Abstract

Intravenous Amphotericin B (IV AmB) is standard therapy for systemic candidiasis, but penetrates the central nervous system (CNS) poorly. From 1971-83, 22 infants in this ICN developed systemic candidiasis, defined by clinical signs of sepsis, blood and/or CSF cultures (19) or deep tissue histologic specimens positive for Candida (3), and failure to improve without antifungal therapy. Seven infants (31%) died of this infection. Fourteen of these 22 infants (64%) had culture or autopsy-proven evidence of Candida CNS infection - 10 had positive CSF cultures; 4 had cerebral or intramedullary cord abscesses at autopsy. Six of these 14 infants (43%) with CNS infection died - none of these 6 had received systemic antifungal therapy (culture results unavailable before death in 2 cases, isolate wrongly considered transient or contaminant in 3 cases, negative blood and CSF cultures in 1 case). Among the 8 treated survivors of CNS candidiasis, CSF was sterilized with IV AmB alone in only 2 cases. Four others required the addition of flucytosine (FC) which penetrates the CNS well, after 5,7,11 and 13 days respectively of IV AmB failed to sterilize CSF; one required intraventricular instillation of AmB after an unsuccessful 21 day course of IV AmB; one required FC only for CSF sterilization. These observations suggest that: 1) systemic candidiasis in ICN infants often involves the CNS; 2) blood/CSF cultures positive for Candida should be considered significant, until proven otherwise; 3) IV AmB alone is often inadequate to sterilize infected CSF and changes in medication or route of administration may be necessary.

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