PROJECT SUMMARY/ABSTRACT Catheter-related bloodstream infection (CRBSI), also called catheter-related sepsis, is one of the most frequent, lethal, and costly complications of central venous catheterization. CRBSI affects hundreds of millions of people worldwide; in the U.S. alone, it affects more than 250,000 patients yearly. These infections are mostly caused by the migration of microorganisms found on the patient's skin flora at the catheter insertion site. Tremendous efforts have been undertaken to reduce catheter-related sepsis, including improvements to the catheter insertion guidelines and the development of dressings impregnated with antibiotics. These methods help reduce the number of bacteria on the patient's skin but do not eliminate them. No available catheter dressing enables automated and early detection of bacterial growth at the catheter insertion site. Such catheter dressing is a critical need for early detection of CRBSI, allowing for the removal/replacement of the catheter, and, as needed, for early treatment of patients with tailored antibiotic therapy. In addition, it remains a clinical challenge to detect bacterial colonization on the skin at early stages without catheter removal due to the human skin's highly flexible and topographical nature. Flexible biosensors that provide conformal and seamless adherence to the skin can help, but previous studies on the merits of wearable and flexible sensors to detect bacterial infection have been limited to wound infections measured by indirect parameters (e.g., pH) that are subject to change with dietary restrictions and not specific to bacterial infection. Therefore, a significant knowledge gap exists in the use of wearable and flexible sensors integrated with electronics for real-time monitoring of direct bacterial growth at the catheter insertion site for the early detection of CRBSI-related infection risks. The overall objective of this application is to address this need and knowledge gap by developing a fully integrated, wirelessly operated catheter dressing that is capable of monitoring bacterial growth at the catheter insertion site in real-time and non- invasively to enable automated early detection of infection originating from the skin. The central hypothesis is that the electrochemical activity of live bacteria at the catheter insertion site can be directly measured, and acquired data can be classified using machine learning, thereby allowing precise monitoring of extraluminal contamination in real-time. To attain the overall objective, the following two specific aims will be pursued: Aim 1: Develop an integrated catheter dressing (ICD) capable of real-time monitoring of bacterial growth at the catheter insertion site. Aim 2: Validate and optimize the ICD for early detection of catheter-related sepsis on a skin phantom and an animal model. These aims will be accomplished by a team of skilled experts and excellent resources. The proposed research is significant because the ICD can transform the current point-of-care practices, ultimately has the potential to reduce infection risks, health care costs, and morbidity and mortality rates related to CRBSI, and monitor the infection status in real-time, non-invasively, and at the point of care.

PROJECT NARRATIVE This project aims to demonstrate the feasibility of a fully integrated, wirelessly operated catheter dressing for the early detection of catheter-related sepsis. The objectives of this proposal are consistent with the goals of the NIH NIGMS Technology Development Program R21 and will have a significant impact on public health by forming the basis for real-time non-invasive and on-body monitoring of an extended range of bacterial species, including antibiotic-resistant bacterial growth. This integrated device can transform the current practices, improve the patients’ quality of life and the ability of clinicians to treat the patients much earlier than the current clinical practice, and help reduce the morbidity and mortality rates and associated healthcare costs.