Saturday, September 7, 2024
9/7/2024
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.
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