Roderick A MacPhee1, Justin Koepsel2, Thomas Tailly3,4, Sai K Vangala5, Liam Brennan1,3,6, Peter A Cadieux6,7, Jeremy P Burton1,3,6, Chris Wattengel2, Hassan Razvi3, Jeffrey Dalsin2. 1. 1 Lawson Health Research Institute, London, Ontario, Canada. 2. 2 DSM Biomedical, Exton, Pennsylvania. 3. 3 Division of Urology, Department of Surgery, Western University, London, Ontario, Canada. 4. 4 Department of Urology, University Hospital Ghent, Ghent, Belgium. 5. 5 Department of Urology, University of Toronto, Toronto, Ontario, Canada. 6. 6 Department of Microbiology and Immunology, Western University, London, Ontario, Canada. 7. 7 School of Health Sciences, Fanshawe College, London, Ontario, Canada.
Abstract
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.
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.
Authors: R Monina Klevens; Jonathan R Edwards; Chesley L Richards; Teresa C Horan; Robert P Gaynes; Daniel A Pollock; Denise M Cardo Journal: Public Health Rep Date: 2007 Mar-Apr Impact factor: 2.792
Authors: R O Darouiche; J A Smith; H Hanna; C B Dhabuwala; M S Steiner; R J Babaian; T B Boone; P T Scardino; J I Thornby; I I Raad Journal: Urology Date: 1999-12 Impact factor: 2.649
Authors: E B H Hume; J Baveja; B Muir; T L Schubert; N Kumar; S Kjelleberg; H J Griesser; H Thissen; R Read; L A Poole-Warren; K Schindhelm; M D P Willcox Journal: Biomaterials Date: 2004-09 Impact factor: 12.479
Authors: Raymond Ko; Peter A Cadieux; Jeffrey L Dalsin; Bruce P Lee; Chelsea N Elwood; Hassan Razvi Journal: J Endourol Date: 2008-06 Impact factor: 2.942
Authors: Thomas Tailly; Rod A MacPhee; Peter Cadieux; Jeremy P Burton; Jeff Dalsin; Chris Wattengel; Justin Koepsel; Hassan Razvi Journal: J Endourol Date: 2020-11-11 Impact factor: 2.942