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Type: Journal article
Title: 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
Author: Espinel-Ingroff, A.
Chakrabarti, A.
Chowdhary, A.
Cordoba, S.
Dannaoui, E.
Dufresne, P.
Fothergill, A.
Ghannoum, M.
Gonzalez, G.
Guarro, J.
Kidd, S.
Lass-Flörl, C.
Meis, J.
Pelaez, T.
Tortorano, A.
Turnidge, J.
Citation: Antimicrobial Agents and Chemotherapy, 2015; 59(3):1745-1750
Publisher: American Society for Microbiology
Issue Date: 2015
ISSN: 0066-4804
Statement of
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 and J. Turnidge
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. Wild-type (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.
Keywords: Humans; Mucorales; Mucormycosis; Amphotericin B; Triazoles; Itraconazole; Antifungal Agents; Microbial Sensitivity Tests; Drug Resistance, Multiple, Fungal
Rights: © 2015 by the American Society for Microbiology.
RMID: 0030022503
DOI: 10.1128/AAC.04435-14
Appears in Collections:Microbiology and Immunology publications

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