Vancomycin is the standard therapy for suspected or confirmed Methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infection (SSTI). Although newer anti-MRSA agents claim improved efficacy and safety, evidence in microbiologically confirmed MRSA-SSTI remains limited and heterogenous. Thus, this study aimed to systematically compare the efficacy and safety of alternative agents versus vancomycin in adults with confirmed MRSA-SSTI. Three databases were searched until August 05, 2025, to retrieve randomized controlled trials (RCTs) from published meta-analyses evaluating vancomycin versus alternatives involving patients with MRSA-confirmed SSTI. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using random-effects model. The study is registered in PROSPERO (CRD420251119756). From 28 meta-analyses, 39 RCTs (n = 20,285; 2,662 patients with MRSA-confirmed SSTI receiving alternative agents and 2,322 receiving vancomycin) were included. No significant difference in clinical success was observed between groups (RR: 1.012, 95% CI: 0.992–1.032; prediction interval: 0.994–1.030). Although alternatives showed modestly higher microbiological success (RR: 1.058, 95% CI 1.001–1.119; prediction interval: 0.895–1.250), the effect lost significance after publication bias adjustment. Alternative agents had significantly lower dermatologic but higher gastrointestinal and hematological risk. Tigecycline had higher adverse events (RR: 1.090, 95% CI: 1.019–1.166), and telavancin had higher drug discontinuation (RR: 1.405, 95% CI: 1.105–1.786). Despite the growth of newer anti-MRSA agents, vancomycin remains clinically comparable for MRSA-confirmed SSTI, with apparent microbiological advantages of alternatives tempered by potential publication bias. Varying safety and pharmacological profiles of these agents emphasize the importance of individualized treatment selection.
Purja et al. (Tue,) studied this question.