In vitro antifungal activity of a novel lipopeptide antifungal agent, FK463, against various fungal pathogens

The antifungal activities of FK463 against Various pathogenic fungi were tested by standard broth microdilution methods, and compared with the activities of five currently available antifungal agents; viz., fluconazole (FLCZ), itraconazole, miconazole, amphotericin B and flucytosine. Fourteen clinical isolates of Candida albicans categorized as FLCZ susceptible, FLCZ susceptible-dose dependent and FLCZ resistant were similarly susceptible to FK463 with geometric (GM) MIC values of 0.010, 0.011 and 0.015 mug/ml, respectively. All of 17 clinical isolates of Aspergillus fumigatus were inhibited by FK463 at 0.0078 mug/ml or lower concentrations. The antifungal activity of FK463 against a wider range of medically important yeasts and filamentous fungi were studied using stock fungal strains. While Cryptococcus, Trichosporon, Fusarium, Pseudallescheria and Alternaria species or zygomycetes were scarcely or not inhibited by 16 mug/ml of FK463, two Candida species (C. albicans, C. glabrata), as well as all species of Aspergillus, Paecilomyces and Penicillium, were highly susceptible with GM-MICs of less than or equal to0.008 mug/ml. The other fungal species including several non-albicans Candida were less susceptible with GM-MICs ranging between 0.016 and 2 mug/ml. MICs of the reference drugs were within the range thus previously reported. These results suggest that FK463 be of use in the treatment of serious fungal infections.