Candidiasis in the Newborn
DEFINITIONS: Candidiasis refers to infection with fungi of the genus Candida.
Candidemia is presence of Candida fungi in the blood. Catheter-related candidemia
refers to candidemia that resolves rapidly after catheter removal and initiation of therapy.
Disseminated, or invasive, candidiasis refers to persistent infection after removal of a
catheter and/or isolation of Candida from other normally sterile body sites.
EPIDEMIOLOGY: Invasive candidiasis in neonates is a serious and common cause of
late onset sepsis and has a high mortality (25 to 35%). The incidence of such fungal
infections has increased 11 fold over the past 15 years. Candida species are the 3rd most
frequent organism (after coagulase negative Staph. and Staph. aureus) isolated in lateonset
sepsis in very low birth weight (VLBW) infants (i.e., <1,500 g). Preterm infants
are predisposed to Candida infections because of immaturity of their immune system and
invasive interventions. Transmission of Candida may be vertical (from maternal vaginal
infection) or nosocomial. Colonization of health workers is as high as 30%. Initial site
of colonization is usually the gastrointestinal tract. Risk factors for candidiasis include:
a) low birth weight (<1,500 g); b) use of broad spectrum and/or multiple antibiotics; c)
central venous catheters; d) parenteral alimentation and intravenous fat emulsion; e)
colonization with Candida and/or previous episode of mucocutaneous candidiasis; f)
prolonged urinary catheterization. Although initial reports indicated most cases were due
to due Candida albicans, more recent studies show emergence on non-albicans species
including C. parapsilosis (cause of majority of cases in some centers), C. glabrata, C.
krusei, C. lusitaniae and C. tropicalis.
CLINICAL MANIFESTATIONS: The classic clinical picture of systemic candidiasis
in neonates is indistinguishable from bacterial sepsis. Common presenting symptoms are
worsening respiratory function, apnea, thrombocytopenia and localized signs of
candidal infection at one or more of the following sites:
-Skin and mucous membranes (thrush, diaper rash or other areas)
-Central nervous system: Meningitis is present in up to 64% of fatal cases, and
survivors have a high incidence of severe sequelae including hydrocephalus,
psychomotor and mental retardation, and aqueductal stenosis
-Eyes: Fundoscopic examination is essential for early diagnosis of invasive disease, as
the incidence of Candida endophthalmitis is as high as 50%.
-Heart: Candida endocarditis is the 2nd most common form of endocarditis in VLBW
infants. Clinical findings may include cardiac murmurs, petechiae, skin abscesses,
arthritis, hepatomegaly and splenomegaly. Right-sided intracardiac fungal masses can
manifest with heart failure or even with pulmonary fungal embolism.
-Kidneys: Candida is the most frequent cause of urinary tract infection in intensive
care nurseries. Up to 50% of these babies have candidemia and are predisposed to
renal candidiasis, with development of renal fungus balls or abscesses and unilateral
or bilateral renal obstruction. Renal insufficiency may be the first clinical
manifestation of invasive candidiasis.
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-Bones and Joints: Warmth and swelling of the extremities in combination with
radiographic evidence of osteolysis or arthritis.
Congenital Candidiasis: A rare entity in which intrauterine infection is evident at birth.
Two forms have been described:
1) Congenital cutaneous candidiasis in which an extensive skin rash presents within 12
hours of birth. A macular erythema that may evolve from a pustular, papular or
vesicular phase finally results in extensive desquamation.
2) Congenital systemic candidiasis: An invasive infection with a high mortality rate,
especially in VLBW infants. At least 50% do not have a cutaneous rash. Presenting
signs are pneumonia (most common), meningitis, candiduria and/or candidemia.
DIAGNOSIS: Consider Candida in the differential diagnosis of neonatal sepsis,
particularly late-onset. When blood culture is positive for Candida, a thorough
evaluation to rule out disseminated infection should include cultures of urine and CSF,
ophthalmological examination, echocardiogram, renal ultrasound and, if clinical
signs of arthritis or osteomyelitis are present, radiographic skeletal survey and consider
diagnostic aspiration of affected area.
TREATMENT: Remove central venous catheter, unless blood stream infection clears
rapidly with antifungal therapy.
Amphotericin B, the gold standard for neonatal antifungal therapy, exerts its mechanism
of action and toxicity through binding to ergosterol in the cell membrane of fungal and
host cells, resulting in formation of membrane pores, cell depolarization followed by cell
death. Side effects include nephrotoxicity, hypokalemia, hypomagnesemia, anemia,
thrombocytopenia and infusion reactions (temperature and hemodynamic instability.
Liposomal Amphotericin B allows targeted antifungal therapy with less toxicity. The
drug is cleared through the reticuloendothelial system allowing higher liver and spleen
concentrations and reduced renal concentrations.
Flucytosine (5-FC) interferes with DNA synthesis. Because of toxicity and development
of resistant strains, it is of limited use in neonatal infections. However, if the infant can
tolerate oral medications, flucytosine is very useful for CNS infections and may act
synergistically with amphotericin B.
Fluconazole, a fungistatic drug, is the most effective of the azoles. Hepatotoxicity, the
main side effect, is transient and resolves with cessation of therapy. It has decreased
activity against C. glabrata and C. krusei.
Consultation with the Infectious Disease Service should be obtained for all neonatal
fungal infections except those limited to skin and mucous