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JAC Advance Access published online on January 19, 2005

Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh531
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JAC © The British Society for Antimicrobial Chemotherapy 2005; all rights reserved
Received September 2, 2004
Revised November 9, 2004
Accepted November 10, 2004

Original article

Daptomycin for treating infected diabetic foot ulcers: evidence from a randomized, controlled trial comparing daptomycin with vancomycin or semi-synthetic penicillins for complicated skin and skin-structure infections

Benjamin A. Lipsky 1* and Uschi Stoutenburgh 2

1 University of Washington School of Medicine, and General Internal Medicine Clinic, VA Puget Sound Health Care System (S-111-GIMC), 1660 S. Columbian Way, Seattle, WA 98108-1597, USA
2 Cubist Pharmaceuticals, Inc, Lexington, MA, USA

* To whom correspondence should be addressed.
Benjamin A. Lipsky, E-mail: Benjamin.Lipsky{at}med.va.gov


   Abstract

The predominant pathogens causing diabetic foot infections are Gram-positive cocci, many of which are now resistant to commonly prescribed antibiotics. Daptomycin is a new agent that is active against most Gram-positive pathogens. To compare the effectiveness of daptomycin against semi-synthetic penicillins or vancomycin, we analysed the subset of diabetic patients with an infected ulcer enrolled in two randomized, controlled investigator-blind trials of patients with complicated skin and soft-tissue infections presumptively caused by Gram-positive organisms.

Patients with a diabetic ulcer infection were prospectively stratified to ensure they were equally represented in the treatment groups, then randomized to either daptomycin [4 mg/kg every 24 h intravenously (iv)] or a pre-selected comparator (vancomycin or a semi-synthetic penicillin) for 7-14 days.

Among 133 patients with a diabetic ulcer infection, 103 were clinically evaluable; 47 received daptomycin and 56 received a comparator. Most infections were monomicrobial, and Staphylococcus aureus was the predominant pathogen. Success rates for patients treated with daptomycin or the comparators were not statistically different for clinical (66% versus 70%, respectively; 95% CI, -14.4, 21.8) or microbiological (overall or by pathogen) outcomes. Both treatments were generally well tolerated, with most adverse events of mild to moderate severity.

The clinical and microbiological efficacy and safety of daptomycin were similar to those of commonly used comparator antibiotics for treating infected diabetic foot ulcers caused by Gram-positive pathogens. Daptomycin should be considered for treating these infections, especially those caused by resistant Gram-positive pathogens.

Keywords: diabetic ulcers; foot infections; soft tissue infections; antibiotic resistance; Gram-positive infections.
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