In vitro activities of a new lipopeptide antifungal agent, FK463, against a variety of clinically important fungi

The in vitro antifungal activity and spectrum of FK463 were compared with t hose of amphotericin B, fluconazole, and itraconazole by using a broth micr odilution method specified by National Committee for Clinical Laboratory St andards document M27-A (National Committee for Clinical Laboratory Standard s, Wayne, Pa., 1997). FK463 exhibited broad-spectrum activity against clini cally important pathogens including Candida species (MIC range, less than o r equal to 0.0039 to 2 mu g/ml) and Aspergillus species (MIC range, less th an or equal to 0.0039 to 0.0313 mu g/ml), and its MICs for such fungi were lower than those of the other antifungal agents tested. FK463 was also pote ntly active against azole-resistant Candida albicans as well as azole-susce ptible strains, and there was no cross-resistance with azoles. FK463 showed fungicidal activity against C. albicans, i.e., a 99% reduction in viabilit y after a 24-h exposure at concentrations above 0.0156 mu g/ml. The minimum fungicidal concentration (MFC) assays indicated that FK463 was fungicidal against most isolates of Candida species. In contrast, the MFCs of FK463 fo r A. fumigatus isolates were much higher than the MICs, indicating that its action is fungistatic against this species. FK463 had no activity against Cryptococcus neoformans, Trichosporon species, or Fusarium solani. Neither the test medium (kind and pH) nor the inoculum size greatly affected the MI Cs of FK463, while the addition of 4% human serum albumin increased the MIC s for Candida species and A. fumigatus more than 32 times. Results from pre clinical in vitro evaluations performed thus far indicate that FK463 should be a potent parenteral antifungal agent.