An antibiotic combination designed to target difficult-to-treat gram-negative bacteria was superior to meropenem in patients with complicated urinary tract infection (UTI), according to the results of a phase 3 trial published today in the New England Journal of Medicine.
Cefepime-taniborbactam combines a fourth-generation cephalosporin antibiotic with a beta-lactamase inhibitor. Developed by Venatorx Pharmaceuticals of Malvern, Pennsylvania, the combination has shown in vitro and in vivo efficacy against carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa, with an acceptable side-effect profile in healthy volunteers.
Venatorx submitted a New Drug Application to the US Food and Drug Administration in August 2023 based on the results of the trial, which were first announced in November 2022.
In the double-blind trial, adults with complicated UTIs, including acute pyelonephritis, in 15 countries were randomized 2:1 to receive intravenous cefepime-taniborbactam or meropenem every 8 hours for 7 days. The primary outcome was both microbiologic and clinical success (composite success) on trial days 19 and 23 in the microbiologic intention-to-treat (microITT) population.
Composite success against carbapenem-resistant isolates
Of the 661 patients who underwent randomization, 436 (mean age, 56.2 years) were included in the microITT population. Of those patients, 57.8% had complicated UTI, 42.2% had acute pyelonephritis, and 13.1% had bacteremia. Enterobacterales accounted for 95.9% of baseline pathogens, and P aeruginosa 4.1%.
Composite success occurred in 207 (70.8%) of 293 patients in the cefepime-taniborbactam group and 83 (58.0%) of 143 patients in the meropenem group. The treatment difference (12.6 percentage points; 95% confidence interval, 3.1 to 22.2) met the superiority criteria for the primary outcome. The difference in treatment response was sustained at late follow-up (trial days 28 and 35), with cefepime-taniborbactam showing higher composite success and clinical success. The combination also had composite success in 8 of 10 patients with meropenem-resistant isolates.
Adverse events occurred in the 35.5% of patients in the cefepime-taniborbactam group and 29.0% in the meropenem group. The frequency of severe adverse events was similar in both groups.
"Thus, cefepime–taniborbactam was shown to be a potential treatment option for patients with complicated UTI and acute pyelonephritis caused by Enterobacterales species and P. aeruginosa, including antimicrobial-resistant strains," the investigators concluded.