Electrochemical Catheter for Prevention of Central Line-Associated Bloodstream Infection

项目总结 中心静脉导管是不可或缺的医疗设备，用于以下一系列应用 对危重病人进行血液透析。不幸的是，中心静脉导管提供了一条进入心脏的途径 病原体进入血液，导致中心线相关血流感染(CLABSI)。这个 CLABSI的病理生理包括两条主要的感染途径：短期中枢感染的腔外途径 静脉导管，其中微生物从插入部位进入并在导管尖端定植；以及 长期中心静脉导管的腔内途径，在这里频繁的线操作引入 微生物进入管腔。虽然许多预防CLABSI的方法都集中在无菌技术上 减轻腔外感染，在某种程度上减轻腔内感染，腔内感染仍然是主要来源 CLABSI的。在这里，我们建议开发一种非抗生素方法来预防CLABSI，使用受控 在导管管腔内发生电化学反应，生成杀生剂次氯酸(HOCl)。在……里面 初步工作，我们展示了在导管表面电化学生成HOCl的抗菌活性，以及 在一个初步的体外导管模型中，证明了这一策略可以预防CLABSI。我们进一步展示了 通过调节电化学参数，可以控制HOCl2的浓度和释放速率。我们把这一点称为 我们计划开发的设备将产生腔内HOCl作为CLABSI的预防策略， 电化学血管内导管(e-导管)。电子导管将使用一种新型的腔内电化学 为防止微生物细胞生长和生物膜形成而设计的提供HOCl2浓度的系统 而不会引起寄主毒性。电子导管将由定制设计的微型电位器控制，以供使用 在动物身上(并最终在人类身上)。开发的设备将对12种细菌和 酵母菌在体外和在兔血管内导管相关感染模型中的评估预防 金黄色葡萄球菌和肺炎克雷伯氏菌。创新的电子导管策略提供了 解决CLABSI预防的独创方法，避免了常规抗生素，因此避免了选择性压力 论共生微生物区系与抗生素耐药性的产生。

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.