Randomized, open-label Bayesian adaptive platform comparison · PMID 42308484
In adults with penicillin-resistant, methicillin-susceptible Staphylococcus aureus bacteremia, cefazolin met the trial’s criterion for noninferiority to cloxacillin or flucloxacillin for 90-day mortality and had less acute kidney injury. This supports cefazolin as a treatment option without proving mortality superiority.
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What was compared
The Staphylococcus aureus Network Adaptive Platform (SNAP) trial randomized 1,341 adults to cefazolin or cloxacillin/flucloxacillin across 91 sites in eight countries. This was an open-label comparison within an ongoing adaptive platform. Its primary outcome was all-cause mortality 90 days after platform entry. Patients receiving maintenance dialysis and those with an active history of allergy to the study antibiotics were excluded.1
The primary result
Among patients with evaluable 90-day outcomes, 97 of 645 (15.0%) assigned cefazolin died, compared with 109 of 642 (17.0%) assigned cloxacillin/flucloxacillin. The adjusted odds ratio was 0.81 (95% credible interval, 0.59–1.12). The posterior probability of noninferiority was 99.2%; the probability of superiority was 89.8%.1
Noninferiority used a prespecified adjusted-odds-ratio boundary below 1.2, and the trial’s stopping criterion required greater than 99% probability of meeting that boundary. Thus, the result supports noninferiority under the trial’s chosen margin. It does not establish equal outcomes in every patient group or a definite mortality reduction.1
The safety difference
Acute kidney injury occurred in 92 of 660 patients (13.9%) assigned cefazolin and 127 of 648 (19.6%) assigned cloxacillin/flucloxacillin. The adjusted odds ratio was 0.67 (95% credible interval, 0.50–0.89), with a 99.7% probability of superiority for this safety outcome. Renal safety is therefore an important part of the treatment discussion, even though mortality superiority was not established.1
Where applicability is narrower
The randomized comparators were cloxacillin and flucloxacillin; applying the result directly to nafcillin or oxacillin is an extrapolation. Endocarditis subgroup estimates were imprecise, and only seven patients had central nervous system infection. The investigators had not yet completed isolate testing for the cefazolin inoculum effect. The trial therefore does not settle every high-burden or central nervous system infection question.1
A practical pharmacist action
Application: once MSSA bacteremia is identified, discuss cefazolin with the treating and infectious-diseases teams, considering the infection site, allergy history, kidney function, and the local treatment pathway. More than 99% of trial participants received infectious-diseases consultation. Antibiotic selection remains one part of care: this comparison does not establish a new treatment duration or replace evaluation for infection foci and source control.1
Sources
- Staphylococcus aureus Network Adaptive Platform (SNAP) Trial Group; Lee TC, Barina LA, Walls G, et al. Cefazolin for Methicillin-Susceptible Staphylococcus aureus Bacteremia. N Engl J Med. 2026;394(23):2329-2339. doi:10.1056/NEJMoa2506905. PubMed.
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