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

• Autores: Espinel-Ingroff, A; Turnidge, J; Alastruey-Izquierdo, A; Dannaoui, E; Garcia-Effron, Guillermo; Guinea, J; Kidd, S; Pelaez, T; Sanguinetti, M; Meletiadis, J; Botterel, F; Bustamante, B; Chen, Y-C; Chakrabarti, A; Chowdhary, A; Chryssanthou, E; Córdoba, Susana; Gonzalez, G.; 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
• Año de publicación: 2018
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Antimicrobrial Agents and Chemotherapy 2018;62(4):e01916-17
• Materia: Aspergillus fumigatus; Pruebas Antimicrobianas de Difusión por Disco; Estudios Epidemiológicos
• Institución: Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"

Fil: Espinel-Ingroff, A. VCU Medical Center, Richmond, Virginia; Estados Unidos.
Fil: Turnidge, J. University of Adelaide; Australia.
Fil: Alastruey-Izquierdo, A. Instituto de Salud Carlos III. National Centre for Microbiology. Mycology Reference Laboratory; España.
Fil: Dannaoui, E. Université Paris-Descartes. Faculté de Médecine. APHP. Service de Microbiologie. Unité de Parasitologie-Mycologie. Hôpital Européen Georges Pompidou; Francia.
Fil: Garcia-Effron, Guillermo. Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET). Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Micología y Diagnóstico Molecular; Argentina.
Fil: Guinea, J. Instituto de Investigación Sanitaria Gregorio Marañón. Hospital General Universitario Gregorio Marañon. Servicio de Microbiología Clínica y Enfermedades Infecciosas-VIH; España.
Fil: Kidd, S. National Mycology Reference Centre. Microbiology & Infectious Diseases. SA Pathology; Australia.
Fil: Pelaez, T. Hospital Universitario Central de Asturias. Servicio de Microbiología; España.
Fil: Sanguinetti, M. Università Cattolica del Sacro Cuore. Institute of Microbiology, Roma; Italia.
Fil: Meletiadis, J. National and Kapodistrian University of Athens. Medical School. Attikon Hospital. Clinical Microbiology Laboratory; Grecia.
Fil: Botterel, F. CHU Henri Mondor. DHU VIC. Parasitologie-Mycologie. Bactériologie-Hygiène. Département de Virologie Créteil. Unité de Parasitologie-Mycologie; Francia.
Fil: Bustamante, B. Universidad Peruana Cayetano Heredia. Instituto de Medicina Tropical Alexander von Humboldt; Perú.
Fil: Chen, Y-C. National Taiwan University Hospital. College of Medicine. Department of Internal Medicine; Taiwan.
Fil: Chakrabarti, A. Postgraduate Institute of Medical Education & Research. Department of Medical Microbiology; India.
Fil: Chowdhary, A. University of Delhi. Vallabhbhai Patel Chest Institute. Department of Medical Mycology; India.
Fil: Chryssanthou, E. Universitetlaboratoriet. Klinisk Mikrobiologi. Universitetssjukhuset; Suecia.
Fil: Córdoba, Susana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.
Fil: Gonzalez, G. M. Universidad Autónoma de Nuevo León, Monterrey, Nuevo León; México.
Fil: Guarro, J. Universitat Rovira i Virgili. Mycology Unit Medical School; España.
Fil: Johnson, E. M. Public Health England. Mycology Reference Laboratory, Bristol; Inglaterra.
Fil: Kus, J. V. Public Health Ontario; Canadá.
Fil: Lass-Flörl, C. Medical University of Innsbruck. Division of Hygiene and Medical Microbiology. National Mycology Reference Centre; Austria.
Fil: Linares-Sicilia, M. J. H. G. U. Reina Sofía. Universidad de Córdoba; España.
Fil: Martín-Mazuelos, E. Hospital de Valme. Unidad de Gestión Clínica de Enfermedades Infecciosas y Microbiología, Sevilla; España.
Fil: Negri, C. E. Universidade Federal de São Paulo. Laboratório Especial de Micologia, São Paulo, Brasil.
Fil: Pfaller, M. A. University of Iowa College of Medicine, Iowa City, Iowa; Estados Unidos.
Fil: Tortorano, A. M. Università degli Studi di Milano. Department of Biomedical Sciences for Health; Italia.
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.