P-1062. <i>In vitro</i> Activity of Gepotidacin and Comparator Agents against a Collection of <i>K. pneumoniae</i> Urine Isolates from the United States During 2019-2022

Abstract Background Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a unique mechanism of action, a distinct binding site and provides well-balanced inhibition (for most uUTI uropathogens) of two different type II topoisomerase enzymes. This study reports on the in vitro activity of gepotidacin and other oral antibiotics tested against contemporary Klebsiella pneumoniae clinical isolates collected from patients with urinary tract infections (UTI) in the United States as part of a gepotidacin global uropathogen surveillance study. Methods A total of 2,001 K. pneumoniae isolates were collected during 2019-2022 from 73 medical centres located in the United States. All isolates were tested for susceptibility by CLSI methods at a central laboratory (Element Iowa City). MIC results for comparator agents were interpreted per CLSI guidelines. MIC results for oral antibiotics approved for the treatment of uncomplicated UTI. Multidrug-resistant (MDR) and extended-spectrum β-lactamase (ESBL) subsets were interpreted per CLSI criteria. Results Gepotidacin (MIC50/90, 4/16 mg/L) displayed activity against 2,001 K. pneumoniae isolates (Table), with 94.9% of all observed gepotidacin MICs ≤ 16 mg/L. Susceptibility rates of oral comparators tested were ≤ 90.0% for amoxicillin-clavulanic acid (90.0%, MIC50/90, 2/8 mg/L), ciprofloxacin (86.3%, MIC50/90, 0.015/0.5 mg/L), levofloxacin (88.3%, MIC50/90, 0.06/1 mg/L), nitrofurantoin (34.0%, MIC50/90, 64/ &amp;gt; 128 mg/L), and trimethoprim-sulfamethoxazole (84.7%, MIC50/90, ≤ 0.12/ &amp;gt; 4 mg/L) (Table). Gepotidacin remained active against the 11.0% and 6.8% of K. pneumoniae isolates that displayed ESBL and MDR phenotypes, respectively, with observed MIC50/90 values of 8/32 mg/L for both. Conclusion Gepotidacin demonstrated potent in vitro activity against contemporary K. pneumoniae, including ESBL-producing and MDR isolates. Almost all oral comparator agents reported against US K. pneumoniae UTI isolates had susceptibility rates between 80-90% while the observed nitrofurantoin susceptibility rates were 34.0%, respectively. Disclosures Renuka Kapoor, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Didem Torumkuney, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Rodrigo E. Mendes, PhD, GSK: Grant/Research Support