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, E. M. Johnson, C. C. Knapp, M. R. Motyl, L. Ostrosky-Zeichner, D. J. Sheehan, T. J. Walsh

Research output: Contribution to journalArticle

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 ≤2 μg/ml against posaconazole and voriconazole using the CLSI BMD method. An ECV of ≤1 μg/ml encompassed the WT population of A. fumigatus for itraconazole and voriconazole, whereas an ECV of ≤0.25 μg/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.

Original languageEnglish (US)
Pages (from-to)3142-3146
Number of pages5
JournalJournal of Clinical Microbiology
Volume47
Issue number10
DOIs
StatePublished - Oct 2009
Externally publishedYes

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Triazoles
Aspergillus fumigatus
Itraconazole
Azoles
Mutation
Sterols
Aspergillus
Fungi
Population
Genes
posaconazole
Voriconazole

ASJC Scopus subject areas

  • Microbiology (medical)

Cite this

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. / Pfaller, M. A.; Diekema, D. J.; Ghannoum, M. A.; Rex, J. H.; Alexander, B. D.; Andes, D.; Brown, S. D.; Chaturvedi, V.; Espinel-Ingroff, A.; Fowler, C. L.; Johnson, E. M.; Knapp, C. C.; Motyl, M. R.; Ostrosky-Zeichner, L.; Sheehan, D. J.; Walsh, T. J.

In: Journal of Clinical Microbiology, Vol. 47, No. 10, 10.2009, p. 3142-3146.

Research output: Contribution to journalArticle

Pfaller, MA, Diekema, DJ, Ghannoum, MA, Rex, JH, Alexander, BD, Andes, D, Brown, SD, Chaturvedi, V, Espinel-Ingroff, A, Fowler, CL, Johnson, EM, Knapp, CC, Motyl, MR, Ostrosky-Zeichner, L, Sheehan, DJ & Walsh, TJ 2009, '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 of Clinical Microbiology, vol. 47, no. 10, pp. 3142-3146. https://doi.org/10.1128/JCM.00940-09
Pfaller, M. A. ; Diekema, D. J. ; Ghannoum, M. A. ; Rex, J. H. ; Alexander, B. D. ; Andes, D. ; Brown, S. D. ; Chaturvedi, V. ; Espinel-Ingroff, A. ; Fowler, C. L. ; Johnson, E. M. ; Knapp, C. C. ; Motyl, M. R. ; Ostrosky-Zeichner, L. ; Sheehan, D. J. ; Walsh, T. J. / 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. In: Journal of Clinical Microbiology. 2009 ; Vol. 47, No. 10. pp. 3142-3146.
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AU - Rex, J. H.

AU - Alexander, B. D.

AU - Andes, D.

AU - Brown, S. D.

AU - Chaturvedi, V.

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AU - Fowler, C. L.

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