JCM Accepts, published online ahead of print on 18 June 2008
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J. Clin. Microbiol. doi:10.1128/JCM.00535-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

In Vitro Survey of Triazole Cross-Resistance Among More Than 700 Clinical Isolates of Aspergillus species

M. A. Pfaller*, S. A. Messer, L. Boyken, C. Rice, S. Tendolkar, R. J. Hollis, and D. J. Diekema

Departments of Pathology, and Medicine, Roy J. and Lucille A. Carver College of Medicine, and Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa 52242

* To whom correspondence should be addressed. Email: michael-pfaller{at}uiowa.edu.


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Abstract

Few data exist to describe in vitro patterns of cross resistance among large collections of clinical Aspergillus, including species other than A. fumigatus. We examined 771 Aspergillus spp. clinical isolates collected from 2000-2006 as part of a global antifungal surveillance program (553 A. fumigatus, 76 A. flavus, 59 A. niger, 35 A. terreus, 24 A. versicolor, and 24 other Aspergillus species). Antifungal susceptibility testing was performed by the Clinical and Laboratory Standards Institute (CLSI) M38-A broth dilution method against itraconazole( ITR), posaconazole (POS), ravuconazole (RAV) and voriconazole (VOR). We examined the potential for cross-resistance using measures of correlation overall and by species. Most Aspergillus had MICs of ≤1 µg/mL to each triazole (from 88% for ITR to 98% for VOR and POS). When all 771 isolates were examined, there were statistically significant correlations for all six triazole-triazole MIC comparisons. For A. fumigatus, the strongest correlations were seen for VOR-RAV (r=0.7) and ITR-POS (r=0.4). Similarly, for A. flavus only VOR-RAV and ITR-POS MICs demonstrated statistically significant positive correlations. We demonstrate a correlation among triazole MICs for Aspergillus, which for the most common species (A. fumigatus and A. flavus) is strongest between VOR-RAV and ITR-POS. However, Aspergillus species with MICs of >2 µg/mL to VOR or POS remain extremely rare (<1%).




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