WASHINGTON — Once-daily treatment with ertapenem was as safe and effective as a four-times daily regimen with two other antibiotics for treating diabetic patients with moderate to severe foot infections in a controlled study with 445 evaluable patients.
“This is the largest and most comprehensive randomized controlled trial of treatment of moderate to severe diabetic foot infection to date, and the only one with a double-blind design,” Benjamin A. Lipsky, M.D., said while presenting a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
The study was sponsored by Merck, which markets ertapenem (Invanz).
The multicenter study enrolled adult men and women with diabetes and a moderate to severe foot infection that required 5–28 days of treatment with a parenteral antibiotic. Patients were randomized to intravenous treatment with either 1 g of ertapenem once daily, or 3.375 g of piperacillin plus tazobactam every 6 hours. Patients could continue on the intravenous regimen, if needed, for up to 28 days, but patients who were treated for at least 5 days and met certain clinical criteria for improvement were switched to an oral regimen with amoxicillin and clavulanate.
The study's primary outcome was the percent of patients who achieved a favorable response of cure or clinical improvement by the time their intravenous therapy was stopped. The study was designed to test whether ertapenem was not inferior to the comparator regimen.
Randomization placed 289 patients in the ertapenem group and 287 in the piperacillin plus tazobactam group. For the primary end point, 226 patients were evaluable in the ertapenem group and 94% had a favorable response by the time their intravenous treatment was stopped, as compared to a 92% response rate among the 219 evaluable patients in the comparator group, reported Dr. Lipsky, professor of medicine at the University of Washington, Seattle. The difference between the two groups was not statistically significant.
The two regimens also had identical effects when assessed by the study's secondary efficacy outcomes: the percentage of patients with a favorable response 10 days after antibiotic therapy was stopped, and the percentage of patients who had both a favorable clinical response and either microbiologic eradication or presumptive eradication by 10 days after treatment was stopped.
The safety profiles of the two regimens also were very similar. The fraction of patients with one or more adverse events was identical in both groups, 47.4%, and the fraction with serious, drug-related adverse events was also identical, 0.3%, Dr. Lipsky reported at the conference, which was sponsored by the American Society for Microbiology.
The fraction of patients who stopped therapy because of drug-related adverse events was 1.0% in the ertapenem group and 2.1% in the piperacillin plus tazobactam group. The most common adverse events in both groups were diarrhea, nausea, and headache, although diarrhea was more common among patients treated with piperacillin plus tazobactam.