Comparative effectiveness of ceftaroline plus vancomycin or daptomycin versus vancomycin or daptomycin monotherapy for MRSA bacteremia: an updated systematic review and meta-analysis

Introduction: MRSA bacteremia is associated with substantial clinical burden. Ceftaroline (CPT)-based combinations with vancomycin or daptomycin are increasingly utilized, but their added benefit remains uncertain. This meta-analysis compared the effectiveness and safety of CPT-based combination therapy versus vancomycin or daptomycin monotherapy. Methods: MEDLINE, Scopus, and Cochrane Central were systematically searched. Primary outcomes were all-cause mortality and microbiological recurrence. Data were pooled using Review Manager, and meta-regression analyses were performed in RStudio. Heterogeneity was assessed using the I² statistic. Results: A total of 22,938 patients were included from 10 cohort studies and one randomized controlled trial, with mean age 53 years, Pitt bacteremia score 2.0, and Charlson Comorbidity Index 2.6. CPT-based combination therapy showed mortality comparable to monotherapy (17.2% vs. 17.2%; RR 1.13; 95% CI 0.80–1.59; p = 0.50; I² = 4%), and the slight increase in microbiological recurrence (2.9% vs 1.4%; RR 0.86; 95% CI 0.51–1.47; p = 0.59; I² = 17%) was not significant. Meta-regression identified no covariate significantly modifying treatment effect. Conclusion: CPT-based combination therapy conferred no significant mortality benefit over vancomycin or daptomycin monotherapy in patients with MRSA bacteremia, and timing of initiation did not influence outcomes. Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD420251084876.