Meta-analysis of randomized controlled trials of vancomycin for the treatment of patients with gram-positive infections: focus on the study design

ObjectiveTo study the effectiveness and safety of vancomycin compared with that of other antibiotics for the treatment of gram-positive infections.MethodsMajor electronic databases were searched. Data from published randomized controlled trials (January 1, 1950, to September 15, 2011) were pooled using a meta-analytic method.ResultsFifty-three trials comparing vancomycin with linezolid, daptomycin, quinupristin-dalfopristin, tigecycline, ceftaroline, ceftobiprole, telavancin, teicoplanin, iclaprim, and dalbavancin were included in the meta-analysis. Individual antibiotics were as effective as vancomycin, except for linezolid, which was more effective than vancomycin for the treatment of skin and soft tissue infections (odds ratio OR], 1.61; 95% confidence interval CI], 1.07-2.43). Comparators were as effective as vancomycin in the intent-to-treat population (OR, 1.08; 95% CI, 0.98-1.18) but were more effective in the clinically evaluable population (OR, 1.14; 95% CI, 1.02-1.27) when all infections were pooled. When available data from all trials were pooled, no differences were noted when patients with febrile neutropenia (OR, 1.07; 95% CI, 0.82-1.39), pneumonia (OR, 1.10; 95% CI, 0.87-1.37), bacteremia (OR, 1.05; 95% CI, 0.76-1.45), and skin and soft tissue infections (OR, 1.11; 95% CI, 0.89-1.39) were studied. Comparators were more effective in open-label (OR, 1.28; 95% CI, 1.08-1.50) but not in double-blind trials (OR, 1.04; 95% CI, 0.90-1.20). Total adverse events attributed to studied antibiotics (OR, 1.07; 95% CI, 0.90-1.28) and patients withdrawn from trials (OR, 0.86; 95% CI, 0.68-1.09) were similar in the compared groups. Mortality was not different between vancomycin and comparator antibiotics when all trials were included in the analysis (OR, 1.09; 95% CI, 0.96-1.23). Comparators were associated with higher mortality in open-label (OR, 1.27; 95% CI, 1.05-1.54) but not double-blind trials (OR, 0.96; 95% CI, 0.80-1.14).ConclusionOn the basis mainly of data from open-label trials, vancomycin is a treatment choice that is as effective as other available antibiotics for patients with gram-positive infections. Study design seems to make a major contribution to the outcome.