Pilar Escribano1, Belén Rodríguez-Sánchez2, Judith Díaz-García1, María Teresa Martín-Gómez3, Elisa Ibáñez-Martínez4, María Rodríguez-Mayo5, Teresa Peláez6, Elia García-Gómez de la Pedrosa7, Rocío Tejero-García8, José María Marimón9, Elena Reigadas1, Antonio Rezusta10, Cristina Labayru-Echeverría11, Ana Pérez-Ayala12, Josefina Ayats13, Fernando Cobo14, Carmen Pazos15, Leyre López-Soria16, Ana Alastruey-Izquierdo17, Patricia Muñoz18, Jesús Guinea19. 1. Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. 2. Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain. 3. Servicio de Microbiología, Hospital Universitario Vall d'Hebron, Barcelona, Spain. 4. Instituto de Investigación Sanitaria La Fe, Valencia, Spain. 5. Servicio de Microbiología Clínica, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain. 6. Servicio de Microbiología, Hospital Universitario Central de Asturias, Oviedo, Spain; Fundacion para la Investigación y la Innovación Biosanitaria del Principado de Asturias, Oviedo, Spain. 7. Servicio de Microbiología, Hospital Ramón y Cajal, Madrid, Spain; Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain; Red Española de Investigación en Patología Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain. 8. Red Española de Investigación en Patología Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain; Servicio de Microbiología Clínica del Hospital Universitario Reina Sofía, Córdoba, Spain; Instituto Maimónides de Investigación Biomédica, Córdoba, Spain. 9. Biodonostia, Infectious Diseases Area, Respiratory Infection and Antimicrobial Resistance Group; Donostialdea Integrated Health Organisation, Microbiology Department, Donostia, Spain. 10. Servicio de Microbiología, Hospital Universitario Miguel Servet, Zaragoza, Spain; Instituto de Investigación Sanitaria Aragón, Universidad de Zaragoza, Zaragoza, Spain. 11. Laboratorio de Microbiología, Hospital Universitario de Burgos, Burgos, Spain. 12. Servicio de Microbiología, Hospital 12 de Octubre, Madrid, Spain; Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain. 13. CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain; Microbiology Department, Hospital Universitari de Bellvitge-Universitat de Barcelona-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain. 14. Instituto de Investigación Biosanitaria IBS, Granada, Spain; Department of Microbiology, University Hospital Virgen de las Nieves, Granada, Spain. 15. Servicio de Microbiología Clínica, Complejo Hospitalario Universitario de Cáceres, Cáceres, Spain. 16. Servicio de Microbiología, Hospital Universitario Cruces, Barakaldo, Spain; Instituto de Investigación Sanitaria Biocruces Bizkaia, Barakaldo, Spain. 17. Red Española de Investigación en Patología Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain; Mycology Reference Laboratory, National Centre for Microbiology (ISCIII), Madrid, Spain. 18. Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain; Medicine Department, Faculty of Medicine, Universidad Complutense de Madrid, Spain. 19. Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain. Electronic address: jguineaortega@yahoo.es.
Abstract
OBJECTIVES: We aimed to assess the percentage of azole resistance in Aspergillus fumigatus in Spain. METHODS: Thirty participating Spanish hospitals stored all morphologically identified A. fumigatus sensu lato clinical isolates-regardless their clinical significance-from 15 February to 14 May 2019. Isolates showing azole resistance according to the EUCAST 9.3.2 methodology were molecularly identified and the cyp51A gene was studied in A. fumigatus sensu stricto isolates. RESULTS: Eight hundred and forty-seven isolates from 725 patients were collected in 29 hospitals (A. fumigatus sensu stricto (n = 828) and cryptic species (n = 19)). Isolates were mostly from the lower respiratory tract (94.0%; 797/847). Only cryptic species were amphotericin B resistant. Sixty-three (7.4%) out of the 847 isolates were resistant to ≥1 azole(s). Azole resistance was higher in cryptic species than in A. fumigatus sensu stricto (95%, 18/19 vs. 5.5%, 45/828); isavuconazole was associated to the lowest number of non-wild type isolates. The dominant mechanism of resistance was the presence of TR34-L98H substitutions (n = 24 out of 63). Out of the 725 patients, 48 (6.6%) carried either cryptic species (n = 14) or A. fumigatus sensu stricto (n = 34; 4.7%) resistant isolates. Aspergillus fumigatus sensu stricto harbouring either the TR34-L98H (n = 19) or TR46/Y121F/T289A (n = 1) mutations were detected in patients in hospitals located at 7/24 studied cities. DISCUSSION: Of the patients, 6.6% carry azole-resistant A. fumigatus sensu lato isolates in Spain. TR34-L98H is the dominant cyp51A gene substitutions, although its presence is not widespread.
OBJECTIVES: We aimed to assess the percentage of azole resistance in Aspergillus fumigatus in Spain. METHODS: Thirty participating Spanish hospitals stored all morphologically identified A. fumigatus sensu lato clinical isolates-regardless their clinical significance-from 15 February to 14 May 2019. Isolates showing azole resistance according to the EUCAST 9.3.2 methodology were molecularly identified and the cyp51A gene was studied in A. fumigatus sensu stricto isolates. RESULTS: Eight hundred and forty-seven isolates from 725 patients were collected in 29 hospitals (A. fumigatus sensu stricto (n = 828) and cryptic species (n = 19)). Isolates were mostly from the lower respiratory tract (94.0%; 797/847). Only cryptic species were amphotericin B resistant. Sixty-three (7.4%) out of the 847 isolates were resistant to ≥1 azole(s). Azole resistance was higher in cryptic species than in A. fumigatus sensu stricto (95%, 18/19 vs. 5.5%, 45/828); isavuconazole was associated to the lowest number of non-wild type isolates. The dominant mechanism of resistance was the presence of TR34-L98H substitutions (n = 24 out of 63). Out of the 725 patients, 48 (6.6%) carried either cryptic species (n = 14) or A. fumigatus sensu stricto (n = 34; 4.7%) resistant isolates. Aspergillus fumigatus sensu stricto harbouring either the TR34-L98H (n = 19) or TR46/Y121F/T289A (n = 1) mutations were detected in patients in hospitals located at 7/24 studied cities. DISCUSSION: Of the patients, 6.6% carry azole-resistant A. fumigatus sensu lato isolates in Spain. TR34-L98H is the dominant cyp51A gene substitutions, although its presence is not widespread.
Authors: Matthew C Fisher; Ana Alastruey-Izquierdo; Judith Berman; Tihana Bicanic; Elaine M Bignell; Paul Bowyer; Michael Bromley; Roger Brüggemann; Gary Garber; Oliver A Cornely; Sarah J Gurr; Thomas S Harrison; Ed Kuijper; Johanna Rhodes; Donald C Sheppard; Adilia Warris; P Lewis White; Jianping Xu; Bas Zwaan; Paul E Verweij Journal: Nat Rev Microbiol Date: 2022-03-29 Impact factor: 78.297