Daptomycin plus fosfomycin versus daptomycin alone for methicillin-resistant staphylococcus aureus bacteremia and endocarditis: a randomized clinical trial

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 tri...

Descripción completa

Detalles Bibliográficos
Autores: Pujol, Miquel, Miró, José María, Shaw, Evelyn, Aguado, Jose María, San Juan, Rafael, Puig Asensio, Mireia, Pigrau, Carles, Calbo Sebastian, Esther, Montejo, Miguel, Rodríguez Álvarez, Regino, García Pais, María Jose, Pintado, Vicente, Escudero Sánchez, Rosa, López Contreras, Joaquín, Morata, Laura, Montero, Milagros, Andrés, Marta, Pasquau, Juan, Arenas, María del Mar, Padilla, Belén, Murillas, Javier, Jover-Saenz, Alfredo, López Cortes, Luis Eduardo, García Pardo, Graciano, Gasch, Oriol, Videla, Sebastian, Hereu, Pilar, Tebé, Cristian, Pallarès, Natalia, Sanllorente, Mireia, Domínguez, María Ángeles, Càmara, Jordi, Ferrer, Anna, Padullés, Ariadna, Cuervo, Guillermo, Carratalà, Jordi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/73000
Acceso en línea:https://doi.org/10.1093/cid/ciaa1081
http://hdl.handle.net/10459.1/73000
Access Level:acceso abierto
Palabra clave:MRSA
Bacteremia
Daptomycin
Fosfomycin
Clinical trial
Descripción
Sumario: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 intra-venously 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 bac-teremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) re-ceiving 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 dif-ference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacte-remia, but it was more often associated with adverse events