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Randomized Controlled Trial
. 2021 May 4;72(9):1517-1525.
doi: 10.1093/cid/ciaa1081.

Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial

Miquel Pujol  1 , José-María Miró  2 , Evelyn Shaw  1 , Jose-María Aguado  3 , Rafael San-Juan  3 , Mireia Puig-Asensio  4 , Carles Pigrau  4 , Esther Calbo  5 , Miguel Montejo  6 , Regino Rodriguez-Álvarez  6 , María-Jose Garcia-Pais  7 , Vicente Pintado  8 , Rosa Escudero-Sánchez  8 , Joaquín Lopez-Contreras  9 , Laura Morata  2 , Milagros Montero  10 , Marta Andrés  11 , Juan Pasquau  12 , María-Del-Mar Arenas  12 , Belén Padilla  13 , Javier Murillas  14 , Alfredo Jover-Sáenz  15 , Luis-Eduardo López-Cortes  16 , Graciano García-Pardo  17 , Oriol Gasch  18 , Sebastian Videla  19 , Pilar Hereu  19 , Cristian Tebé  20 , Natalia Pallarès  20 , Mireia Sanllorente  19 , María-Ángeles Domínguez  21 , Jordi Càmara  21 , Anna Ferrer  22 , Ariadna Padullés  22 , Guillermo Cuervo  1 , Jordi Carratalà  1 ; MRSA Bacteremia (BACSARM) Trial Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial

Miquel Pujol et al. Clin Infect Dis. .

Abstract

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.

Clinical trials registration: NCT01898338.

Keywords: MRSA; bacteremia; clinical trial; daptomycin; fosfomycin.

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Figures

Figure 1.
Figure 1.
Trial profile. *Reasons for exclusion after randomization were as follows: patient randomized twice (n = 2); positive blood culture >72 hours before randomization (n = 3); patient received <1 day of antibiotic treatment (n = 3); protocol violation (n = 4).
Figure 2.
Figure 2.
Primary endpoint.
See this image and copyright information in PMC

Comment in

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