Comparison of the efficacy of polyenes and triazoles against hematogenous Candida krusei infection in neutropenic mice.

Abstract

Candida krusei is reported to cause serious infections in immunocompromised patients, particularly those receiving prophylaxis with antifungal azoles. Treatment of this infection can be very challenging. The efficacy of amphotericin B, liposomal amphotericin B (three dosages), fluconazole, and D0870 (a new experimental oral bis-triazole) was assessed in a CF1 mouse model of hematogenous C. krusei infection. Increased survival time and reduced kidney fungal burden were achieved with treatment with amphotericin B at 2 mg/kg/day and liposomal amphotericin B at 8 and 15 mg/kg/day. D0870 at 25 mg/kg/day increased survival time but had no effect on clearance from organs, while the survival and clearance from organs of mice treated with fluconazole at a dose of 100 mg/kg/day did not differ from those of untreated animals. These findings suggest that deoxycholate and liposome-encapsulated amphotericin B are active against disseminated C. krusei infection in neutropenic mice and confirm the in vitro and in vivo resistance of this species to fluconazole.