Objective Hospital-acquired pneumonia remains the most lethal and expensive nosocomial infection worldwide. Optimal therapy remains controversial. We aimed to compare mortality and clinical response outcomes in patients treated with either linezolid or vancomycin.

Design Systematic review and meta-analysis.

Data sources PubMed, EMBASE, Cochrane Library, American College of Physicians Journal Club, Evidence-based Medicine BMJ and abstracts from infectious diseases and critical care meetings were searched through April 2013.

Eligibility criteria for selecting studies All randomised clinical trials comparing linezolid to vancomycin for hospital-acquired pneumonia.

Data extraction Preferred reporting items for systematic reviews and meta-analyses guidelines were followed. One author extracted the data and two authors rechecked and verified all data.

Results Nine randomised trials with a total of 4026 patients were included. The adjusted absolute mortality risk difference (RD) between linezolid and vancomycin was 0.01% (95% CI −2.1% to 2.1%; p=0.992; I²=13.5%. The adjusted absolute clinical response difference was 0.9% (95% CI −1.2% to 3.1%; p=0.409; I²=0%. The risk of both microbiological (RD=5.6%, 95% CI −2.2% to 13.3%; p=0.159; I²=0%) and methicillin-resistant Staphylococcus aureus (RD=6.4%, 95% CI −4.1% to 16.9%; p=0.230; I²=0%) eradication were not different between linezolid and vancomycin. Gastrointestinal side effects were more frequent with linezolid (RD=0.8% (95% CI 0% to 1.5%; p=0.05), but no differences were found with renal failure, thrombocytopenia and drug discontinuation due to adverse events. Our sample size provided 99.9% statistical power to detect differences between drugs regarding clinical response and mortality.

Conclusions Linezolid and vancomycin have similar efficacy and safety profiles. The high statistical power and the near-zero efficacy difference between both antibiotics demonstrates that no drug is superior for the treatment of hospital-acquired pneumonia.