Cefazolin versus Antistaphylococcal Penicillins for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Systematic Review and Meta-Analysis

BackgroundThere is debate on whether cefazolin or antistaphylococcal penicillins should be the first-line treatment for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Ongoing trials are investigating whether cefazolin is non-inferior to (flu)cloxacillin, but it remains uncertain whether these findings would apply to other antistaphylococcal penicillins. ObjectiveWe conducted a systematic review and meta-analysis comparing cefazolin to each of the individual antistaphylococcal penicillins for MSSA bacteremia. MethodsO_ST_ABSData SourcesC_ST_ABSWe updated a 2019 systematic review but specifically focused on evaluating outcomes by individual antistaphylococcal penicillins. Study Eligibility CriteriaComparative observational studies. ParticipantsPatients with MSSA bacteremia. InterventionsCefazolin versus the antistaphylococcal penicillins. Assessment of Risk of BiasThe risk of bias in non-randomized studies of interventions tool. Methods of Data SynthesisThe primary outcome was 30-day all-cause mortality, and we assessed for non-inferiority of cefazolin using a prespecified non-inferiority margin of a pooled odds ratio (OR) <1.2. Secondary outcomes were 90-day mortality, treatment-related adverse events (TRAEs), discontinuation due to toxicity, and nephrotoxicity. ResultsNo randomized data have been published. 30 observational studies at moderate or high risk of bias were included, which comprised 3869 patients who received cefazolin and 11644 patients who received antistaphylococcal penicillins (flucloxacillin=6721, unspecified=2440, nafcillin=1305, cloxacillin=1258, and oxacillin=120). Cefazolin was associated with a reduced odds of 30-day all-cause mortality (OR=0.73, 95%CI=0.62-0.85) compared to antistaphylococcal penicillins, meeting pre-specified non-inferiority as well as superiority. This effect was consistent versus flucloxacillin (OR=0.92, 95%CI=0.73-1.16), nafcillin (OR=0.58, 95%CI=0.28-1.17), cloxacillin (OR=0.42, 95%CI=0.11-1.58), and oxacillin (OR=0.31, 95%CI=0.03-2.75). Point estimates favored cefazolin for 90-day mortality, TRAEs, nephrotoxicity, and discontinuation due to toxicity overall and in each comparison with individual antistaphylococcal penicillins, except for TRAEs versus cloxacillin. ConclusionsIn moderate to low quality observational data, cefazolin was associated with superior effectiveness and safety as compared to antistaphylococcal penicillins overall and individually.