Issue: Newsletter 23 | June 18, 2026
| Citation of Articles | PICO | Main Results | Risk of Bias |
|---|---|---|---|
| The Staphylococcus aureus Network Adaptive Platform (SNAP) Trial Group. Cefazolin for methicillin-susceptible Staphylococcus aureus bacteremia. N Engl J Med. 2026 Jun 17;394(23):2329-2339. doi:10.1056/NEJMoa2506905 |
P: 1,308 adults with penicillin-resistant, methicillin-susceptible Staphylococcus aureus bacteremia (645 evaluable in cefazolin group; 642 evaluable in antistaphyloccal-penicillin group) I: Cefazolin C: Antistaphylococcal penicillin (flucloxacillin or cloxacillin) O: Primary: all-cause mortality at 90 days. Secondary: acute kidney injury within 14 days. |
Cefazolin met the prespecified criterion for noninferiority for 90-day mortality, with deaths occurring in 15.0% of patients versus 17.0% with flucloxacillin/cloxacillin (adjusted OR 0.81, 95% credible interval [CrI] 0.59–1.12; probability of noninferiority 99.2%; probability of superiority 89.8%). Acute kidney injury occurred less frequently with cefazolin (13.9% vs 19.6%; adjusted OR 0.67, 95% CrI 0.50–0.89), with a 99.7% probability of superiority. Overall, cefazolin was noninferior for survival and demonstrated a superior renal safety profile. | Moderate risk: Randomized design and large sample size strengthen internal validity, but the open-label design may introduce performance bias and influence co-interventions. The primary outcome of 90-day mortality is objective and unlikely to be affected by lack of blinding, reducing detection bias. The adaptive Bayesian platform design is appropriate but adds analytical complexity. Attrition appeared low, and the multicenter international setting enhances generalizability. Overall risk of bias is moderate, primarily due to the open-label nature of the trial. |
|
The Staphylococcus aureus Network Adaptive Platform (SNAP) Trial Group. Benzylpenicillin versus flucloxacillin or cloxacillin for the treatment of penicillin-susceptible Staphylococcus aureus bacteraemia (SNAP): an international, multicentre, open-label, non-inferiority randomised controlled trial. Lancet. 2026 Jun 17; doi:10.1016/S0140-6736(26)00761-0 • Editorial Commentary: Westgeest AC, Fowler VG Jr. Treating penicillin-susceptible Staphylococcus aureus bacteraemia: confusing the issue with facts. Lancet. 2026 Jun 17; doi:10.1016/S0140-6736(26)00857-3 |
P: 281 adults with penicillin-susceptible Staphylococcus aureus (PSSA) bacteraemia from 67 hospitals across eight countries (median age 67 years; 31% female) I: Intravenous benzylpenicillin C: Intravenous flucloxacillin or cloxacillin O: Primary: all-cause mortality at 90 days. Secondary: acute kidney injury (AKI), serious adverse reactions. |
At trial closure, 90-day mortality occurred in 14% (21/152) of patients receiving benzylpenicillin versus 22% (26/121) receiving flucloxacillin/cloxacillin (adjusted OR 0.67, 95% CrI 0.35–1.28), corresponding to a 96.1% posterior probability of non-inferiority and 88.9% probability of superiority, although the prespecified non-inferiority threshold was not formally reached. AKI occurred less frequently with benzylpenicillin (11% vs 22%; adjusted OR 0.50, 95% CrI 0.26–0.94), with a 98.4% probability of superiority. Serious adverse reactions were also less common with benzylpenicillin (4% vs 7%). Overall, benzylpenicillin showed similar survival outcomes with substantially improved renal safety. | Moderate risk: The randomized multicentre design strengthens internal validity, but the open-label design introduces potential performance bias and may influence co-interventions or reporting of adverse events. The primary outcome of all-cause mortality is objective and unlikely to be affected by lack of blinding. Early trial termination due to excess AKI in the comparator arm may have reduced statistical power and prevented formal achievement of the prespecified non-inferiority threshold. The Bayesian adaptive platform design is appropriate but complex. Overall risk of bias is moderate, driven mainly by the open-label design and early stopping. |
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