Cefazolin in MSSA Bacteremia

Key Takeaways

• Cefazolin met noninferiority for 90-day mortality versus flucloxacillin or cloxacillin in adults with methicillin-susceptible S. aureus bacteremia.
• Acute kidney injury within 14 days was observed less often with cefazolin than with the antistaphylococcal penicillin comparator.
• The comparison came from an open-label, randomized international Bayesian adaptive platform trial in adults with penicillin-resistant, methicillin-susceptible S. aureus bacteremia.

Among evaluable adults with methicillin-susceptible Staphylococcus aureus bacteremia, 90-day mortality was 15.0% with cefazolin and 17.0% with flucloxacillin or cloxacillin in an NEJM trial. The randomized comparison enrolled adults with penicillin-resistant, methicillin-susceptible S. aureus bacteremia and assessed death from any cause within 90 days after enrollment. Cefazolin was compared with flucloxacillin or cloxacillin across multiple countries in this bacteremia treatment domain. The prespecified noninferiority criterion was met. Cefazolin was noninferior for the primary mortality endpoint in this trial population.

The study used an open-label design, and the primary outcome was death from any cause within 90 days after enrollment. The mortality analysis used a hierarchical Bayesian logistic-regression model tied to the study's probabilistic decision thresholds. Noninferiority was prespecified as an adjusted odds ratio below 1.2, and superiority required an adjusted odds ratio below 1.0.

Among evaluable patients, 97 of 645 patients assigned to cefazolin died within 90 days, compared with 109 of 642 assigned to flucloxacillin or cloxacillin. Those event rates were 15.0% and 17.0%, respectively, in the two randomized groups. The adjusted odds ratio for death was 0.81, with a 95% credible interval from 0.59 to 1.12. Researchers estimated a 99.2% posterior probability of noninferiority and an 89.8% posterior probability of superiority for the mortality comparison.

For acute kidney injury within 14 days, 92 of 660 patients in the cefazolin group met the outcome, versus 127 of 648 in the antistaphylococcal-penicillin group. The corresponding rates were 13.9% and 19.6%, with an adjusted odds ratio of 0.67 and a 95% credible interval from 0.50 to 0.89. Investigators also reported a 99.7% probability of superiority for this safety outcome, consistent with the difference in event frequencies. The authors concluded that cefazolin was noninferior to flucloxacillin or cloxacillin for 90-day mortality and was associated with a lower incidence of acute kidney injury in this randomized comparison.