Sulopenem not as effective as ertapenen for treating complicated UTIs, pyelonephritis: Study

Sulopenem is a thiopenem antibiotic that is being developed for treating multidrug-resistant infections. The accessibility of both oral and intravenous (IV) formulations will ease the early discharge of hospitalized patients.

The study included hospitalized patients with bacteriuria, pyuria, and signs and symptoms of complicated UTI. They were randomized to receive five days of IV sulopenem followed by oral sulopenem etzadroxil/probenecid or five days of IV ertapenem followed by oral ciprofloxacin or amoxicillin-clavulanate. The randomization was dependent on baseline uropathogen susceptibility. The primary endpoint was the overall combined microbiological and clinical response at the Test of Cure visit on the 21st day.

The study led to the following findings:

• Of 1392 treated patients, 444 and 440 were respectively treated with sulopenem, and ertapenem had a positive urine culture at baseline and were suitable for the primary efficacy analyses.
• The researchers identified organisms producing extended-spectrum beta-lactamase (ESBL) in 26.6% of patients and fluoroquinolone non-susceptible pathogens in 38.6%.
• Noninferiority of sulopenem to the comparator regimen was not shown for the primary endpoint, 67.8% vs. 73.9% (difference, -6.1%). The difference was driven by the lower rate of asymptomatic bacteriuria in the subgroup of ertapenem-treated patients who stepped down to oral ciprofloxacin.
• The researchers did not observe a substantial difference in overall response at any other timepoint. The IV and oral sulopenem formulations were well-tolerated and compared favorably to the comparator regimen.

"We found that Sulopenem followed by oral sulopenem-etzadroxil/probenecid for not non-inferior than ertapenem followed by oral step-down therapy for treating complicated UTI, driven by a reduced rate of asymptomatic bacteriuria in patients who received ciprofloxacin," the researchers wrote. "Both sulopenem formulations were well-tolerated."

Reference:

Michael W Dunne, Steven I Aronin, Anita F Das, Karthik Akinapelli, Jeanne Breen, Michael T Zelasky, Sailaja Puttagunta, Sulopenem For The Treatment of Complicated Urinary Tract Infection Including Pyelonephritis: A Phase 3 Randomized Trial, Clinical Infectious Diseases, 2022;, ciac704, https://doi.org/10.1093/cid/ciac704