Trial reportNature medicine2023
Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial.
Trial report in Nature medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Multicenter, Randomised, Open-label Phase III-IV Study to Evaluate the Efficacy of Cloxacillin and Fosfomycin Combination Versus Cloxacillin Monotherapy in Patients With Methicillin-susceptible Staphylococcus Aureus Bacteraemia: SAFO Trial
Adjunctive Fosfomycin for Treatment of Staphylococcus Aureus Bacteraemia: Protocol for a Pooled Post-hoc Analysis of Two Randomised Clinical Trials
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Antibiotic synergy againstAntimicrobial agents and chemotherapy · 2025Pooled it
- Preclinical and clinical evaluation of vancomycin plus delpazolid combination therapy for MRSA bacteremia: a multicenter, double-blinded, randomized, parallel design, phase IIa clinical trial.Microbiology spectrum · 2026Trial
- Rationalizing Heterogeneity in Staphylococcus aureus Bacteremia: Current Progress and Future Goals.The Journal of infectious diseases · 2026Review
- Real-World Data on the Use of Intravenous Fosfomycin for the Treatment of Central Nervous System Infections: a Subgroup Analysis from the FORTRESS Study.Infectious diseases and therapy · 2026Article
- Combination antibiotic therapy in Staphylococcus aureus endocarditis: evidence, controversies, and future directions.Infection · 2026Review
- A review of the randomized clinical trial results from the Staphylococcus aureus network adaptive platform (SNAP) meticillin-susceptible (MSSA) and penicillin-susceptible (PSSA) domains and CloCeBa.The Journal of antimicrobial chemotherapy · 2026Review
- Reproducible Identification of Staphylococcus aureus Bacteremia Clinical Subphenotypes.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Observational
- Subphenotype- and complication-guided adjunctive fosfomycin versus standard monotherapy inThe Lancet regional health. Europe · 2026Article
- Adjunctive Fosfomycin for the Treatment of Staphylococcus aureus Bacteremia: A Pooled Post Hoc Analysis of Individual Participant Data From 2 Randomized Trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
- [Staphylococcus aureus bacteremia: the long road to adequate therapy : Recent studies].Innere Medizin (Heidelberg, Germany) · 2026Review
- Methicillin-resistant and susceptible Staphylococcus aureus: tolerance, immune evasion and treatment.Nature reviews. Microbiology · 2026Review
- Fatal Panton-Valentine leukocidin-positive MSSA toxic shock syndrome: a call for rapid virulence detection and optimized antimicrobial therapy.Frontiers in cellular and infection microbiology · 2026Article
- Analysis of Clinical Subphenotypes in Methicillin-ResistantOpen forum infectious diseases · 2025Article
- Intravenous Fosfomycin for Gram-Negative and Gram-Positive Bacterial Infections: A Systematic Review of the Clinical Evidence.Antibiotics (Basel, Switzerland) · 2025Review
- Review
- Synergistic activity of fosfomycin and flucloxacillin against methicillin-susceptible and methicillin-resistant Staphylococcus aureus: in vitro and in vivo assessment.Medical microbiology and immunology · 2025Article
- Combination therapy with fosfomycin forJAC-antimicrobial resistance · 2025Review
- Identification and validation of clinical phenotypes inEClinicalMedicine · 2025Article
- Emerging Concepts for the Treatment of Biofilm-Associated Bone and Joint Infections with IV Fosfomycin: A Literature Review.Microorganisms · 2025Review
- Real-World Use, Effectiveness, and Safety of Intravenous Fosfomycin: The FORTRESS Study.Infectious diseases and therapy · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
34 authors at 20 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 .
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.