SCH-51048, A NEW ANTIFUNGAL TRIAZOLE ACTIVE AGAINST HEMATOGENOUS CANDIDA-KRUSEI INFECTIONS IN NEUTROPENIC MICE

Candida krusei is increasingly recognized as an opportunistic pathogen in immunocompromised patients and is inherently resistant to fluconaz ole. We tested the in vivo efficacy of SCH 51048, an investigational a ntifungal triazole, in experimental hematogenous murine infection caus ed by two C. krusei isolates and compared its activity with those of a mphotericin B and fluconazole. CF1 mice were immunosuppressed with cyc lophosphamide and cortisone acetate and were challenged intravenously with infecting inocula of each C. krusei isolate. Treatment with SCH 5 1048 (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 mite and significantly reduced fungal titers in the kidney s (P less than or equal to 0.05). Treatment with fluconazole (100 mg/k g/day orally) had no effect. Both dosages of SCH 51048 were as effecti ve as amphotericin B in improving survival, but the higher dosage was significantly (P less than or equal to 0.05) better in reducing the fu ngal burden in the kidneys of infected animals. A dose-dependent respo nse was observed with SCH 51048 treatment, especially in organ clearan ce. Our results indicate that SCH 51048 is the first triazole that has in vivo activity against experimental infection with C. krusei and de serves further evaluation.