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 te sted by standard broth microdilution methods, and compared with the activit ies of five currently available antifungal agents; viz., fluconazole (FLCZ) , itraconazole, miconazole, amphotericin B and flucytosine. Fourteen clinic al isolates of Candida albicans categorized as FLCZ susceptible, FLCZ susce ptible-dose dependent and FLCZ resistant were similarly susceptible to FK46 3 with geometric (GM) MIC values of 0.010, 0.011 and 0.015 mug/ml, respecti vely. All of 17 clinical isolates of Aspergillus fumigatus were inhibited b y FK463 at 0.0078 mug/ml or lower concentrations. The antifungal activity o f FK463 against a wider range of medically important yeasts and filamentous fungi were studied using stock fungal strains. While Cryptococcus, Trichos poron, Fusarium, Pseudallescheria and Alternaria species or zygomycetes wer e 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 equa l to0.008 mug/ml. The other fungal species including several non-albicans C andida were less susceptible with GM-MICs ranging between 0.016 and 2 mug/m l. MICs of the reference drugs were within the range thus previously report ed. These results suggest that FK463 be of use in the treatment of serious fungal infections.