The post hoc analysis discussed in the session involved comparing the efficacy of a new combination, Cefepime and Enmetazobactam, with Piperacillin/Tazobactam for adult patients in treating complicated urinary tract infections (cUTIs) or acute pyelonephritis (AP). It was found that Cefepime/Enmetazobactam, administered by 2-hour infusion every 8 hours, demonstrated non-inferiority compared to Piperacillin/Tazobactam regarding clinical cure and microbiotic eradication. A post hoc analysis was conducted to reassess efficacy outcomes in a clinical trial designed before the update of MIC breakpoints for Piperacillin/Tazobactam in 2021. The analysis applied the updated 2021 EUCAST breakpoints, defining susceptible as ≤8 mg/L and resistant as ≥60 mg/L, to the primary efficacy population. The objective was to reevaluate the primary efficacy outcomes of Cefepime/Enmetazobactam versus a comparator in adults with cUTIs or AP using this updated EUCAST Piperacillin/Tazobactam breakpoint.

The results in the revised microbiological modification intended to treat the population (m-MITT) demonstrated that 27 out of 345 patients in the Cefepime/Enmetazobactam group and 29 out of 333 patients in the Piperacillin/Tazobactam group were excluded due to MIC considerations. Overall success, as determined by the new EUCAST MIC criteria, was observed in 78.9% of patients receiving Cefepime/Enmetazobactam compared to 60.2% receiving Piperacillin/Tazobactam, indicating an adjusted treatment difference of 19.1% primarily driven by microbiological eradication outcomes. The clinical cure rates were similar between treatment groups, and the overall success of the revised Cefepime/Enmetazobactam was due to improved microbiological eradication. Therefore, when applied the updated EUCAST 2021 susceptibility requirements to the primary efficacy population, Cefepime/Enmetazobactam was not found to be inferior to Piperacillin/Tazobactam in adult patients with cUTIs, including AP.

European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 2024, 27th April–30th April 2024, Barcelona, Spain