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

Objective: The objective was to conduct a systematic review and network meta-analysis (NMA) of existing treatments for ABSSSI focusing on the novel lipoglycopeptide oritavancin. Methods: EMBASE, MEDLINE, MEDLINE in Process, CENTRAL (Cochrane), and select conferences were searched for randomized controlled trials investigating antimicrobial agents for the treatment of ABSSSI. NMA was used to estimate the odds ratios of the Test-Of-Cure (TOC) and Early Clinical Response (ECR) outcomes for treatments relative to vancomycin in the ITT populations. Sub-group analyses in MRSA and MSSA populations were conducted for TOC; sensitivity analyses investigated the use of the clinically evaluable (CE) populations and the restriction to trials following the recent FDA guidelines for clinical trials. Results: The systematic review identified 52 trials. The most commonly investigated treatments were vancomycin and linezolid; most trials reported TOC, but not ECR. The posterior mean and 95% credible intervals for odds ratios of TOC for antimicrobial agents relative to vancomycin were: linezolid (1.55; 0.91-2.57), daptomycin (2.18; 0.90-5.42), and oritavancin 1200 mg (1.06; 0.80-1.43). The odds ratio of ECR for oritavancin 1200 mg was 1.02 (0.23-4.33). In the MRSA sub-group the odds ratios relative to vancomycin for TOC were: linezolid (1.55; 0.96-2.46), daptomycin (0.74; 0.13-3.66), and oritavancin 1200 mg (0.94; 0.44-2.02). In the MSSA sub-group they were linezolid (1.36; 0.15-13.34) and oritavancin 1200 mg (0.82; 0.08-7.83). These results were robust to the sensitivity analyses. Conclusions: This NMA provides a unified framework for the comparison of all available antimicrobial agents used in the treatment of ABSSSI and is the first to assess the ECR end-point. The results suggest equivalence of clinical efficacy between vancomycin, daptomycin, linezolid, and novel antimicrobial agents including oritavancin for the treatment of ABSSSI at TOC. The wide uncertainty margins indicate the heterogeneity of the available evidence and the need for further research.