Τίτλος:
Posaconazole MIC distributions for aspergillus fumigatus species complex by four methods: Impact of cyp51a mutations on estimation of epidemiological cutoff values
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 theAspergillus 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 Yeast- One 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. © Copyright 2018 American Society for Microbiology. All Rights Reserved.
Συγγραφείς:
Espinel-Ingroff, A.
Turnidge, J.
Alastruey-Izquierdo, A.
Dannaoui, E.
Garcia-Effron, G.
Guinea, J.
Kidd, S.
Pelaez, T.
Sanguinetti, M.
Meletiadis, J.
Botterel, F.
Bustamante, B.
Chen, Y.-C.
Chakrabarti, A.
Chowdhary, A.
Chryssanthou, E.
Córdoba, S.
Gonzalez, G.M.
Guarro, J.
Johnson, E.M.
Kus, J.V.
Lass-Flörl, C.
Linares-Sicilia, M.J.
Martín-Mazuelos, E.
Negri, C.E.
Pfaller, M.A.
Tortorano, A.M.
Περιοδικό:
Antimicrobial Agents and Chemotherapy
Εκδότης:
American Society for Microbiology
Λέξεις-κλειδιά:
posaconazole; antifungal agent; posaconazole; triazole derivative; voriconazole, analytic method; antifungal susceptibility; Article; Aspergillus fumigatus; CLSI method; cyp51A gene; derivatization; epidemiological cutoff endpoint; epsilometer test; EUCAST method; fungal gene; fungal strain; fungus isolation; fungus mutant; gene mutation; minimum inhibitory concentration; nonhuman; parameters; priority journal; antifungal resistance; Aspergillus fumigatus; drug effect; genetics; microbial sensitivity test; mutation, Antifungal Agents; Aspergillus fumigatus; Drug Resistance, Fungal; Microbial Sensitivity Tests; Mutation; Triazoles; Voriconazole
DOI:
10.1128/AAC.01916-17
