A New Drug Combination Effective in Treating Urinary Tract Infections

A recent randomized clinical trial showed that a new drug combination for treating complicated urinary tract infections (UTIs) and acute pyelonephritis, a bacterial infection causing kidney inflammation, was more effective than the current standard treatment approach.

Researchers compared the drug combination of cefepime and enmetaobactam with piperacillin and tazobactam, a common drug combination to treat UTIs. In the randomized clinical trial, the researchers found that the former was superior in treating patients with complicated UTIs.

For the phase 3, randomized, double-blind, active-controlled study across multiple centers, the researchers included 1041 patients and divided them into 2 cohorts: one group received cefepime, 2 g/enmetazobactam, 0.5 g (n = 520), the other received piperacillin 4 g/tazobactam, 0.5 g (n = 521). Patients received the medication by 2-hour infusion every 8 hours for 7 days.

Overall treatment success—the study’s primary outcome—occurred in 79.1% of patients who received cefepime and enmetazobactam. In patients who received piperacillin and tazobactam, 58.9% of patients achieved treatment success.

Further, treatment-emergent adverse events occurred in 50.0% of patients who were treated with cefepime and enmetazobactam compared with 44% who were treated with piperacillin and tazobactam. The researchers noted that adverse effects were mild to moderate. Among the total patients, 995 (95.6%) patients completed the trial. Some patients did not complete the study due to adverse events.

“In adults with complicated UTI or acute pyelonephritis, cefepime and enmetazobactam was noninferior to piperacillin and tazobactam for the primary outcome of clinical and microbiological cure,” the researchers concluded. “Additionally, cefepime and enmetazobactam was superior to piperacillin and tazobactam for the primary outcome. These findings suggest that cefepime and enmetazobactam may be an appropriate empirical therapy for suspected gram-negative complicated UTI.”


—Jessica Ganga


Kaye KS, Belley A, Barth P, et al. Effect of cefepime/enmetazobactam vs piperacillin/tazopactam on clinical cure of microbiological eradication in patients with complicated urinary tract infection or acute pyelonephritis. JAMA. Published online October 4, 2022. doi:10.1001/jama.2022.17034