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

Espinel Ingroff, A. y Turnidge, J. y Alastruey Izquierdo, A. y Dannaoui, E. y Garcia Effron, G. y Guinea, J. y Kidd, S. y Pelaez, T. y Sanguinetti, M. y Meletiadis, J. y Botterel, F. y Bustamante, B. y Chen, Y.-C. y Chakrabarti, A. y Chowdhary, A. y Chryssanthou, E. y Córdoba, S. y Gonzalez, G. M. y Guarro, J. y Johnson, E. M. y Kus, J. V. y Lass Flörl, C. y Linares Sicilia, M. J. y Martín Mazuelos, E. y Negri, C. E. y Pfaller, M. A. y Tortorano, A. M. (2018) Posaconazole MIC Distributions for Aspergillus fumigatus Species Complex by Four Methods: Impact of cyp51A Mutations on Estimation of Epidemiological Cutoff Values. Antimicrobial Agents and Chemotherapy, 62 (4). pp. 1-11. ISSN 0066-4804

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URL o página oficial: http://doi.org/10.1128/AAC.01916-17

Resumen

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. KEYWORDS Aspergillus fumigatus, CLSI ECVs, ECVs, EUCAST ECVs, Etest, SYO, cyp51A mutants, posaconazole, triazole resistance, wild type

Tipo de elemento: Article
Materias: R Medicina > RM Terapéutica, Farmacología
Divisiones: Medicina
Usuario depositante: Lic. Josimar Pulido
Creadores:
CreadorEmailORCID
Espinel Ingroff, A.NO ESPECIFICADONO ESPECIFICADO
Turnidge, J.NO ESPECIFICADONO ESPECIFICADO
Alastruey Izquierdo, A.NO ESPECIFICADONO ESPECIFICADO
Dannaoui, E.NO ESPECIFICADONO ESPECIFICADO
Garcia Effron, G.NO ESPECIFICADONO ESPECIFICADO
Guinea, J.NO ESPECIFICADONO ESPECIFICADO
Kidd, S.NO ESPECIFICADONO ESPECIFICADO
Pelaez, T.NO ESPECIFICADONO ESPECIFICADO
Sanguinetti, M.NO ESPECIFICADONO ESPECIFICADO
Meletiadis, J.NO ESPECIFICADONO ESPECIFICADO
Botterel, F.NO ESPECIFICADONO ESPECIFICADO
Bustamante, B.NO ESPECIFICADONO ESPECIFICADO
Chen, Y.-C.NO ESPECIFICADONO ESPECIFICADO
Chakrabarti, A.NO ESPECIFICADONO ESPECIFICADO
Chowdhary, A.NO ESPECIFICADONO ESPECIFICADO
Chryssanthou, E.NO ESPECIFICADONO ESPECIFICADO
Córdoba, S.NO ESPECIFICADONO ESPECIFICADO
Gonzalez, G. M.NO ESPECIFICADONO ESPECIFICADO
Guarro, J.NO ESPECIFICADONO ESPECIFICADO
Johnson, E. M.NO ESPECIFICADONO ESPECIFICADO
Kus, J. V.NO ESPECIFICADONO ESPECIFICADO
Lass Flörl, C.NO ESPECIFICADONO ESPECIFICADO
Linares Sicilia, M. J.NO ESPECIFICADONO ESPECIFICADO
Martín Mazuelos, E.NO ESPECIFICADONO ESPECIFICADO
Negri, C. E.NO ESPECIFICADONO ESPECIFICADO
Pfaller, M. A.NO ESPECIFICADONO ESPECIFICADO
Tortorano, A. M.NO ESPECIFICADONO ESPECIFICADO
Fecha del depósito: 01 Jun 2020 13:11
Última modificación: 01 Jun 2020 13:11
URI: http://eprints.uanl.mx/id/eprint/16313

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