Repositori URV

Author, as appears in the article.: Grillo, S; Pujol, M; Miró, JM; López-Contreras, J; Euba, G; Gasch, O; Boix-Palop, L; Garcia-País, MJ; Pérez-Rodríguez, MT; Gomez-Zorrilla, S; Oriol, I; López-Cortés, LE; Pedro-Botet, ML; San-Juan, R; Aguado, JM; Gioia, F; Iftimie, S; Morata, L; Jover-Sáenz, A; García-Pardo, G; Loeches, B; Izquierdo-Cárdenas, A; Goikoetxea, AJ; Gomila-Grange, A; Dietl, B; Berbel, D; Videla, S; Hereu, P; Padulles, A; Pallarès, N; Tebé, C; Cuervo, G; Carratalà, J; SAFO Study Grp

Department: Medicina i Cirurgia

URV's Author/s: Garcia Pardo, Graciano / Iftimie Iftimie, Simona Mihaela / TEBÉ CORDOMÍ, CRISTIAN

Keywords: Good health and well-being

Abstract: Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .© 2023. The Author(s).

Thematic Areas: Psicología Medicine, research & experimental Medicine (miscellaneous) Medicine (all) Medicina veterinaria Medicina iii Medicina ii Medicina i General medicine General biochemistry,genetics and molecular biology Farmacia Enfermagem Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Cell biology Biotecnología Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all) Biochemistry & molecular biology

licence for use: https://creativecommons.org/licenses/by/3.0/es/

Author's mail: graciano.garcia@urv.cat simonamihaela.iftime@urv.cat

Author identifier: 0000-0003-0714-8414

Record's date: 2024-11-23

Papper version: info:eu-repo/semantics/publishedVersion

Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Nature Medicine. 29 (10): 2518-2525

APA: Grillo, S; Pujol, M; Miró, JM; López-Contreras, J; Euba, G; Gasch, O; Boix-Palop, L; Garcia-País, MJ; Pérez-Rodríguez, MT; Gomez-Zorrilla, S; Oriol, I (2023). Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial. Nature Medicine, 29(10), 2518-2525. DOI: 10.1038/s41591-023-02569-0

Entity: Universitat Rovira i Virgili

Journal publication year: 2023

Publication Type: Journal Publications