Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia : a randomized trial
Grillo, Sara (Hospital Universitari de Bellvitge)
Pujol, Miquel (Hospital Universitari de Bellvitge)
Miró, José M (Hospital Clínic i Provincial de Barcelona)
López-Contreras, Joaquín (Institut d'Investigació Biomèdica Sant Pau)
Euba, Gorane (Hospital Universitario de Cruces (Barakaldo, País Basc))
Gasch Blasi, Oriol (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Boix-Palop, Lucía (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Garcia-País, Maria José (Instituto de Investigación Sanitaria de Santiago (IDIS))
Pérez-Rodríguez, Maria Teresa (Complexo Hospitalario Universitario de Vigo)
Gómez-Zorrilla, Silvia (Institut Hospital del Mar d'Investigacions Mèdiques)
Oriol, Isabel (Hospital de Sant Joan Despi Moises Broggi)
López-Cortés, Luis Eduardo (Universidad de Sevilla)
Pedro-Botet, Maria Luisa (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
San-Juan, Rafael (Hospital Universitario 12 de Octubre)
Aguado, José María (Universidad Complutense de Madrid)
Gioia, Francesca (Instituto Ramon y Cajal de Investigacion Sanitaria)
Iftimie, Simona (Hospital Universitari de Sant Joan)
Morata, Laura (Hospital Clínic i Provincial de Barcelona)
Jover-Sáenz, Alfredo (Hospital Arnau de Vilanova (Lleida, Catalunya))
García-Pardo, Graciano (Hospital Universitari Joan XXIII de Tarragona)
Loeches, Belén (Hospital Universitario La Paz (Madrid))
Izquierdo-Cárdenas, Álvaro (Institut d'Investigació Biomèdica Sant Pau)
Goikoetxea, Ane Josune (Instituto de Investigación Sanitaria Biocruces Bizkaia)
Gomila, Aina (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Dietl, Beatriz (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Berbel, Dàmaris (Hospital Universitari de Bellvitge)
Videla, Sebastián (Hospital Universitari de Bellvitge)
Hereu, Pilar (Hospital Universitari de Bellvitge)
Padullés, Ariadna (Hospital Universitari de Bellvitge)
Pallarès, Natalia (Institut d'Investigació Biomèdica de Bellvitge)
Tebé, Cristian (Institut d'Investigació Biomèdica de Bellvitge)
Cuervo, Guillermo (Hospital Clínic i Provincial de Barcelona)
Carratalà, Jordi (Universitat de Barcelona)
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	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. ClinicalTrials. gov registration: . New treatments are essential for methicillin-susceptible Staphylococcus aureus bacteremia, but progress is slow. In this phase III-IV trial, cloxacillin plus fosfomycin failed to show superiority over cloxacillin alone, underscoring the challenges to improving patient outcomes.
Grants:	Instituto de Salud Carlos III PI17/01116
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Antimicrobial therapy ; Randomized controlled trials
Published in:	Nature Medicine, Vol. 29 (october 2023) , p. 2518-2525, ISSN 1546-170X

DOI: 10.1038/s41591-023-02569-0
PMID: 37783969

16 p, 3.2 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles