Articles producció científica> Medicina i Cirurgia

Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial

  • Identification data

    Identifier: imarina:9330545
    Handle: https://hdl.handle.net/20.500.11797/imarina9330545
    Authors:
    Grillo, SPujol, MMiró, JMLópez-Contreras, JEuba, GGasch, OBoix-Palop, LGarcia-País, MJPérez-Rodríguez, MTGomez-Zorrilla, SOriol, ILópez-Cortés, LEPedro-Botet, MLSan-Juan, RAguado, JMGioia, FIftimie, SMorata, LJover-Sáenz, AGarcía-Pardo, GLoeches, BIzquierdo-Cárdenas, AGoikoetxea, AJGomila-Grange, ADietl, BBerbel, DVidela, SHereu, PPadulles, APallarès, NTebé, CCuervo, GCarratalà, JSAFO Study Grp
    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 b

  • Others:

    Author, as appears in the article.: Grillo, S; Pujol, M; Miró, JM; López-Contreras, J; Euba, G; Gasch, O; Boix-Palop, L; Garcia-País, MJ; Pérez-Rodríguez, MT; Gomez-Zorrilla, S; Oriol, I; López-Cortés, LE; Pedro-Botet, ML; San-Juan, R; Aguado, JM; Gioia, F; Iftimie, S; Morata, L; Jover-Sáenz, A; García-Pardo, G; Loeches, B; Izquierdo-Cárdenas, A; Goikoetxea, AJ; Gomila-Grange, A; Dietl, B; Berbel, D; Videla, S; Hereu, P; Padulles, A; Pallarès, N; Tebé, C; Cuervo, G; Carratalà, J; SAFO Study Grp
    Department: Medicina i Cirurgia
    URV's Author/s: Garcia Pardo, Graciano / Iftimie Iftimie, Simona Mihaela / TEBÉ CORDOMÍ, CRISTIAN
    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: NCT03959345 .© 2023. The Author(s).
    Thematic Areas: Psicología Medicine, research & experimental Medicine (miscellaneous) Medicine (all) Medicina veterinaria Medicina iii Medicina ii Medicina i General medicine General biochemistry,genetics and molecular biology Farmacia Enfermagem Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Cell biology Biotecnología Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all) Biochemistry & molecular biology
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: graciano.garcia@urv.cat simonamihaela.iftime@urv.cat
    Author identifier: 0000-0003-0714-8414
    Record's date: 2024-08-03
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://www.nature.com/articles/s41591-023-02569-0#citeas
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Nature Medicine. 29 (10): 2518-2525
    APA: Grillo, S; Pujol, M; Miró, JM; López-Contreras, J; Euba, G; Gasch, O; Boix-Palop, L; Garcia-País, MJ; Pérez-Rodríguez, MT; Gomez-Zorrilla, S; Oriol, I (2023). Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial. Nature Medicine, 29(10), 2518-2525. DOI: 10.1038/s41591-023-02569-0
    Article's DOI: 10.1038/s41591-023-02569-0
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2023
    Publication Type: Journal Publications

  • Keywords:

    Biochemistry & Molecular Biology,Biochemistry, Genetics and Molecular Biology (Miscellaneous),Cell Biology,Medicine (Miscellaneous),Medicine, Research & Experimental
    Psicología
    Medicine, research & experimental
    Medicine (miscellaneous)
    Medicine (all)
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    General medicine
    General biochemistry,genetics and molecular biology
    Farmacia
    Enfermagem
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Cell biology
    Biotecnología
    Biochemistry, genetics and molecular biology (miscellaneous)
    Biochemistry, genetics and molecular biology (all)
    Biochemistry & molecular biology

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