Impact of methicillin resistance on mortality in Staphylococcus aureus endocarditis: a systematic review and meta-analysis

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a leading cause of endocarditis with poor outcomes. The magnitude and consistency of its mortality risk compared with methicillin-susceptible S. aureus (MSSA) remain uncertain. Data were extracted from PubMed, Embase, Scopus, and Cochrane Library from database inception to 30 November 2025, without language restrictions. A random-effects model (Restricted Maximum-Likelihood) was used to calculate pooled risk ratios (RRs). Heterogeneity was explored by stratified and meta-regression analyses. Publication bias was assessed using funnel plot symmetry and Egger’s regression. Twenty-four studies, comprising 3291 patients (1,011 with MRSA and 2280 with MSSA), met the inclusion criteria. Pooled short-term mortality was significantly higher in MRSA endocarditis (30.9% vs 25.6%; RR 1.48, 95% CI 1.21-1.80; I² = 34%). Across stratified analyses by study design, setting, region, and study era, mortality remained consistently higher in MRSA endocarditis. No significant differences were found for heart failure (RR 1.08, 95% CI 0.90-1.30), embolic events (RR 0.82, 95% CI 0.51-1.33), stroke (RR 0.88, 95% CI 0.78-1.00), or surgery performed (RR 0.97, 95% CI 0.56-1.68) in MRSA and MSSA groups. No publication bias was revealed by Funnel-plot inspection and Egger’s test (p = 0.082). Meta-regression showed no effect modification by age, hospital-acquired infection, prosthetic valve, or right-sided endocarditis. MRSA endocarditis carries a significantly higher short-term mortality than MSSA, consistent across study designs and study-level characteristics. The major complications were comparable between the two groups. Infective endocarditis is a serious infection of the heart valves caused by bacteria such as Staphylococcus aureus. Some strains are resistant to common antibiotics (called MRSA), which may affect patient outcomes. We conducted a systematic review and meta-analysis of published studies to compare outcomes between MRSA and antibiotic-sensitive (MSSA) infections. We found that MRSA infections are associated with a higher risk of death in the early period after diagnosis compared with MSSA. These findings suggest that antibiotic resistance remains an important determining factor in patient outcomes. Improving early diagnosis and optimising treatment strategies may help in reducing mortality in such cases. Meena et al., evaluate findings from 24 studies (3,291 patients) comparing outcomes of MRSA versus MSSA endocarditis. MRSA endocarditis shows higher short-term mortality, while major complications, including heart failure, stroke, and surgery rates remain similar between groups.