Nc. Karyotakis et al., SCH-51048, A NEW ANTIFUNGAL TRIAZOLE ACTIVE AGAINST HEMATOGENOUS CANDIDA-KRUSEI INFECTIONS IN NEUTROPENIC MICE, Antimicrobial agents and chemotherapy, 39(3), 1995, pp. 775-777
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.