Evaluation of Polyethylene Glycol-Based Antimicrobial Coatings on Urinary Catheters in the Prevention of Escherichia coli Infections in a Rabbit Model.

Introduction and Objective: Catheter-associated urinary tract infections are a major cause of patient morbidity and mortality. Despite many attempts to design biomaterials that might reduce the risk, none has had a profound impact on reducing the incidence of this most common nosocomial infection. Recent in vitro work, however, has shown promise for a silver-based biomaterial coating composed of methoxylated polyethylene glycol 3,4-dihydroxyphenylalanine (mPEG-DOPA3) in reducing uropathogen attachment and biofilm formation. The aim of this work was to investigate whether these results translate into a meaningful impact on infection development and bacterial adherence in an in vivo rabbit model. Materials and Methods: New Zealand white rabbits were randomized into groups of 12 and had the following catheters inserted: Group 1-uncoated polyurethane, Group 2-Coating A (mPEG-DOPA3 + 2 mg/mL AgNO3), and Group 3-Coating B (mPEG-DOPA3 + 10 mg/mL AgNO3). Each rabbit was challenged with 108 colony-forming units of Escherichia coli GR-12 instilled directly into the bladder at the time of catheter insertion and urine was monitored over 7 days for bacterial counts. Catheters were retrieved and evaluated for encrustation and attachment analysis, and tissues collected for histopathologic characterization and bacterial invasion. Results: Urinary bacterial colony counts were lower among rabbits in the Coating A group vs controls (4/11 vs 10/12, respectively) (p = 0.029), and there were fewer rabbits with invasive infections (3/12 vs 9/12, p = 0.02). More encrustation was observed among animals in the Coating B group vs controls (7.22 vs 2.69 mg/cm2, p = 0.033). There were no significant differences in tissue effects between groups. Conclusions: The use of a mPEG-DOPA3 urinary catheter coating effectively reduced urinary pathogen counts, while not causing adverse tissue effects in this model. Further clinical evaluation is warranted.

Application of Novel 3,4-Dihydroxyphenylalanine-Containing Antimicrobial Polymers for the Prevention of Uropathogen Attachment to Urinary Biomaterials.

Introduction and Objective: Urinary catheters and stents are frequently prone to catheter-associated urinary tract infections (CAUTI) through biofilm formation. Several strategies have been evaluated in search of a stent coating to reliably prevent adherence of bacteria and biofilm. Previous in vivo and in vitro research with methoxylated polyethylene glycol 3,4-dihydroxyphenylalanine (DOPA) copolymer as a candidate coating showed promising results to reduce the bacterial attachment. We aimed to further enhance this antimicrobial activity by adding antimicrobial agents to newly synthesized DOPA-based copolymers. Materials and Methods: Building on our previous experience, novel copolymers were engineered based on DOPA. Quaternary ammonium groups and silver particles were added by cross-linking to increase the antimicrobial activity through both kill-by-contact and planktonic killing. After coating polyurethane sheets and measuring contact angles, all candidate coatings were challenged in vitro with an Escherichia coli culture. The most promising coatings were then further evaluated against a panel of seven clinically relevant uropathogens and planktonic killing, and microbial attachment was determined. Results: Initially, seven coatings were developed, referred to as Surphys 093-099. The most significant increase in contact angle was identified in Surphys-095 and -098. Surphys coatings S-094, S-095, and S-098 were cross-linked with silver and exhibited profound antimicrobial properties when challenged with E. coli. Further testing demonstrated S-095 to have antimicrobial efficacy against gram-positive and gram-negative bacteria at different silver-loading concentrations. The final coating, consisting of a 2 mg/mL solution of S-095 cross-linked with 0.25 mg/mL AgNO3, appeared to be highly bactericidal showing a ≥99.9% bacterial killing effect while remaining below cytotoxicity levels. Conclusions: We were able to engineer DOPA-based copolymers and add quaternary ammonium and silver particles, thus increasing the bactericidal properties of the coating. These coatings have exhibited a biologically significant ability to prevent uropathogens from attaching to biomaterials and represent a realistic opportunity to combat CAUTI.