Project Summary Central line-associated bloodstream infections (CLABSIs) cost the healthcare system around $2 billion annually with an estimated >80,000 incidents each year in US intensive care units (ICUs). That is not surprising with over 5 million central venous catheters (CVCs) used annually in the United States and an estimated 27 million units sold globally. Most CVC-associated infections are caused by microorganisms introduced from patient skin during catheter insertion. These microorganisms can also get into the lumen during manipulation and attach to device surfaces, enhance biofilm growth and complications and result in infections. Currently, there are two main approaches to reducing CVC-related infections either (1) adding antimicrobial functionality or (2) adding antifouling functionality. Our approach combines antifouling and antimicrobial killing functionalities to prevent catheter-associated infections and thrombosis into a new polymer additive product (HaloAddTM) that catheter manufacturers can blend with thermoplastic polyurethane (TPU). We are aware of no other similar approach that combines antimicrobial agents with anti-inflammatory and/or anti-adhesion agents to address the complex problem of CLABSI. This Phase I effort is geared towards answering basic performance, safety, and efficacy issues. We propose to optimize polymer blending parameters to develop HaloAdd-modified PU material with maximum antimicrobial and antifouling efficacy without impacting critical mechanical properties, determine in vitro anti-thrombin and anti- biofilm properties, and verify the biocompatibility and stability of HaloAdd-blended PU for the CVC application.