In vitro fungicidal activities of voriconazole, itraconazole, and amphotericin B against opportunistic moniliaceous and dematiaceous fungi

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 conce ntrations [MFCs]). This study evaluated the in vitro fungistatic and fungic idal activities of voriconazole, itraconazole, and amphotericin B against 2 60 common and emerging molds (174 Aspergillus sp. isolates [five species], 23 Fusarium sp. isolates [three species], 6 Paecilomyces lilacinus isolates , 6 Rhizopus arrhizus isolates, 23 Scedasporium sp. isolates, 23 dematiaceo us fungi, and 5 Trichoderma longibrachiatum isolates). MICs were determined by following the NCCLS M38-P broth microdilution method. MFCs mere the low est drug dilutions that resulted in fewer than three colonies. Voritonazole showed similar or better fungicidal activity (MFC at which 90% of isolates tested are killed [MFC90], 1 to 2 mug/ml) than the reference agents for As pergillus spp. with the exception of Aspergillus terreus (MFC90 of voricona zole and amphotericin B, >8 mug/ml). The voriconazole geometric mean (G mea n) MFC for Scedosporium apiospermum was lower (2.52 mug/ml) than those of t he other two agents (5.75 to 7.5 mug/ml). In contrast, amphotericin B and i traconazole G mean MFCs for R. arrhizus were 2.1 to 2.2 mug/ml, but that fo r voriconazole was >8 mug/ml. Little or no fungicidal activity was shown fo r Fusarium spp. (2 to >8 mug/ml) and Scedosporium prolificans (>8 mug/ml) b y the three agents, but voriconazole had some activity against P. lilacinus and T. longibrachiatum (G mean MFCs, 1.8 and 4 mug/ml, respectively). The fungicidal activity of the three agents was similar (G mean MFC, 1.83 to 2. 36 mug/ml) for the dematiaceous fungi with the exception of the azole MFCs (>8 mug/ml) for some Bipolaris spicifera and Dactylaria constricta var. gal lopava. These data extend and corroborate the available fungicidal results for the three agents. The role of the MFC as a predictor of clinical outcom e needs to be established in clinical trials by following standardized test ing conditions for determination of these in vitro values.