Cefazolin associated with lower mortality than antistaphylococcal penicillins in MSSA bacteremia

A multicenter retrospective comparative-effectiveness study published in Antimicrobial Agents and Chemotherapy evaluated cefazolin versus antistaphylococcal penicillins for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Investigators used the international TriNetX database to identify hospitalized patients with monomicrobial MSSA bacteremia during 2015–2025. Of 110,275 patients identified, 3,908 met inclusion criteria; the abstract reports 1,954 patients per group after propensity score matching. The primary endpoint was all-cause mortality within 90 days.

Mortality was 9.7% with cefazolin versus 14.7% with antistaphylococcal penicillins, with a reported hazard ratio of 0.620 (interval 0.515–0.748). Clostridioides difficile infection within 90 days occurred in 4.9% versus 7.20%, respectively (hazard ratio 0.631; interval 0.482–0.827). Other prespecified safety outcomes included renal, liver, allergic, and hematological disorders within 30 days, but their results were not provided in the abstract.

These findings support cefazolin as a treatment option for MSSA bacteremia but do not establish superiority. Residual confounding remains possible despite matching, and the small proportion meeting inclusion criteria may limit generalizability. Full text was unavailable for assessment of treatment selection, matching methods, and the complete safety results.