2026-04-18T06:03:32Zhttps://recercat.cat/oai/request

oai:recercat.cat:10459.1/4647562025-11-10T19:03:58Zcom_2072_3622col_2072_479130

00925njm 22002777a 4500 dc Grillo, Sara author Pujol, Miquel author Miró, Josep M. author López-Contreras, Joaquín author Euba, Gorane author Gasch, Oriol author Boix-Palop, Lucia author Garcia-País, Maria José author Pérez-Rodríguez, Maria Teresa author Gomez-Zorrilla, Silvia author Oriol, Isabel author López-Cortés, Luis Eduardo author Pedro-Botet, Maria Luisa author San-Juan, Rafael author Aguado, José María author Gioia, Francesca author Iftimie, Simona author Morata, Laura author Jover-Saenz, Alfredo author García-Pardo, Graciano author Loeches, Belén author Izquierdo-Cárdenas, Álvaro author Goikoetxea, Ane Josune author Gomila-Grange, Aina author Dietl, Beatriz author Berbel, Damaris author Videla, Sebastian author Hereu, Pilar author Padullés, Ariadna author Pallarès, Natalia author Tebé, Cristian author Cuervo, Guillermo author Carratalà, Jordi author 2023 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. Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial