In Vitro Fungicidal Activities of Voriconazole, Itraconazole, and Amphotericin B against Opportunistic Moniliaceous and Dematiaceous Fungi

摘要

The NCCLS proposed standard M38-P describes standard parameters for testing the fungistatic antifungal activities (MICs) of established agents against filamentous fungi (molds); however, standard conditions are not available for testing their fungicidal activities (minimum fungicidal or lethal concentrations [MFCs]). This study evaluated the in vitro fungistatic and fungicidal activities of voriconazole, itraconazole, and amphotericin B against 260 common and emerging molds (174 Aspergillus sp. isolates [five species], 23Fusarium sp. isolates [three species], 6Paecilomyces lilacinus isolates, 6 Rhizopus arrhizus isolates, 23 Scedosporium sp. isolates, 23 dematiaceous fungi, and 5 Trichoderma longibrachiatumisolates). MICs were determined by following the NCCLS M38-P broth microdilution method. MFCs were the lowest drug dilutions that resulted in fewer than three colonies. Voriconazole showed similar or better fungicidal activity (MFC at which 90% of isolates tested are killed [MFC₉₀], 1 to 2 μg/ml) than the reference agents forAspergillus spp. with the exception of Aspergillus terreus (MFC₉₀ of voriconazole and amphotericin B, >8 μg/ml). The voriconazole geometric mean (G mean) MFC forScedosporium apiospermum was lower (2.52 μg/ml) than those of the other two agents (5.75 to 7.5 μg/ml). In contrast, amphotericin B and itraconazole G mean MFCs for R. arrhizuswere 2.1 to 2.2 μg/ml, but that for voriconazole was >8 μg/ml. Little or no fungicidal activity was shown for Fusariumspp. (2 to >8 μg/ml) and Scedosporium prolificans (>8 μg/ml) by the three agents, but voriconazole had some activity against P. lilacinus and T. longibrachiatum (G mean MFCs, 1.8 and 4 μg/ml, respectively). The fungicidal activity of the three agents was similar (G mean MFC, 1.83 to 2.36 μg/ml) for the dematiaceous fungi with the exception of the azole MFCs (>8 μg/ml) for some Bipolaris spicifera and Dactylaria constricta var. gallopava. These data extend and corroborate the available fungicidal results for the three agents. The role of the MFC as a predictor of clinical outcome needs to be established in clinical trials by following standardized testing conditions for determination of these in vitro values.