Characterization of gepotidacin activity, including

Gepotidacin is a novel, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication through a distinct binding site and unique mechanism of action that provides well-balanced inhibition of two different type II topoisomerase enzymes (DNA gyrase and topoisomerase IV) for most pathogens. Gepotidacin was recently approved by the US Food and Drug Administration (FDA) and the Medicines and Healthcare Products Regulatory Agency (MHRA) for the treatment of uncomplicated urinary tract infections (uUTI) and by the FDA for uncomplicated urogenital gonorrhea. This study investigated the IMPORTANCE: Antibiotic resistance continues to limit treatment options for common infections such as urinary tract infections (UTIs). Gepotidacin is a recently approved antibiotic that works in a new way compared with existing drugs, allowing it to remain active against bacteria that are resistant to many commonly used treatments. In this study, we examined how effectively gepotidacin kills several bacterial species that cause UTIs, including organisms that are resistant to fluoroquinolones or produce extended-spectrum β-lactamases. Gepotidacin was shown to rapidly reduce bacterial populations at clinically relevant concentrations and continued to suppress bacterial growth even after short exposures. Importantly, gepotidacin did not interfere with the activity of other commonly used antibiotics, suggesting it can potentially be used alongside existing therapies if needed. These findings provide additional evidence supporting the effectiveness of gepotidacin against a broad range of UTI pathogens and help improve our understanding of how this new antibiotic may perform in clinical treatment.