Neonatal
candidiasis is an increasingly common occurrence causing significant morbidity and mortality and a higher risk of dissemination to the central nervous system (CNS) than that seen with older patients. The current understanding of optimal antifungal
therapy in this setting is limited. We have developed a model of disseminated
candidiasis with CNS involvement in juvenile mice to assess the efficacy of the
echinocandin caspofungin relative to
amphotericin B (AmB). Juvenile mice were inoculated intravenously with 5.64 × 10(4) CFU of Candida albicans MY1055. Treatment with
caspofungin at 1, 2, 4, and 8 mg/kg of
body weight/day, AmB at 1 mg/kg/day, or a vehicle control (VC) was initiated 30 h after
infection and continued for 7 days. Pharmacokinetic parameters for
caspofungin were also determined. Culture and histology showed evidence of disseminated
candidiasis with multifocal
encephalitis at the start of antifungal
therapy. Survival was 100% in all treated groups, while mortality was 100% in the VC by day 11 after
infection. By day 5, all mice in the
caspofungin treatment (four doses) groups showed reductions in kidney and brain burden relative to the VC, while AmB treatment reduced kidney burden but gave no reduction of brain fungal burden. Systemic levels of
caspofungin were similar in infected and uninfected mice, while brain levels were higher in infected animals. In this juvenile mouse model,
caspofungin demonstrated dose-dependent activity, equivalent to or better than that of AmB at 1 mg/kg, against disseminated
candidiasis with CNS involvement.