In Vitro Activities of Voriconazole (UK-109,496) and Four Other Antifungal Agents against 394 Clinical Isolates of Candida spp

Abstract

Voriconazole (formerly UK-109,496) is a new monotriazole antifungal agent which has potent activity against Candida , Cryptococcus , and Aspergillus species. We investigated the in vitro activity of voriconazole compared to those of fluconazole, itraconazole, amphotericin B, and flucytosine (5FC) against 394 bloodstream isolates of Candida (five species) obtained from more than 30 different medical centers. MICs of all antifungal drugs were determined by the method recommended by the National Committee for Clinical Laboratory Standards using RPMI 1640 test medium. Overall, voriconazole was quite active against all the yeast isolates (MIC at which 90% of the isolates are inhibited [MIC ₉₀ ], ≤0.5 μg/ml). Candida albicans was the most susceptible species (MIC ₉₀ , 0.06 μg/ml) and Candida glabrata and Candida krusei were the least (MIC ₉₀ , 1 μg/ml). Voriconazole was more active than amphotericin B and 5FC against all species except C. glabrata and was also more active than itraconazole and fluconazole. For isolates of Candida spp. with decreased susceptibility to fluconazole and itraconazole MICs of voriconazole were also higher. Based on these results, voriconazole has promising antifungal activity and further in vitro and in vivo investigations are warranted.