Cefepime/enmetazobactam combo bests piperacillin/tazobactam for severe UTI treatment: JAMA

A new study published in the Journal of American Medical Association found that, cefepime/enmetazobactam was well superior to piperacillin/tazobactam in providing clinical cure and microbiological eradication in patients with severe urinary tract infection (UTI) or acute pyelonephritis brought on by gram-negative bacteria.

A new -lactam/-lactamase inhibitor combination called cefepime/enmetazobactam has the potential to be used as an empirical treatment for resistant gram-negative infections. When treating patients with severe urinary tract infections (UTIs) or acute pyelonephritis, Keith Kaye and colleagues conducted this trial to determine if cefepime/enmetazobactam was noninferior to piperacillin/tazobactam for the evaluation of treatment effectiveness.

An multicenter, phase 3 randomized clinical study that was done across 90 different countries in Europe, North and Central America, South America, and Africa was used for this work. Between September 24, 2018, and November 2, 2019, there was recruitment. The last follow-up took place on November 26, 2019. Adult patients who were 18 years of age or older and had a clinical diagnosis of complex UTI or acute pyelonephritis brought on by gram-negative urine pathogens were included in the study. Cefepime, 2 g/enmetazobactam, 0.5 g (n = 520), or piperacillin, 4 g/tazobactam, 0.5 g (n = 521) were administered to eligible patients according to a randomization process over the course of seven days.

The key findings of this study were:

1. 1034 (99.3%) of the 1041 randomly assigned patients got the research medicine, and 995 (95.6%) of them finished the experiment.

2. In the primary analysis set, patients receiving cefepime/enmetazobactam experienced the primary outcome in 79.1% (273/345) of cases compared to 58.9% (196/333) of patients receiving piperacillin/tazobactam (between-group difference, 21.2% [95% CI, 14.3% to 27.9%]).

3. 50.0% (258/516) of patients receiving cefepime/enmetazobactam and 44.0% (228/518) of patients receiving piperacillin/tazobactam experienced treatment-emergent adverse events; the majority of these events were mild to severe in severity (89.9% vs. 88.6%, respectively).

4. Participants who took cefepime/enmetazobactam in a total of 1.7% (9/516) and piperacillin/tazobactam in a total of 0.8% (4/518) did not finish the prescribed medication because of adverse events.

Reference: 

Kaye, K. S., Belley, A., Barth, P., Lahlou, O., Knechtle, P., Motta, P., & Velicitat, P. (2022). Effect of Cefepime/Enmetazobactam vs Piperacillin/Tazobactam on Clinical Cure and Microbiological Eradication in Patients With Complicated Urinary Tract Infection or Acute Pyelonephritis. In JAMA (Vol. 328, Issue 13, p. 1304). American Medical Association (AMA). https://doi.org/10.1001/jama.2022.17034