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

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 of Candida spp., Cryptococcus neoformans , and Trichosporon 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 [MFC 90 s], 0.5 to 4 μg/ml for 6 of 9 species tested) than SCH56592 (MFC 90 s, 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.