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

Abstract

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 CrI_95% for each agent was: vancomycin (74.7%; CrI_95%: 64.1%–83.5%), dalbavancin (87.7%; CrI_95%: 74.6%–95.4%), linezolid (84.4%; CrI_95%: 76.6%–90.6%), telavancin (83.5%; CrI_95%: 73.6%–90.8%), daptomycin (78.1%; CrI_95%: 54.6%–93.2%) and tigecycline (70.4%; CrI_95%: 48.0%–87.6%). Comparisons between antibiotics suggested differences versus vancomycin for linezolid (+9.7%; CrI_95%: 4.4%–15.8%), dalbavancin (+13.1%; CrI_95%: 1.0%–23.8%), and telavancin (+8.8%; CrI_95%: 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.

Key words::

• Antimicrobials
• Bayesian
• cSSTI
• Infection
• MRSA
• Skin
• Soft-tissue
• Meta-analysis

Transparency

Declaration of funding

This study was sponsored by Pfizer Inc. Employees of the sponsor were involved with the study design, interpretation of results, and development of the manuscript.

Declaration of financial/other relationships

J.F.S.L and B.H. have disclosed that they are employed by Pharmerit, a paid consultant to Pfizer in connection with the development of this manuscript. J.S. and B.A.v.H. have disclosed that they are partners of Pharmerit. S.H. and J.C. have disclosed that they are employed by Pfizer. D.N. has disclosed that he has accepted payment as an advisory board member, consultant and/or speaker for meetings supported by Wyeth, Novartis, Pfizer and Johnson and Johnson. S.H. and J.C. have disclosed owning employee stock options through Pfizer. A.T. has disclosed that he has received honoraria, consulting fees or research funding from Astellas, Cubist, Merck, Ortho-McNeil, Pfizer, Roche and Wyeth.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgment

The authors acknowledge Maarten Treur and Bram Verheggen for statistical analysis and programming assistance; Alex van der Steen, Joep Damen and Fay McCracken for assistance in the literature search; and Frank de Charro for his editorial assistance. All were employed by Pharmerit with funding through Pfizer.

The results of this study were presented as a poster at the 11th European Congress of the International Society for Pharmacoeconomics and Outcomes Research, held in Athens, Greece from 8 to 11 November 2008.