title: In Vitro Activity of Gepotidacin, a Novel Triazaacenaphthylene Bacterial Topoisomerase Inhibitor, against a Broad Spectrum of Bacterial Pathogens.
abstract: Gepotidacin inhibits bacterial DNA replication through a mode different from that of fluoroquinolones. Gepotidacin and comparators were tested by broth and agar dilution against clinical isolates. The in vitro activities of gepotidacin were comparable against methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) isolates (MIC90, 0.5 μg/ml). The gepotidacin MIC90s were as follows (in micrograms per milliliter) for the indicated bacteria: Streptococcus pyogenes, 0.25; Escherichia coli, 2; Moraxella catarrhalis, ≤ 0.06; Streptococcus pneumoniae (0.25), Haemophilus influenzae, 1; Clostridium perfringens, 0.5; and Shigella spp., 1, including levofloxacin-resistant subsets. Gepotidacin warrants further investigation for clinical development.
authors.affiliation: International Health Management Associates, Inc., Schaumburg, Illinois, USA dbiedenbach@ihmainc.com.
authors.forename: D J
authors.initials: DJ
authors.lastname: Biedenbach
authors.affiliation: International Health Management Associates, Inc., Schaumburg, Illinois, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Bouchillon
authors.affiliation: International Health Management Associates, Inc., Schaumburg, Illinois, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hackel
authors.affiliation: GlaxoSmithKline, Collegeville, Pennsylvania, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Miller
authors.affiliation: GlaxoSmithKline, Collegeville, Pennsylvania, USA.
authors.forename: N E
authors.initials: NE
authors.lastname: Scangarella-Oman
authors.affiliation: GlaxoSmithKline, Collegeville, Pennsylvania, USA.
authors.forename: C
authors.initials: C
authors.lastname: Jakielaszek
authors.affiliation: International Health Management Associates, Inc., Schaumburg, Illinois, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Sahm
mesh_terms: D000073:Acenaphthenes / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003016:Clostridium perfringens / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects*; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000187:drug effects; D006193:Haemophilus influenzae / Q000187:drug effects; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects; D012760:Shigella / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology*
chemical_list: D000073:Acenaphthenes; D000900:Anti-Bacterial Agents; D006575:Heterocyclic Compounds, 3-Ring; D059005:Topoisomerase II Inhibitors; C000612856:gepotidacin