A Novel Photonic Central Venous Catheter for Mitigation of Catheter-Associated Infections

About This Grant

PROJECT SUMMARY/ABSTRACT Central venous catheter (CVC) infections, primarily driven by bacterial biofilm formation on CVCs, contribute to substantial morbidity and mortality. Despite current antibiotic treatments and preventive measures, the incidence of CVC infections continues to rise. Hence, there is a critical need for alternative strategies. The objective of this R21 application is to explore the potential of a novel photonic CVC (P-CVC) to mitigate CVC infections. P-CVC is designed to uniformly emit antimicrobial blue light (aBL; 405 nm) across the CVC surface, aiming to prevent biofilm formation or eradicate existing biofilms on CVC. Our central hypothesis is that P- CVC can effectively reduce the risk of CVC infections. To test this hypothesis, we propose two Specific Aims. In Aim 1, we will evaluate the in vitro anti-biofilm efficacy of P-CVC. Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa, the common bacteria identified in CVC infections, will be studied. Biofilms will be formed on miniature P-CVCs preconditioned with human plasma. To prevent biofilm formation, P-CVCs will be "activated" by aBL within three (3) h following bacterial inoculation; while to eradicate existing biofilms, P-CVCs will be "activated" 24, 48, and 96 h after bacterial inoculation when biofilms of different stages have formed. The efficacy found with P-CVCs will be compared with that of antibiotic lock therapy and commercial antimicrobial-coated CVCs. In Aim 2, we will evaluate the in vivo anti-biofilm efficacy and safety of P-CVC in rats. To evaluate the anti- biofilm efficacy of P-CVC, 24 h after insertion with P-CVCs in rats, S. aureus or P. aeruginosa suspensions (~106 CFU) will be instilled into the P-CVC lumens. To prevent biofilm formation, P-CVCs will be activated by aBL within three (3) h after bacterial challenge. To eradicate existing biofilms, the activation of P-CVCs will be delayed until 24-48 h following bacterial challenge to allow for mature biofilm formation. aBL treatment will be applied twice daily at 8-h intervals for five (5) days. The bacterial loads of P-CVCs, surrounding tissues, blood, and major organs will then be determined. To assess the safety (both short-term and long-term) of P-CVC, healthy uninfected rats will be used. Blood samples will be analyzed periodically for complete blood count, liver and kidney function markers, and systemic inflammatory markers. At the study endpoint, catheterized veins, surrounding tissues, and major organs will be harvested. Histological evaluation will assess local tissue reactions (inflammation, thrombosis, endothelial injury, and fibrosis). Additionally, we will determine whether there is a long-term carcinogenic effect associated with P-CVC and whether long-term aBL exposure affects the physical properties and biocompatibility of P-CVC in rats receiving aBL treatment for up to 18 months. The most significant impact of this R21 application resides in its potential to establish a new paradigm for mitigating CVC infections. The successful completion of the proposed Specific Aims will provide initial preclinical evidence to evaluate the effectiveness and safety of P-CVC.