Comparison of the in vitro activities of the echinocandin LY303366, the pneumocandin MK-0991, and fluconazole against Candida species and Cryptococcus neoformans

Abstract

Two new glucan synthesis inhibitors, the echinocandin LY303366 and the pneumocandin MK-0991 (formerly L-743,872), were studied for their antifungal activities in vitro in relation to each other and in relation to the activity of the triazole fluconazole. Systematic analysis of broth macrodilution testing by varying the starting inoculum size, medium composition, medium pH, temperature of incubation, length of incubation, or selection of endpoints failed to identify significant differences in antifungal activity for either LY303366 or MK-0991 in comparison to the activity under standard test conditions specified for other antifungal agents in National Committee for Clinical Laboratory Standards (NCCLS) document M27A. Under standardized conditions, both drugs exhibited prominent activity against Candida species including Candida glabrata and Candida krusei but showed little activity against Cryptococcus neoformans. This spectrum of activity differed from that of fluconazole, which exhibited marginal activity against C. glabrata and C. krusei but prominent activity against other Candida species and C. neoformans. For individual strains, broth microdilution MICs of LY303366 and MK-0991 were similar to but frequently higher than broth macrodilution results. In contrast, fluconazole broth microdilution MICs were often lower than broth microdilution results. We conclude that the test conditions specified in NCCLS document M27A are applicable to these two new glucan synthesis inhibitors and that systematic differences between broth microdilution procedures and the broth macrodilution reference standard will need to be addressed before the two test methods can be used interchangeably.