The β-lactam and β-lactamase inhibitor combination cefepime-taniborbactam offers a higher treatment success rate in the treatment of complicated urinary tract infection (UTI) compared with meropenem, reports a clinical trial in The New England Journal of Medicine.
The phase 3 “Safety and Efficacy Study of Cefepime/VNRX-5133 in Patients with Complicated Urinary Tract Infections” (CERTAIN-1) trial enrolled 661 patients with complicated UTI. Patients were randomly assigned in a 2:1 ratio to treatment with cefepime-taniborbactam (2.5 g intravenously [IV]) or meropenem (1 g IV), every 8 hours for 7 days. In patients with bacteremia, treatment could be extended to 14 days.
Microbiologic and clinical success rates were assessed at 19 to 23 days in a microbiologic intention-to-treat population of 436 patients with positive urine culture for a qualifying gram-negative pathogen, most commonly Enterobacterales species. In this group, the mean age was approximately 56 years, and 53% of patients were women. The diagnosis was complicated UTI in 57.8% of patients and acute pyelonephritis in 42.2%.
Composite microbiologic and clinical success rates were 70.6% with cefepime-taniborbactam versus 58.0% with meropenem. A prespecified superiority analysis showed a significant 12.6 percentage-point difference between groups. At late follow-up (28 to 35 days), composite and clinical success rates remained higher with cefepime-taniborbactam. Among patients with bacteremia, composite success rates at test of cure were 81.6% with cefepime-taniborbactam versus 68.4% with meropenem.
Headache, gastrointestinal events, and hypertension were the most common adverse events with cefepime-taniborbactam. Serious adverse events occurred in approximately 2% of both groups.
Emerging resistance to β-lactam antibiotics poses a challenge to treatment of complicated UTI, as for other serious infections. The cefepime-taniborbactam combination has shown promise for treatment of serious gram-negative infections.
The CERTAIN-1 findings suggest that cefepime-taniborbactam is superior to meropenem for treatment of complicated UTI including acute pyelonephritis. Safety profiles are similar between the two treatments. Cefepime-taniborbactam is “a potential treatment option for patients with complicated UTI and acute pyelonephritis caused by Enterobacterales species and Pseudomonas aeruginosa, including antimicrobial-resistant strains,” the investigators conclude [Wagenlehner FM, et al.; CERTAIN-1 Study Team. Cefepime-taniborbactam in complicated urinary tract infection. N Engl J Med 2024; 390:611–622. doi: 10.1056/NEJMoa2304748].
