Efficacy And Safety Of Linezolid Versus Vancomycin For Methicillin-Resistant Staphylococcus Aureus (Mrsa)-Related Pneumonia: Updated Systematic Review And Meta-Analysis

Background: Existing guidelines, clinical trials, and meta-analyses have provided conflicting conclusions regarding the comparison of clinical or microbiological efficacy of linezolid versus vancomycin in the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-related pneumonia. Objective: This updated meta-analysis aimed to pool data comparing the efficacy and safety of linezolid versus vancomycin for treatment of MRSA-related pneumonia. Methods: A systematic review with meta-analysis was performed by searching PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL), through April 4, 2018. Eligible studies that compared linezolid to vancomycin for subjects with MRSA-related infections, including pneumonia, were identified. This study analyzed outcomes for evaluation, including clinical success, microbiological success, mortality, therapy duration, days on mechanical ventilation, length of ICU stay, length of hospital stay, drug-related adverse events (DRAEs), and drug discontinuation. Main endpoints for efficacy outcomes were end of treatment (EOT) and end of study (EOS). Risk ratios (RRs) or mean differences (MDs), respectively, with 95% confidence intervals (CIs), were calculated for relevant comparisons of efficacy and safety. Heterogeneity of results for included studies was assessed using I-2 statistics. Results: Fifteen studies, encompassing 7,003 subjects with MRSA-related pneumonia, met the inclusion criteria. This meta-analysis found the superiority of linezolid to vancomycin in terms of higher clinical success at EOT [RR 1.18, 95% CI (1.10 - 1.27), p < 0.00001] and microbiological success at EOT [RR 1.39 (1.25 - 1.55), p < 0.00001] (both statistical power > 99.9%), along with lower occurrence of nephrotoxicity [RR 0.52 (0.36 - 0.73), p = 0.0002; power = 96.4%]. Results showed inferiority, however, regarding a higher occurrence of diarrhea [RR (1.24 - 3.74), p = 0.006; power = 88.9%]. The present meta-analysis also found comparable mortality [RR 0.93 (0.81 - 1.07); p = 0.31], incidence of total DRAEs [RR 1.19 (0.95 - 1.49), p = 0.14], and drug discontinuation [RR 1.02 (0.83 - 1.27), p = 0.82] between the two therapies. Conclusion: The present meta-analysis supports the claim that linezolid is an advantageous alternative to vancomycin for treatment of MRSA-related pneumonia, due to superior clinical and microbiological success at EOT and lower incidence of nephrotoxicity. This meta-analysis, at least partially, addressed the current controversy and public health concern regarding the optimal treatment for MRSA-related pneumonia.