Antifungal activities of fluconazole, caspofungin (MK0991), and anidulafungin (LY 303366) alone and in combination against Candida spp. and Crytococcus neoformans via time-kill methods

The activities of the echinocandins caspofungin and anidulafungin were evaluated alone and in combination With fluconazole using time-kill methods against isolates of Candida albicans, Candida glabrata, Candida tropicalis, Candida krusei, and Cryptococcus neoformans. Antifungal concentrations tested against each isolate were 0.5 mug/mL and 20 mug/mL of fluconazole and 0.007 mug/mL and 2 mug/mL of both caspofungin and anidulafungin. In addition, 20 mug/mL of fluconazole was tested with 2 mug/mL of caspofungin and anidulafungin to test for additive or antagonistic activity. Finally 0.5 mug/mL of fluconazole was tested with 0.007 mug/mL of caspofungin and anidulafungin to test for synergy. Combinations of fluconazole and caspofungin or anidulafungin resulted in indifference. Azoleechinocandin combinations do not produce antagonistic effects; therefore, combinations of these agents may warrant future clinical evaluation. (C) 2002 Elsevier Science Inc. All rights reserved.