Oka Daisuke, Yamaya Naomitsu, Kuno Takuya, Asakawa Yuta, Shiragiku Toshiyuki, Chen Liang, Xue Jingbo, Mamuti Abudusaimi, Ye Fangguo, Sun Jiangqin, Ohguro Kinue, Miyamoto Hisashi, Uematsu Yukitaka, Inagaki Katsuya, Cheng Jie-Fei, Matsumoto Makoto
Department of Medical Innovations, New Drug Research Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan
Department of Drug Metabolism and Pharmacokinetics, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
Antimicrob Agents Chemother. 2021 Mar 18;65(4). doi: 10.1128/AAC.01170-20.
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 and antibacterial activities of OPS-2071 against were evaluated in comparison to vancomycin and fidaxomicin. OPS-2071 exhibited potent antibacterial activity against 54 clinically isolated strains with a MIC of 0.125 μg/ml (MIC) and 0.5 μg/ml (MIC), making it more active than vancomycin on a concentration basis (MIC, 2 μg/ml; MIC, 4 μg/ml) and comparable to fidaxomicin (MIC, 0.063 μg/ml; MIC, 8 μg/ml). OPS-2071 showed equally potent antibacterial activity against both hypervirulent and nonhypervirulent 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. The mutant prevention concentration of OPS-2071 was 16-fold lower than those of fidaxomicin and vancomycin, and the postantibiotic 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 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 infection. OPS-2071 has the potential to become a new therapeutic option for treating infection.
OPS - 2071是一种新型喹诺酮类抗菌剂，其特点是口服吸收低，降低了氟喹诺酮类抗生素典型不良事件的风险。将OPS - 2071对[具体细菌名称未给出]的抗菌活性与万古霉素和非达霉素进行了比较评估。OPS - 2071对54株临床分离的[具体细菌名称未给出]菌株表现出强大的抗菌活性，其最低抑菌浓度（MIC）为0.125μg/ml（MIC₅₀）和0.5μg/ml（MIC₉₀），在浓度基础上比万古霉素更具活性（MIC₅₀为2μg/ml；MIC₉₀为4μg/ml），且与非达霉素相当（MIC₅₀为0.063μg/ml；MIC₉₀为8μg/ml）。OPS - 2071对高毒力和非高毒力菌株均表现出同等强大的抗菌活性，而观察到对非达霉素的敏感性存在显著差异。未观察到对OPS - 2071和万古霉素的自发耐药性；然而，在4倍MIC时观察到对非达霉素的耐药性。OPS - 2071的突变预防浓度比非达霉素和万古霉素低16倍，且OPS - 2071的抗生素后效应比非达霉素和万古霉素更长。此外，OPS - 2071显示出低全身暴露，在大鼠中1mg/kg时OPS - 2071的口服生物利用度为2.9%。此外，在仓鼠[具体感染名称未给出]感染模型中，OPS - 2071在0.0313mg/kg/天（50%有效剂量）时显示出显著疗效，分别比万古霉素和非达霉素低39.0倍和52.1倍。OPS - 2071有潜力成为治疗[具体感染名称未给出]感染的新治疗选择。
