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 <i>Mucorales</i>

Abstract

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