Fungal infections are responsible for considerable morbidity and mortality in the neonatal period, particularly among premature neonates. Four classes of
antifungal agents are commonly used in the treatment of
fungal infections in pediatric patients: polyene
macrolides, fluorinated
pyrimidines,
triazoles, and
echinocandins. Due to the paucity of pediatric data, many recommendations for the use of
antifungal agents in this population are derived from the experience in adults. The purpose of this article was to review the published data on
fungal infections and
antifungal agents, with a focus on neonatal patients, and to provide an overview of the differences in antifungal pharmacology in neonates compared with adults. Pharmacokinetic data suggest dosing differences in children versus adult patients with some antifungals, but not all agents have been fully evaluated. The available pharmacokinetic data on the
amphotericin B deoxycholate formulation in neonates exhibit considerable variability; nevertheless, the dosage regimen suggested in the neonatal population is similar to that used in adults. More pharmacokinetic information is available on the liposomal and
lipid complex preparations of
amphotericin B and
fluconazole, and it supports their use in neonates; however, the optimal dosage and
duration of therapy is difficult to establish. All
amphotericin-B formulations, frequently used in combination with
flucytosine, are useful for treating
disseminated fungal infections and Candida
meningitis in neonates.
Fluconazole, with potent in vitro activity against Cryptococcus neoformans and almost all Candida spp., has been used in neonates with
invasive candidiasis at dosages of 6 mg/kg/day, and for antifungal prophylaxis in high-risk neonates. There are limited data on
itraconazole,
voriconazole, and
posaconazole use in neonates.
Caspofungin, which is active against Candida spp. and Aspergillus spp., requires higher doses in children relative to adults, and dosing is best accomplished based on body surface area.
Micafungin shows a clear trend toward lower levels in the smallest patients. There are no data on the use of other new antifungal drugs (
ravuconazole and
anidulafungin) in neonates. In summary, the initial data suggest dosage differences in neonates for some
antifungal agents, although the newer agents have not been fully tested for optimal administration in these patients.