Candida Infection in Newborn

Candida is a common cause of oral mucous membrane infections (thrush) and perineal skin infections (candidal diaper dermatitis) in newborn infants. Disseminated candidiasis and candidemia have become a frequent problem in neonatal intensive care units.

Epidemiology.
C. albicans is commonly part of the gastrointestinal and vaginal flora of adults. Pregnancy increases the rate of maternal vaginal colonization from <20% to >30%. Maternal colonization rates at time of delivery correlate with the colonization rates of the newborns. Approximately 10% of full-term infants become colonized in the gastrointestinal and respiratory tract in the 1st 5 days of life. Neonatal risk factors for invasive candidiasis include very low birthweight status, broad-spectrum antibiotic administration, abdominal surgery, prolonged ventilatory support, prolonged intravenous catheterization, and parenteral alimentation.

Pathogenesis
The inability of the newborn infant to localize, control, and eradicate Candida infections is related to the relative impairment of specific and nonspecific host defense mechanisms. Overgrowth of Candida on mucocutaneous surfaces and colonization of intravenous catheters favor entry and penetration, with development of clinical infection directly related to extent of colonization. Hematogenous spread may lead to vasculitis and miliary nodules in multiple organs, including the skin, liver, spleen, lungs, kidneys, gastrointestinal tract, heart, eyes, and meninges.

Clinical Manifestations.
The manifestations of systemic neonatal candidiasis vary in acuteness and severity from thrush and candidal diaper dermatitis to fungemia that may rarely be asymptomatic or may be associated with sepsis and shock indistinguishable from bacterial sepsis.

Central nervous system involvement occurs in up to ? of cases and may involve the meninges, ventricles, or cerebral cortex with abscess formation. Since clinical manifestations of central nervous system disease may not be apparent, evaluation of the cerebrospinal fluid in all neonates with disseminated candidiasis is required. Endophthalmitis has been noted in as many as 45% of cases, but with earlier effective treatment it is now less than 5%. It remains important to perform retinal examinations in neonates with systemic candidiasis; repeat examinations are necessary to monitor resolution of the retinal lesions.

Congenital Candidiasis.
Congenital candidiasis is a rare manifestation. It occurs in otherwise healthy neonates and presents at birth with widespread skin involvement, especially in the intertriginous areas. Congenital candidiasis follows ascending infection from a mother with heavy vaginal colonization or vulvar infection with Candida. The newborn rash is maculopapular, vesicular, or pustular with little or no mucous membrane involvement. Nodular lesions may be seen on the umbilical cord and placental membranes. In the absence of systemic manifestations, topical antifungal therapy is the treatment of choice for congenital cutaneous candidiasis in full-term infants.

Diagnosis.
Definitive diagnosis requires histologic demonstration of the fungus in tissue specimens or recovery of the fungus from normally sterile body fluids. Buffy coat smears of blood may show yeast, allowing a preliminary diagnosis. Skin scrapings of generalized rashes in very low birthweight infants with suspected systemic candidiasis should be examined microscopically for yeast. Because cultures of blood and cerebrospinal fluid are often intermittently positive, multiple samples should be obtained.

Polymerase chain reaction (PCR) can be used to diagnose Candida blood stream infection in high-risk patients, as well as for genotyping strains of Candida for outbreak investigation.

Treatment.Transient candidemia and disseminated candidiasis associated with a contaminated intravascular catheter requires removal of the catheter. Amphotericin B (0.5–1.0 mg/kg/day IV) had been the mainstay of therapy for systemic candidiasis and is active against both yeast and mycelial forms. The duration of therapy varies widely according to the extent of infection, clinical response, and drug toxicity. The total recommended dose is 20–30 mg/kg. Nephrotoxicity is common in the newborn infant and generally presents with oliguria, azotemia, and hyperkalemia. Lipid-complex formulations of amphotericin B (5 mg/kg/day) are recommended for neonates with compromised renal function (including doubling of the serum creatinine with amphotericin B desoxycholate therapy), also receiving other nephrotoxic therapy, or otherwise intolerant of amphotericin B desoxycholate. The addition of flucytosine (100–150 mg/kg/day divided every 6 hr PO) may be used to treat central nervous system and parenchymal kidney infections. Patients must be observed for bone marrow, gastrointestinal, and hepatic toxicities.

Fluconazole is very useful for treatment of invasive neonatal Candida infections, especially urinary tract infections. Fluconazole is inactive against all strains of C. krusei and approximately 20% of strains of C. glabrata. These strains are usually susceptible to voriconazole and itraconazole, but cross-resistance to other azoles does occur. The susceptibility of these clinical isolates should be tested if treatment with azoles is contemplated. Caspofungin has excellent activity against most Candida species and has been used successfully in patients with resistant organisms or in whom other therapies have failed.