P-1492. Patient Characteristics Associated with Extended-Spectrum Beta-Lactamase-Producing Uropathogens: Pooled Results from Two Phase 3 Clinical Trials of Gepotidacin for the Treatment of Uncomplicated Urinary Tract Infection
Authors: Dennison Jeremy , Sheets Amanda , Perry Caroline R , Wagenlehner Florian , Wilcox Mark H , Scangarella-Oman Nicole E , Butler Deborah , Breton John , Millns Helen , Mulgirigama Aruni , Helgeson Matthew , Janmohamed Salim 
Published: January 2025

Abstract

Background
Uncomplicated urinary tract infections (uUTIs), usually caused by Escherichia coli (E. coli), are common infections, affecting ∼50% of women globally in their lifetime. The presence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales limits effective oral treatment options for uUTI. Using uropathogen susceptibility data from two randomized controlled trials (RCTs) in uUTI, we compared baseline characteristics of patients with ESBL-positive (ESBL+) versus non-ESBL uropathogens.

Methods
EAGLE-2 (NCT04020341) and -3 (NCT04187144) were Phase 3, double-blind RCTs of oral gepotidacin versus nitrofurantoin for uUTI. Patients were female, aged ≥ 12 years, with ≥ 2 uUTI symptoms and urinary nitrite and/or pyuria. Pretreatment clean-catch midstream urine samples were collected for quantitative culture and susceptibility. In this post-hoc exploratory analysis, patients in the intent-to-treat population (all randomized patients), with ≥ 103 colony-forming units/mL E. coli, Klebsiella pneumoniae, Klebsiella oxytoca, and/or Proteus mirabilis, were grouped by ESBL status of their uropathogen(s), per Clinical and Laboratory Standards Institute guidelines.

Results
Overall, 1423 patients with culture-confirmed uUTI were included in the analysis; 203 (14%) had an ESBL+ uropathogen. Baseline characteristics by ESBL status are presented in the Table, and ESBL+ uropathogen prevalence by subgroup in the Figure. Generally, versus patients with non-ESBL uropathogens, more patients with ESBL+ uropathogens were: of Asian, American Indian or Alaska Native race (though sample sizes were small); of Hispanic/Latinx ethnicity; had milder symptoms; aged &gt; 50 years with history of recurrent urinary tract infection.

Conclusion
This post-hoc analysis of contemporary uUTI trial data describes baseline characteristics for patients with ESBL+ versus non-ESBL uropathogens. These data could inform future studies to identify clinical risk factors linked to ESBL+ uropathogens and improve patient outcomes.

Funding
EAGLE-2 was funded in part by GSK and in part with Federal funds from the US Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority (HHSO100201300011C). EAGLE-3 was funded by GSK.

Disclosures
Jeremy Dennison, MD PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Amanda Sheets, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Caroline R. Perry, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Florian Wagenlehner, MD, Astellas: Advisor/Consultant|AstraZeneca: Advisor/Consultant|Bionorica: Advisor/Consultant|DFG (German Research Foundation) funded research group BARICADE (FOR5427/1-466687329): Speaker|GSK: Advisor/Consultant|GSK: Principal investigator in a GSK-sponsored study|Janssen: Advisor/Consultant|Klosterfrau: Advisor/Consultant|MIP Pharma: Advisor/Consultant|OM Pharma: Advisor/Consultant|Spero: Advisor/Consultant|VenatoRX: Advisor/Consultant Mark H. Wilcox, MD, Astra Zeneca: Advisor/Consultant|Debiopharm International S.A.: Advisor/Consultant|Debiopharm International S.A.: Grant/Research Support|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|GSK: Honoraria|Nestle: Advisor/Consultant|Paion: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Phico therapeutics: Advisor/Consultant|QPex Biopharma: Advisor/Consultant|Seres: Advisor/Consultant|Seres: Grant/Research Support|Seres: Lecture Fees|Summit: Advisor/Consultant|Summit: Grant/Research Support|The European Tissue Symposium: Advisor/Consultant|The European Tissue Symposium: Grant/Research Support|Tillotts: Advisor/Consultant|Tillotts: Grant/Research Support|Tillotts: Lecture Fees|Vedanta: Advisor/Consultant Nicole E. Scangarella-Oman, MS, GSK: Employee|GSK: Stocks/Bonds (Public Company) Deborah Butler, PharmD, GSK: Employee|GSK: Stocks/Bonds (Public Company) John Breton, MCM, GSK: Employee|GSK: Stocks/Bonds (Public Company) Helen Millns, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Aruni Mulgirigama, MBBS, GSK: Employee|GSK: Stocks/Bonds (Public Company) Matthew Helgeson, PharmD, MBA, GSK: Employee|GSK: Stocks/Bonds (Public Company) Salim Janmohamed, MD, GSK: Employee|GSK: Stocks/Bonds (Public Company)