Activity of BAL 4815 against filamentous fungi

Objectives: BAL 4815 is a new antifungal drug and it is the active component of the antifungal triazole BAL 8557 (the water-soluble precursor). We studied the in vitro fungistatic and fungicidal activities of BAL 4815 against 103 clinical isolates of filamentous fungi, including 51 isolates of Aspergillus spp. and 52 isolates of non-Aspergillus filamentous fungi. Methods: We evaluated the in vitro activity of BAL 4815 against 51 isolates of Aspergillus spp., 20 isolates of dematiaceous fungi, 18 isolates of hyaline Hyphomycetes and 14 isolates of Zygomycetes. MICs were determined following the CLSI M38-A broth microdilution method, using RPMI 1640 medium buffered to pH 7.0 with MOPS. Microdilution plates were incubated at 35 degrees C and read at 24 and 48 h (Mucorales were read at 24 h). Minimal fungicidal concentrations were also determined. Results: For all isolates, geometric mean MICs, MIC(50)s, MIC(90)s and MIC ranges (mg/L) were: Aspergillus spp., 1.67, 2, 4 and 0.5-4; dematiaceous fungi, 1.62, 1, > 8 and 0.03 to > 8; hyaline Hyphomycetes, 2.41, 2, > 8 and 0.03 to > 8; and Zygomycetes, 6.81, 8, > 8 and 0.03 to > 8. Differences in susceptibility between genera were noted. Scedosporium prolificans, Fusarium spp., Mucor spp. and Rhizopus spp. (MIC90 > 8 mg/L) were less susceptible than Aspergillus spp. (MIC90 = 4 mg/L). Conclusions: BAL 4815 has excellent in vitro activity against Aspergillus spp. and variable activity against other filamentous fungi.