Cefazolin for Methicillin-Susceptible

Summary

In an international Bayesian adaptive, open-label randomized comparison, cefazolin achieved noninferior 90-day mortality versus antistaphylococcal penicillins and significantly reduced acute kidney injury. Probabilities strongly favored noninferiority for mortality and superiority for kidney safety.

Key Findings

• 90-day mortality: 15.0% (cefazolin, 97/645) vs 17.0% (anti-staphylococcal penicillin, 109/642); adjusted OR 0.81 (95% CrI 0.59–1.12); probability of noninferiority 99.2%.
• Acute kidney injury: 13.9% (92/660) vs 19.6% (127/648); adjusted OR 0.67 (95% CrI 0.50–0.89); probability of superiority 99.7%.
• Bayesian adaptive platform domain met noninferiority criterion between Feb 2022 and Aug 2024.

Clinical Implications

For methicillin-susceptible Staphylococcus aureus infections presenting with sepsis or bacteremia, cefazolin can be prioritized over antistaphylococcal penicillins to minimize nephrotoxicity while maintaining outcomes. Institutions should update empiric/definitive therapy pathways accordingly.

Limitations

• Open-label design may introduce performance bias.
• Abstract truncation limits clarity on infection syndromes and full protocol details.

Future Directions

Subgroup analyses (e.g., endocarditis, high-inoculum infections), pharmacokinetic-pharmacodynamic correlates, and cost-effectiveness across settings to inform guideline updates.