What type of study is this?

This is a In Vitro Study study.

What question did this study set out to answer?

Evaluate the in vitro activity of gepotidacin against E. coli and K. pneumoniae urinary isolates.

January 14, 2026Open Forum Infectious Diseases0 citationsOpen Access

P-1174. In vitro Activity of Gepotidacin and Comparator Agents Against a Collection of Escherichia coli and Klebsiella pneumoniae Urine Isolates From the United States During 2023

SAS J Ryan ArendsJMI Laboratories RKRenuka KapoorEmory University NSNicole E. Scangarella-OmanInfectious Disease Consultants

Key Points

Evaluate the in vitro activity of gepotidacin against E. coli and K. pneumoniae urinary isolates.
Collected 1,011 E. coli and 398 K. pneumoniae isolates from 58 medical centers in the US in 2023.
Tested susceptibility of isolates using CLSI methods and guidelines.
Categorized MDR and ESBL subsets per CLSI criteria.
Gepotidacin showed 100% susceptibility against E. coli with 2/4 µg/mL MIC values.
Other agents like fosfomycin and nitrofurantoin demonstrated high susceptibility rates (99% and 97%, respectively).
Gepotidacin remained effective against 92% of K. pneumoniae isolates.
Overall susceptibility to oral agents was ≥80% except for ampicillin and trimethoprim-sulfamethoxazole against E. coli.

Abstract

Abstract Background Gepotidacin (GEP) is a recently approved, bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct binding site, unique mechanism of action and provides well-balanced inhibition (for most pathogens) of two different type II topoisomerase enzymes. This study reports on the in vitro activity of GEP and other oral antibiotics tested against contemporary E. coli (EC) and K. pneumoniae (KPN) clinical isolates collected from patients with urinary tract infections (UTI) in the United States (US). Methods 1,011 EC and 398 KPN isolates were collected in 2023 from 58 medical centers in the US. Isolates were tested for susceptibility by CLSI methods. MIC results for comparator agents were interpreted per CLSI guidelines. Multidrug-resistant (MDR) and extended-spectrum β-lactamase (ESBL) subsets were categorized per CLSI criteria. Results GEP (MIC50/90, 2/4 µg/mL) displayed activity against EC isolates, with all (100%) isolates having GEP MICs ≤16 µg/mL. Other oral agents demonstrated the following rates of susceptibility: amoxicillin-clavulanate (AMC, 88%), ampicillin (AM, 52%), ciprofloxacin (CIP, 80%), fosfomycin (FOS, 99%), mecillinam (MEC, 95%), nitrofurantoin (FM, 97%), and trimethoprim-sulfamethoxazole (SXT, 72%). GEP maintained similar MIC50 values (1–2 µg/mL) and MIC90 values (4 µg/mL) against drug not susceptible (NS) subsets of EC. GEP (MIC50/90, 4/16 µg/mL) was also active against KPN isolates tested, with 92% of isolates having GEP MICs ≤16 µg/mL. Other oral agents demonstrated the following rates of susceptibility: AMC (90%), CIP (82%), FM (28%), and SXT (81%). The majority of GEP MIC50/90 values were within 1- to 2-dilutions (MIC50/90 values 4-16/16-64 µg/mL) against drug-NS subsets of KPN. Conclusion GEP demonstrated in vitro activity against contemporary EC and KPN, including ESBL-producing and MDR isolates. This activity remained unaffected for EC isolates NS to other oral standard-of-care antibiotics and was within 1- to 2- dilutions of the value for the total population for drug-NS subsets of KPN. Susceptibility to other oral agents was ≥80% except for AM and SXT against EC isolates, and was between 80-90% except for FM against KPN isolates. Disclosures Renuka Kapoor, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Nicole E. Scangarella-Oman, MS, GSK: Employee|GSK: Stocks/Bonds (Public Company) Rodrigo E. Mendes, PhD, GSK: Grant/Research Support|Shionogi & Co., Ltd.: Grant/Research Support|United States Food and Drug Administration: FDA Contract Number: 75F40123C00140

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