Candida krusei is increasingly recognized as an opportunistic pathogen in immunocompromised patients and is inherently resistant to
fluconazole. We tested the in vivo efficacy of
SCH 51048, an investigational antifungal
triazole, in experimental hematogenous murine
infection caused by two C. krusei isolates and compared its activity with those of
amphotericin B and
fluconazole. CF1 mice were immunosuppressed with
cyclophosphamide and
cortisone acetate and were challenged intravenously with infecting inocula of each C. krusei isolate. Treatment with
SCH 51048 (50 or 100 mg/kg of
body weight per day orally) or
amphotericin B (2 mg/kg/day intraperitoneally) significantly prolonged the survival of infected mice and significantly reduced fungal titers in the kidneys (P < or = 0.05). Treatment with
fluconazole (100 mg/kg/day orally) had no effect. Both dosages of
SCH 51048 were as effective as
amphotericin B in improving survival, but the higher dosage was significantly (P < or = 0.05) better in reducing the fungal burden in the kidneys of infected animals. A dose-dependent response was observed with
SCH 51048 treatment, especially in organ clearance. Our results indicate that
SCH 51048 is the first
triazole that has in vivo activity against experimental
infection with C. krusei and deserves further evaluation.