Meta-analysis of Randomized Controlled Trials of Vancomycin for the Treatment of Patients With Gram-Positive Infections: Focus on the Study Design

Abstract

Objective: To study the effectiveness and safety of vancomycin compared with that of other antibiotics for the treatment of gram-positive infections. Methods: Major electronic databases were searched. Data from published randomized controlled trials (January 1, 1950, to September 15, 2011 were pooled using a meta-analytic method. Results: Fifty-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 Total adverse events attributed to studied antibiotics (OR, 1.07; 95% CI, 0.90-1.28) and patients withdrawn from trials (OR, 0.86; 95% CI, 0.68-1.09) were similar in the compared groups.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). Conclusion: On 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.

Comparative efficacy of antibiotics for the treatment of acute bacterial skin and skin structure infections (ABSSSI): a systematic review and network meta-analysis

“…However, the present study is based on a larger and more recent set of trials and includes indirect evidence via the NMA methodology. A recent large meta-analysis 24 of 53 studies in the treatment of ABSSSI comparing vancomycin with linezolid and other anti-microbial agents found only significant differences in efficacy for linezolid (OR ¼ 1.61; 95% CI ¼ 1.07-2.43). This study also neglected indirect evidence and was restricted to comparisons with vancomycin.…”

“…The majority of published randomized controlled trials (RCTs) have been compared to vancomycin and have not achieved statistically significant differences 15 , although, arguably, the strongest results have been found in favor of linezolid over vancomycin [20][21][22][23] . Thirteen meta-analyses have been conducted comparing the efficacy of vancomycin, linezolid, and other anti-microbial agents, the majority comparing linezolid with vancomycin and finding clinical superiority of linezolid 7,12,[24][25][26][27][28][29][30][31][32][33][34] . However, most of these considered only direct comparisons of two treatments and neglected the impact of indirect evidence.…”

The Efficacy and Safety of Linezolid and Glycopeptides in the Treatment of Staphylococcus aureus Infections

“…Another meta-analysis showed no inferiority of linezolid treated MRSA skin and soft tissue infections [25]. One meta-analysis comparing vancomycin with linezolid detected no difference between two treatments, which seemed to contradict the other meta-analysis postulating that linezolid therapy was associated with higher clinical cure in patients with gram-positive bacterial infections [24], [26].In light of this controversy, further evaluation of linezolid for its efficacy compared to glycopeptides in the treatment of infections caused by known or suspected MRSA is important. Given the fact that several randomized controlled trials have been performed, and data have become available, we performed a meta-analysis with the goal to study the effectiveness and safety of linezolid in comparison with glycopeptide antibiotics in the treatment of infections caused by known or suspected MRSA.…”

Alternative clinical indications for novel antibiotics licensed for skin and soft tissue infection?

“…Daptomycin is indicated for the treatment of infections in adults with cSSTI [38], or right-sided infective endocarditis caused by S. aureus [7,39,40]. Its cidal activity supports its use in bacteraemia, although superiority has not been demonstrated in clinical trials [41,42].…”