In vitro activity of gepotidacin against urine isolates of Escherichia coli from outpatient departments in Germany

Background Escherichia coli is the leading pathogen of community-acquired urinary tract infections. Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene oral antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action that confers activity against most strains of target pathogens, such as E. coli, Staphylococcus saprophyticus and Neisseria gonorrhoeae, including those resistant to other antibiotics. Objectives This study assessed the in vitro activity of gepotidacin in comparison with ciprofloxacin and other oral standard-of-care antibiotics using a large collection of urine isolates of E. coli obtained from outpatients in Germany. Methods Four hundred and sixty E. coli collected from 23 laboratories during a surveillance study in 2019/2020 were tested. Forty-six isolates (10.0%) produced an ESBL of the CTX-M family, half of which belonged to MDR clonal subgroups of E. coli ST131. Antibiotic susceptibilities were tested at a reference laboratory by broth microdilution according to the standard ISO 20776-1. Results Fifty-three (11.5%) isolates were ciprofloxacin resistant, 25 (47.2%) of which also produced an ESBL. Overall, MIC50/90 values for gepotidacin were 2/4 mg/L (MIC range 0.125-16 mg/L), with no differences in activity between ciprofloxacin-susceptible and ciprofloxacin-resistant isolates, ESBL-producing and non-ESBL isolates, O25b-ST131 isolates, and isolates susceptible or resistant to fosfomycin, mecillinam or nitrofurantoin. Conclusions Gepotidacin showed promising in vitro activity against urine isolates of E. coli, including ciprofloxacin-resistant isolates, ESBL-producing isolates and isolates resistant to oral standard-of-care antibiotics.