Efficacy and safety of ertapenem compared with piperacillin/tazobactam for diabetic foot infections: The SIDESTEP Study

Abstract number: 1133_250

Lipsky B., Armstrong D., Citron D., Erb T., King T., Morgenstern D., Rawlins S., Abramson M.

Objectives:  

Diabetic foot infections (DFI) are a frequent cause of hospitalization for diabetics and the most common non-traumatic cause of lower extremity amputations world-wide. Few randomized controlled trials have compared the efficacy of different antibiotic regimens for DFI. Most previous studies were small and not blinded.

Methods:  

This double-blind randomized study was designed to determine noninferiority of intravenous (IV) ertapenem (E) to piperacillin/tazobactam (P/T) (3.375 g qid) for the treatment of patients with moderate to severe DFI. IV antibiotic therapy was required for a minimum of 5 days. Patients could be switched to oral therapy (amoxicillin/clavulanate) for a maximum cumulative treatment of 28 days. Baseline and follow-up visits included evaluation of tissue wound cultures and quantitative wound scores. Assessments were made at discontinuation of IV therapy (DCIV) and at day 10 post-treatment (IV or IV and oral if given) follow-up.

Results:  

576 patients were randomized to treatment (E: 289; P/T:287); 445 were clinically evaluable at the end of IV therapy (E: 226; P/T: 219). The mean duration of IV therapy was 11.1 d for E and 11.3 d for P/T. Clinical success rates were similar between the treatments at DCIV (E: 94.2%, P/T: 92.2%; between treatment difference: 1.9; 95% CI: ­2.9, 6.9). In the microbiologically evaluable population, the overall rate of eradication (presumed or documented) at the 10 d follow-up was also comparable (E: 87.8%, P/T: 84.4%; between treatment difference: 3.4%; 95% CI: ­4.5, 11.9). Clinical response rates were similar in both treatment groups across baseline wound scores and the response rates generally decreased with increasing baseline wound scores. There were no differences in drug-related adverse events during parenteral therapy (E: 15.2%, P/T: 19.9%; RR E/(P/T): 0.77; 95% CI: 0.54, 1.10; p = 0.147) or discontinuations due to drug-related adverse events during parenteral therapy (E: 1.0%, P/T: 2.1%; RR E/(P/T) 0.50; 95% CI: 0.15, 1.94; p = 0.341).

Conclusions:  

This study, the largest and most comprehensive randomized controlled trial of antibiotics for DFI, found that clinical and microbiological outcomes for patients treated with E once daily were equivalent to that of patients treated with P/T q6h. Both E and P/T were generally well-tolerated.