title: Multilaboratory study of epidemiological cutoff values for detection of resistance in eight Candida species to fluconazole, posaconazole, and voriconazole.
abstract: Although epidemiological cutoff values (ECVs) have been established for Candida spp. and the triazoles, they are based on MIC data from a single laboratory. We have established ECVs for eight Candida species and fluconazole, posaconazole, and voriconazole based on wild-type (WT) MIC distributions for isolates of C. albicans (n=11,241 isolates), C. glabrata (7,538), C. parapsilosis (6,023), C. tropicalis (3,748), C. krusei (1,073), C. lusitaniae (574), C. guilliermondii (373), and C. dubliniensis (162). The 24-h CLSI broth microdilution MICs were collated from multiple laboratories (in Canada, Brazil, Europe, Mexico, Peru, and the United States). The ECVs for distributions originating from ≥6 laboratories, which included ≥95% of the modeled WT population, for fluconazole, posaconazole, and voriconazole were, respectively, 0.5, 0.06 and 0.03 μg/ml for C. albicans, 0.5, 0.25, and 0.03 μg/ml for C. dubliniensis, 8, 1, and 0.25 μg/ml for C. glabrata, 8, 0.5, and 0.12 μg/ml for C. guilliermondii, 32, 0.5, and 0.25 μg/ml for C. krusei, 1, 0.06, and 0.06 μg/ml for C. lusitaniae, 1, 0.25, and 0.03 μg/ml for C. parapsilosis, and 1, 0.12, and 0.06 μg/ml for C. tropicalis. The low number of MICs (<100) for other less prevalent species (C. famata, C. kefyr, C. orthopsilosis, C. rugosa) precluded ECV definition, but their MIC distributions are documented. Evaluation of our ECVs for some species/agent combinations using published individual MICs for 136 isolates (harboring mutations in or upregulation of ERG11, MDR1, CDR1, or CDR2) and 64 WT isolates indicated that our ECVs may be useful in distinguishing WT from non-WT isolates.
authors.affiliation: VCU Medical Center, Richmond, Virginia, USA.
authors.forename: A
authors.initials: A
authors.lastname: Espinel-Ingroff
authors.forename: M A
authors.initials: MA
authors.lastname: Pfaller
authors.forename: B
authors.initials: B
authors.lastname: Bustamante
authors.forename: E
authors.initials: E
authors.lastname: Canton
authors.forename: A
authors.initials: A
authors.lastname: Fothergill
authors.forename: J
authors.initials: J
authors.lastname: Fuller
authors.forename: G M
authors.initials: GM
authors.lastname: Gonzalez
authors.forename: C
authors.initials: C
authors.lastname: Lass-Flörl
authors.forename: S R
authors.initials: SR
authors.lastname: Lockhart
authors.forename: E
authors.initials: E
authors.lastname: Martin-Mazuelos
authors.forename: J F
authors.initials: JF
authors.lastname: Meis
authors.forename: M S C
authors.initials: MS
authors.lastname: Melhem
authors.forename: L
authors.initials: L
authors.lastname: Ostrosky-Zeichner
authors.forename: T
authors.initials: T
authors.lastname: Pelaez
authors.forename: M W
authors.initials: MW
authors.lastname: Szeszs
authors.forename: G
authors.initials: G
authors.lastname: St-Germain
authors.forename: L X
authors.initials: LX
authors.lastname: Bonfietti
authors.forename: J
authors.initials: J
authors.lastname: Guarro
authors.forename: J
authors.initials: J
authors.lastname: Turnidge
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects*; D015725:Fluconazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D011743:Pyrimidines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; C101425:posaconazole; D015725:Fluconazole; D065819:Voriconazole