Over 20% of the hemodialysis patients develop life-threatening central line-associated bloodstream infections (CLABSIs). 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 hemodialysis 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. In other words, host biomolecules and cellular debris from dead microorganisms can accumulate upon their surface, thereby facilitating adherence of living microbia and their associated biofilms. In addition, most antimicrobial CVCs function by gradually releasing embedded biocides/antibiotics with risk of developing antimicrobial resistance. To address the problems, we hypothesized that incorporating biofilm-repellent zwitterionic moieties together with antimicrobial gemini dicationic moieties into CVC surfaces, a synergistic effect could be realized. Our preliminary study confirmed the synergetic effect. Technology innovation is 1) the new CVC surface covalently immobilized with gemini dicationic moieties to provide best-in-class antimicrobial properties without concerns of development of antimicrobial resistance; and 2) the new CVC surface containing both biofilm-repellant and antimicrobial moieties to overcome the deficiencies of each alone to prevent the root cause of CLABSIs. To demonstrate the feasibility of our technology, in Aim 1, we will maximize the synergetic effect by iteratively optimizing the ratio between the antimicrobial and repellent moieties with respect to antimicrobial efficacy, biofilm repellency, coating anti-infective durability, over varying timeframes. In Aim 2, we will produce prototype hybrid CVCs, and compare their infection risks relative to commercial antimicrobial CVCs against pathogens responsible for >90% of CLABSIs. In Aim 3, we will evaluate bio- and hemo-compatibility of the prototypes using assays specified in ISO 10993-4 for hemolysis, coagulation, complement-activation, and inflammation as well as leachate toxicity. Expected outcomes in this Phase I include >20% reductions in proliferation, antimicrobial, and biofilm assays with a similar/better blood compatibility compared to current antimicrobial CVCs. >20% reduction in the national infection rate with our CVC product would prevent >50,000 CLABSIs, saving >16,000 lives and >$500 million direct healthcare costs each year. Phase II will include in-vivo studies to ensure accurate translation of in-vitro and ex-vivo properties. In Phase II, we will also initiate production of our prototype CVCs at a FDA cGMP compliant manufacturing facility, subsequently apply for 510(k) clearance for subsequent clinical evaluation. Our serviceable obtainable market (SOM) is the US CVC market, estimated to grow $1.3 billion in 2026. As our hybrid-coating can be applied to nearly all types of catheters including IV and urinary tract catheters, the total available market (TAM) is the global catheter market, expected to reach $74.8 billion by 2028.
Public Health Relevance Statement: Project Narrative/Public Health Statement In the United States each year more than 400,000 Americans undergoing hemodialysis therapy receive placement of a central venous catheter (CVC, or central line), and more than 20% of these suffer from a central line-associated bloodstream infection (CLABSI) with mortality rates estimated at 14-40% as a result. CLABSI pathology is exacerbated by the formation of highly adherent biofilms to the CVC surface. In this SBIR ACatechol proposes to develop a hybrid CVC, providing both antimicrobial efficacy and biofilm repellency simultaneously, to prevent the root cause (i.e., biofilm formation) that current CVCs fail to adequately address.
Project Terms: Anti-Infective Drugs; Anti-Infectives; Anti-infective Preparation; AntiInfective Drugs; AntiInfectives; Antiinfective Agents; communicable disease control agent; Anti-Infective Agents; Antibiotic Agents; Antibiotic Drugs; Miscellaneous Antibiotic; Antibiotics; Biological Assay; Assay; Bioassay; Biologic Assays; Biotechnology; Biotech; Blood; Blood Reticuloendothelial System; Certification; Complement Activation; complement pathway regulation; Equilibrium; balance; balance function; Goals; Cyclic GMP; Guanosine Cyclic Monophosphate; cGMP; Healthcare Systems; Health Care Systems; Hemodialysis; Hemodialyses; Hemolysis; erythrolysis; Heparin; Heparinic Acid; Hybrids; Immobilization; orthopedic freezing; In Vitro; Infection; Inflammation; Kidney Diseases; Nephropathy; Renal Disease; kidney disorder; renal disorder; Marketing; Medical Device; mortality; Pain; Painful; Pathology; Patients; Play; Polymers; polymer; polymeric; Production; Public Health; Risk; Technology; Translations; translation; United States; Urinary tract; Microbial Biofilms; biofilm; Health Costs; Healthcare Costs; Health Care Costs; Catheters; Resistance to antibiotics; Resistant to antibiotics; antibiotic drug resistance; antibiotic resistant; Antibiotic Resistance; Surface; Specified; Specific qualifier value; Phase; Ensure; Susceptibility; Predisposition; Licensing; Relative Risks; tool; Venous; Knowledge; Life; Mechanics; mechanic; mechanical; Frequencies; Biocide; microorganism; American; biomaterial compatibility; biocompatibility; experience; hydrophilicity; synergism; microbial; Toxic effect; Toxicities; novel; technological innovation; Prevention; Property; surface coating; Manufacturer; preventing; prevent; Coagulation Process; Clotting; Coagulation; Address; Antimicrobial Resistance; Antimicrobial resistant; Resistance to antimicrobial; anti-microbial resistance; anti-microbial resistant; resistance to anti-microbial; resistant to anti-microbial; resistant to antimicrobial; Adherence; Data; Proliferating; in vivo; research clinical testing; Clinical Evaluation; Clinical Testing; clinical test; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Development; developmental; cost; blood infection; bloodstream infection; Sepsis; Outcome; manufacturing plants; production plants; manufacturing facility; pathogen; innovate; innovative; innovation; resistant; Resistance; anti-microbial; antimicrobial; iPS; iPSC; iPSCs; induced pluripotent cell; inducible pluripotent stem cell; induced pluripotent stem cell; commercial application; prototype; commercialization; biological systems; Phase I Study; phase 1 study; hemocompatibility; infection risk; rate of infection; infection rate
