In vitro antifungal activities of voriconazole and reference agents as determined by NCCLS methods: Review of the literature

Voriconazole (Vfend(TM)) is a new triazole that currently is undergoing pha se III clinical trials. This review summarizes the published data obtained by NCCLS methods on the in vitro antifungal activity of voriconazole in com parison to itraconazole, amphotericin B, fluconazole, ketoconazole and fluc ytosine. Voriconazole had fungistatic activity against most yeasts and yeas tlike species (minimum inhibitory concentrations [MICs] <2 mug/ml) that was similar or superior to those of fluconazole, amphotericin B, and itraconaz ole. Against Candida glabrata and C. krusei, voriconazole MIC ranges were 0 .03 to 8 and 0.01 to >4 mug/ml, respectively. For four of the six Aspergill us spp. evaluated, voriconazole MICs (<0.03 to 2 mug/ml) were lower than am photericin B (0.25 to 4 mug/ml) and similar to itraconazole MICs. Voriconaz ole fungistatic activity against Fusarium spp. has been variable. Against F . oxysporum and solani, most studies showed MICs ranging from 0.25 to 8 mug /ml. Voriconazole had excellent fungistatic activity against five of the si x species of dimorphic fungi evaluated (MIC(90)s < 1.0 mug/ml). The excepti on was Sporothrix schenckii (MIC(90)s and geometric mean MICs greater than or equal to 8 mug/ml). Only amphotericin B had good fungistatic activity ag ainst the Zygomycetes species (voriconazole MICs ranged from 2 to > 32 mug/ ml). Voriconazole showed excellent in vitro activity (MICs < 0.03 to 1.0 mu g/ml) against most of the 50 species of dematiaceous fungi tested, but the activity of all the agents was poor against most isolates of Scedosporium p rolificans and Phaeoacremonium parasiticum (Phialophora parasitica) . Voric onazole had fungicidal activity against most Aspergillus spp., B. dermatiti dis, and some dematiaceous fungi. In vitro/in vivo correlations should aid in the interpretation of these results.