United States: Study on Sulopenem for Uncomplicated Urinary Tract Infections (uUTI)

A study declared safety, superiority, and non-inferiority of Sulopenem based on the susceptibility of the pathogen to Ciprofloxacin in uncomplicated Urinary Tract Infections (uUTI), a phase 3 randomized trial published in the Clinical Infectious Diseases.

The availability of treatment options for uUTI caused by resistant pathogens remains limited. This problem should be addressed with the availability of anti-bacterial against multidrug-resistant pathogens. Ciprofloxacin is the most commonly used antibiotic for treating uUTI despite increasing resistance rates and collateral damage.

Study Overview

Based on the above background, Michael W. Dunni and the team conducted a study to evaluate the efficacy of Sulopenem in women based on pathogenic susceptibility to Ciprofloxacin. In the study, patients received Sulopenem etzadroxil 500mg/probenecid 500mg bilayer tablet twice daily for five days. Ciprofloxacin was given 250 mg twice a day for three days. The primary endpoint was a combined clinical and microbiological response on Day 12, with additional assessments on Day 5 and day 28.

Key Findings

• Baseline pathogens were resistant to Ciprofloxacin in 27% of participants.
• Collateral damage associated with Ciprofloxacin was evidenced by increased quinolone resistance.
• 1802 patients were screened, out of which 1671 were randomized.
• Clinical response was observed in 300/370 patients (81.1%) treated with Sulopenem and 349/415 (84.1%) treated with Ciprofloxacin.
• The response rate for Sulopenem was higher compared to Ciprofloxacin (83% vs 62.6%) in pathogen non-susceptible to Ciprofloxacin.
• Sulopenem had superiority over Ciprofloxacin, 62.6% vs 36.0% with a difference of 26.6% and p-value < 0.001, in the non-susceptible population. The uropathogen was resistant to Ciprofloxacin.
• Sulopenem was not non-inferior to Ciprofloxacin, 66.8% vs. 78.6%, with a -11.8% difference in the susceptible population.
• Sulopenem was non-inferior to Ciprofloxacin, 65.6% vs. 67.9%, with a difference of -2.3%.
• The most common side effect of Sulopenem use was diarrhoea in 12.4% of patients.
• A 54-year-old patient treated with Sulopenem developed angioedema which was treated successfully.

Conclusion

The researchers commented, "Sulopenem is well tolerated with mild self-limited diarrhoea as an only adverse event; it is an important option in treating uUTI by drug-resistant pathogen and should be used judiciously."

References

Michael W Dunne, Steven I Aronin, Anita F Das, Karthik Akinapelli, Michael T Zelasky, Sailaja Puttagunta, Helen W Boucher, Sulopenem or Ciprofloxacin for the Treatment of Uncomplicated Urinary Tract Infections in Women: A Phase 3 Randomized Trial, Clinical Infectious Diseases, 2022; ciac738