title: Propensity Score Analysis of the Role of Initial Antifungal Therapy in the Outcome of Candida glabrata Bloodstream Infections.
abstract: Candida glabrata isolates have reduced in vitro susceptibility to azoles, which raises concerns about the clinical effectiveness of fluconazole for treating bloodstream infection (BSI) by this Candida species. We aimed to evaluate whether the choice of initial antifungal treatment (fluconazole versus echinocandins or liposomal amphotericin B [L-AmB]-based regimens) has an impact on the outcome of C. glabrata BSI. We analyzed data from a prospective, multicenter, population-based surveillance program on candidemia conducted in 5 metropolitan areas of Spain (May 2010 to April 2011). Adult patients with an episode of C. glabrata BSI were included. The main outcomes were 14-day mortality and treatment failure (14-day mortality and/or persistent C. glabrata BSI for ≥48 h despite antifungal initiation). The impact of using fluconazole as initial antifungal treatment on the patients' prognosis was assessed by logistic regression analysis with the addition of a propensity score approach. A total of 94 patients with C. glabrata BSI were identified. Of these, 34 had received fluconazole and 35 had received an echinocandin/L-AmB-based regimen. Patients in the echinocandin/L-AmB group had poorer baseline clinical status than did those in the fluconazole group. Patients in the fluconazole group were more frequently (55.9% versus 28.6%) and much earlier (median time, 3 versus 7 days) switched to another antifungal regimen. Overall, 14-day mortality was 13% (9/69) and treatment failure 34.8% (24/69), with no significant differences between the groups. On multivariate analysis, after adjusting for baseline characteristics by propensity score, fluconazole use was not associated with an unfavorable evolution (adjusted odds ratio [OR] for 14-day mortality, 1.16, with 95% confidence interval [CI] of 0.22 to 6.17; adjusted OR for treatment failure, 0.83, with 95% CI of 0.27 to 2.61). In conclusion, initial fluconazole treatment was not associated with a poorer outcome than that obtained with echinocandins/L-AmB regimens in patients with C. glabrata BSI. (This study has been registered at ClinicalTrials.gov under registration no. NCT01236261.).
authors.affiliation: Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Medicine Department, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: M
authors.identifier: 0000-0002-0722-2218
authors.initials: M
authors.lastname: Puig-Asensio
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Medicine Department, Universidad Complutense, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Fernández-Ruiz
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Medicine Department, Universidad Complutense, Madrid, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Aguado
authors.affiliation: Clinical Microbiology Department, Hospital Universitario Clínico San Carlos, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Merino
authors.affiliation: Clinical Research Unit, Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Lora-Pablos
authors.affiliation: Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: J
authors.identifier: 0000-0002-7901-8355
authors.initials: J
authors.lastname: Guinea
authors.affiliation: Infectious Diseases Department, Hospital Ramón y Cajal, Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Martín-Dávila
authors.affiliation: Department of Mycology, Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Cuenca-Estrella
authors.affiliation: Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Medicine Department, Universitat Autònoma de Barcelona, Barcelona, Spain balmirante@vhebron.net.
authors.forename: B
authors.initials: B
authors.lastname: Almirante
mesh_terms: D000368:Aged; D000666:Amphotericin B / Q000493:pharmacokinetics / Q000627:therapeutic use; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D041221:Candida glabrata / Q000187:drug effects* / Q000472:pathogenicity*; D058387:Candidemia / Q000097:blood / Q000188:drug therapy*; D054714:Echinocandins / Q000627:therapeutic use; D005260:Female; D015725:Fluconazole / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; C068538:liposomal amphotericin B; D000666:Amphotericin B; D015725:Fluconazole