Patient Characteristics Associated with Extended-Spectrum Beta-Lactamase-ProducingUropathogens: PooledResults fromTwo Phase 3 Clinical Trials of Gepotidacin for the Treatment of Uncomplicated Urinary Tract Infection.

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All Authors

Dennison, J.
Sheets, A.
Perry, C.R.
Wagenlehner, F.
Wilcox, M.H.
Scangarella-Oman, N.E.
Butler, D.
Breton, J.
Millns, H.
Mulgirigama, A.

LTHT Author

Wilcox, Mark

LTHT Department

Pathology
Microbiology

Non Medic

Publication Date

2025

Item Type

Conference Abstract

Language

Subject

Subject Headings

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 > 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.

Journal

Open Forum Infectious Diseases