Piperacillin/tazobactam versus cefotaxime plus metronidazole for the treatment of severe intra-abdominal infection in hospitalized pediatric patients

Background: Intra-abdominal infections (IAIs) are especially difficult to t reat. Piperacillin/tazobactam (pip/tazo), a beta -lactam/beta -lactamase in hibitor combination, has been shown to be effective against intra-abdominal , gynecologic, and skin/soft tissue infections as well as infections of the lower respiratory and urinary tracts. Objective: The purpose of this study was to compare the efficacy of pip/taz o with that of cefotaxime plus metronidazole (cef + met) in pediatric patie nts with severe, complicated IAI. Methods: In this multinational, multicenter, randomized, open-label, parall el-group study, patients aged 2 to 12 years who were hospitalized for sever e, complicated IAI were randomly assigned to receive infusions of pip/tazo (100 mg/kg piperacillin/12.5 mg/kg tazobactam) over 30 to 60 minutes every 8 hours or cef + met (50 mg/kg cefotaxime plus 7.5 mg/kg metronidazole) ove r 30 minutes every 8 hours. The primary efficacy end point was clinical res ponse (cure or failure) in the efficacy evaluable population at the end of treatment and at follow-up, as assessed by an independent committee of revi ewers who were blinded to treatment (the blinded evaluation committee [BEC] ). Secondary end points were clinical response in the intent-to-treat popul ation at the end of treatment and at follow-up as assessed by the investiga tors, and bacteriologic response in patients with an identified baseline pa thogen. Results: Of the 545 patients enrolled in 46 centers, 402 were evaluable for efficacy (201 in each treatment group). Based on the BEC's assessment of c linical response, the cure rate was 93.5% in both groups at the end of trea tment; at follow-up the cure rate was 90.0% in the pip/tazo group and 91.0% in the cef + met group. Success rates at the end of treatment in the inten t-to-treat population, as assessed by the investigators, were similar to th e cure rates found bythe BEC for the evaluable population - 87.8% in the pi p/tazo group and 89.5% in the cef + met group. Clinical cure rates in patie nts who had an identifiable pathogen at baseline were > 80% for all pathoge n species for which greater than or equal to 10 isolates were obtained, exc ept for Pseudomonas species. Rates of bacteriologic success (eradication of all baseline pathogens, with no relapse or superinfection) in the pip/tazo and cef + met groups were similar at the end of treatment (90.1% and 91.0% , respectively) and at follow-up (88.2% and 89.7%, respectively). Adverse-e vent profiles and incidence rates were similar in the 2 treatment groups. L ength of hospital stay was significantly shorter for patients treated with pip/tazo than for patients treated with cef + met (P less than or equal to 0.011). Conclusion: Monotherapy with pip/tazo was as effective as combination treat ment with cefotaxime plus metronidazole in children with severe, complicate d IAI and should be considered when deciding on a first-line therapy.