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 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], 23 Fusarium sp. isolates [three species], 6 Paecilomyces lilacinus isolates, 6 Rhizopus arrhizus isolates, 23 Scedosporium sp. isolates, 23 dematiaceous fungi, and 5 Trichoderma longibrachiatum isolates). 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 [MFC(90)], 1 to 2 microg/ml) than the reference agents for Aspergillus spp. with the exception of Aspergillus terreus (MFC(90) of voriconazole and amphotericin B, >8 microg/ml). The voriconazole geometric mean (G mean) MFC for Scedosporium apiospermum was lower (2.52 microg/ml) than those of the other two agents (5.75 to 7.5 microg/ml). In contrast, amphotericin B and itraconazole G mean MFCs for R. arrhizus were 2.1 to 2.2 microg/ml, but that for voriconazole was >8 microg/ml. Little or no fungicidal activity was shown for Fusarium spp. (2 to >8 microg/ml) and Scedosporium prolificans (>8 microg/ml) by the three agents, but voriconazole had some activity against P. lilacinus and T. longibrachiatum (G mean MFCs, 1.8 and 4 microg/ml, respectively). The fungicidal activity of the three agents was similar (G mean MFC, 1.83 to 2.36 microg/ml) for the dematiaceous fungi with the exception of the azole MFCs (>8 microg/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.
Division of Infectious Diseases, Medical Mycology Research Laboratory, Medical College of Virginia, Virginia Commonwealth University, P.O. Box 980049, Richmond, VA 23298-0049, USA. avingrof@hsc.vcu.edu
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Espinel-Ingroff
D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D005658:Fungi / Q000187:drug effects*; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests / Q000379:methods / Q000592:standards; D009181:Mycoses / Q000382:microbiology; D009894:Opportunistic Infections / Q000382:microbiology; D011743:Pyrimidines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D017964:Itraconazole; D000666:Amphotericin B; D065819:Voriconazole