Cefazolin Versus Anti-Staphylococcal Penicillins for the Treatment of Patients with Methicillin-Susceptible Staphylococcus aureus Infection: A Meta-Analysis with Trial Sequential Analysis

INTRODUCTION: Methicillin-susceptible Staphylococcus aureus (MSSA) is a common cause of infection in humans. Beta-lactam antibiotics are the preferred agents, with anti-staphylococcal penicillins (ASPs) or the first-generation cephalosporin, cefazolin, favored by clinicians. Recent studies comparing the two strategies suggest similar outcomes between the agents. The purpose of this meta-analysis was to explore differences between cefazolin and ASPs for the treatment of MSSA infections. METHODS: We performed a meta-analysis with trial sequential analysis (TSA) of observational or cohort studies using a random-effects model. Two blinded reviewers independently assessed studies for inclusion, risk of bias, and data extraction. The primary outcome was all-cause mortality. Secondary outcomes included clinical failure, infection recurrence, and antibiotic discontinuation due to adverse events. Subgroup analyses were conducted for the primary outcome by type of ASP, studies with a high percentage of deep-seated infections, and studies of low to moderate risk of bias. RESULTS: After performing a comprehensive search of the literature, and screening for study inclusion, 19 studies (13,390 patients) were included in the final meta-analysis. Fifteen of the 19 studies (79%) were judged as having a low or moderate risk of bias. Use of cefazolin was associated with lower all-cause mortality [odds ratio (OR) 0.71, 95% confidence interval (CI) 0.56–0.91, p = 0.006, I(2) = 28%], clinical failure (OR 0.55, 95% CI 0.41–0.74, p < 0.001, I(2) = 0%), and antibiotic discontinuation due to adverse events (OR 0.25, 95% CI 0.16–0.39, p < 0.001, I(2) = 23%). Infection recurrence was higher in the cefazolin patients (OR 1.41, 95% CI 1.04–1.93, p = 0.03, I(2) = 0%). CONCLUSION: This meta-analysis demonstrated that the use of cefazolin was associated with significant reductions in all-cause mortality, clinical failure, and discontinuation due to adverse events, but was associated with an increased risk of infection recurrence. FUNDING: University of Florida Open Access Publishing Fund funded the Rapid Service Fees. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews (study ID: CRD42018106442). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40121-019-00259-4) contains supplementary material, which is available to authorized users.