BACKGROUND AND PURPOSE:

• Gepotidacin is a novel, bactericidal, triazaacenaphthylene antibiotic that inhibits bacterial DNA replication
  • Active against most E. coli strains including those exhibiting resistance
• Wagenlehner et al. (The Lancet, 2024) compared the efficacy and safety of oral gepotidacin vs nitrofurantoin in adolescent and adult women with uncomplicated urinary tract infections (UTIs)

METHODS:

• Phase 3, randomized, multicenter, double-blind, double-dummy, non-inferiority trials
  • EAGLE-2 and EAGLE-3
• Participants
  • Non-pregnant
  • 12 years old or older
  • ≥40 kg
  • ≥2 symptoms of urinary tract infection
  • Presence of urinary nitrite and/or pyuria
• Interventions
  • Oral gepotidacin: 1500 mg twice daily for 5 days
  • Oral nitrofurantoin: 100 mg twice daily for 5 days
• Study design
  • Randomization was stratified by
    • Age category | History of recurrent uncomplicated UTIs
• Primary outcome
  • Therapeutic success at day 10 to 13
    • Combined clinical success (ie, complete symptom resolution) and microbiological success (ie, reduction of qualifying uropathogens to <103 CFU/mL)

RESULTS:

• Gepotidacin group: 1531 | Nitrofurantoin group: 1605
  • Both studies were stopped for efficacy at interim analysis
• Gepotidacin was non-inferior to nitrofurantoin in both studies and superior to nitrofurantoin in EAGLE-3
  • EAGLE-2
    • Gepotidacin: 50.6% | Nitrofurantoin: 47.0%
    • Adjusted difference 4.3% (95% CI, –3.6 to 12.1)
  • EAGLE-3
    • Gepotidacin: 58.5% | Nitrofurantoin: 43.6%
    • Adjusted difference 14.6% (95% CI, 6.4 to 22.8)
• Most common adverse events
  • Gepotidacin: diarrhea
    • EAGLE-2: 14% | EAGLE-3: 18%
  • Nitrofurantoin: nausea
    • EAGLE-2: 4% | EAGLE-3: 4%
  • Cases were mostly mild or moderate
  • There were no life-threatening or fatal events

CONCLUSION:

• Gepotidacin is a safe and effective treatment for patients with uncomplicated UTI
• The authors state

The availability of a new oral antibiotic with in-vitro activity and in-vivo efficacy against common uropathogens causing uncomplicated urinary tract infections, including clinically important drug resistance phenotypes, would offer a substantial benefit for patients

Learn More – Primary Sources:

Oral gepotidacin versus nitrofurantoin in patients with uncomplicated urinary tract infection (EAGLE-2 and EAGLE-3): two randomised, controlled, double-blind, double-dummy, phase 3, non-inferiority trials