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Wild-type MIC distribution and epidemiological cutoff values for Aspergillus fumigatus and three triazoles as determined by the Clinical and Laboratory Standards Institute broth microdilution methods
Journal article   Open access   Peer reviewed

Wild-type MIC distribution and epidemiological cutoff values for Aspergillus fumigatus and three triazoles as determined by the Clinical and Laboratory Standards Institute broth microdilution methods

M A Pfaller, D J Diekema, M A Ghannoum, J H Rex, B D Alexander, D Andes, S D Brown, V Chaturvedi, A Espinel-Ingroff, C L Fowler, …
Journal of clinical microbiology, Vol.47(10), pp.3142-3146
10/2009
DOI: 10.1128/JCM.00940-09
PMCID: PMC2756953
PMID: 19692559
url
https://doi.org/10.1128/JCM.00940-09View
Published (Version of record) Open Access

Abstract

Antifungal susceptibility testing of Aspergillus species has been standardized by both the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Recent studies suggest the emergence of strains of Aspergillus fumigatus with acquired resistance to azoles. The mechanisms of resistance involve mutations in the cyp51A (sterol demethylase) gene, and patterns of azole cross-resistance have been linked to specific mutations. Studies using the EUCAST broth microdilution (BMD) method have defined wild-type (WT) MIC distributions, epidemiological cutoff values (ECVs), and cross-resistance among the azoles. We tested a collection of 637 clinical isolates of A. fumigatus for which itraconazole MICs were < or = 2 microg/ml against posaconazole and voriconazole using the CLSI BMD method. An ECV of < or = 1 microg/ml encompassed the WT population of A. fumigatus for itraconazole and voriconazole, whereas an ECV of < or = 0.25 microg/ml was established for posaconazole. Our results demonstrate that the WT distribution and ECVs for A. fumigatus and the mold-active triazoles were the same when determined by the CLSI or the EUCAST BMD method. A collection of 43 isolates for which itraconazole MICs fell outside of the ECV were used to assess cross-resistance. Cross-resistance between itraconazole and posaconazole was seen for 53.5% of the isolates, whereas cross-resistance between itraconazole and voriconazole was apparent in only 7% of the isolates. The establishment of the WT MIC distribution and ECVs for the azoles and A. fumigatus will be useful in resistance surveillance and is an important step toward the development of clinical breakpoints.
 Antifungal Agents - pharmacology Aspergillus fumigatus - drug effects Microbial Sensitivity Tests Triazoles - pharmacology Aspergillus fumigatus - isolation & purification Aspergillosis - microbiology Drug Resistance, Fungal

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