We have identified a major gap in knowledge relating to the microbiomes that grow and persist on medical devices. This is particularly significant in catheters used to treat chronically ill patients across a range of diseases. For example, the annual mortality rate for hemodialysis patients is greater than 40% in the first year of renal replacement therapy. Despite active efforts to initiate hemodialysis with a permanent vascular access in place, 80% of end-stage renal disease (ESRD) patients initiate hemodialysis with a tunneled central venous catheter (TCVC). Current data suggest that TCVC biofilm is the predominant source of inflammation in ESRD however, little is known about the composition and functional properties of the catheter microbiome and the molecular and physiologic events that may ultimately culminate to result in chronic systemic inflammation, bacteremia, and fatal infections.
TCVC use is associated with the highest rates of infection-related death and all-cause mortality compared to other vascular access types (permanent arteriovenous (AV) fistula or AV graft). Hemodialysis patients with TCVCs have significantly higher C-reactive protein levels and lower serum albumin concentrations, both biomarkers of inflammation with robust associations with mortality in this population. Among ESRD patients with TCVCs, the risk of death from congestive heart failure within one-year of dialysis initiation is 64% higher after hospitalization for bacteremia suggesting a pathophysiologic link between infection, inflammation and cardiovascular disease.
This proposal will examine the central hypothesis that microbial biofilms in TCVCs from dialysis patients are comprised of multi-organism communities that can be characterized using metagenomic DNA sequencing to enable identification of effective interventions to mitigate catheter biofilm formation and persistence, and reduce the incidence of catheter-induced inflammation and bacterial infections.