Ertapenem Produces Results Comparable to Piperacillin/Tazobactam in Diabetic Foot Infections

Paula Moyer, MA

November 01, 2004

Nov. 1, 2004 (Washington) — Patients with diabetic foot infections respond as well to ertapenem (Invanz) as they do to the standard treatment, piperacillin/tazobactam (Zosyn), according to investigators whose findings were presented here at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy.

Both of the treatments are administered intravenously; however, ertapenem is given on a once-daily basis, while the piperacillin/tazobactam combination must be taken four times daily. The finding increases physicians' treatment options for these difficult infections and makes home care more feasible rather than hospitalization, according to coinvestigator Murray Abramson, MD.

"It's crucial to note that ertapenem was comparable in efficacy to the standard treatment for diabetic foot infections," Dr. Abramson told Medscape. "The once-daily dosing schedule adds a layer of convenience for a primarily elderly population, and the added feasibility of home care means that the treatment will be less costly." Dr. Abramson is the director of clinical development in infectious diseases at Merck & Co., Inc., which manufactures ertapenem and funded the study.

Dr. Abramson and colleagues conducted the Study of Infections in Diabetic Feet Comparing Efficacy, Safety, and Tolerability of Ertapenem versus Piperacillin/Tazobactam (SIDESTEP) to address the paucity of randomized controlled trials regarding the efficacy of antibiotic regimens, and to determine the efficacy of ertapenem compared with piperacillin/tazobactam.

They recruited 576 patients to participate in a randomized, double-blind, multicenter trial of the two regimens. Of these patients, 289 were assigned to receive 1 g daily of ertapenem, and 287 were assigned to receive 3.375 g four times daily of piperacillin/tazobactam. All patients recruited to the study had moderate to severe diabetic foot infections. Patients received treatment for at least five days. They also had the option of switching to oral therapy, consisting of amoxicillin/clavulanate (Augmentin), so that the cumulative treatment time was a maximum of 28 days.

The patients participated in baseline and follow-up visits that involved evaluation of tissue wound cultures, quantitative wound scores, digital photography, dermal thermography, and hematological studies. The investigators wanted to know the proportion of patients in each group who had a favorable clinical response at the visit during which the intravenous antibiotic was discontinued. A favorable response was defined as either a cure or an improvement. The investigators further assessed patients 10 days after the intravenous antibiotic was discontinued.

By the end of intravenous therapy, 445 patients were evaluable; 226 patients received ertapenem and 219 patients received piperacillin/tazobactam. Clinical success rates at the point of discontinuation of intravenous therapy were 94.2% for the ertapenem group and 92.2% for the piperacillin/tazobactam group (95% confidence interval [CI], –2.9 to 6.9). At the 10-day follow-up assessment, 402 patients were evaluable; success rates were 87.4% for the ertapenem group and 82.7% for the piperacillin/tazobactam group (95% CI, –2.2 to 11.9).

During the intravenous therapy period, the investigators observed no difference in the incidence of drug-related clinical adverse events, which occurred in 15.2% of ertapenem patients and 19.9% of piperacillin/tazobactam patients. The most common adverse events were diarrhea, nausea, and headache, with no significant differences between the groups. Serious clinical drug-related adverse events occurred in 0.3% of the patients in each group, and one patient died in each group.

"This is an interesting study that shows that another drug is efficacious in treating diabetic foot infections," Adolf Karchner, MD, told Medscape in an interview seeking outside comment. He is chief of infectious diseases at Beth Israel Deaconess Hospital in Boston, Massachusetts.

"It broadens treatment options and has the added convenience of being a once-daily treatment. However, since ertapenem is a beta-lactam drug, it cannot be used in patients with a penicillin allergy," Dr. Karchner said.

44th ICAAC: Abstract 3776. Presented Oct. 31, 2004.

Reviewed by Gary D. Vogin, MD