Chelsea N. Elwood

Use of triclosan-eluting ureteral stents in patients with long-term stents.

BACKGROUND AND PURPOSE Long-term use of ureteral stents is prevented by biofilm-related infection and encrustation mandating stent changes every few months. Triclosan is a broad-spectrum antimicrobial in numerous consumer and medical products and has been incorporated into a ureteral stent. We sought to determine the clinical effects of the triclosan-eluting stent in patients who needed long-term ureteral stenting. PATIENTS AND METHODS Eight patients with long-term stents were enrolled prospectively. All received a control stent for 3 months along with preoperative and postoperative antibiotics. After 3 months, the control stent was removed, and a triclosan-eluting stent was placed for 3 months with no antibiotics administered. For both indwelling periods, urine cultures were obtained weekly and biweekly for the first and last 6 weeks, respectively, and antibiotics were prescribed when patients had both a positive urine culture and symptoms of urinary tract infection. On removal, stents were assessed for microorganisms and encrustation. RESULTS Overall, similar microorganisms were isolated during each indwell period, although Staphylococcus and Enterococcus strains were isolated more frequently during control and triclosan stenting, respectively. Significantly fewer antibiotics were used during triclosan stenting, coinciding with a slightly higher number of positive urine cultures and significantly fewer symptomatic infections. No bacterial isolates developed antibiotic resistance during triclosan stent placement. CONCLUSIONS Antibiotic use with control stents resulted in bacterial antibiotic resistance, which was not the case with the triclosan-eluting stents. Although triclosan-eluting stents did not show a clinical benefit in terms of urine and stent cultures or overall subject symptoms compared with controls, their use did result in decreased antibiotic usage and significantly fewer symptomatic infections. The triclosan-eluting stent alone is not sufficient to reduce device-associated infections in this difficult patient population.

Uropathogen Interaction With the Surface of Urological Stents Using Different Surface Properties

PURPOSE Ureteral stents commonly become infected or encrusted. Various coatings have been developed to decrease bacterial adherence. To our knowledge there has been no in vitro testing of coating with heparin to date. We determined the effects of heparin coating on bacterial adherence of common uropathogens and physical stent properties. MATERIALS AND METHODS Heparin coated Radiance ureteral stents (Cook) and noncoated Endo-Sof control stents were tested against triclosan eluting Triumph(R) stents and noneluting Polaris control stents for adherence of Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Staphylococcus aureus and Pseudomonas aeruginosa for 7 days. Adherent bacteria were determined and biofilms were visualized using fluorescent dyes. Radial, tensile and coil strength of the Radiance and Polaris stents was compared to determine the effect of heparin coating on physical stent characteristics. RESULTS Heparin coating did not decrease bacterial adhesion compared to its control. E. coli adhesion was limited by all stents tested. The Polaris stent showed significantly greater resistance to bacterial adherence for Klebsiella, Pseudomonas and Enterococcus than the Endo-Sof and Radiance stents but was more susceptible to S. aureus adherence. The Triumph stent resisted all bacteria except Pseudomonas and Enterococcus. Mature biofilms were observed on all stents with lower viability on the Triumph stent. Radiance stents showed higher tensile and lower compression strength than its control. CONCLUSIONS Heparin coating does not decrease bacterial adherence to ureteral stents. Drug eluting antimicrobials have an inhibitory effect on bacterial adherence and the Polaris stent showed the least bacterial adherence of the nondrug eluting ureteral stents tested.

The use of triclosan eluting stents effectively reduces ureteral stent symptoms: a prospective randomized trial.

Study Type – Therapy (RCT)

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

PURPOSE 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. MATERIALS AND METHODS 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. RESULTS 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). CONCLUSIONS 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.

First Prize: Novel Uropathogen-Resistant Coatings Inspired by Marine Mussels

BACKGROUND AND PURPOSE Success in the prevention of urinary device infections has been elusive, largely due to multiple bacterial attachment strategies and the development of urinary conditioning films. We investigated a novel anti-fouling coating consisting of mussel adhesive protein mimics conjugated to polyethylene glycol (mPEG-DOPA(3)) for its potential to resist conditioning film formation and uropathogen attachment in human urine. METHODS Model TiO(2) -coated silicon disks ( approximately 75 mm(2)) were either coated with mPEG-DOPA(3) or left uncoated and sterilized using ethylene oxide gas. For bacterial attachment experiments, coated and uncoated surfaces were separately challenged with bacterial strains comprising six major uropathogenic species for 24 hours at 37 degrees C in human pooled urine. Starting inoculum for each strain was 10(5) CFU/mL and 0.5 mL was used per disk. Following incubation, the disks were thoroughly rinsed in phosphate buffered saline to remove non-adherent and weakly-adherent organisms and cell scrapers were employed to dislodge those that were firmly attached. Adherent bacteria were quantitated using dilution plating. Representative disks were also examined using scanning electron microscopy, energy dispersive x-ray analysis, and live/dead viability staining. RESULTS The mPEG-DOPA(3) coating significantly resisted the attachment of all uropathogens tested, with a maximum >231-fold reduction in adherence for Escherichia coli GR-12, Enterococcus faecalis 23241, and Proteus mirabilis 296 compared to uncoated TiO(2) disks. Scanning electron microscopy and viability staining analyses also reflected these results and demonstrated the ability of the coating to resist urinary constituent adherence as well. CONCLUSION Model surfaces coated with mPEG-DOPA(3) strongly resisted both urinary film formation and bacterial attachment in vitro. Future in vitro and in vivo studies will be conducted to assess whether similar findings can be demonstrated when these polymer coatings are applied to urologic devices.

Novel in vitro model for studying ureteric stent-induced cell injury.

To develop a novel in vitro model for the study of bladder and kidney epithelial cell injury akin to stent movement, as ureteric stents are associated with urinary tract complications that can significantly add to patient morbidity. These sequelae may be linked to inflammation triggered by stent‐mediated mechanical injury to the urinary tract.

Understanding urinary conditioning film components on ureteral stents: profiling protein components and evaluating their role in bacterial colonization

Ureteral stents are fraught with problems. A conditioning film attaches to the stent surface within hours of implantation; however, differences between stent types and their role in promoting encrustation and bacterial adhesion and colonization remain to be elucidated. The present work shows that the most common components do not differ between stent types or patients with the same indwelling stent, and contain components that may drive stent encrustation. Furthermore, unlike what was previously thought, the presence of a conditioning film does not increase bacterial adhesion and colonization of stents by uropathogens. Genitourinary cytokeratins are implicated in playing a significant role in conditioning film formation. Overall, stent biomaterial design to date has been unsuccessful in discovering an ideal coating to prevent encrustation and bacterial adhesion. This current study elucidates a more global understanding of urinary conditioning film components. It also supports specific focus on the importance of physical characteristics of the stent and how they can prevent encrustation and bacterial adhesion.

Biomaterials in Urology - Beyond Drug Eluting and Degradable - A Rational Approach to Ureteral Stent Design

Ureteral stents are commonly used in urology to provide urinary drainage of the upper tracts, particularly following treatment of urolithiasis. Stents are commonly plagued with infections and encrustation, particularly in stone-forming patients (Denstedt and Cadieux 2009). This involves a multistep process outlined in Figure 1. The first step is formation of a conditioning film comprised of urinary proteins, ions, and crystals that are deposited at the stent surface (Tieszer, Reid et al. 1998). The conditioning film becomes an attractive surface for bacteria to adhere to and forms a biofilm which can lead to a urinary tract infection or encrustation (Wollin, Tieszer et al. 1998; Choong and Whitfield 2000; Choong, Wood et al. 2001; Shaw, Choong et al. 2005). Bacteria have been demonstrated to adhere to the stent surface in up to 90% of indwelling stents, which in 27% of cases leads to a positive urine culture (Reid, Denstedt et al. 1992). Ideally, ureteral stent biomaterials would be able to limit or completely prevent the processes shown in Figure 1. Various attempts have been made to reduce the deposition of crystals, bacteria, and protein on stent surfaces including using low surface energy biomaterials (Tieszer, Reid et al. 1998), heparin coating (Cauda, Cauda et al. 2008), antimicrobial eluting biomaterials (Cadieux, Chew et al. 2006; Chew, Cadieux et al. 2006; Wignall, Goneau et al. 2008; Cadieux, Chew et al. 2009), diamond-like carbon coatings (Laube, Kleinen et al. 2007), polyethylene glycol and marine mussel adhesive proteins (Pechey, Elwood et al. 2009) to name just a few. Most have limited effectiveness and some have even shown increased bacterial adhesion compared to controls in the case of heparin coating (Lange, Elwood et al. 2009). While drug-eluting technology of biomaterials is both readily available and used clinically in other fields, its role in urology has been limited. Triclosan was used recently in ureteral stents. It held promise in in vitro (Chew, Cadieux et al. 2006) and animal infection models (Cadieux, Chew et al. 2006) but it fared poorly in those patients requiring chronic ureteral stents (Cadieux, Chew et al. 2009). The current methodology of technological implementation surrounding ureteral stent coating and design have come from trial and error or are borrowed technologies from coronary and vascular stenting. The time has come for the urological world to apply the same types of scientific discovery and development to problems specific to urinary devices rather than just applying the end product from other areas of medicine. What works in vascular stenting may not be directly applicable to the urinary environment.