Antimicrobial Agents and Chemotherapy · Oct 7, 2026
In vitro activity of gepotidacin against baseline Neisseria gonorrhoeae phenotypes and genotypes recovered from a clinical trial for uncomplicated urogenital gonorrhea (EAGLE-1)
By Jakielaszek C, Flight W, Lythgoe D et al.
There is an urgent need for novel antimicrobials to treat multidrug-resistant strains of Neisseria gonorrhoeae. In a phase III trial (EAGLE-1), gepotidacin, a first-in-class triazaacenaphthylene antibacterial, demonstrated non-inferiority to ceftriaxone plus azithromycin as measured by microbiological success for the treatment of uncomplicated urogenital gonorrhea. Here, we assessed the in vitro activity of gepotidacin against key N. gonorrhoeae drug-resistant phenotypes and genotypes from EAGLE-1. There were 408 baseline urogenital isolates recovered from 406 patients during the EAGLE-1 study. Agar dilution minimum inhibitory concentration (MIC) susceptibility testing was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines, and all isolates were molecularly characterized. All of the isolates were susceptible to ceftriaxone. All isolates had gepotidacin MICs of ≤2 µg/mL, with values ranging from ≤0.06 to 2 µg/mL; MIC₅₀, 0.25 µg/mL, and MIC₉₀, 0.5 µg/mL. As defined by the Food and Drug Administration (FDA) breakpoints and interpretive criteria (MIC breakpoints of ≤1 µg/mL [susceptible]; 2 µg/mL [intermediate]; and ≥4 µg/mL [resistant]), 99% of the study isolates were susceptible to gepotidacin, 1% were intermediate, and no isolates were resistant. Susceptibility percentages remained high across resistance phenotypes and genotypes. These findings support the in vitro activity of gepotidacin against the N. gonorrhoeae isolates, including drug-resistant phenotypes and genotypes, recovered in the EAGLE-1 clinical study.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04010539.