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 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.
Karyotakis
N C
NC
Department of Internal Medicine, University of Texas Medical School, Houston.
Dignani
M C
MC
Anaissie
E J
EJ
D000666:Amphotericin B / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D002177:Candidiasis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D015725:Fluconazole / Q000627:therapeutic use; D007165:Immunosuppression Therapy; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009503:Neutropenia / Q000150:complications*; D014230:Triazoles / Q000627:therapeutic use*
D000935:Antifungal Agents; C094161:SCH 51048; D014230:Triazoles; D000666:Amphotericin B; D015725:Fluconazole