Yao Huijuan, Xu Ajing, Liu Jingxian, Wang Fang, Yao Huimin, Chen Jihui
Department of Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
Clinical Laboratory, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
Front Pharmacol. 2022 Aug 19;13:973551. doi: 10.3389/fphar.2022.973551. eCollection 2022.
This study was developed to assess the antimicrobial activity of specific drugs using a model system consisting of () infected with Carbapenem-resistant (CRKP) in an effort to identify promising drugs for CRKP-infected patient treatment. A -CRKP liquid assay platform was developed and used to conduct limited screening for antimicrobial agents with potential activity against CRKP. Time curves for 10 different concentrations of tested antimicrobial agents were tested in this model system at 0, 2, 6, 8, and 12 h after treatment. The protective effects of these different antimicrobial agents were compared at different time points. Furthermore, ten CRKP strains samples were isolated from clinical specimens to demonstrate the applicability of the nematode model method, and two typical clinical cases are presented. CRKP bacteria were sufficient to induce death in a dose- and time-dependent fashion, while effective antimicrobial agents improved the survival of these nematodes in a dose-dependent manner. Notably, PB and TGC exhibited robust antibacterial protection within 12 h even at low tested concentrations, and clear efficacy remained evident for high doses of CAZ at this same time point as mediators of improved nematode survival. The results of model method were well consistent with that using the Kirby-Bauer method in 10 CRKP strains samples, and two typical clinical cases showed applicability, reliability and efficacy of model method. Overall, nematode models in drug sensitivity testing have shown advantages in clinical settings. Our results highlight the value of model systems as tools for the simultaneous screening of different agents for antibacterial efficacy and are deserved further study.
本研究旨在利用一个由感染耐碳青霉烯类肺炎克雷伯菌(CRKP)的()组成的模型系统,评估特定药物的抗菌活性,以确定用于治疗CRKP感染患者的有前景的药物。开发了一种CRKP液体检测平台,并用于对具有抗CRKP潜在活性的抗菌剂进行有限筛选。在该模型系统中,在治疗后0、2、6、8和12小时测试了10种不同浓度的受试抗菌剂的时间曲线。在不同时间点比较了这些不同抗菌剂的保护作用。此外,从临床标本中分离出10株CRKP菌株样本,以证明线虫模型方法的适用性,并展示了两个典型临床病例。CRKP细菌足以以剂量和时间依赖性方式诱导死亡,而有效的抗菌剂以剂量依赖性方式提高了这些线虫的存活率。值得注意的是,即使在低测试浓度下,PB和TGC在12小时内也表现出强大的抗菌保护作用,并且在同一时间点,高剂量的CAZ作为改善线虫存活的介质,其明显的疗效仍然明显。线虫模型方法的结果与在10株CRKP菌株样本中使用 Kirby-Bauer 方法的结果高度一致,两个典型临床病例显示了线虫模型方法的适用性、可靠性和有效性。总体而言,线虫模型在药物敏感性测试中已在临床环境中显示出优势。我们的结果突出了该模型系统作为同时筛选不同药物抗菌疗效工具的价值,值得进一步研究。