Randomized, Multicenter, Double-Blind Study of Efficacy, Safety, And Tolerability of Intravenous Ertapenem Versus Piperacillin/Tazobactam in Treatment of Complicated Intra-Abdominal Infections in Hospitalized Adults

Background: Complicated intra-abdominal infections are a common problem in surgical practice. This study compared the effectiveness of ertapenem (1 g qd) and piperacillin/tazobactam (3.375 g q6h) in the treatment of these infections. Methods: This was a multicenter, double-blinded, randomized study conducted in patients with complicated intra-abdominal infections. Of the 535 patients screened, 500 were stratified on the basis of disease severity (Acute Physiology and Chronic Health Evaluation [APACHE] II score ≤10 or >10), then randomized (1:1) to 4–14 days of treatment with one of the regimens and six weeks of followup. Nearly all patients (N = 494) were treated. The primary endpoint was the proportion of microbiologically evaluable patients with a favorable clinical response (cure) at two weeks. Non-inferiority of ertapenem was based on a difference in response rate of <15 percentage points compared with piperacillin/tazobactam (lower bound of the 95% CI > −15). Results: Of the 494 treated patients, 231 were microbiologically evaluable, with 123 and 108 patients in the ertapenem and piperacillin/tazobactam groups, respectively. Statistically similar cure rates were observed in the ertapenem (82.1%) and piperacillin/tazobactam (81.7%) groups (difference 0.3 [95% CI: −9.6, 10.5]). The pathogens isolated most frequently were Escherichia coli, Bacteroides fragilis, and Bacteroides thetaiotamicron, typical isolates associated with intra-abdominal infections. There were no statistical differences between the groups in serious drug-related clinical adverse events, drug-related clinical adverse experiences leading to study discontinuation, or mortality. Conclusions: Ertapenem was non-inferior to piperacillin/tazobactam in the cure of intra-abdominal infections caused by susceptible pathogens. Both study drugs generally were well tolerated.