title: Multicenter study of isavuconazole MIC distributions and epidemiological cutoff values for Aspergillus spp. for the CLSI M38-A2 broth microdilution method.
abstract: Epidemiological cutoff values (ECVs) were established for the new triazole isavuconazole and Aspergillus species wild-type (WT) MIC distributions (organisms in a species-drug combination with no detectable acquired resistance mechanisms) that were defined with 855 Aspergillus fumigatus, 444 A. flavus, 106 A. nidulans, 207 A. niger, 384 A. terreus, and 75 A. versicolor species complex isolates; 22 Aspergillus section Usti isolates were also included. CLSI broth microdilution MIC data gathered in Europe, India, Mexico, and the United States were aggregated to statistically define ECVs. ECVs were 1 μg/ml for the A. fumigatus species complex, 1 μg/ml for the A. flavus species complex, 0.25 μg/ml for the A. nidulans species complex, 4 μg/ml for the A. niger species complex, 1 μg/ml for the A. terreus species complex, and 1 μg/ml for the A. versicolor species complex; due to the small number of isolates, an ECV was not proposed for Aspergillus section Usti. These ECVs may aid in detecting non-WT isolates with reduced susceptibility to isavuconazole due to cyp51A (an A. fumigatus species complex resistance mechanism among the triazoles) or other mutations.
authors.affiliation: VCU Medical Center, Richmond, Virginia, USA. avingrof@vcu.edu
authors.forename: A
authors.initials: A
authors.lastname: Espinel-Ingroff
authors.forename: A
authors.initials: A
authors.lastname: Chowdhary
authors.forename: G M
authors.initials: GM
authors.lastname: Gonzalez
authors.forename: C
authors.initials: C
authors.lastname: Lass-Flörl
authors.forename: E
authors.initials: E
authors.lastname: Martin-Mazuelos
authors.forename: J
authors.initials: J
authors.lastname: Meis
authors.forename: T
authors.initials: T
authors.lastname: Peláez
authors.forename: M A
authors.initials: MA
authors.lastname: Pfaller
authors.forename: J
authors.initials: J
authors.lastname: Turnidge
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000382:microbiology; D001230:Aspergillus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D025141:Drug Resistance, Fungal; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005800:Genes, Fungal; D005843:Geography; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods / Q000592:standards*; D009154:Mutation; D009570:Nitriles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology; D012016:Reference Values; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D009570:Nitriles; D011725:Pyridines; D011743:Pyrimidines; D014230:Triazoles; C508735:isavuconazole; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus; D065819:Voriconazole