Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial
Por:
Pujol, M, Miro, JM, Shaw, E, Aguado, JM, San-Juan, R, Puig-Asensio, M, Pigrau, C, Calbo, E, Montejo, M, Rodriguez-Alvarez, R, Garcia-Pais, MJ, Pintado, V, Escudero-Sanchez, R, Lopez-Contreras, J, Morata, L, Montero, M, Andres, M, Pasquau, J, Arenas, MDM, Padilla, B, Murillas, J, Jover-Saenz, A, Lopez-Cortes, LE, Garcia-Pardo, G, Gasch, O, Videla, S, Hereu, P, Tebe, C, Pallares, N, Sanllorente, M, Dominguez, MA, Camara, J, Ferrer, A, Padulles, A, Cuervo, G, Carratala, J
Publicada:
1 may 2021
Resumen:
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.
Filiaciones:
Pujol, M:
Univ Barcelona, Hosp Univ Bellvitge, Inst Invest Biomed Bellvitge, Dept Infect Dis, Barcelona, Spain
Miro, JM:
Univ Barcelona, Hosp Clin, Inst Invest Biomed Agust Pi & Sunyer, Dept Infect Dis, Barcelona, Spain
Shaw, E:
Univ Barcelona, Hosp Univ Bellvitge, Inst Invest Biomed Bellvitge, Dept Infect Dis, Barcelona, Spain
Aguado, JM:
Univ Complutense, Inst Invest Hosp 12 Octubre, Hosp Univ 12 Octubre, Dept Infect Dis, Madrid 12, Spain
San-Juan, R:
Univ Complutense, Inst Invest Hosp 12 Octubre, Hosp Univ 12 Octubre, Dept Infect Dis, Madrid 12, Spain
Puig-Asensio, M:
Vall dHebron Inst Recerca, Hosp Vall dHebron, Dept Infect Dis, Barcelona, Spain
Pigrau, C:
Vall dHebron Inst Recerca, Hosp Vall dHebron, Dept Infect Dis, Barcelona, Spain
Calbo, E:
Univ Int Catalunya, Fundacio Docencia & Recerca Mutua de Terrassa, Hosp Univ Mutua de Terrassa, Infect Dis Unit, Barcelona, Spain
Montejo, M:
Hosp Univ Cruces, Biocruces Bizkaia, Dept Infect Dis, Bilbao, Spain
Rodriguez-Alvarez, R:
Hosp Univ Cruces, Biocruces Bizkaia, Dept Infect Dis, Bilbao, Spain
Garcia-Pais, MJ:
Inst Invest Sanitaria Santiago Compostela, Hosp Lucus Augusti, Infect Dis Unit, Lugo, Spain
Pintado, V:
Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria, Dept Infect Dis, Madrid, Spain
Escudero-Sanchez, R:
Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria, Dept Infect Dis, Madrid, Spain
Lopez-Contreras, J:
Hosp Univ St Pau, Inst Invest Biomed St Pau, Dept Infect Dis, Barcelona, Spain
Morata, L:
Univ Barcelona, Hosp Clin, Inst Invest Biomed Agust Pi & Sunyer, Dept Infect Dis, Barcelona, Spain
Montero, M:
Hosp del Mar, Inst Recerca Hosp del Mar, Dept Infect Dis, Barcelona, Spain
Andres, M:
Consorci Sanitari Terrassa, Infect Dis Unit, Terrassa, Spain
Pasquau, J:
Hosp Univ Virgen de las Nieves, Inst Invest Sanitaria Granada, Dept Infect Dis, Granada, Spain
Arenas, MDM:
Hosp Univ Virgen de las Nieves, Inst Invest Sanitaria Granada, Dept Infect Dis, Granada, Spain
Padilla, B:
Hosp Univ Gregorio Maranon, Inst Invest Sanitaria Gregorio Maranon, Dept Clin Microbiol & Infect Dis, Madrid, Spain
Murillas, J:
Hosp Univ Son Espases, Fundacio Inst Invest Sanitaria Illes Balears, Dept Internal Med, Mallorca, Spain
Jover-Saenz, A:
Hosp Arnau Vilanova, Inst Recerca Biomed Lleida, Terr Unit Nosocomial Infect, Lleida, Spain
Lopez-Cortes, LE:
Hosp Univ Virgen Macarena, Inst Biomed Sevilla, Dept Infect Dis, Seville, Spain
Garcia-Pardo, G:
Univ Rovira & Virgili, Hosp Univ Joan XXIII, Dept Internal Med, Tarragona, Spain
Gasch, O:
Fundacio Inst Invest & Innovacio Parc Tauli, Dept Infect Dis, Consorci Sanitari Hosp Parc Tauli, Sabadell, Spain
Videla, S:
Inst Invest Biomed Bellvitge, Dept Clin Pharmacol, Clin Res & Clin Trials Unit, Plataform Spanish Clin Res Network, Barcelona, Spain
Hereu, P:
Inst Invest Biomed Bellvitge, Dept Clin Pharmacol, Clin Res & Clin Trials Unit, Plataform Spanish Clin Res Network, Barcelona, Spain
Tebe, C:
Inst Invest Biomed Bellvitge, Biostat Unit, Lhospitalet De Llobregat, Spain
Pallares, N:
Inst Invest Biomed Bellvitge, Biostat Unit, Lhospitalet De Llobregat, Spain
Sanllorente, M:
Inst Invest Biomed Bellvitge, Dept Clin Pharmacol, Clin Res & Clin Trials Unit, Plataform Spanish Clin Res Network, Barcelona, Spain
Dominguez, MA:
Univ Barcelona, Hosp Univ Bellvitge, Inst Invest Biomed Bellvitge, Dept Microbiol & Parasitol, Barcelona, Spain
Camara, J:
Univ Barcelona, Hosp Univ Bellvitge, Inst Invest Biomed Bellvitge, Dept Microbiol & Parasitol, Barcelona, Spain
Ferrer, A:
Univ Barcelona, Dept Pharm, Inst Invest Biomed Bellvitge, Hosp Univ Bellvitge, Barcelona, Spain
Padulles, A:
Univ Barcelona, Dept Pharm, Inst Invest Biomed Bellvitge, Hosp Univ Bellvitge, Barcelona, Spain
Cuervo, G:
Univ Barcelona, Hosp Univ Bellvitge, Inst Invest Biomed Bellvitge, Dept Infect Dis, Barcelona, Spain
Carratala, J:
Univ Barcelona, Hosp Univ Bellvitge, Inst Invest Biomed Bellvitge, Dept Infect Dis, Barcelona, Spain
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