++
Candida species
are yeast forms that are ubiquitous in nature and frequent colonizers
of the skin and mucous membranes in humans, although they rarely
cause invasive disease in immunocompetent individuals. Only a small number
of the more than 150 species of Candida that have
been described are considered to be pathogenic. Candida
albicans remains the most frequent cause of human candidiasis, but
infections owing to other species of Candida are
increasingly recognized.1-4 In addition, the incidence
of infections owing to C albicans isolates that
are resistant to azole antifungals is increasing. This changing
epidemiology has implications for appropriate treatment of antifungal-resistant Candida infections.
++
Non-albicans species known to cause human disease
include C glabrata, C guilliermondii, C
keyfr (formerly C pseudotropicalis), C
krusei, C lusitaniae, C parapsilosis,
and C tropicalis. Candida parapsilosis is
the non-albicans species isolated most commonly
in children, and in some neonatal units has surpassed C
albicans as the most commonly isolated Candida species.1,4-8 Clinicians should be aware of echinocandin resistance
with C parapsilosis. Candida glabrata is
the second most commonly isolated species in adults, which also
has important implications for treatment, as C glabrata exhibits
variable resistance to azole antifungals. Candida tropicalis may
be an emerging pathogen in immunocompromised hosts, in whom it is
associated with significant morbidity and mortality.9
++
The incidence of colonization with Candida spp
depends upon host characteristics such as age and overall health.
Neonates are frequently colonized with Candida spp,
and localized oropharyngeal candidiasis (thrush) is not uncommon
in this population. Hospitalized and ill children are more frequently
colonized than are healthy children. Candida spp
have relatively low virulence factors compared to other organisms,
and therefore rarely cause disease in the normal host. For candidiasis
to occur, the host must have impaired resistance to disease, the
number of yeast organisms must be high, or both.
++
Neonates and pregnant women have impaired host resistance to Candida species,
as do patients with immunodeficiencies (congenital or acquired),
induced immunosuppression (eg, owing to chemotherapy or corticosteroids),
or debilitation (owing to trauma or surgery). Advances in health
care that have decreased mortality for many conditions (eg, prematurity
and malignancy) have been associated also with changes in host defense
and normal flora, which have in turn led to a larger population
at risk for invasive Candida infection. Preterm
newborns and oncology patients frequently receive multiple and long-term courses
of medications, particularly antimicrobials (altering the normal
flora), and have defects in mucosal or skin barriers (eg, owing to
intravascular catheters), which puts them at high risk for development
of candidiasis.
++
In recent years, Candida species have become increasingly
important causes of health-care-associated infections. Most health-care-associated
pediatric fungal infections are candidemias, and these are most
frequently diagnosed in children in neonatal and surgical intensive
care units. The source of transmission in these cases is frequently
unclear, although recent studies using molecular diagnostics have
implicated acquisition of Candida colonization
from hospital staff members and the environment of closed hospital
units.10,11Nevertheless, analysis of available
data neither supports nor refutes cohorting or isolation rooms as
effective measures to decrease transmission of Candida from
colonized neonates in closed units.12
++
Candida species may cause disease at any body
site. The anatomic site and the extent of the infection depend upon
the relative immunocompetence of the host: superficial infections
of skin and mucous membranes may occur in the normal host, but systemic
or disseminated disease is seen only in those with impaired host
defense.
++
Direct microscopic examination of specimens mounted in 20% potassium
hydroxide (KOH) or Calcofluor will reveal budding yeast cells and/or
pseudohyphae. Periodic acid–Schiff, Gomori methenamine silver nitrate, toluidine blue, and Gram stains will reveal Candida organisms.
On solid media such as Sabouraud dextrose agar, Candida species
appear as moist, white or cream-colored colonies with well-demarcated
borders. Candida albicans will produce germ tubes when
suspended in serum for a period of 1 to 4 hours, which allows for
rapid presumptive identification of this Candida species. Candida species
are definitively identified by biochemical tests of fermentation
and assimilation.
++
Antibody testing is not useful in diagnosis. Those who are only
colonized with Candida species may have positive
antibody testing, and immunocompromised patients may test falsely
negative.
++
There are many new molecular diagnostic tests in development
for diagnosis of candidiasis. At present, the β-1,3
glucan assay (testing for a component of the Candida cell
wall that is not found in humans) is the only nonculture-based method
approved by the Food and Drug Administration (FDA).61,62
+++
Clinical Manifestations
and Treatment
+++
Oropharyngeal
(Thrush) and Esophageal Candidiasis
++
Thrush, almost exclusively the result of C albicans, is
the most common type of candidiasis in infants and children and
is not uncommon in infants up to age 5 months. Thrush may be seen in
older infants or children who are receiving antibiotic therapy but
are otherwise healthy. Recurrent or recalcitrant thrush in children
not receiving antibiotic therapy should prompt an evaluation of
the immune system (see Chapter 187).
++
The lesions of thrush appear most commonly as pearly white patches
on the dorsal and lateral aspects of the tongue, the pharynx, gingivae,
and buccal mucosa. These patches coalesce into plaques that cause
punctate bleeding when removed from the mucosal surface. Removal
of the patches by scraping with a tongue depressor reveals an erythematous, eroded
base; a KOH examination reveals ovoid yeast forms and pseudohyphae.
++
Thrush usually can be treated topically, with nystatin or clotrimazole.
Systemic therapy may be indicated for immunocompromised patients or
in cases refractory to topical therapy.20 Fluconazole
is usually effective therapy in this case but there is an increasing
incidence of non-albicans species and azole-resistant C
albicans isolates that may require alternate therapies.
++
It is important to address sites that may be colonized with Candida to
effectively treat thrush in infants. Nystatin may be applied to skin
that has sustained contact with the infant’s mouth, such
as the mother’s nipple for breast-fed infants or the fingers
of infants who habitually suck them. Bottle nipples, pacifiers, or
other objects with sustained contact with the infant’s
mouth should be boiled after each use.
++
Other oropharyngeal infections include acute atrophic candidiasis
(glossitis) and angular cheilosis (perlèche). Glossitis
usually occurs following the use of broad-spectrum antibiotics that
later the oral bacterial flora. Papillae on the dorsum of the tongue
are eroded, which results in a smooth and erythematous tongue that
is often painful. This condition typically resolves with discontinuation
of the antibiotics. Angular cheilitits (perlèche) is characterized
by painful fissuring and erythema at the corners of the mouth, due
to habitual licking, although it may also be seen in individuals
with iron deficiency, vitamin B12 or folate deficiency,
or in children with poor oral secretion control. Treatment with
topical antifungal and/or steroids are useful in persistent
cases.
++
Esophageal candidiasis typically presents with dysphagia. Children
may also have nausea or vomiting, and esophagitis may be manifested in
infants by decreased oral intake. Esophagitis may occur without
oropharyngeal candidiasis. Empiric therapy may be prescribed for
symptomatic immunocompromised patients but in more severe or refractory
cases intravenous therapy may be required (see Chapter 394 and eFig. 394.4).
+++
Cutaneous Candidiasis
++
Cutaneous candidiasis involves moist areas, such as the perineum
and intertriginous areas. Candida diaper dermatitis
is discussed in Chapter 367.
++
Infants who suck their fingers may develop sucking blisters,
and infection of the nails (paronychia) may also occur. Paronychia
resulting from Candida species also may follow
other trauma to the nail or surrounding tissue.
++
A maculopapular rash in an immunocompromised patient with Candida infection
is often associated with disseminated disease. The skin lesions
that have been described in patients with hematologic malignancies
are typically discrete erythematous papules measuring 0.5 to 1.0
cm in diameter, which may have a nodular center. Biopsy of the skin
lesions may be necessary for definitive diagnosis, in order to exclude
other infectious etiologies in an immunocompromised host.
++
Recurrent or persistent indolent Candidal skin infections occur
in patients with chronic mucocutaneous candidiasis as discussed
in Chapter 188. Infection may be controlled through use of chronic
azole therapy.