title: Breakthrough candidaemia in the era of broad-spectrum antifungal therapies.
abstract: We aimed to assess the characteristics, treatment, risk factors and outcome of patients with breakthrough candidaemia (BrC) in the era of broad-spectrum antifungal therapies. We carried out a multicentre study of hospitalized adults with candidaemia at six hospitals in three countries. BrC episodes were compared with the remaining episodes (non-BrC). Of 409 episodes of candidaemia, 37 (9%) were BrC. Among them, antifungal treatment was administered as prophylaxis in 26 severely immunosuppressed patients (70%) and as a fever-driven approach in 11 (30%). Candida albicans was significantly less common in patients with BrC (24% versus 46%, p 0.010) whereas Candida krusei was more frequent (16% versus 2.4%, p < 0.001). BrC was associated with infections caused by fluconazole non-susceptible isolates (50% versus 18%, p < 0.001). Candida albicans BrC was associated with previous fluconazole treatment whereas Candida parapsilosis candidaemia was mostly catheter-related and/or associated with previous echinocandin therapy. The empirical antifungal therapy was more often appropriate in the non-BrC group (57% versus 74%, p 0.055). No significant differences were found in outcomes (early and overall mortality: 11% versus 13% p 0.802 and 40% versus 40% p 0.954, respectively). Fluconazole non-susceptibility was independently associated with the risk of BrC (adjusted OR 5.57; 95% CI 1.45-21.37). In conclusion, BrC accounted for 9% of the episodes in our multicentre cohort. The Candida spp. isolated were different depending on the previous antifungal therapy: previous azole treatment was associated with fluconazole non-susceptible strains and previous echinocandin treatment was associated with BrC caused by C. parapsilosis. These results should be taken into account to improve the empirical treatment of BrC.
authors.affiliation: Hospital Universitari de Bellvitge, IDIBELL (Institut D'investigació Biomèdica de Bellvitge), Universitat de Barcelona, Barcelona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Cuervo
authors.affiliation: Hospital Universitari de Bellvitge, IDIBELL (Institut D'investigació Biomèdica de Bellvitge), Universitat de Barcelona, Barcelona, Spain. Electronic address: carolgv75@hotmail.com.
authors.forename: C
authors.initials: C
authors.lastname: Garcia-Vidal
authors.affiliation: University Hospital, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Nucci
authors.affiliation: Hospital Universitari i Politecnic 'La Fe', Valencia, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Puchades
authors.affiliation: Hospital Universitario '12 de Octubre', Instituto de Investigación Hospital '12 de Octubre' (i+12), Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Fernández-Ruiz
authors.affiliation: Hospital Interzonal de Agudos 'Dr Rodolfo Rossi', La Plata, Argentina.
authors.forename: M
authors.initials: M
authors.lastname: Obed
authors.affiliation: Hospital 'Dr Guillermo Rawson', San Juan, Argentina.
authors.forename: A
authors.initials: A
authors.lastname: Manzur
authors.affiliation: Hospital Universitari de Bellvitge, IDIBELL (Institut D'investigació Biomèdica de Bellvitge), Universitat de Barcelona, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Gudiol
authors.affiliation: Hospital Universitari i Politecnic 'La Fe', Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Pemán
authors.affiliation: Hospital Universitario '12 de Octubre', Instituto de Investigación Hospital '12 de Octubre' (i+12), Madrid, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Aguado
authors.affiliation: Hospital Universitari de Bellvitge, IDIBELL (Institut D'investigació Biomèdica de Bellvitge), Universitat de Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Ayats
authors.affiliation: Hospital Universitari de Bellvitge, IDIBELL (Institut D'investigació Biomèdica de Bellvitge), Universitat de Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Carratalà
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002175:Candida / Q000145:classification* / Q000187:drug effects / Q000302:isolation & purification; D002176:Candida albicans / Q000187:drug effects / Q000302:isolation & purification; D058387:Candidemia / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D002177:Candidiasis / Q000382:microbiology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007297:Inpatients; D008297:Male; D008875:Middle Aged; D016533:Mycological Typing Techniques; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents
keywords: Antifungal therapy; breakthrough infection; candidaemia; posaconazole; prophylaxis