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Journal of Clinical Microbiology, March 2001, p. 954-958, Vol. 39, No. 3
0095-1137/01/$04.00+0   DOI: 10.1128/JCM.39.3.954-958.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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

Ana Espinel-Ingroff*

Division of Infectious Diseases, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298-0049

Received 8 August 2000/Returned for modification 22 November 2000/Accepted 14 December 2000

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 [MFC90], 1 to 2 µg/ml) than the reference agents for Aspergillus spp. with the exception of Aspergillus terreus (MFC90 of voriconazole and amphotericin B, >8 µg/ml). The voriconazole geometric mean (G mean) MFC for Scedosporium 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. arrhizus were 2.1 to 2.2 µg/ml, but that for voriconazole was >8 µg/ml. Little or no fungicidal activity was shown for Fusarium spp. (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.

* Mailing address: Medical Mycology Research Laboratory, Medical College of Virginia/VCU, P.O. Box 980049, 1101 E. Marshall St., Sanger Hall, Room 7049, Richmond, VA 23298-0049. Phone: (804) 828-9711. Fax: (804) 828-3097. E-mail: avingrof{at}hsc.vcu.edu.

Journal of Clinical Microbiology, March 2001, p. 954-958, Vol. 39, No. 3
0095-1137/01/$04.00+0   DOI: 10.1128/JCM.39.3.954-958.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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