Electrochemical Catheter for Prevention of Central Line-Associated Bloodstream Infection

用于预防中心静脉导管相关血流感染的电化学导管

基本信息

批准号：
10560927
负责人：
Haluk Beyenal
金额：
$ 39.54万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-02-20 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10560927
关键词：
Acinetobacter baumannii Address Animal Model Animal Testing Animals Antibiotics Bacteria Bacterial Drug Resistance Biocide Blood Cells Blood Circulation COVID-19 pandemic COVID-19 patient Candida Candida albicans Candida auris Caring Catheters Clinical Critical Illness Custom Devices Drug resistance Enterobacter cloacae Enterococcus faecium Escherichia coli Experimental Animal Model Functional disorder Generations Healthcare Hemodialysis Hour Human Hypochlorous Acid In Vitro Infection Infection prevention Klebsiella pneumoniae Laboratories Length of Stay Life Liquid substance Local Anti-Infective Agents Microbial Biofilms Modeling Oryctolagus cuniculus Parenteral Nutrition Patients Pharmaceutical Preparations Prevention Prevention approach Prevention strategy Pseudomonas aeruginosa Reaction Reporting Route Sepsis Site Source Staphylococcus aureus Staphylococcus epidermidis Surface System Techniques Testing Toxic effect Vascular Endothelial Cell Venous Work Yeasts antimicrobial antimicrobial drug breakthrough infection catheter related infection cell growth commensal microbes design emerging antibiotic resistance in vitro Model infection rate innovation medication administration microbial microbial colonization microorganism mortality novel pathogen pressure prevent

项目摘要

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.

项目摘要中央静脉导管是必不可少的医疗设备，用于一系列应用血液透析为重症患者。不幸的是，中央静脉导管提供了进入病原体进入血液，导致中央线相关的血液感染（CLABSI）。 Clabsi的病理生理学包括两种主要感染途径：短期中心的腔外途径静脉导管，微生物从插入部位进入并定居于导管尖端；和长期中央静脉导管的腔内途径，经常引入线路操纵微生物进入管腔。而许多预防克拉布斯的方法都集中在无菌技术上减轻腔外，并在某种程度上减轻腔内感染，腔内感染仍然是主要来源 Clabsi。在这里，我们建议开发一种非抗生素方法，以防止使用受控的电化学反应发生在导管管腔中，以产生杀生物剂次氯酸（HOCL）。初步工作，我们显示了电化学HOCL在导管表面的抗菌活性，以及在初步的体外导管模型中，证明了这种策略可以防止克拉比。我们进一步显示 HOCL浓度和输送率通过调整电化学参数来控制。我们称为我们建议开发的设备将产生腔内HOCL作为CLABSI预防策略，电化学性血管内导管（电子调查器）。 Ecatheters将使用一种新型的腔内电化学旨在以“调节”浓度输送HOCL以防止微生物细胞生长和生物膜形成的系统而不会引起宿主毒性。电子测试器将由自定义设计的微管静脉曲器控制在动物中（最终，在人类中）。开发的设备将针对12种细菌和体外酵母菌，并在血管内成型相关感染的兔模型中进行评估以评估预防金黄色葡萄球菌和肺炎肺炎的肺炎。创新的电子通用策略提供了解决CLABSI预防的原始方法，避免常规抗生素，因此选择性压力关于共生微生物群和抗生素耐药性的紧急情况。