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Journal of Clinical Microbiology, September 2002, p. 3204-3208, Vol. 40, No. 9
0095-1137/02/$04.00+0     DOI: 10.1128/JCM.40.9.3204-3208.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Testing Conditions for Determination of Minimum Fungicidal Concentrations of New and Established Antifungal Agents for Aspergillus spp.: NCCLS Collaborative Study

A. Espinel-Ingroff,1* A. Fothergill,2 J. Peter,3 M. G. Rinaldi,2 and T. J. Walsh3

Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, Virginia;,1 University of Texas Health Science Center, San Antonio, Texas;,2 National Cancer Institute, Bethesda, Maryland3

Received 7 March 2002/ Returned for modification 16 April 2002/ Accepted 13 June 2002

Standard conditions are not available for evaluating the minimum fungicidal concentrations (MFCs) of antifungal agents. This multicenter collaborative study investigated the reproducibility in three laboratories of itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B MFCs for 15 selected isolates of Aspergillus spp. After MIC determinations for the 15 isolates in each center by the NCCLS M38-A broth microdilution method with four media, standard RPMI 1640 (RPMI), RPMI with 2% dextrose, antibiotic medium 3 (M3), and M3 with 2% dextrose, MFCs were determined for each isolate-medium-drug combination. MFCs were defined as the lowest drug dilutions that yielded <3 colonies (approximately 99 to 99.5% killing activity). The highest reproducibility (96 to 100%) was for amphotericin B MFCs with the four media. Although reproducibility was more variable and medium dependent for the azoles (91 to 98%), agreement was good to excellent for itraconazole, ravuconazole, and voriconazole MFCs with RPMI and M3 (93 to 98%). For posaconazole, the agreement was higher with M3 media (91 to 96%) than with RPMI media (91%). These data extend the refinement of testing guidelines for susceptibility testing of Aspergillus spp. and warrant consideration for introduction into future versions of the M38 document. The role of the MFC under these standardized testing conditions as a predictor of clinical outcome needs to be established in clinical trials.

* Corresponding author. Mailing address: Medical College of Virginia Campus/VCU, 1101 Marshall St., Sanger Hall Room 7-049, P.O. Box 980049, Richmond, VA 23298-0049. Phone: (804) 828-9711. Fax: (804) 828-3097. E-mail: avingrof{at}hsc.vcu.edu.

Journal of Clinical Microbiology, September 2002, p. 3204-3208, Vol. 40, No. 9
0095-1137/02/$04.00+0     DOI: 10.1128/JCM.40.9.3204-3208.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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