Gepotidacin: The first-in-class triazaacenaphthylene antibiotic approved for the treatment of uncomplicated urinary tract infections.

Abstract

Uncomplicated urinary tract infection (uUTI) is a common bacterial infection in women. While the condition typically has a favorable prognosis, the widespread use of antibiotics has led to increasingly bacterial resistance, reducing the efficacy of traditional antibiotics. On March 25, 2025, the US Food and Drug Administration approved gepotidacin for the treatment of uUTIs caused by susceptible bacteria in female adult and pediatric patients 12 years of age and older weighing at least 40 kg. Gepotidacin is the first triazaacenaphthylene antibiotic approved for clinical use. It selectively binds to and inhibits both bacterial DNA gyrase and topoisomerase IV, disrupting bacterial DNA replication through a unique mechanism and thereby killing the pathogen. Results of clinical trials indicated the non-inferiority of gepotidacin compared to the current standard therapy, nitrofurantoin. The most frequently reported adverse reaction to gepotidacin was mild to moderate diarrhea. The approval of gepotidacin represents a progress in antibiotic innovation, offering novel perspectives on drug development while spurring global efforts to tackle the escalating challenge of antimicrobial resistance.