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INFECTIOUS DISEASES

Daptomycin Versus Other Antimicrobial Agents for the Treatment of Skin and Soft Tissue Infections: A Meta-Analysis

Researcher, Alfa Institute of Biomedical Sciences, Athens, Greece

Eleni Plessa, MD

Researcher, Alfa Institute of Biomedical Sciences

George Peppas, MD

Researcher, Alfa Institute of Biomedical Sciences

Matthew E Falagas, MD MSc DSc

Scientific Director, Alfa Institute of Biomedical Sciences

Reprints: Dr. Falagas, Alfa Institute of Biomedical Sciences, 9 Neapoleos St., 151 23 Marousi, Athens, Greece, fax 30-210-68.39.605, matthew.falagas{at}tufts.edu

BACKGROUND: Skin and soft tissue infections (SSTIs) are common in everyday clinical practice. Daptomycin has been shown to achieve very good concentrations in skin and soft tissues.

OBJECTIVE: To compare the effectiveness and toxicity of daptomycin with that of other antimicrobials for the treatment of SSTIs.

METHODS: PubMed, Scopus, and the Cochrane Central Register of Controlled Trials were searched for articles published up to March 2009. Comparative studies in which daptomycin was used in the intervention group were included in this meta-analysis. The primary outcome of interest was clinical success; secondary outcomes were microbiologic success, clinical success in subsets with complicated SSTIs (cSSTIs) or infections due to methicillin-resistant Staphylococcus aureus (MRSA), clinical success of daptomycin-versus vancomycin-treated patients, time to clinical cure, treatment-related adverse events, withdrawal from treatment due to toxicity, all-cause mortality, and development of resistance.

RESULTS: Four studies were included in the analysis (3 were randomized controlled trials [RCTs]). Vancomycin and semisynthetic penicillins were used in the comparator arm. Three studies reported on patients with cSSTIs. The intention-to-treat (ITT) population was 1557 patients. No statistically significant difference between daptomycin and comparators was found regarding clinical success in clinically evaluable (OR 0.89; 95% CI 0.63 to 1.25 in the 3 RCTs and OR 1.34; 95% CI 0.38 to 4.66 with all 4 studies included), ITT, MRSA-infected patients, and those with cSSTIs. Two studies reported that significantly fewer patients with cSSTIs required prolonged treatment in the daptomycin arm and that clinical cure was faster than with comparators. No difference between the compared regimens was found in other outcomes.

CONCLUSIONS: Daptomycin is effective and safe for the treatment of SSTIs. Studies evaluating the optimal duration of daptomycin therapy for cSSTIs, comparing daptomycin with new agents, and focusing on proven MRSA SSTIs will be helpful for the further evaluation of the drug.

Key Words: abscess, burn, cellulitis, erysipelas, glycopeptide, lipopeptide, ulcer

Published Online, November 24, 2009. www.theannals.com, DOI 10.1345/aph.1M264