Electrochemical Catheter for Prevention of Central Line-Associated Bloodstream Infection

项目摘要 中心静脉导管是不可或缺的医疗器械，用于各种应用， 血液透析给危重病人。不幸的是，中心静脉导管提供了一个进入的途径， 病原体进入血流，导致中心线相关血流感染（CLABSI）。的 CLABSI的病理生理学包括两种主要的感染途径： 静脉导管，微生物从插入部位进入并定植在导管头端;以及 长期中心静脉导管的腔内路径，其中频繁的管线操作引入 微生物进入管腔。虽然许多预防CLABSI的方法集中在无菌技术上， 减轻腔外和在一定程度上减轻腔内感染，腔内感染仍然是主要来源 关于CLABSI在这里，我们建议开发一种非抗生素的方法来预防CLABSI， 在导管腔中发生电化学反应以产生杀生物剂次氯酸（HOCl）。在 初步工作中，我们显示了电化学HOCl生成对导管表面的抗菌活性， 在初步的体外导管模型中，证明了这种策略可以预防CLABSI。我们进一步研究发现 HOCl浓度和输送速率可通过调节电化学参数来控制。我们称之为 我们建议开发的设备将产生管腔内HOCl作为CLABSI预防策略， 电化学血管内导管（电子导管）。eCatheter将使用一种新型的腔内电化学 系统设计用于以“调节”浓度输送HOCl，以防止微生物细胞生长和生物膜形成 而不引起宿主毒性。电子导管将由定制设计的微恒电位仪控制使用 在动物身上（最终在人类身上）。开发的设备将针对12种细菌进行测试， 酵母体外培养，并在血管内导管相关感染的兔模型中进行评价，以评估预防 金黄色葡萄球菌和肺炎克雷伯菌CLABSI。创新的电子导管策略提供了 解决CLABSI预防的原始方法，避免常规抗生素，因此选择性压力 对肠道菌群和抗生素耐药性的影响。

PROJECT SUMMARY Central venous catheters are indispensable healthcare devices used for a range of applications from hemodialysis to critically ill patients. Unfortunately, central venous catheters provide a route for entry of pathogens into the bloodstream, resulting in central line-associated bloodstream infection (CLABSI). The pathophysiology of CLABSI comprises two main routes of infection: the extraluminal route for short-term central venous catheters, where microorganisms enter from the insertion site and colonize the catheter tip; and the intraluminal route for long-term central venous catheters, where frequent line manipulation introduces microorganisms into the lumen. While many approaches for CLABSI prevention focus on aseptic techniques to mitigate extraluminal and, to some extent, intraluminal infections, intraluminal infections remain a major source of CLABSI. Here, we propose to develop a non-antibiotic approach to prevent CLABSI using controlled electrochemical reactions occurring in the catheter lumen to generate the biocide hypochlorous acid (HOCl). In preliminary work, we showed antimicrobial activity of electrochemical HOCl generation on catheter surfaces, and in a preliminary in vitro catheter model, demonstrated that this strategy may prevent CLABSI. We further showed that HOCl concentrations and delivery rates are controllable by tuning electrochemical parameters. We term the devices we propose to develop that will generate intraluminal HOCl as a CLABSI prevention strategy, electrochemical intravascular catheters (e-catheters). eCatheters will use a novel intraluminal electrochemical system designed to deliver HOCl at concentrations ‘tuned” to prevent microbial cell growth and biofilm formation without causing host toxicity. The e-catheters will be controlled by custom-designed micropotentiostats for use in animals (and, eventually, in humans). The developed devices will be tested against 12 species of bacteria and yeast in vitro and evaluated in a rabbit model of intravascular catheter-associated infection to assess prevention of Staphylococcus aureus and Klebsiella pneumoniae CLABSI. The innovative e-catheter strategy provides an original way to address CLABSI prevention, avoiding conventional antibiotics and therefore selective pressure on commensal microbiota and emergence of antibiotic resistance.