Multicenter evaluation of MIC distributions for epidemiologic cutoff value definition to detect amphotericin B, posaconazole, and itraconazole resistance among the most clinically relevant species of Mucorales

A. Espinel-Ingroff, A. Chakrabarti, A. Chowdhary, S. Cordoba, E. Dannaoui, P. Dufresne, A. Fothergill, M. Ghannoum, G. M. Gonzalez, J. Guarro, S. Kidd, C. Lass-Flörl, J. F. Meis, T. Pelaez, A. M. Tortorano, J. Turnidge

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Clinical breakpoints (CBPs) have not been established for the Mucorales and any antifungal agent. In lieu of CBPs, epidemiologic cutoff values (ECVs) are proposed for amphotericin B, posaconazole, and itraconazole and four Mucorales species. Wildtype (WT) MIC distributions (organisms in a species-drug combination with no detectable acquired resistance mechanisms) were defined with available pooled CLSI MICs from 14 laboratories (Argentina, Australia, Canada, Europe, India, Mexico, and the United States) as follows: 10 Apophysomyces variabilis, 32 Cunninghamella bertholletiae, 136 Lichtheimia corymbifera, 10 Mucor indicus, 123 M. circinelloides, 19 M. ramosissimus, 349 Rhizopus arrhizus, 146 R. microsporus, 33 Rhizomucor pusillus, and 36 Syncephalastrum racemosum isolates. CLSI broth microdilution MICs were aggregated for the analyses. ECVs comprising ≥95% and ≥97.5% of the modeled populations were as follows: amphotericin B ECVs for L. corymbifera were 1 and 2 μg/ml, those for M. circinelloides were 1 and 2 μg/ml, those for R. arrhizus were 2 and 4 μg/ml, and those for R. microsporus were 2 and 2 μg/ml, respectively; posaconazole ECVs for L. corymbifera were 1 and 2, those for M. circinelloides were 4 and 4, those for R. arrhizus were 1 and 2, and those for R. microsporus were 1 and 2, respectively; both itraconazole ECVs for R. arrhizus were 2 μg/ ml. ECVs may aid in detecting emerging resistance or isolates with reduced susceptibility (non-WT MICs) to the agents evaluated.

Original languageEnglish (US)
Pages (from-to)1745-1750
Number of pages6
JournalAntimicrobial agents and chemotherapy
Volume59
Issue number3
DOIs
StatePublished - Mar 1 2015

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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