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.
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.
authors.affiliation: VCU Medical Center, Richmond, Virginia, USA avingrof@vcu.edu.
authors.forename: A
authors.initials: A
authors.lastname: Espinel-Ingroff
authors.affiliation: Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: A
authors.initials: A
authors.lastname: Chakrabarti
authors.affiliation: Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
authors.forename: A
authors.initials: A
authors.lastname: Chowdhary
authors.affiliation: Instituto Nacional de Enfermedades Infecciosas Dr. C. G. Malbrán, Buenos Aires, Argentina.
authors.forename: S
authors.initials: S
authors.lastname: Cordoba
authors.affiliation: Université Paris-Descartes, Faculté de Médecine, APHP, Hôpital Européen Georges Pompidou, Unité de Parasitologie-Mycologie, Service de Microbiologie, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Dannaoui
authors.affiliation: Institut National de Santé Publique du Québec, Laboratoire de Santé Publique du Québec, Sainte-Anne-de-Bellevue, Québec, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Dufresne
authors.affiliation: University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: A
authors.initials: A
authors.lastname: Fothergill
authors.affiliation: University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ghannoum
authors.affiliation: Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México.
authors.forename: G M
authors.initials: GM
authors.lastname: Gonzalez
authors.affiliation: Facultat de Medicina, IISPV, URV, Reus, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Guarro
authors.affiliation: National Mycology Reference Centre, SA Pathology, Adelaide, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Kidd
authors.affiliation: The Innsbruck Medical University, Innsbruck, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Lass-Flörl
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital and Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: J F
authors.initials: JF
authors.lastname: Meis
authors.affiliation: Hospital General Universitario Gregorio Marañón, School of Medicine-Universidad Complutense, Madrid, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Pelaez
authors.affiliation: Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Tortorano
authors.affiliation: University of Adelaide, Adelaide, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Turnidge
mesh_terms: D000666:Amphotericin B / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D026141:Drug Resistance, Multiple, Fungal / Q000187:drug effects*; D006801:Humans; D017964:Itraconazole / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D009090:Mucorales / Q000187:drug effects*; D009091:Mucormycosis / Q000188:drug therapy*; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; D017964:Itraconazole; C101425:posaconazole; D000666:Amphotericin B