Comparative effectiveness of antibiotics for the treatment of MRSA complicated skin and soft tissue infections

Objective: With a growing number of studies and comparators in MRSA skin infections, a unified framework for comparing treatments is needed for health technology assessment (HTA). The objective was to systematically assess the success rates of common antimicrobial agents for the treatment of complicated skin and soft tissue infections (cSSTIs) caused by MRSA. Methods: MEDLINE, EMBASE, and Cochrane databases were searched to identify published clinical trials in which dalbavancin, daptomycin, linezolid, telavancin, teicoplanin, tigecycline, and vancomycin were used to treat cSSTIs. Pooled efficacy estimates were generated from clinical and microbiological determinations of success for the MRSA-subgroups in cSSTI clinical trials using a Bayesian meta-analytic approach. Success rates for each antibiotic were reported with 95% Bayesian confidence intervals (called credible intervals [CrI]). In sensitivity analyses the impact of different model parameters and article quality were investigated. Results: Out of 36 identified studies, 14 studies on six antibiotics with 28 treatment arms (n = 1840) were included in the analysis. No MRSA data in cSSTI were found for teicoplanin. The pooled success rate and CrI95% for each agent was: vancomycin (74.7%; CrI95%: 64.1%-83.5%), dalbavancin (87.7%; CrI95%: 74.6%-95.4%), linezolid (84.4%; CrI95%: 76.6%-90.6%), telavancin (83.5%; CrI95%: 73.6%-90.8%), daptomycin (78.1%; CrI95%: 54.6%-93.2%) and tigecycline (70.4%; CrI95%: 48.0%-87.6%). Comparisons between antibiotics suggested differences versus vancomycin for linezolid (+9.7%; CrI95%: 4.4%-15.8%), dalbavancin (+13.1%; CrI95%: 1.0%-23.8%), and telavancin (+8.8%; CrI95%: 1.5-16.7%). The finding of lower vancomycin efficacy in MRSA cSSTI did not change in sensitivity analyses. Conclusion: The results of this meta-analysis suggest higher success rates for linezolid and the new glycopeptides (dalbavancin and telavancin) in MRSA-confirmed cSSTIs. The uncertainty margins reflect the study limitations including number of cases and indirect nature of the comparisons. This example of Bayesian meta-analysis for MRSA cSSTI provides a potential framework for comparisons that is useful for HTA and formulary decision-making.