title: Caspofungin versus fluconazole as prophylaxis of invasive fungal infection in high-risk liver transplantation recipients: A propensity score analysis.
abstract: Targeted prophylaxis has proven to be an efficient strategy in liver transplantation recipients (LTRs). The aim of this study was to compare the effectiveness and safety of caspofungin with that of fluconazole in high-risk (HR) LTRs. Caspofungin and fluconazole were compared in a multicenter, retrospective, cohort study in HR-LTRs in Spain. Outcomes were assessed at 180 days after transplantation. A propensity score approach was applied. During the study period (2005-2012), we analyzed 195 HR-LTRs from 9 hospitals. By type of prophylaxis, 97 patients received caspofungin and 98 received fluconazole. Of a total of 17 (8.7%) global invasive fungal infections (IFIs), breakthrough IFIs accounted for 11 (5.6%) and invasive aspergillosis (IA) accounted for 6 (3.1%). By univariate analysis, no differences were observed in the prevention of global IFIs. However, caspofungin was associated with a significant reduction in the rate of breakthrough IFIs (2.1% versus 9.2%, P = 0.04). In patients requiring dialysis (n = 62), caspofungin significantly reduced the frequency of breakthrough IFIs (P = 0.03). The propensity score analysis confirmed a significant reduction in the frequency of IA in patients receiving caspofungin (absolute risk reduction, 0.06; 95% confidence interval [CI], 0.001-0.11; P = 0.044). Linear regression analysis revealed a significant decrease in blood alanine aminotransferase levels and a significant increase in bilirubin levels after administration of caspofungin. Caspofungin and fluconazole have similar efficacy for the prevention of global IFIs in HR-LTRs in this observational, multicenter cohort study. However, caspofungin was associated with a significant reduction of breakthrough IFIs and, after adjusting for confounders, caspofungin was associated with a lower rate of IA. This benefit is probably more favorable in patients on dialysis. Caspofungin is safe in HR-LTRs, although bilirubin levels may be increased.
authors.affiliation: Department of Infectious Diseases, Hospital Universitario Ramon y Cajal, Instituto de Investigación Ramón y Cajal, Universidad de Alcalá, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Fortún
authors.affiliation: Unit of Biostatistics, Ramón y Cajal Hospital, Centro de Investigación Biomédica en Red Epidemiología y Salud Pùblica, Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Muriel
authors.affiliation: Department of Infectious Diseases, Hospital Universitario Ramon y Cajal, Instituto de Investigación Ramón y Cajal, Universidad de Alcalá, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Martín-Dávila
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario Cruces, Barakaldo-Bilbao, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Montejo
authors.affiliation: Department of Infectious Diseases, Hospital Universitari Vall d´Hebron.
authors.forename: Oscar
authors.initials: O
authors.lastname: Len
authors.affiliation: Department of Infectious Diseases, Hospital Universitario Reina Sofía-IMIBIC (Instituto Maimónides de Investigación Biomédica de Córdoba)-Universidad de Córdoba, Córdoba, Spain.
authors.forename: Julian
authors.initials: J
authors.lastname: Torre-Cisneros
authors.affiliation: Department of Infectious Diseases, Hospital Universitari de Bellvitge-IDIBELL, University of Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Carratalá
authors.affiliation: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Muñoz
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, Santander, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Fariñas
authors.affiliation: Department of Infectious Diseases, Hospital Universitari Clinic, Barcelona, Universidad Autónoma, Barcelona, Spain.
authors.forename: Asunción
authors.initials: A
authors.lastname: Moreno
authors.affiliation: Department of Infectious Diseases, Hospital Universitario Ramon y Cajal, Instituto de Investigación Ramón y Cajal, Universidad de Alcalá, Madrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Fresco
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario Cruces, Barakaldo-Bilbao, Spain.
authors.forename: Josune
authors.initials: J
authors.lastname: Goikoetxea
authors.affiliation: Department of Infectious Diseases, Hospital Universitari Vall d´Hebron.
authors.forename: Joan
authors.initials: J
authors.lastname: Gavaldá
authors.affiliation: Department of Infectious Diseases, Hospital Universitario Reina Sofía-IMIBIC (Instituto Maimónides de Investigación Biomédica de Córdoba)-Universidad de Córdoba, Córdoba, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Pozo
authors.affiliation: Department of Infectious Diseases, Hospital Universitari de Bellvitge-IDIBELL, University of Barcelona, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Bodro
authors.affiliation: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Vena
authors.affiliation: Department of Digestive Diseases, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Casafont
authors.affiliation: Department of Infectious Diseases, Hospital Universitari Clinic, Barcelona, Universidad Autónoma, Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cervera
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario "12 de Octubre," Instituto de Investigación Hospital "12 de Octubre,", Madrid, Spain.
authors.forename: José Tiago
authors.initials: JT
authors.lastname: Silva
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario "12 de Octubre," Instituto de Investigación Hospital "12 de Octubre,", Madrid, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Aguado
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000453:epidemiology / Q000517:prevention & control*; D001663:Bilirubin / Q000097:blood; D000077336:Caspofungin; D015331:Cohort Studies; D054714:Echinocandins / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D006801:Humans; D000072742:Invasive Fungal Infections / Q000453:epidemiology / Q000517:prevention & control*; D055666:Lipopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D008107:Liver Diseases / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D065129:Pre-Exposure Prophylaxis / Q000379:methods; D057216:Propensity Score; D012189:Retrospective Studies; D012306:Risk; D013030:Spain / Q000453:epidemiology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D015725:Fluconazole; D000410:Alanine Transaminase; D000077336:Caspofungin; D001663:Bilirubin