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
ABSTRACTClinical breakpoints (CBPs) have not been established for theMucoralesand any antifungal agent. In lieu of CBPs, epidemiologic cutoff values (ECVs) are proposed for amphotericin B, posaconazole, and itraconazole and fourMucoralesspecies. 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: 10Apophysomyces variabilis, 32Cunninghamella bertholletiae, 136Lichtheimia corymbifera, 10Mucor indicus, 123M. circinelloides, 19M. ramosissimus, 349Rhizopus arrhizus, 146R. microsporus, 33Rhizomucor pusillus, and 36Syncephalastrum racemosumisolates. 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 forL. corymbiferawere 1 and 2 μg/ml, those forM. circinelloideswere 1 and 2 μg/ml, those forR. arrhizuswere 2 and 4 μg/ml, and those forR. microsporuswere 2 and 2 μg/ml, respectively; posaconazole ECVs forL. corymbiferawere 1 and 2, those forM. circinelloideswere 4 and 4, those forR. arrhizuswere 1 and 2, and those forR. microsporuswere 1 and 2, respectively; both itraconazole ECVs forR. arrhizuswere 2 μg/ml. ECVs may aid in detecting emerging resistance or isolates with reduced susceptibility (non-WT MICs) to the agents evaluated.