FLUCONAZOLE, D0870, AND FLUCYTOSINE TREATMENT OF DISSEMINATED CANDIDA-TROPICALIS INFECTIONS IN MICE

D0870 is a recently developed triazole with characteristics of a broad spectrum of activity and slow clearance by nonrenal mechanisms. Herei n we have evaluated the efficacy of D0870, alone and combined with flu cytosine, in a murine model of disseminated Candida tropicalis infecti on. Four isolates of C. tropicalis were evaluated. Two were highly sus ceptible in vitro to fluconazole, and two were resistant to fluconazol e. All were highly susceptible to flucytosine and D0870. Animals were pretreated with 5-fluorouracil 1 day before infection because C. tropi calis has reduced virulence in immunocompetent mice. This was done to render them neutropenic for >10 days. Mice were infected intravenously and treated orally with D0870 or fluconazole, alone or combined with flucytosine. Survival and tissue burden of the spleen and kidneys were used to evaluate the efficacy of antifungal therapy. Fluconazole was less effective for treatment of resistant C. tropicalis than susceptib le C. tropicalis. D0870 was more potent than fluconazole and was effec tive in fluconazole-resistant isolates. Flucytosine was consistently e ffective when used alone but did not consistently add to the benefit o f D0870 or fluconazole. D0870 has potential in treatment of candidiasi s caused by C. tropicalis, including fluconazole-resistant isolates.