Novel one-step approach to a universal anti-adhesion coating to prevent P. mirabilis induced catheter-associated urinary tract infection

Introduction: Catheter-associated urinary tract infections (CAUTIs) account for a vast number of hospital-acquired infections and are a significant burden to healthcare systems. In the USA and Canada, more than 33 million catheters are inserted each year. Urinary catheters provide ideal surfaces for bacterial attachment and biofilm formation. Several attempts to change catheter biomaterial design to prevent biofilm formation have met with poor success. We have developed a two-component coating that is highly biocompatible and effective in preventing bacterial biofilm formation. Here, we present data showing the efficacy of the coating against a difficult to treat uropathogen, Proteus mirabilis and show decreased biofilm formation and encrustation in vitro and in a murine model of CAUTI . Materials and methods: A novel binary coating composed of polydopamine (PDA) and poly (N,N-dimethylacrylamide)(PDMA) was developed and applied via a simple dip coating mechanism. The antifouling activity was determined in vitro following incubation of coated and uncoated catheter material to P. mirabilis at 4, 8, 12, and 24 hours post-exposure. Adherent bacteria were quantified via colony forming units (CFU) counts. The in vivo efficacy of our coating was determined using a murine model of CAUTI. Briefly, 4 mm (24G) catheters (coated and uncoated) were introduced into the mouse bladder percutaneously with ultrasound guidance followed by inoculation of 105 P. mirabilis. Adherent bacteria and struvite formation were quantified following 3-days post-infection. Results: The in vitro study showed that our novel coating decreased P. mirabilis adhesion to polyurethane (PU) surfaces by 99% reduction compared to uncoated surfaces. Furthermore, in vivo studies showed an 87.9% reduction in P. mirabilis adhesion on coated compared to uncoated catheters. In both in vitro and in vivo models, the accumulation of struvite and calcium oxalate encrustations on the coated surfaces were significantly reduced. Conclusions: Using relevant in vitro and in vivo models, we have shown our novel binary coating to be highly efficacious at decreasing P. mirabilis attachment and subsequent biofilm formation and inorganic crystal accumulation on urinary materials. Further testing of this novel coating in validating the results in a porcine infection model will be importantMedicine, Faculty ofExperimental Medicine, Division ofMedicine, Department ofGraduat