In vitro antifungal activity of BMS-207147 and itraconazole against yeast strains that are non-susceptible to fluconazole

The activities of itraconazole and the new triazole BMS-207147 were determi ned against Candida strains that were susceptible-dose dependent (fluconazo le MICs 16 to 32 mu g/mL) or resistant (MICs greater than or equal to 64 mu g/mL) to fluconazole. These strains included clinical isolates of Candida krusei, Candida glabrata, and Candida albicans. In addition, 16 isogenic, g enetically characterized isolates of C. albicans, with progressively decrea sed susceptibility to fluconazole, were tested. BMS-207147 MICs to C. kruse i, a species considered intrinsically resistant to fluconazole, were at 0.1 3 to 0.5 mu g/mL. The population distribution of the fluconazole-nonsuscept ible C. glabrata was bimodal with BMS-207147/itraconazole A MICs at 0.5 to 2 mu g/mL and greater than or equal to 16 mu g/mL The EMS-207147 MICs to th e majority of fluconazole-nonsusceptible C. albicans strains tested were le ss than or equal to 1 mu g/mL. The activity of EMS-207147 was minimally aff ected by overexpression of the gene encoding the efflux pump MDR1, bmt MIC increases were observed with changes in ERG11 and with overexpression of th e CDR transporter gene. Nonetheless, EMS-207147 can be active against C. al bicans mutants containing cumulative resistance mechanisms to azoles. In ot her words, fluconazole-resistant candidal strains may be susceptible to BMS -207147. (C) 1999 Elsevier Science Inc.