To synthesize mortality and key safety outcomes from the CloCeBa and SNAP randomized trials comparing cefazolin with antistaphylococcal penicillins for MSSA bacteremia.
Approach:
Evidence: Bayesian meta-analysis of the two identified randomized trials, including 1,579 evaluable patients for 90-day mortality.
Methods: Combined CloCeBa outcome data with covariate-adjusted SNAP estimates; assessed mortality, treatment discontinuation due to adverse events, and acute kidney injury.
Key Findings:
For 90-day mortality, the pooled odds ratio was 0.84 (95% credible interval, 0.59–1.28); the posterior probability of noninferiority within the prespecified margin was 95.5%, and the probability of superiority was 81.0%.
Cefazolin had a 99.9% probability of superiority for fewer treatment discontinuations due to adverse events (OR, 0.25; 95% CrI, 0.13–0.48).
Cefazolin had a 98.4% probability of superiority for lower acute kidney injury incidence (OR, 0.54; 95% CrI, 0.25–0.97).
Endocarditis subgroup results from SNAP were consistent with the overall mortality analysis, but subgroup numbers were small.
Interpretation:
The authors concluded that cefazolin was noninferior to cloxacillin or flucloxacillin for 90-day mortality and was associated with fewer treatment discontinuations due to adverse events and less acute kidney injury. They stated that the findings support preferring cefazolin for adults with MSSA bacteremia.
Limitations:
Only two randomized trials were available, and SNAP contributed 82% of the data.
Outcome definitions differed slightly between trials, including acute kidney injury definitions; CloCeBa estimates were not covariate adjusted.
The trials included too few patients with endocarditis or S. aureus type A blaZ gene to support meaningful subgroup conclusions.
Both trials were open-label and were judged to have some concern for bias.
by Todd C. Lee, Steven Y. C. Tong, Joshua S. Davis, Arthur M. Albuquerque, Matthew P. Cheng, Jacob Dye, Nesrin Ghanem-Zoubi, Anna L. Goodman, Nynke G. L. Jager, Achim J. Kaasch, Ilse J. E. Kouijzer, David C. Lye, Alistair R. D. McLean, Brendan J. McMullan, David L. Paterson, Connor Prosty, Jason A. Roberts, Pierre Tattevin, Jonas Tverring, Dafna Yahav, Emily G. McDonald
Federal prosecutors allege that a Florida physician and research staff fabricated clinical trial records that were submitted into database systems used to evaluate investigational drugs.
