抗菌新药zoliflodacin研究进展  

Research progress of the new antibacterial drug zoliflodacin

作　　者：陈虹彤 李国庆[1] 游雪甫[1] 杨信怡[1] Chen Hong-tong;Li Guo-qing;You Xue-fu;Yang Xin-yi(Beijing Key Laboratory of Antimicrobial Agents,Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050)

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所,抗感染药物研究北京市重点实验室,北京100050

出　　处：《中国抗生素杂志》2023年第2期121-132,共12页Chinese Journal of Antibiotics

摘　　要：Zoliflodacin是螺嘧啶三酮类抗菌药,结构新颖,是一种新型细菌Ⅱ型拓扑异构酶抑制剂,其作用位点不同于氟喹诺酮类药物,目前正开发用于单纯性淋病的治疗。Zoliflodacin对包括多重耐药菌株在内的淋病奈瑟球菌具有良好的体外抗菌活性,单用zoliflodacin或与其他抗菌药物联用对淋病奈瑟球菌具有快速杀菌作用,对多种革兰阳性菌、革兰阴性苛养菌、非典型病原体也具有良好抗菌活性。实验室条件下,zoliflodacin诱导淋病奈瑟球菌及金黄色葡萄球菌发生自发耐药突变的频率较低(10-8~10-9)。已有研究中,未观察到zoliflodacin与氟喹诺酮类、大环内酯类、β-内酰胺类、糖肽类、恶唑烷酮类和四环素类抗菌药存在交叉耐药性。Ⅰ期临床试验显示zoliflodacin具有良好的口服生物利用度及较高的安全性;Ⅱ期临床试验表明zoliflodacin可有效治疗泌尿生殖道和直肠淋病奈瑟球菌感染,主要药物相关不良反应为胃肠道反应。目前,正在开展一项zoliflodacin的全球Ⅲ期临床试验研究。该药有望成为一种治疗耐药淋病奈瑟球菌感染的新型口服抗菌药,应用前景良好。Zoliflodacin is a novel spiropyrimidinetrione antibacterial agent,which inhibits bacterial typeⅡtopoisomerase at a unique site of action different from that of fluoroquinolones,and is currently being developed for the treatment of uncomplicated gonorrhea.Zoliflodacin has an excellent in vitro antibacterial activity against Neisseria gonorrhoeae including multi-drug resistant strains.It alone or in combination with other antibacterial drugs shows a rapid bactericidal effect on Neisseria gonorrhoeae.Zoliflodacin also shows good in vitro antibacterial activities against other Gram-positive bacteria,Gram-negative fastidious bacteria,and atypical pathogens.Under laboratory conditions,the frequency of spontaneous mutation of Neisseria gonorrhoeae and Staphylococcus aureus induced by zoliflodacin was low(10-8~10-9).There is no cross-resistance that has been observed between zoliflodacin and antibiotics including fluoroquinolones,macrolides,β-lactams,glycopeptides,oxazolidinones,and tetracyclines in previous studies.Zoliflodacin showed good oral bioavailability and high safety in healthy volunteers in phase I clinical trials.A phaseⅡclinical trial demonstrated that zoliflodacin could effectively treat gonococcal urogenital and rectal infections,and the main drugrelated adverse reactions for this antibiotic were gastrointestinal problems.At present,a global phaseⅢclinical trial of zoliflodacin for the treatment of uncomplicated gonorrhoea is underway and the antibiotic is expected to become a new type of oral treatment option for drug-resistant Neisseria gonorrhoeae infections with good application prospects.

关 键 词：Zoliflodacin 药效学 药动学 临床应用 不良反应 

分 类 号：R978.1[医药卫生—药品]