Honorable Mention: Redesigning Catheter Vascular Access for Dialysis: Metagenomic DNA Sequencing to Characterize Microbial Communities in Dialysis Catheter Biofilms for Inhibitor Discovery and Materials Engineering

Significance: Vascular access infections are associated with significant morbidity and mortality in both the peritoneal dialysis (PD) and hemodialysis (HD) populations. Peritonitis is the most frequent complication of PD and can lead to PD failure and need to transfer to HD. More than 80% of patients initiate HD with a tunneled central venous catheter (TCVC) and use of a TCVC in the first year of HD is associated with systemic inflammation and poor cardiovascular outcomes. Vascular access infections induce anxiety among patients because of the potential of an unanticipated infection and/or hospitalization which adversely affects their patient experience. Hospitalizations and treatment for vascular access infections are associated with tremendous healthcare costs. Despite the persistence and magnitude of the problems associated with vascular access infections, there has been little innovation to reduce the burden of infection and inflammation among PD patients and HD patients with TCVCs.

Innovation: We propose a well-designed clinical and translational program with tremendous potential to rapidly acquire clinical biomarker information, accelerate future biofilm inhibitor discovery and new catheter biomaterials. We will obtain catheters removed from PD and HD patients and fully characterize microbial biofilm communities with metagenomic sequencing techniques, an approach that uses state-of-the-art techniques that have not been reported in the literature. Using patient-specific microbiome data FDA approved antibiotics and/or novel biofilm inhibitors can be identified to target pathogenic and pro-inflammatory to convention PD and TCVC materials. The antibacterial agents can then be immobilized and adhered to either exterior or luminal surfaces of catheters. This will be achieved by creating reactive polymer coatings that act as connective interfaces between catheter surface and active antimicrobial agents. Thus, our approach represents a significant innovation in patient-centered catheter redesign using a precision medicine approach.

To learn more, please email Amy Barton Pai, PharmD, MHI at amypai@med.umich.edu.