Neonatal candidosis: clinical picture, management controversies and consensus, and new therapeutic options.

Candida infections are increasingly being recognized as a major cause of septicaemia in neonatal intensive care units, and are associated with high morbidity (25%) and mortality (25-54%). Low birth weight pre-term infants are especially vulnerable to this devastating disease. The most frequently encountered fungal infections are caused by Candida albicans, Candida parapsilosis and, rarely, by Candida tropicalis. Amphotericin B (with or without flucytosine) is the treatment of choice for Candida infections in neonates. Conventional amphotericin B use is often limited by its severe side effects, although these tend to be fewer in neonates than in adults. Possible alternatives to amphotericin B include triazoles (such as fluconazole) and lipid preparations of amphotericin B. Liposomal encapsulation of amphotericin B has been shown to decrease the toxicity of the drug while maintaining its antifungal activity. The liposomal formulation AmBisome has proved to be effective in the treatment of severe fungal infections in adult and paediatric immunocompromised patients who fail to respond to conventional amphotericin B. The experience with AmBisome in the treatment of fungal infections in neonates is limited, and the drug has been used mainly in infants either failing conventional amphotericin B or having intolerable toxicity. Pharmacokinetic studies have not yet been performed in neonates. Three uncontrolled studies published between 1997 and 1998 on AmBisome (dose range 1-7 mg/kg/day) in the treatment of neonatal candidosis revealed that the drug was effective and safe. New information is accumulating on the safe use of high-dose AmBisome (5-7 mg/kg/day) in very low birth weight infants, and successful use of the drug as first-line therapy of neonatal candidosis. These promising results suggest a potential role for AmBisome as an additional first-line treatment of systemic candidosis in neonates.