Gepotidacin is a triazaacenaphthylene inhibitor of bacterial type II topoisomerase that, while targeting similar enzymes as fluoroquinolones, is structurally distinct and expected to have a lower potential for resistance development, serving as a novel antibacterial agent.

Gepotidacin has in vitro activity against causative pathogens of acute bacterial skin and skin structure infections (ABSSSIs) [3]. Gepotidacin inhibits bacterial DNA gyrase and topoisomerase IV via a unique mechanism and has demonstrated in vitro activity against gram-negative and gram-positive bacteria, including drug-resistant strains. It also targets pathogens associated with other conventional and biothreat infections. The MIC50 and MIC90 for gepotidacin against the 25 N. gonorrhoeae isolates tested are 0.12 and 0.25 μg/mL, respectively [1]. The gepotidacin MIC90s are as follows: Streptococcus pyogenes (0.25 μg/mL), Escherichia coli (2 μg/mL), Moraxella catarrhalis (≤0.06 μg/mL), Streptococcus pneumoniae (0.25 μg/mL), Haemophilus influenzae (1 μg/mL), Clostridium perfringens (0.5 μg/mL), and Shigella spp. (1 μg/mL) [2].

For six methicillin-resistant Staphylococcus vitis vinifera (MRSA) isolates, the minimum inhibitory concentration (MIC) of Gepotidacin ranged between 0.125~0.5 mg/L. The alveolar epithelial lining fluid (ELF) penetration ratio of this drug was 1.1~1.4. In a neutropenic murine model, the maximum bacterial clearance effect reached 1.1~3.1 log10 CFU. The mean free drug area under the curve to minimum inhibitory concentration ratios (fAUC/MIC) required to achieve bacterial growth stasis and a 1-log reduction were 59.3 ± 34.6 and 148.4 ± 83.3, respectively [4].