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.

OBJECTIVES: 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 AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.