The in vitro antifungal activity and spectrum of FK463 was compared with those of amphotericin B, fluconazole and itraconazole by using M27-A in a microdilution format. FK463 exhibited broad-spectrum activity against clinically important pathogens including Candida (MIC range, ≤0.0039 to 2 micro g/mL) and Aspergillus species (MIC range, ≤0.0039 to 0.0313 micro /mL), and its MIC levels against such fungi were lower than those of other antifungal agents tested. FK463 was also potently active against azole-resistant Candida albicans as well as azole-susceptible strains, and there was no cross-resistance with azole compounds. FK463 showed fungicidal activity against C. albicans, i.e., a 99% reduction in viability after 24-hour exposure at concentrations above 0.0156 micro g/mL. The minimum fungicidal concentrations of FK463 against 5 Candida species did not differ more than twofold from the MICs. Neither the test medium (kind and pH) nor the inoculum size greatly affected the activities of FK463, while addition of human serum albumin lowered the activity. Only a twofold increase in the MIC against C. albicans occurred during repeated exposure to subinhibitory concentrations indicating that FK463 has a low potential for causing resistance development. Results from preclinical evaluations performed thus far indicate that FK463 should be a potent parenteral antifungal agent.
Full conference title:
38th Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC 38th