Efficacy and in vitro activity of gepotidacin against bacterial uropathogens, including drug-resistant phenotypes, in females with uncomplicated urinary tract infections: results from two global, pivotal, phase 3 trials (EAGLE-2 and EAGLE-3).

Abstract

Two recent Phase 3 trials demonstrated the efficacy of gepotidacin compared with nitrofurantoin to treat uncomplicated urinary tract infections (uUTIs) in females. Pretreatment urine specimens were obtained from all participants. Based on pooled trial data (treatment groups combined), central laboratory culture results identified 1,421 (45%) participants with ≥1 baseline qualifying (≥10⁵ CFU/mL) uropathogen (i.e., pooled microbiological Intent-to-Treat population). Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were the most common qualifying uropathogens. Among 1,159 E. coli isolates, 28%, 28%, 15%, and 28% were fluoroquinolone resistant (FQ-R), trimethoprim-sulfamethoxazole resistant (SXT-R), extended-spectrum β-lactamase positive (ESBL+), and multidrug resistant (MDR), respectively. For 114 K. pneumoniae isolates, 25%, 23%, 16%, and 16% were nitrofurantoin resistant, SXT-R, FQ-R, and ESBL+, respectively. Of 67 P. mirabilis isolates, 25%, 21%, and 31% were SXT-R, FQ-R, and MDR, respectively. Gepotidacin MIC₉₀ values against all qualifying uropathogens and drug-resistant phenotypes ranged from 0.25 to 32 µg/mL, with no isolates of Enterobacterales, Staphylococcus saprophyticus, or Enterococcus faecalis considered resistant to gepotidacin. For all uropathogen drug-resistant phenotypes, gepotidacin MIC₉₀ values were similar (i.e., lower, equal to, or 1-dilution higher) compared with the MIC₉₀ of the overall species. Gepotidacin's efficacy, based on therapeutic, clinical, and microbiological success rates, was generally consistent across phenotypic subgroups of E. coli, K. pneumoniae, and P. mirabilis. This pooled analysis represents a robust, contemporary, clinically relevant, and unbiased (i.e., baseline urine specimens obtained from all enrolled participants regardless of uUTI history) collection of data from community-acquired uUTIs in females.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04020341 and NCT04187144.