Comparison of In Vitro Activities of the New Triazole SCH56592 and the Echinocandins MK-0991 (L-743,872) and LY303366 against Opportunistic Filamentous and Dimorphic Fungi and Yeasts

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Abstract
The in vitro antifungal activities of SCH56592, MK-0991, and LY303366 against 83 isolates of Acremonium strictum,Aspergillus flavus, Aspergillus fumigatus,Aspergillus terreus, Bipolaris spp.,Blastomyces dermatitidis, Cladophialophora bantiana, Fusarium oxysporum, Fusarium solani, Histoplasma capsulatum,Phialophora spp., Pseudallescheria boydii,Rhizopus arrhizus, Scedosporium prolificans, and Sporothrix schenckii were compared. The in vitro activities of these agents against 104 isolates of yeast pathogens ofCandida spp., Cryptococcus neoformans, andTrichosporon beigelii were also compared. MICs were determined by following a procedure under evaluation by the National Committee for Clinical Laboratory Standards (NCCLS) for broth microdilution testing of the filamentous fungi (visual MICs) and the NCCLS M27-A broth microdilution method for yeasts (both visual and turbidimetric MICs). The in vitro fungicidal activity of SCH56592 was superior (minimum fungicidal concentrations [MFCs], 0.25 to 4 μg/ml for 7 of 18 species tested) to those of MK-0991 and LY303366 (MFCs, 8 to >16 μg/ml for all species tested) for the molds tested, but the echinocandins had a broader spectrum of fungicidal activity (MFCs at which 90% of strains are inhibited [MFC90s], 0.5 to 4 μg/ml for 6 of 9 species tested) than SCH56592 (MFC90s, 0.25 to 8 μg/ml for 4 of 9 species tested) against most of the yeasts tested. Neither echinocandin had in vitro activity (MICs, >16 μg/ml) against C. neoformans and T. beigelii, while the SCH56592 MICs ranged from 0.12 to 1.0 μg/ml for these two species. The MICs of the three agents for the other species ranged from <0.03 to 4 μg/ml. These results suggest that these new agents have broad-spectrum activities in vitro; their effectiveness in the treatment of human mycoses is to be determined.

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