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Posaconazole MIC Distributions for Aspergillus fumigatus Species Complex by Four Methods: Impact of cyp51A Mutations on Estimation of Epidemiological Cutoff Values

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dc.contributor.author Espinel-Ingroff, A.
dc.contributor.author Turnidge, J.
dc.contributor.author Alastruey-Izquierdo, A.
dc.contributor.author Dannaoui, E.
dc.contributor.author Garcia-Effron, G.
dc.contributor.author Guinea, J.
dc.contributor.author Kidd, S.
dc.contributor.author Pelaez, T.
dc.contributor.author Sanguinetti, M.
dc.contributor.author Meletiadis, J.
dc.contributor.author Botterel, F.
dc.contributor.author Bustamante, B.
dc.contributor.author Chen, Y.-C.
dc.contributor.author Chakrabarti, A.
dc.contributor.author Chowdhary, A.
dc.contributor.author Chryssanthou, E.
dc.contributor.author Córdoba, S.
dc.contributor.author Gonzalez, G. M.
dc.contributor.author Guarro, J.
dc.contributor.author Johnson, E. M.
dc.contributor.author Kus, J. V.
dc.contributor.author Lass-Flörl, C.
dc.contributor.author Linares-Sicilia, M. J.
dc.contributor.author Martín-Mazuelos, E.
dc.contributor.author Negri, C. E.
dc.contributor.author Pfaller, M. A.
dc.contributor.author Tortorano, A. M.
dc.date.accessioned 2018-11-30T22:50:35Z
dc.date.available 2018-11-30T22:50:35Z
dc.date.issued 2018
dc.identifier.uri https://hdl.handle.net/20.500.12866/4154
dc.description.abstract Estimating epidemiological cutoff endpoints (ECVs/ECOFFS) may be hindered by the overlap of MICs for mutant and nonmutant strains (strains harboring or not harboring mutations, respectively). Posaconazole MIC distributions for the Aspergillus fumigatus species complex were collected from 26 laboratories (in Australia, Canada, Europe, India, South and North America, and Taiwan) and published studies. Distributions that fulfilled CLSI criteria were pooled and ECVs were estimated. The sensitivity of three ECV analytical techniques (the ECOFFinder, normalized resistance interpretation [NRI], derivatization methods) to the inclusion of MICs for mutants was examined for three susceptibility testing methods (the CLSI, EUCAST, and Etest methods). The totals of posaconazole MICs for nonmutant isolates (isolates with no known cyp51A mutations) and mutant A. fumigatus isolates were as follows: by the CLSI method, 2,223 and 274, respectively; by the EUCAST method, 556 and 52, respectively; and by Etest, 1,365 and 29, respectively. MICs for 381 isolates with unknown mutational status were also evaluated with the Sensititre YeastOne system (SYO). We observed an overlap in posaconazole MICs among nonmutants and cyp51A mutants. At the commonly chosen percentage of the modeled wild-type population (97.5%), almost all ECVs remained the same when the MICs for nonmutant and mutant distributions were merged: ECOFFinder ECVs, 0.5 μg/ml for the CLSI method and 0.25 μg/ml for the EUCAST method and Etest; NRI ECVs, 0.5 μg/ml for all three methods. However, the ECOFFinder ECV for 95% of the nonmutant population by the CLSI method was 0.25 μg/ml. The tentative ECOFFinder ECV with SYO was 0.06 μg/ml (data from 3/8 laboratories). Derivatization ECVs with or without mutant inclusion were either 0.25 μg/ml (CLSI, EUCAST, Etest) or 0.06 μg/ml (SYO). It appears that ECV analytical techniques may not be vulnerable to overlap between presumptive wild-type isolates and cyp51A mutants when up to 11.6% of the estimated wild-type population includes mutants. en_US
dc.language.iso eng
dc.publisher American Society for Microbiology
dc.relation.ispartof urn:issn:1098-6596
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Aspergillus fumigatus en_US
dc.subject CLSI ECVs en_US
dc.subject cyp51A mutants en_US
dc.subject ECVs en_US
dc.subject Etest en_US
dc.subject EUCAST ECVs en_US
dc.subject posaconazole en_US
dc.subject SYO en_US
dc.subject triazole resistance en_US
dc.subject wild type en_US
dc.title Posaconazole MIC Distributions for Aspergillus fumigatus Species Complex by Four Methods: Impact of cyp51A Mutations on Estimation of Epidemiological Cutoff Values en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1128/AAC.01916-17
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.08
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.05


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