In Vitro and In Vivo Antibacterial Activities of a Novel Quinolone Compound, OPS-2071, against Clostridioides difficile

Abstract

OPS-2071 is a novel quinolone antibacterial agent characterized by low oral absorption that reduces the risk of adverse events typical of fluoroquinolone class antibiotics. The in vitro and in vivo antibacterial activities of OPS-2071 against Clostridioides difficile were evaluated in comparison to vancomycin and fidaxomicin. OPS-2071 exhibited potent antibacterial activity against 54 clinically isolated C. difficile strains with a minimum inhibitory concentration of 0.125 μg/mL (MIC50) and 0.5 μg/mL (MIC90), making it more active than vancomycin on a concentration basis (MIC50: 2 μg/mL, MIC90: 4 μg/mL) and comparable to fidaxomicin (MIC50: 0.063 μg/mL, MIC90: 8 μg/mL). OPS-2071 showed equally potent antibacterial activity against both hypervirulent and non-hypervirulent strains, while a significant difference in susceptibility to fidaxomicin was observed. Spontaneous resistance to OPS-2071 and vancomycin was not observed, however, resistance to fidaxomicin was observed at 4× MIC concentration. The mutant prevention concentration of OPS-2071 was 16-fold lower than those of fidaxomicin and vancomycin, and the post-antibiotic effect of OPS-2071 was longer than those of fidaxomicin and vancomycin. Also, OPS-2071 showed low systemic exposure, with OPS-2071 having 2.9% oral bioavailability at 1 mg/kg in rats. Furthermore, OPS-2071 showed significant in vivo efficacy at 0.0313 mg/kg/day (50% effective doses), 39.0-fold and 52.1-fold lower than those of vancomycin and fidaxomicin, respectively, in a hamster model of C. difficile infection. OPS-2071 has the potential to become a new therapeutic option for treating C. difficile infection.

Pathogenic Species of Clostridia and Their Antibiotic Resistance, Virulence Factors, and Genomic Features

“…Ридинилазол -новый низкомолекулярный противомикробный препарат с высокоспецифичной активностью против C. difficile [47,48]. Установлено, что противоревматический препарат ауранофин [41] и антибиотики, такие как фузидовая кислота, рифампин и тигециклин [49], а также -OPS-2071 -новый хинолоновый антибактериальный препарат активны в отношении C. difficile in vitro и in vivo [50]. Проведенные исследования продемонстрировали хорошую активность эравациклина (синтетический антибиотик из группы тетрациклинов) in vitro в отношении большой коллекции клинических штаммов C. difficile, на которые не влияло наличие генов устойчивости к тетрациклину [40].…”