Interaction of rifampin with other antifungal agents in experimental murine candidiasis

A murine model of systemic candidiasis was used for evaluation of the interaction of rifampin with ketoconazole and amphotericin B. In vitro studies with a clinical isolate of Candida albicans showed that rifampin modestly potentiated the antifungal activity of both of these drugs. When mice were challenged iv with C. albicans, therapy with rifampin plus ketoconazole or rifampin plus amphotericin B significantly reduced counts in kidney tissue from levels in untreated controls. However, rifampin plus amphotericin B was no more effective than amphotericin B alone, and rifampin plus ketoconazole was no more effective than ketoconazole alone. In challenges with lethal numbers of organisms, amphotericin B or ketoconazole alone increased the rate of survival from 0% to approximately 50%, and the addition of rifampin to the regimen conferred no further benefit. Therefore, the use of rifampin with either of these antifungal agents resulted in minimal, if any, increase in efficacy.