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

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...

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Autores principales: Espinel Ingroff, A., Turnidge, J., Alastruey Izquierdo, A., Dannaoui, E., García Effron, G., Guinea, J., Kidd, S. E., Pelaez, T., Sanguinetti, M., Meletiadis, J., Botterel, F., Bustamante, B., Chen, Y.-C., Chakrabarti, A., Chowdhary, A., Chryssanthou, E., Córdoba, S., González González, Gloria María, Guarro, Josep, Johnson, E. M., Kus, J. V., Lass Flörl, Cornelia, Linares Sicilia, M. J., Martín Mazuelos, E., Negri, C. E., Pfaller, M. A., Tortorano, A. M.
Formato: Artículo
Lenguaje:inglés
Publicado: American Society for Microbiology 2018
Materias:
Acceso en línea:http://eprints.uanl.mx/16313/1/158.pdf
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author Espinel Ingroff, A.
Turnidge, J.
Alastruey Izquierdo, A.
Dannaoui, E.
García Effron, G.
Guinea, J.
Kidd, S. E.
Pelaez, T.
Sanguinetti, M.
Meletiadis, J.
Botterel, F.
Bustamante, B.
Chen, Y.-C.
Chakrabarti, A.
Chowdhary, A.
Chryssanthou, E.
Córdoba, S.
González González, Gloria María
Guarro, Josep
Johnson, E. M.
Kus, J. V.
Lass Flörl, Cornelia
Linares Sicilia, M. J.
Martín Mazuelos, E.
Negri, C. E.
Pfaller, M. A.
Tortorano, A. M.
author_facet Espinel Ingroff, A.
Turnidge, J.
Alastruey Izquierdo, A.
Dannaoui, E.
García Effron, G.
Guinea, J.
Kidd, S. E.
Pelaez, T.
Sanguinetti, M.
Meletiadis, J.
Botterel, F.
Bustamante, B.
Chen, Y.-C.
Chakrabarti, A.
Chowdhary, A.
Chryssanthou, E.
Córdoba, S.
González González, Gloria María
Guarro, Josep
Johnson, E. M.
Kus, J. V.
Lass Flörl, Cornelia
Linares Sicilia, M. J.
Martín Mazuelos, E.
Negri, C. E.
Pfaller, M. A.
Tortorano, A. M.
author_sort Espinel Ingroff, A.
collection Repositorio Institucional
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. KEYWORDS Aspergillus fumigatus, CLSI ECVs, ECVs, EUCAST ECVs, Etest, SYO, cyp51A mutants, posaconazole, triazole resistance, wild type
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spelling eprints-163132024-03-05T17:54:24Z http://eprints.uanl.mx/16313/ Posaconazole MIC Distributions for Aspergillus fumigatus Species Complex by Four Methods: Impact of cyp51A Mutations on Estimation of Epidemiological Cutoff Values Espinel Ingroff, A. Turnidge, J. Alastruey Izquierdo, A. Dannaoui, E. García Effron, G. Guinea, J. Kidd, S. E. Pelaez, T. Sanguinetti, M. Meletiadis, J. Botterel, F. Bustamante, B. Chen, Y.-C. Chakrabarti, A. Chowdhary, A. Chryssanthou, E. Córdoba, S. González González, Gloria María Guarro, Josep Johnson, E. M. Kus, J. V. Lass Flörl, Cornelia Linares Sicilia, M. J. Martín Mazuelos, E. Negri, C. E. Pfaller, M. A. Tortorano, A. M. RM Terapéutica, Farmacología 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 American Society for Microbiology 2018 Article PeerReviewed text en cc_by_nc_nd http://eprints.uanl.mx/16313/1/158.pdf http://eprints.uanl.mx/16313/1.haspreviewThumbnailVersion/158.pdf Espinel Ingroff, A. y Turnidge, J. y Alastruey Izquierdo, A. y Dannaoui, E. y García Effron, G. y Guinea, J. y Kidd, S. E. 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 González González, Gloria María y Guarro, Josep y Johnson, E. M. y Kus, J. V. y Lass Flörl, Cornelia 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 http://doi.org/10.1128/AAC.01916-17 doi:10.1128/AAC.01916-17
spellingShingle RM Terapéutica, Farmacología
Espinel Ingroff, A.
Turnidge, J.
Alastruey Izquierdo, A.
Dannaoui, E.
García Effron, G.
Guinea, J.
Kidd, S. E.
Pelaez, T.
Sanguinetti, M.
Meletiadis, J.
Botterel, F.
Bustamante, B.
Chen, Y.-C.
Chakrabarti, A.
Chowdhary, A.
Chryssanthou, E.
Córdoba, S.
González González, Gloria María
Guarro, Josep
Johnson, E. M.
Kus, J. V.
Lass Flörl, Cornelia
Linares Sicilia, M. J.
Martín Mazuelos, E.
Negri, C. E.
Pfaller, M. A.
Tortorano, A. M.
Posaconazole MIC Distributions for Aspergillus fumigatus Species Complex by Four Methods: Impact of cyp51A Mutations on Estimation of Epidemiological Cutoff Values
thumbnail https://rediab.uanl.mx/themes/sandal5/images/online.png
title Posaconazole MIC Distributions for Aspergillus fumigatus Species Complex by Four Methods: Impact of cyp51A Mutations on Estimation of Epidemiological Cutoff Values
title_full Posaconazole MIC Distributions for Aspergillus fumigatus Species Complex by Four Methods: Impact of cyp51A Mutations on Estimation of Epidemiological Cutoff Values
title_fullStr Posaconazole MIC Distributions for Aspergillus fumigatus Species Complex by Four Methods: Impact of cyp51A Mutations on Estimation of Epidemiological Cutoff Values
title_full_unstemmed Posaconazole MIC Distributions for Aspergillus fumigatus Species Complex by Four Methods: Impact of cyp51A Mutations on Estimation of Epidemiological Cutoff Values
title_short Posaconazole MIC Distributions for Aspergillus fumigatus Species Complex by Four Methods: Impact of cyp51A Mutations on Estimation of Epidemiological Cutoff Values
title_sort posaconazole mic distributions for aspergillus fumigatus species complex by four methods impact of cyp51a mutations on estimation of epidemiological cutoff values
topic RM Terapéutica, Farmacología
url http://eprints.uanl.mx/16313/1/158.pdf
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