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00925njm 22002777a 4500 dc Pujol, Miquel author Miró, José María author Shaw, Evelyn author Aguado, José María author San-Juan, Rafael author Puig-Asensio, Mireia author Pigrau, Carles author Calbo, Esther author Montejo, Miguel author Rodriguez-Alvarez, Regino author Garcia-Pais, Maria-Jose author Pintado, Vicente author Escudero-Sanchez, Rosa author Lopez-Contreras, Joaquin author Morata, Laura author Montero, Milagros author Andres, Marta author Pasquau, Juan author Arenas, Maria-del-Mar author Padilla, Belen author Murillas, Javier author Jover-Saenz, Alfredo author Lopez-Cortes, Luis Eduardo author Garcia-Pardo, Graciano author Gasch, Oriol author Videla, Sebastian author Hereu, Pilar author Tebe, Cristian author Pallares, Natalia author Sanllorente, Mireia author Dominguez, Maria-Angeles author Camara, Jordi author Ferrer, Ana author Padulles, Ariadna author Cuervo, Guillermo author Carratalà, Jordi author MRSA Bacteremia (BACSARM) Trial Investigators author 2021-05-01 Background. We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. Methods. A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. Results. of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93-1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018). Conclusions. Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events. Pujol M, Miro JM, Shaw E, Aguado JM, San-Juan R, Puig-Asensio M, et al. Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial. Clin Infect Dis. 2021 May 1;72(9):1517-25. 10.1093/cid/ciaa1081 1537-6591 1058-4838 Clinical Infectious Diseases https://hdl.handle.net/20.500.13003/19522 32725216 L2017162870 2-s2.0-85099091169 https://hdl.handle.net/20.500.12105/23328 757528700062 MRSA Bacteremia Daptomycin Fosfomycin Clinical trial Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial