Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
27
04
2023
accepted:
25
08
2023
medline:
23
10
2023
pubmed:
3
10
2023
entrez:
2
10
2023
Statut:
ppublish
Résumé
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: NCT03959345 .
Identifiants
pubmed: 37783969
doi: 10.1038/s41591-023-02569-0
pii: 10.1038/s41591-023-02569-0
pmc: PMC10579052
doi:
Substances chimiques
Anti-Bacterial Agents
0
Cloxacillin
O6X5QGC2VB
Fosfomycin
2N81MY12TE
Methicillin
Q91FH1328A
Banques de données
ClinicalTrials.gov
['NCT03959345']
Types de publication
Clinical Trial, Phase III
Clinical Trial, Phase IV
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2518-2525Investigateurs
Maria Alba Rivera
(MA)
Malen Aguirregabiria
(M)
Regino Rodríguez-Álvarez
(R)
María José Blanco-Vidal
(MJ)
Marina Alguacil-Guillen
(M)
Mariona Xercavins
(M)
Virginia Pomar
(V)
Ana Siverio-Parés
(A)
Marina de Cueto
(M)
Elisa Moreno-Mellado
(E)
Adrián Sousa
(A)
Francisco José Vasallo-Vidal
(FJ)
Beatriz Borjabad
(B)
Ana Coloma-Conde
(A)
Raquel Clivillé-Abad
(R)
Sabina Ximena González-di Lauro
(SX)
Jose Tiago-Silva
(J)
Maria Angeles Orellana
(MA)
Mario Ruíz-Bastián
(M)
Pilar Vizcarra
(P)
Carles Garcia
(C)
Frédéric Ballester
(F)
María Fernanda Ramírez-Hidalgo
(MF)
Alba Bellés-Bellés
(A)
Yolanda Meije
(Y)
Alba Ribera
(A)
Jaume LLaberia
(J)
María Ángeles Domínguez
(MÁ)
Raul Francisco Rigo-Bonnin
(RF)
Gertrudis Horna
(G)
Dominica Mediavilla
(D)
Mireia Sanllorente
(M)
Ester Picó-Plana
(E)
Alex Soriano
(A)
Cristina Pitart
(C)
Ana Maria Sanchez-Diaz
(AM)
Informations de copyright
© 2023. The Author(s).
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