Cefazolin Noninferior to Antistaphylococcal Penicillins for MSSA Bacteremia: Study
A recent study published in The New England Journal of Medicine demonstrated that cefazolin is an effective treatment for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Cefazolin achieved noninferiority to the antistaphylococcal penicillins cloxacillin and flucloxacillin for 90-day mortality, with rates of 15% versus 17%, respectively. In addition, patients receiving cefazolin experienced a lower incidence of acute kidney injury within 14 days when compared to those treated with antistaphylococcal penicillins (13.9% vs 19.6%). These findings challenge longstanding preferences for antistaphylococcal penicillins and support cefazolin as a safe and effective alternative for MSSA bacteremia.
A fatal bloodstream infection, methicillin-susceptible Staphylococcus aureus bacteremia need immediate, focused antibiotic treatment. Antistaphylococcal penicillins were the gold standard for many years. However, the recommended first-line therapy is now cefazolin, a first-generation cephalosporin. According to clinical data, cefazolin is just as effective as penicillins, but it has a far better safety record, less hepatotoxicity cases, and more flexible dosage schedules. As a result, cefazolin is now essential for treating MSSA bacteremia, improving patient outcomes while reducing side effects. Thus, this study evaluated the effectiveness o cefazolin against MSSA.
Cefazolin and an antistaphylococcal penicillin (flucloxacillin or cloxacillin) in adult patients with penicillin-resistant, methicillin-susceptible S. aureus bacteremia were compared as part of an ongoing multinational Bayesian adaptive platform study. A hierarchical Bayesian logistic-regression model was used to assess the main outcome, which was mortality from any cause within ninety days after platform registration. This study evaluated both the posterior probability of superiority and the posterior probability of cefazolin's noninferiority to flucloxacillin or cloxacillin (the criterion for noninferiority was predetermined as an adjusted odds ratio of <1.2, which approximates an absolute difference in mortality of <2.5 percentage points if mortality in the antistaphylococcal-penicillin group is 15%). Acute renal damage within 14 days was one of the secondary safety outcomes.
This portion of the continuing experiment was carried out between February 17, 2022, and August 7, 2024, at which point the noninferiority criteria had been satisfied. The cefazolin group had a mortality rate of 15.0% (97 deaths among 645 patients) at 90 days, while the antistaphylococcal-penicillin group had a mortality rate of 17.0% (109 deaths among 642 patients) (adjusted odds ratio, 0.81; 95% credible interval, 0.59 to 1.12; probability of noninferiority, 99.2%; probability of superiority, 89.8%).
92 out of 660 patients (13.9%) in the cefazolin group and 127 out of 648 patients (19.6%) in the antistaphylococcal-penicillin group experienced acute kidney damage (adjusted hazard ratio, 0.67; 95% credible range, 0.50 to 0.89; likelihood of superiority, 99.7%). Overall, cefazolin was linked to a decreased incidence of acute renal damage and was noninferior to flucloxacillin or cloxacillin in terms of 90-day mortality in patients with methicillin-susceptible S. aureus bacteremia.
Source:
The Staphylococcus aureus Network Adaptive Platform (SNAP) Trial Group. (2026). Cefazolin for methicillin-susceptible staphylococcus aureus bacteremia. The New England Journal of Medicine, 394(23), 2329–2339. https://doi.org/10.1056/nejmoa2506905
