Cefazolin versus Antistaphylococcal Penicillins for Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
- 1UCPel
Abstract
PurposeTo compare the efficacy and safety of intravenous cefazolin versus antistaphylococcal penicillins for the treatment of MSSA bacteremia in adults using evidence exclusively from randomized controlled trials.
MethodsWe searched 5 databases for RCTs comparing definitive intravenous cefazolin with ASPs (oxacillin, cloxacillin, flucloxacillin, nafcillin) in adults with MSSA bacteremia. Primary outcomes were 90-day all-cause mortality and acute kidney injury (AKI). Secondary outcomes included adverse event-related treatment discontinuation and persistent bacteremia ([≥]72h). Dichotomous outcomes were synthesized as risk ratios (RRs) with 95% confidence intervals (CIs) using random-effects models with Paule-Mandel estimation and Hartung-Knapp-Sidik-Jonkman inference. Fixed-effect Mantel-Haenszel models were performed as sensitivity analyses.
ResultsTwo RCTs randomized 1,656 participants (SNAP, n = 1,341; CloCeBa, n = 315), of whom 1,579 contributed to the 90-day mortality analysis. There was no statistically significant difference in 90-day mortality (RR 0.90, 95% CI 0.57-1.41; I2 = 0%). Both trials favoured cefazolin for acute kidney injury, but the random-effects estimate was highly imprecise (RR 0.26, 95% CI 0.00-939,970.59; I2 = 81.7%). Treatment discontinuation also favoured cefazolin directionally, although the random-effects estimate was imprecise (RR 0.24, 95% CI 0.00-24.41; I2 = 36.2%). Microbiological outcomes were synthesized narratively because definitions and assessment time points differed between trials.
ConclusionRandomized evidence supports cefazolin as a potential definitive treatment option when adequate source control, appropriate antimicrobial dosing, and clinical monitoring can be achieved. However, the limited number of trials and imprecision in pooled estimates warrant cautious interpretation.
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BibTeX
@misc{pozzebon2026cefazolin,
title = {{Cefazolin versus Antistaphylococcal Penicillins for Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials}},
author = {F. Pozzebon and G. Pacheco and G. Cabral and B. Dias and R. Macedo and A. Assis},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.12.26365331},
url = {https://www.medrxiv.org/content/10.64898/2026.10.12.26365331v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Cefazolin versus Antistaphylococcal Penicillins for Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
AU - F. Pozzebon
AU - G. Pacheco
AU - G. Cabral
AU - B. Dias
AU - R. Macedo
AU - A. Assis
PY - 2026
DA - 2026/10/12
PB - medRxiv
DO - 10.64898/2026.10.12.26365331
UR - https://www.medrxiv.org/content/10.64898/2026.10.12.26365331v1
AB - PurposeTo compare the efficacy and safety of intravenous cefazolin versus antistaphylococcal penicillins for the treatment of MSSA bacteremia in adults using evidence exclusively from randomized controlled trials. MethodsWe searched 5 databases for RCTs comparing definitive intravenous cefazolin with ASPs (oxacillin, cloxacillin, flucloxacillin, nafcillin) in adults with MSSA bacteremia. Primary outcomes were 90-day all-cause mortality and acute kidney injury (AKI). Secondary outcomes included adverse event-related treatment discontinuation and persistent bacteremia ([≥]72h). Dichotomous outcomes were synthesized as risk ratios (RRs) with 95% confidence intervals (CIs) using random-effects models with Paule-Mandel estimation and Hartung-Knapp-Sidik-Jonkman inference. Fixed-effect Mantel-Haenszel models were performed as sensitivity analyses. ResultsTwo RCTs randomized 1,656 participants (SNAP, n = 1,341; CloCeBa, n = 315), of whom 1,579 contributed to the 90-day mortality analysis. There was no statistically significant difference in 90-day mortality (RR 0.90, 95% CI 0.57-1.41; I2 = 0%). Both trials favoured cefazolin for acute kidney injury, but the random-effects estimate was highly imprecise (RR 0.26, 95% CI 0.00-939,970.59; I2 = 81.7%). Treatment discontinuation also favoured cefazolin directionally, although the random-effects estimate was imprecise (RR 0.24, 95% CI 0.00-24.41; I2 = 36.2%). Microbiological outcomes were synthesized narratively because definitions and assessment time points differed between trials. ConclusionRandomized evidence supports cefazolin as a potential definitive treatment option when adequate source control, appropriate antimicrobial dosing, and clinical monitoring can be achieved. However, the limited number of trials and imprecision in pooled estimates warrant cautious interpretation.
ER -