Lee Ching-Chi, Yan Xiang-Zhe, Wu Hung-Tsung, Ko Wen-Chien, Tsai Pei-Jane, Hung Yuan-Pin
Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Front Microbiol. 2024 Aug 20;15:1418817. doi: 10.3389/fmicb.2024.1418817. eCollection 2024.
Antimicrobial therapy plays a crucial role in the management of CDI patients. However, the standard agent for treating CDIs is limited to oral fidaxomicin or vancomycin. For patients made nil by mouth, there is a clinically urgent and essential need to develop an intravenous antibiotic.
For with the lowest MIC of nemonoxacin and vancomycin, the inhibitory effects were tested using the kinetic time-kill assay and ex vivo co-culture model. The effectiveness of nemonoxacin and vancomycin in inhibiting spore germination, the sporicidal activity, and the treatment of mice with CDIs were compared.
For clinical isolates and laboratory strains, lower MICs of nemonoxacin against than levofloxacin and ciprofloxacin were observed, even in those harboring point mutations in the quinolone-resistance determining region. Although nemonoxacin failed to suppress spore outgrowth and germination in , it exhibited an effective inhibitory effect against in the kinetic time-kill assay and the co-culture model. Mice receiving intraperitoneal nemonoxacin had less weight loss, higher cecum weight, a longer colon length, and lower expression of the gene, compared with untreated mice. Notably, there were no significant differences observed in weight loss, cecum weight, colon length, or tcdB gene expression between mice treated with vancomycin and those treated with any dose of nemonoxacin. Similarly, no significant differences were found between mice receiving combination therapy of intraperitoneal nemonoxacin plus oral vancomycin and those treated with intraperitoneal nemonoxacin or oral vancomycin alone.
The potential role of nemonoxacin, which can be administered parenterally, for treating CDIs was evidenced through the , , and mouse models.
抗菌治疗在艰难梭菌感染（CDI）患者的管理中起着关键作用。然而，治疗CDI的标准药物仅限于口服非达霉素或万古霉素。对于禁食患者，临床上迫切需要开发一种静脉用抗生素。
对于非莫西沙星和万古霉素最低抑菌浓度（MIC）的[具体菌株名称未给出]，使用动态时间杀菌试验和体外共培养模型测试其抑制作用。比较了非莫西沙星和万古霉素在抑制孢子萌发、杀孢子活性以及治疗CDI小鼠方面的有效性。
对于临床分离株和实验室菌株，观察到非莫西沙星对[具体菌株名称未给出]的MIC低于左氧氟沙星和环丙沙星，即使在喹诺酮耐药决定区存在点突变的菌株中也是如此。尽管非莫西沙星未能抑制[具体菌株名称未给出]的孢子生长和萌发，但在动态时间杀菌试验和[具体共培养模型名称未给出]共培养模型中，它对[具体菌株名称未给出]表现出有效的抑制作用。与未治疗的小鼠相比，接受腹腔注射非莫西沙星的小鼠体重减轻较少、盲肠重量增加、结肠长度更长，且[具体基因名称未给出]基因表达较低。值得注意的是，接受万古霉素治疗的小鼠与接受任何剂量非莫西沙星治疗的小鼠在体重减轻、盲肠重量、结肠长度或tcdB基因表达方面均未观察到显著差异。同样，接受腹腔注射非莫西沙星加口服万古霉素联合治疗的小鼠与单独接受腹腔注射非莫西沙星或口服万古霉素治疗的小鼠之间也未发现显著差异。
通过[具体试验名称未给出]、[具体试验名称未给出]和小鼠模型证明了可胃肠外给药的非莫西沙星在治疗CDI方面的潜在作用。
