Project Grant R44AI177051

HIGH-PERFORMANCE ANTIBIOFILM CENTRAL VENOUS CATHETERS FOR PREVENTION OF CENTRAL LINE ASSOCIATED BLOODSTREAM INFECTIONS - PROJECT SUMMARY/ABSTRACT ACCORDING TO THE CDC, >250,000 CLABSIS, HAVING MORTALITY RATES OF 14-40%, OCCUR IN THE US ANNUALLY, AND AMONG THEM >100,000 CASES ARE DIRECTLY RELATED TO CENTRAL VENOUS CATHETER (CVC). ONE OF THE TOOLS CURRENTLY USED TO REDUCE CLABSIS IS THE USE OF ANTIMICROBIAL CVCS. HOWEVER, THE CURRENT ANTIMICROBIAL CVCS REMAIN SUSCEPTIBLE TO BIOFOULING (I.E., BIOFILM FORMATION) AS THEY DO NOT DISPLAY REPELLENCY TO BIOFOULANTS. TO ADDRESS THE LIMITATIONS OF EXISTING CVCS, ZWITTERIONIC SURFACES HAVE BEEN STUDIED OWING TO THEIR SUPERIOR BIOFILM-REPELLING AND ANTI-THROMBOTIC PROPERTIES, BUT THE BENEFITS WERE NOT ABLE TO BE INCORPORATED INTO CVCS TO DATE. IN PHASE I, WE SUCCESSFULLY INCORPORATED BIOFILM-REPELLENT ZWITTERIONIC MOIETIES TOGETHER WITH ANTIBIOTICS INTO CVC SURFACES, AND DEMONSTRATED A STATISTICALLY SIGNIFICANT REDUCTION (>99%) IN VIABILITY OF BIOFILM OF MICROBES, RESPONSIBLE FOR CLABSI, COMPARED TO CURRENT CVCS OVER 30 DAYS. FURTHERMORE, OUR IN VIVO ANIMAL STUDY IN A RAT MODEL SHOWED A GREATER THAN 80% REDUCTION IN INFECTION RATE AND EQUIVALENT SAFETY, COMPARED TO COMMERCIAL PREDICATE CVCS. OUR INNOVATION FEATURES THE CREATION OF AN INTERPENETRATED NETWORK (OR DOUBLE-NETWORK) SCAFFOLD WHERE TWO DISTINCT POLYMER NETWORKS COEXIST WITHIN THE SAME STRUCTURE. THIS STRATEGIC INTEGRATION LEADS TO MULTIPLE ANTI- INFECTIVE MECHANISMS, RESULTING IN A SIGNIFICANT REDUCTION IN INFECTION RATE. IN THE PHASE II STUDY, WE PLAN TO MANUFACTURE PROTOTYPE CVCS AND DEMONSTRATE A SUPERIOR LONG-TERM REDUCTION IN BIOFILM WITH EQUIVALENT BIO/HEMOCOMPATIBILITY COMPARED TO EXISTING CVCS (AIM 1). WE WILL ALSO VALIDATE IN VIVO EXTENDED EFFICACY AND SAFETY OF OUR MANUFACTURED PROTOTYPE CVCS USING A PIG MODEL TO FURTHER DEMONSTRATE CLINICAL RELEVANCE (AIM 2). EXPECTED OUTCOMES IN THIS PHASE II INCLUDE: (1) ESTABLISHING SCALABLE MANUFACTURING PROTOCOLS WITH LEADING CATHETER MANUFACTURERS, (2) DEMONSTRATING SUPERIOR BIOFILM EFFICACY AND SAFETY, COMPARED TO PREDICATE ANTIMICROBIAL CVCS, IN VITRO, AND (3) DEMONSTRATING >80% REDUCTION IN INFECTION RATES IN ANIMAL MODELS, COMPARED TO CURRENT CVCS. WE ANTICIPATE THE COMPLETION OF THESE MILESTONES WILL ENABLE US TO UNDERTAKE ADDITIONAL GLP STUDIES WHICH ARE ESSENTIAL FOR OBTAINING 510(K) CLEARANCE. THE REGULATORY CLEARANCE WILL PROVIDE A STRUCTURED PATH TO MARKET ENTRY VIA LICENSING OR ACQUISITION. REDUCTION OF INFECTIVE BIOFILM WILL LEAD TO REDUCED ANTIBIOTIC USAGE, MINIMIZED RISK OF ANTIBIOTIC RESISTANCE, AND DECREASED PATIENT MORBIDITY AND MORTALITY. THIS HAS THE POTENTIAL TO SAVE OVER 100,000 AMERICAN LIVES ANNUALLY AND ALLEVIATE THE SUFFERING OF MORE THAN 250,000 AMERICANS EACH YEAR, WHILE CONTRIBUTING TO ANNUAL COST SAVINGS OF OVER $12.5 BILLION. IN 2023, THE U.S. CVC MARKET (SERVICEABLE OBTAINABLE MARKET) IS VALUED AT $1.3 BILLION, WHILE THE GLOBAL CVC MARKET (SERVICEABLE AVAILABLE MARKET) REACHED AN ESTIMATED $3.1 BILLION. THE GLOBAL CATHETER MARKET (TOTAL AVAILABLE MARKET) IS PROJECTED TO REACH $85.2 BILLION BY 2030.