In vitro activity of gepotidacin against baseline Neisseria gonorrhoeae phenotypes and genotypes recovered from a clinical trial for uncomplicated urogenital gonorrhea (EAGLE-1)
- 1Infectious Diseases Research, GSK, Collegeville, Pennsylvania, USA
- 2Infectious Diseases Research, GSK, London, United Kingdom
- 3Biostatistics, GSK, Stevenage, United Kingdom
Abstract
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 TRIALS: This study is registered with ClinicalTrials.gov as NCT04010539.
Related
- In vitro activity of zoliflodacin against Neisseria gonorrhoeae collected in the United States from 2020 to 2022
- Pathogenicity and virulence of Neisseria gonorrhoeae
- Mucosal ACP subunit vaccine formulated with a small molecule STING agonist drives protective TH1/TH17 responses and serum bactericidal antibodies against Neisseria gonorrhoeae
- Structural and functional examination of Neisseria gonorrhoeae TfpC reveals a dynamic two-domain architecture required for type IV pilus function
- The global epidemiology of antibiotic-resistant Neisseria gonorrhoeae
BibTeX
@article{jakielaszek2026vitro,
title = {{In vitro activity of gepotidacin against baseline Neisseria gonorrhoeae phenotypes and genotypes recovered from a clinical trial for uncomplicated urogenital gonorrhea (EAGLE-1)}},
author = {Charles Jakielaszek and William Flight and Dan Lythgoe and Caroline Perry and Nicole E. Scangarella-Oman},
journal = {Antimicrobial Agents and Chemotherapy},
year = {2026},
month = oct,
doi = {10.1128/aac.00752-26},
url = {https://doi.org/10.1128/aac.00752-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - In vitro activity of gepotidacin against baseline Neisseria gonorrhoeae phenotypes and genotypes recovered from a clinical trial for uncomplicated urogenital gonorrhea (EAGLE-1)
AU - Charles Jakielaszek
AU - William Flight
AU - Dan Lythgoe
AU - Caroline Perry
AU - Nicole E. Scangarella-Oman
PY - 2026
DA - 2026/10/07
JO - Antimicrobial Agents and Chemotherapy
DO - 10.1128/aac.00752-26
UR - https://doi.org/10.1128/aac.00752-26
AB - 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 TRIALS: This study is registered with ClinicalTrials.gov as NCT04010539.
SN - 0066-4804
SN - 1098-6596
ER -