Fluconazole‐resistant Candida parapsilosis genotypes from hospitals located in five Spanish cities and one in Italy: Description of azole‐resistance profiles associated with the Y132F ERG11p substitution

Author:

Mesquida Aina12,Alcoceba Eva3,Padilla Eduardo4,Ramírez Aída5,Merino Paloma67,González‐Romo Fernando67,De Carolis Elena8,Sanguinetti Maurizio8ORCID,Mantecón‐Vallejo María de los Ángeles9,Muñoz‐Algarra María10,Durán‐Valle Teresa11,Pérez‐Ayala Ana1213,Gómez‐García‐de‐la‐Pedrosa Elia141516,del Carmen Martínez‐Jiménez María17,Sánchez‐Castellano Miguel Ángel17,Quiles‐Melero Inmaculada18,Cuétara María Soledad19,Sánchez‐García Aída20,Muñoz Patricia122122,Escribano Pilar1223ORCID,Guinea Jesús122123ORCID,

Affiliation:

1. Clinical Microbiology and Infectious Diseases Hospital General Universitario Gregorio Marañón Madrid Spain

2. Instituto de Investigación Sanitaria Gregorio Marañón Madrid Spain

3. Clinical Microbiology Department Hospital Universitari Son Espases Palma de Mallorca Spain

4. Laboratorio de Refèrencia de Catalunya Barcelona Spain

5. Clinical Microbiology Department, Hospital del Mar Barcelona Spain

6. Clinical Microbiology Department Hospital Universitario Clínico San Carlos Madrid Spain

7. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos IdISSC Madrid Spain

8. Dipartimento di Scienze di Laboratorio e Infettivologiche Fondazione Policlinico Universitario “A. Gemelli” IRCCS Rome Italy

9. Clinical Microbiology Department Complejo Asistencial Universitario de Burgos Burgos Spain

10. Clinical Microbiology Department Hospital Universitario Puerta de Hierro‐Majadahonda Majadahonda Spain

11. Clinical Microbiology Department Hospital Universitario de Móstoles Móstoles Spain

12. Clinical Microbiology Department Hospital Universitario 12 de Octubre Madrid Spain

13. Instituto de Investigación Sanitaria del Hospital 12 de Octubre Madrid Spain

14. Clinical Microbiology Department Hospital Universitario Ramón y Cajal Madrid Spain

15. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) Madrid Spain

16. CIBER de Enfermedades Infecciosas (CIBERINFEC) Instituto de Salud Carlos III Madrid Spain

17. Clinical Microbiology Department Hospital Nuestra Señora de Sonsoles Ávila Spain

18. Clinical Microbiology Department Hospital Universitario La Paz Madrid Spain

19. Clinical Microbiology Department Hospital Universitario Severo Ochoa Leganés Spain

20. Laboratorio Central de la CAM‐UR Salud‐Hospital Infanta Sofía Madrid Spain

21. CIBER Enfermedades Respiratorias‐CIBERES (CB06/06/0058) Madrid Spain

22. Department of Medicine, School of Medicine Universidad Complutense de Madrid Madrid Spain

23. Faculty of Health Sciences – HM Hospitals Universidad Camilo José Cela Madrid Spain

Abstract

AbstractBackgroundFluconazole‐resistant Candida parapsilosis is a matter of concern.ObjectivesTo describe fluconazole‐resistant C. parapsilosis genotypes circulating across hospitals in Spain and Rome and to study their azole‐resistance profile associated with ERG11p substitutions.Patients/MethodsWe selected fluconazole‐resistant C. parapsilosis isolates (n = 528 from 2019 to 2023; MIC ≥8 mg/L according to EUCAST) from patients admitted to 13 hospitals located in five Spanish cities and Rome. Additionally, we tested voriconazole, posaconazole, isavuconazole, amphotericin B, micafungin, anidulafungin and ibrexafungerp susceptibility.ResultsOf the 53 genotypes found, 49 harboured the Y132F substitution, five of which were dominating city‐specific genotypes involving almost half the isolates. Another genotype involved isolates harbouring the G458S substitution. Finally, we found two genotypes with the wild‐type ERG11 gene sequence and one with the R398I substitution. All isolates were fully susceptible/wild‐type to amphotericin B, anidulafungin, micafungin and ibrexafungerp. The azole‐resistance patterns found were: voriconazole‐resistant (74.1%) or voriconazole‐intermediate (25.2%), posaconazole‐resistant (10%) and isavuconazole non‐wild‐type (47.5%). Fluconazole‐resistant and voriconazole non‐wild‐type isolates were likely to harbour substitution Y132F if posaconazole was wild type; however, if posaconazole was non‐wild type, substitution G458S was indicated if isavuconazole MIC was >0.125 mg/L or substitution Y132F if isavuconazole MIC was ≤0.125 mg/L.ConclusionsWe detected a recent clonal spread of fluconazole‐resistant C. parapsilosis across some cities in Spain, mostly driven by dominating city‐specific genotypes, which involved a large number of isolates harbouring the Y132F ERG11p substitution. Isolates harbouring substitution Y132F can be suspected because they are non‐susceptible to voriconazole and rarely posaconazole‐resistant.

Funder

European Regional Development Fund

Publisher

Wiley

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