Anti-Adhesive Coating and Clearance of Device Associated Uropathogenic Escherichia coli Cystitis

Abstract

A previous study showed decreased uropathogen adherence using a novel anti-fouling coating consisting of mussel adhesive protein mimics conjugated to poly(ethylene glycol). We assessed the ability of methoxy polyethylene glycol-dihydroxyphenylalanine (Nerites Corp. Ltd., Madison, Wisconsin) coated ureteral stents to resist bacterial adherence, infection development and encrustation in a rabbit model of uropathogenic Escherichia coli cystitis. Sof-Flex stent curls that were uncoated and coated with 3 coatings, including Surphys 002, 008 and 009, respectively, and uncoated Percuflex Plus stents were inserted transurethrally into the bladder of 50 male New Zealand White rabbits (Charles River Laboratories, Montreal, Quebec, Canada), followed by instillation of uropathogenic E. coli strain GR12 (10(7) cfu). Urine was examined for bacteria on days 0, 1, 3 and 7, and for cytokine levels on day 7. On day 7 the animals were sacrificed. Stent curls and bladders were harvested for analysis. In a parallel experiment stents were challenged in vitro for 7 days with GR12 in human urine. Surphys 009 coated devices showed decreased urine and stent bacterial counts compared to those in controls. Eight of 10 rabbits in the Surphys 009 group had sterile urine by day 3 vs 1 in each control group (p = 0.013), while stent adherent organisms were decreased by more than 75%. While no statistical differences were found in encrustation and bladder inflammation across the groups, immune scoring was lowest in the uncoated Sof-Flex control and Surphys 009 groups (p = 0.030). Surphys 009 strongly resisted bacterial attachment, resulting in improved infection clearance over that of uncoated devices. However, this did not translate to decreased encrustation, which appeared to be independent of infection in this model.