2832. Gepotidacin Efficacy in E. coli Drug-Resistant Phenotypes: A Pooled Analysis of the EAGLE-2 and EAGLE-3 Randomized Controlled Trials in Uncomplicated Urinary Tract Infection

BACKGROUND: Uncomplicated urinary tract infections (uUTI) are among the most common community-acquired infections in women worldwide. Recommended treatment is largely empiric. Rates of antimicrobial resistance among Escherichia coli (E. coli) isolates, specifically extended-spectrum beta-lactamase positive (ESBL+) and multidrug-resistant (MDR) strains, are increasing worldwide. Gepotidacin is a first-in-class, triazaacenaphthylene, bactericidal antibiotic that inhibits bacterial DNA replication by inhibiting two enzymes, where a target-specific single mutation does not significantly impact susceptibility. We report gepotidacin efficacy against E. coli drug-resistant phenotypes in a pooled analysis of the EAGLE-2 and EAGLE-3 trials in uUTI. METHODS: EAGLE-2 and EAGLE-3 were near-identical global, Phase 3, randomized, double-blind, double-dummy, active-controlled noninferiority trials comparing gepotidacin with nitrofurantoin. Females aged ≥ 12 years with ≥ 2 UTI symptoms were eligible and were randomized 1:1 to oral gepotidacin (1500mg) or nitrofurantoin (100mg), twice daily for 5 days. Therapeutic success at test-of-cure visit (Day 10–13) was defined as combined clinical success (complete symptom resolution) and microbiological success (from ≥ 10(5) to < 10(3) CFU/mL) without the need for other systemic antimicrobials. Analysis of the pooled microbiological intent-to-treat (micro-ITT) population was performed. RESULTS: The pooled micro-ITT population comprised 1421 patients (732 gepotidacin, 689 nitrofurantoin). Table 1 shows E. coli drug-resistant phenotypes at baseline. Therapeutic, clinical and microbiological success rates at test-of-cure numerically favored gepotidacin over nitrofurantoin for clinically important E. coli drug-resistant phenotypes: ESBL+, fluroquinolone-resistant (FQ-R), trimethoprim/sulfamethoxazole-resistant (SXT-R), and MDR (Figure 1). Adverse events were reported in 35% (gepotidacin) and 23% (nitrofurantoin) of patients. [Figure: see text] CONCLUSION: Gepotidacin showed consistent efficacy (therapeutic, clinical and microbiological success) versus nitrofurantoin in patients with E. coli drug-resistant phenotypes (ESBL+, FQ-R, SXT-R, MDR). Gepotidacin has potential as a novel oral treatment for uUTI in key patient subgroups. [Figure: see text] DISCLOSURES: Thomas M. Hooton, MD, GSK: Advisor/Consultant Caroline R. Perry, PhD, GSK: Employee and shareholder Salim Janmohamed, MD, GSK: Employee and shareholder Amanda Sheets, PhD, GSK: Employee and shareholder Jeremy Dennison, MD, GSK: Employee and shareholder Helen Millns, PhD, GSK: Employee and shareholder Emily Jarvis, MSc, GSK: Employee and shareholder Nicole E. Scangarella-Oman, MS, GSK: Employee and shareholder Chun Huang, PhD, GSK: Employee and shareholder