Both

Candida cholecystitis: This is uncommon and is

Respiratory candidiasis - Bacterial pneumonia, viral

initiating antifungal therapy in patients with fever that

microbroth dilution (CLSI M27-A2, 2002) or the disk

Nonculture Candida detection assays

Ultrasonography may be useful for diagnosing hepatosplenic

Fluconazole is still considered a first-line agent in

Cutaneous candidiasis: Most localized cutaneous

Oropharyngeal candidiasis OPC

immune dysfunction with HAART, higher doses of

restriction of its use to uncomplicated lower urinary