Adjunctive Fosfomycin for the Treatment of <i>Staphylococcus aureus</i> Bacteremia: A Pooled Post Hoc Analysis of Individual Participant Data From 2 Randomized Trials
Bibliographic record
Abstract
BACKGROUND: The role of adjunctive fosfomycin in Staphylococcus aureus bacteremia (SAB) remains uncertain. METHODS: We performed a post hoc pooled analysis of individual participant data from the multicenter BACSARM and SAFO randomized controlled trials, which assessed fosfomycin combined with daptomycin or cloxacillin versus monotherapy for methicillin-resistant and methicillin-susceptible SAB. The primary outcome was treatment success at 8 weeks, defined as the patient being alive, without signs of relapse, and showing resolution of fever and improvement in clinical signs and symptoms of infection. Secondary outcomes included persistent bacteremia at days 3 and 7; all-cause mortality at days 14, 30, and 60; and adverse events leading to treatment discontinuation. Bayesian and frequentist methods were used to estimate treatment effects, with the primary Bayesian analysis using a minimally informative prior centered on no treatment effect. RESULTS: The intention-to-treat population comprised 369 participants, of whom 178 received fosfomycin combination therapy and 191 received monotherapy. The primary Bayesian analysis showed a 91.8% posterior probability that fosfomycin improves treatment success at 8 weeks (median relative risk [RR], 1.10 [95% credible interval {Crl}, .97-1.26]) with sensitivity analyses (using pessimistic, skeptical, and optimistic priors) yielding probabilities between 75.8% and 97.2%. Fosfomycin was associated with a significant reduction in persistent bacteremia at day 3 (median RR, 0.19 [95% CrI, .07-.41]) and day 7 (median RR, 0.22 [95% CrI, .03-.84]). The adjusted frequentist analysis demonstrated an association between fosfomycin combination therapy and treatment success at 8 weeks (RR, 1.04 [95% confidence interval {CI}, 1.02-1.06]; P < .001). Combination therapy was associated with a higher risk of adverse events (RR, 2.03 [95% CI, 1.13-3.63]; P = .017). CONCLUSIONS: Adjunctive fosfomycin may improve early bacterial clearance and treatment success in SAB but at the cost of increased toxicity. Clinical Trials Registration. NCT06695832.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.113 | 0.120 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.010 | 0.034 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".