Abstract
Background
Sulopenem is a thiopenem antibiotic being developed for the treatment of multidrug-resistant infections. The availability of both IV and oral formulations will facilitate earlier discharge of hospitalized patients.
Methods
Hospitalized adults with pyuria, bacteriuria and signs and symptoms of cUTI were randomized to five days of IV sulopenem followed by oral sulopenem etzadroxil/probenecid or five days of IV ertapenem followed by oral ciprofloxacin or amoxicillin-clavulanate, depending on baseline uropathogen susceptibility. The primary endpoint was the overall combined clinical and microbiologic response at the Test of Cure visit on Day 21.
Results
Of 1392 treated patients, 444 and 440 treated with sulopenem and ertapenem, respectively, had a positive urine culture at baseline and were eligible for the primary efficacy analyses. Organisms producing an extended spectrum beta-lactamase (ESBL) were identified in 26.6% of patients and fluoroquinolone non-susceptible pathogens in 38.6%. For the primary endpoint, noninferiority of sulopenem to the comparator regimen was not demonstrated, 67.8% vs. 73.9% (difference, -6.1%; 95% CI: -12.0, -0.1%). The difference was driven by the lower rate of asymptomatic bacteriuria in the subgroup of ertapenem-treated patients who stepped down to oral ciprofloxacin. No substantial difference in overall response was observed at any other timepoint. Both the IV and oral formulations of sulopenem were well-tolerated and compared favorably to the comparator regimen.
Conclusions
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 those receiving ciprofloxacin. Both formulations of sulopenem were well-tolerated.
Clinical Trial Registration: NCT03357614
