In Vitro Activity of Gepotidacin, a Novel Triazaacenaphthylene Bacterial Topoisomerase Inhibitor, against a Broad Spectrum of Bacterial Pathogens

• Published in: Antimicrobial agents and chemotherapy 2016-03, Vol.60 (3), p.1918-1923
• Main Authors: Biedenbach, D J, Bouchillon, S K, Hackel, M, Miller, L A, Scangarella-Oman, N E, Jakielaszek, C, Sahm, D F
• Format: Article
• Language: English
• Subjects: Acenaphthenes; Acenaphthenes - pharmacology; Anti-Bacterial Agents; Anti-Bacterial Agents - pharmacology; Clostridium perfringens - drug effects; DNA Replication; DNA Replication - drug effects; Drug Resistance, Multiple, Bacterial; Escherichia coli - drug effects; Haemophilus influenzae - drug effects; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, 3-Ring - pharmacology; Humans; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - isolation & purification; Microbial Sensitivity Tests; Moraxella (Branhamella) catarrhalis - drug effects; Shigella - drug effects; Streptococcus pneumoniae - drug effects; Streptococcus pyogenes - drug effects; Susceptibility; Topoisomerase II Inhibitors; Topoisomerase II Inhibitors - pharmacology
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.02820-15

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.