In vitro susceptibilities of Candida bloodstream isolates to the new triazole antifungal agents BMS-207147, Sch 56592, and voriconazole

BMS-207147, Sch 56592, and voriconazole are three new investigational triaz oles with broad-spectrum antifungal activity. The in vitro activities of th ese three agents were compared,vith those of itraconazole and fluconazole a gainst 1,300 bloodstream isolates of Candida species obtained from over 50 different medical centers in the United States. The MICs of all of the anti fungal drugs were determined by broth microdilution tests performed accordi ng to the National Committee for Clinical Laboratory Standards method using RPMI 1640 as a test medium. BMS-207147, Sch 56592, and voriconazole were a ll quite active against all Candida sp. isolates (MICs for 90% of the isola tes tested [MIC(90)s], 0.5, 1.0, and 0.5 mu g/ml, respectively). Candida al bicans was the most susceptible species (MIC(90)s, 0.03, 0.06, and 0.06 mu g/ml, respectively), and C. glabrata was the least susceptible (MIC(90)s, 4 .0, 4.0, and 2.0 mu g/ml, respectively). BMS-207147, Sch 56592, and voricon azole mere all more active than itraconazole and fluconazole against C. alb icans, C. parapsilosis, C. tropicalis, and C. krusei. There existed a clear rank order of in vitro activity of the five azoles examined in this study when they were tested versus C. glabrata: voriconazole > BMS-207147 = Sch 5 6592 = itraconazole > fluconazole (MIC(90)s, 2.0, 4.0, 4.0, 4.0, and 64 mu g/ml, respectively). For isolates of Candida spp, with decreased susceptibi lity to both itraconazole and fluconazole, the MICs of BMS-207147, Sch 5659 2, and voriconazole were also elevated. These results suggest that BMS-2071 47, Sch 56592, and voriconazole all possess promising antifungal activity a nd that further in vitro and in vivo investigations are warranted to establ ish the clinical value of this improved potency.