Abstract
Background
Sulopenem is a broad-spectrum IV and oral penem antibiotic being developed for the treatment of infections caused by multidrug-resistant bacteria to allow for earlier discharge of hospitalized patients.
Methods
1,395 hospitalized adults with pyuria, bacteriuria, and clinical signs and symptoms of cUTI were randomized to sulopenem IV once daily for 5 days followed by a bilayer tablet of sulopenem-etzadroxil and probenecid bid or ertapenem IV once daily for 5 days followed by either oral ciprofloxacin or amoxicillin-clavulanate bid, depending on susceptibility of the baseline uropathogen. The primary endpoint was overall (clinical and microbiologic) response at Day 21 [Test of Cure (TOC)] in the micro-MITT population.
Results
The sulopenem and ertapenem treatment arms were well-balanced at baseline.
The difference in overall response was driven by a difference in asymptomatic bacteriuria occurring between the end of treatment (EOT) and TOC in the subgroup of patients with a ciprofloxacin susceptible uropathogen at baseline who received ertapenem IV followed by oral ciprofloxacin. No difference in overall response was identified at EOT [86.7% vs 88.9%, sulopenem and ertapenem, respectively; difference, 95% CI: -2.2% (-6.5, 2.2)].
19% of patients remained on ertapenem IV as the baseline pathogen was both resistant to quinolones and ESBL positive; overall response for patients with these resistant pathogens on IV sulopenem who stepped down to oral sulopenem was higher [64/80 vs 55/84 on sulopenem IV/oral and ertapenem IV, respectively; difference, 95% CI: 14.5% (0.8, 27.8)].
Treatment emergent adverse events (all, 14.8% vs 16.1%; related, 6.0% vs 9.2%) and serious adverse events (2.0% vs 0.9%) were similar for patients on sulopenem and ertapenem, respectively.
Overall Response at Test of Cure, micro-MITT Population
Conclusion
Sulopenem followed by oral sulopenem-etzadroxil probenecid was not non-inferior to ertapenem followed by oral step-down therapy for the treatment of cUTI driven by a lower rate of asymptomatic bacteriuria in patients receiving oral ciprofloxacin. Sulopenem, both IV and oral, was well-tolerated; its oral formulation allowed patients with baseline pathogens resistant to both quinolones and β-lactams an opportunity to successfully step down from IV therapy.
Disclosures
Michael W. Dunne, MD, Iterum Therapeutics (Employee, Shareholder) Steven I. Aronin, MD, Iterum Therapeutics (Employee, Shareholder)