Determination of frequency of spontaneous resistance for gepotidacin and levofloxacin against a collection of gram-positive and gram-negative organisms

ABSTRACT Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antimicrobial recently approved by the Food and Drug Administration (FDA) and Medicines and Healthcare products Regulatory Agency for the treatment of uncomplicated urinary tract infections (uUTI) and by the FDA for uncomplicated urogenital gonorrhea. Gepotidacin selectively inhibits type II topoisomerases involved in bacterial DNA replication by a distinct binding site and novel mechanism of action, conferring in vitro activity against most uropathogens, including those resistant to current antimicrobials. This study evaluated the potential of gepotidacin to select for spontaneous resistance in Citrobacter freundii , Enterobacter cloacae species complex, Klebsiella aerogenes , Klebsiella pneumoniae , Proteus mirabilis , Providencia rettgeri , Enterococcus faecalis , and Staphylococcus saprophyticus clinical isolates. Mutant frequencies ranged from 6.1 × 10 −8 to