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This article appeared originally on our sister site, Contemporary OB/GYN.

The investigational antibiotic, Cefepime–taniborbactam, demonstrated greater efficacy for complicated urinary tract infection (UTI) treatment than meropenem, according to a recent study published in the New England Journal of Medicine. The investigational antibiotic was developed by Venatorx Pharmaceuticals, and the therapy has its FDA Prescription Drug User Fee Act (PDUFA) on February 22.

In terms of the scope of this medical issue, at least 600,000 hospitalizations are attributed to complicated UTI in the United States, and treatment can be challenging because of emerging resistance to β-lactam antibiotics. Infections are often treated using cefepime, a fourth-generation cephalosporin. However, spreading extended-spectrum β-lactamase and carbapenemase enzymes have led to increased cefepime resistance.

Taniborbactam, a β-lactamase inhibitor, can be used in combination with cefepime against carbapenem-resistant Enterobacterales species. Data has indicated in vivo efficacy from cefepime–taniborbactam against cefepime- and carbapenem-resistant Enterobacterales species, with an acceptable safety profile.

Investigators conducted a phase 3, double-blind, double-dummy, randomized, active-controlled trial to determine the safety of efficacy of cefepime-taniborbactam compared to meropenem in hospitalized patients with complicated UTI. Patients aged 18 years or older diagnosed with complicated UTI or acute pyelonephritis were included in the analysis.

UTI was determined based on pyuria, at least 1 systemic sign and at least 1 local sign or symptom, and 1 or more complicating factor. Exclusion criteria included more than 24 hours of antibacterial drug therapy against UTI before randomization, meropenem-resistant infection, and nontribal system antibacterial therapy.

Participants were assigned 2:1 to the cefepime-taniborbactam and meropenem groups. Patients in the cefepime-taniborbactam group received a 2.5 g cefepime 0.5 g taniborbactam dose every 8 hours plus meropenem placebo. Patients in the meropenem group received a 1 g dose of meropenem every 8 hours plus a cefepime-taniborbactam placebo.

All randomized patients were placed into the intention-to-treat (ITT) population, and all patients who received at least 1 dose of a trial drug were included in the safety population. Patients with a positive baseline urine culture with at least 105 colony-forming units (CFU) per millimeter of a qualifying pathogen were included in the microbiologic ITT (microITT) group.

Microbiologic and clinical success in the microITT group was measured at days 19 to 23 as the primary outcome of the analysis. Investigators defined microbiologic success as, “a reduction of all gram-negative bacterial pathogens found at baseline to less than 103 CFU per millimeter.” Symptomatic resolution or return to preinfection baseline of symptoms defined clinical success.

There were 661 patients enrolled into the study, 66% of whom were in the microITT population and 99.4% in the safety population. Similar clinical and demographic characteristics were reported at baseline across treatment groups. Patients were aged a mean 56.2 years, with 38.1% aged 65 years or older.

Complicated UTI was reported in 57.8% of patients in the microITT population and acute pyelonephritis in 42.2%. Most baseline pathogens were Enterobacterales species. Trial treatment was completed by 93.9% of the cefepime-taniborbactam group and 96.4% of the meropenem group.

In the cefepime-taniboractam group, 70.6% of microITT patients reached microbiologic and clinical success on days 19 to 23, compared to 58% of the meropenem group. This indicated superiority for cefepime-taniboractam vs meropenem, with a 12.6% difference.

During follow-up, composite success and clinical success remained higher in the cefepime-taniboractam group. Composite success findings in subgroups based on age, disease severity, and infection type remained consistent with primary efficacy results.

Adverse events during treatment were reported in 35.5% of the cefepime-taniboractam group and 29% of the meropenem group. Premature discontinuation occurred in 3% and 0.9% of these groups, respectively.

Common adverse events in the cefepime-taniboractam group included headache, gastrointestinal events, and hypertension. Adverse trends were not significantly different between groups. Severe adverse events were reported in 2% of the cefepime-taniboractam group and 1.8% of the meropenem group.

These results indicated safety and improved efficacy from cefepime-taniboractam in treating complicated UTI compared to meropenem. Investigators concluded cefepime-taniboractam is a potential option for treating patients with complicated UTI and acute pyelonephritis.

Reference

Wagenlehner FM, Gasink LB, McGovern PC. Cefepime–taniborbactam in complicated urinary tract infection. N Engl J Med. 2024;390:611-622 doi:10.1056/NEJMoa2304748