title: Antifungal resistance to fluconazole and echinocandins is not emerging in yeast isolates causing fungemia in a Spanish tertiary care center.
abstract: Accurate knowledge of fungemia epidemiology requires identification of strains to the molecular level. Various studies have shown that the rate of resistance to fluconazole ranges from 2.5% to 9% in Candida spp. isolated from blood samples. However, trends in antifungal resistance have received little attention and have been studied only using CLSI M27-A3 methodology. We assessed the fungemia epidemiology in a large tertiary care institution in Madrid, Spain, by identifying isolates to the molecular level and performing antifungal susceptibility testing according to the updated breakpoints of European Committee for Antimicrobial Susceptibility Testing (EUCAST) definitive document (EDef) 7.2. We studied 613 isolates causing 598 episodes of fungemia in 544 patients admitted to our hospital (January 2007 to December 2013). Strains were identified after amplification and sequencing of the ITS1-5.8S-ITS2 region and further tested for in vitro susceptibility to amphotericin B, fluconazole, posaconazole, voriconazole, micafungin, and anidulafungin. Resistance was defined using EUCAST species-specific breakpoints, and epidemiological cutoff values (ECOFFs) were applied as tentative breakpoints. Most episodes were caused by Candida albicans (46%), Candida parapsilosis (28.7%), Candida glabrata (9.8%), and Candida tropicalis (8%). Molecular identification enabled us to better detect cryptic species of Candida guilliermondii and C. parapsilosis complexes and episodes of polyfungal fungemia. The overall percentage of fluconazole-resistant isolates was 5%, although it was higher in C. glabrata (8.6%) and non-Candida yeast isolates (47.4%). The rate of resistance to echinocandins was 4.4% and was mainly due to the presence of intrinsically resistant non-Candida species. Resistance mainly affected non-Candida yeasts. The rate of resistance to fluconazole and echinocandins did not change considerably during the study period.
authors.affiliation: Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Laura Judith
authors.initials: LJ
authors.lastname: Marcos-Zambrano
authors.affiliation: Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Escribano
authors.affiliation: Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Sánchez
authors.affiliation: Clinical Microbiology and Infectious Diseases Department, 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, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Muñoz
authors.affiliation: Clinical Microbiology and Infectious Diseases Department, 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, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Bouza
authors.affiliation: Clinical Microbiology and Infectious Diseases Department, 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, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain jguineaortega@yahoo.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Guinea
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology; D002175:Candida / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D004271:DNA, Fungal / Q000235:genetics*; D021901:DNA, Intergenic / Q000235:genetics; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000494:pharmacology; D016469:Fungemia / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D016533:Mycological Typing Techniques; D013030:Spain; D063128:Tertiary Health Care
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D004271:DNA, Fungal; D021901:DNA, Intergenic; D054714:Echinocandins; D000666:Amphotericin B