title: Echinocandin Resistance in Candida Species Isolates from Liver Transplant Recipients.
abstract: Liver transplant recipients are at risk of invasive fungal infections, especially candidiasis. Echinocandin is recommended as prophylactic treatment but is increasingly associated with resistance. Our aim was to assess echinocandin drug resistance in Candida spp. isolated from liver transplant recipients treated with this antifungal class. For this, all liver-transplanted patients in a University Hospital (Créteil, France) between January and June of 2013 and 2015 were included. Susceptibilities of Candida isolates to echinocandins were tested by Etest and the EUCAST reference method. Isolates were analyzed by FKS sequencing and genotyped based on microsatellites or multilocus sequence typing (MLST) profiles. Ninety-four patients were included, and 39 patients were colonized or infected and treated with echinocandin. Echinocandin resistance appeared in 3 (8%) of the treated patients within 1 month of treatment. One patient was colonized by resistant Candida glabrata, one by resistant Candida dubliniensis, and one by resistant Candida albicans Molecular analysis found three mutations in FKS2 HS1 (F659S, S663A, and D666E) for C. glabrata and one mutation in FKS1 HS1 (S645P) for C. dubliniensis and C. albicans Susceptible and resistant isolates belonged to the same genotype. To our knowledge, this is the first study on echinocandin resistance in Candida spp. in a liver transplant population. Most resistant isolates were found around/in digestive sites, perhaps due to lower diffusion of echinocandin in these sites. This work documents the risk of emergence of resistance to echinocandin, even after short-term treatment.
authors.affiliation: Unité de Parasitologie-Mycologie, Département de Virologie, Bactériologie-Hygiène, Parasitologie-Mycologie, DHU VIC, CHU Henri Mondor, AP-HP, Créteil, France.
authors.forename: Gwénolé
authors.initials: G
authors.lastname: Prigent
authors.affiliation: Unité de Parasitologie-Mycologie, Département de Virologie, Bactériologie-Hygiène, Parasitologie-Mycologie, DHU VIC, CHU Henri Mondor, AP-HP, Créteil, France.|EA Dynamyc UPEC, ENVA, Faculté de Médecine, Créteil, France.
authors.forename: Nawel
authors.initials: N
authors.lastname: Aït-Ammar
authors.affiliation: Réanimation Digestive et Hépato-Biliaire, Service d'Anesthésie et des Réanimations Chirurgicales, CHU Henri Mondor, AP-HP, Créteil, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Levesque
authors.affiliation: Service de Parasitologie-Mycologie, CHU La Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Fekkar
authors.affiliation: EA Dynamyc UPEC, ENVA, Faculté de Médecine, Créteil, France.|Laboratoire Cerba, Saint-Ouen-l'Aumône, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Costa
authors.affiliation: Unité de Parasitologie-Mycologie, Département de Virologie, Bactériologie-Hygiène, Parasitologie-Mycologie, DHU VIC, CHU Henri Mondor, AP-HP, Créteil, France.
authors.forename: Sarra
authors.initials: S
authors.lastname: El Anbassi
authors.affiliation: Unité de Parasitologie-Mycologie, Département de Virologie, Bactériologie-Hygiène, Parasitologie-Mycologie, DHU VIC, CHU Henri Mondor, AP-HP, Créteil, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Foulet
authors.affiliation: Service d'Hépatologie, CHU Henri Mondor, AP-HP, Créteil, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Duvoux
authors.affiliation: Réanimation Digestive et Hépato-Biliaire, Service d'Anesthésie et des Réanimations Chirurgicales, CHU Henri Mondor, AP-HP, Créteil, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Merle
authors.affiliation: EA Dynamyc UPEC, ENVA, Faculté de Médecine, Créteil, France.|Unité de Parasitologie-Mycologie, Service de Microbiologie, Université Paris-Descartes, Faculté de Médecine, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors.forename: Eric
authors.identifier: 0000-0002-2817-3830
authors.initials: E
authors.lastname: Dannaoui
authors.affiliation: Unité de Parasitologie-Mycologie, Département de Virologie, Bactériologie-Hygiène, Parasitologie-Mycologie, DHU VIC, CHU Henri Mondor, AP-HP, Créteil, France francoise.botterel@aphp.fr.|EA Dynamyc UPEC, ENVA, Faculté de Médecine, Créteil, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Botterel
mesh_terms: D000328:Adult; D000368:Aged; D002175:Candida / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D025141:Drug Resistance, Fungal / Q000187:drug effects*; D054714:Echinocandins / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005602:France; D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation
chemical_list: D054714:Echinocandins; D005656:Fungal Proteins; D051718:MutS Homolog 2 Protein
keywords: Candida; Candida albicans; Candida dubliniensis; Candida glabrata; echinocandin; liver transplantation; resistance