No abstract

Urinary tract infections affect many patients, especially those who are admitted to hospital and receive a bladder catheter for drainage. Catheter associated urinary tract infections are some of the most common hospital infections and cost the health care system billions of dollars. Early removal is one of the mainstays of prevention as 100% of catheters become colonized. Patients with ureteral stents are also affected by infection and antibiotic therapy alone may not be the answer. We will review the current evidence on how to prevent infections of urinary biomaterials by using different coatings, new materials, and drug eluting technologies to decrease infection rates of ureteral stents and catheters.

Bacterial attachment and biofilm formation pose major challenges to the optimal performance of indwelling devices. Current coating methods have significant deficiencies including the lack of long-term activity, easy of application, and adaptability to diverse materials. Here we describe a coating method that could potentially overcome such limitations and yield an ultrathin coating with long-term antibiofilm activity. We utilized the interaction between polydopamine (PDA) nanoaggregates/nanoparticles and ultrahigh molecular weight (uHMW) hydrophilic polymers to generate stable coatings with broad spectrum antibiofilm activity. We used a short-term bacterial adhesion assay as an initial screening method to identify coating compositions that give superior performance and found that only selected polymers (out of 13 different types) and molecular weights gave promising antifouling activity. Optimization of PDA self-assembly, polymer− PDA interaction, and deposition on the surface using uHMW poly(N,N-dimethylacrylamide) (PDMA) (∼795 kDa) resulted in a stable ultrathin coating (∼19 nm) with excellent antifouling and antibiofilm properties (>4 weeks) against diverse bacteria (∼10 8 CFU/mL) in shaking and flow conditions. The ultrathin coating is effective on diverse substrates including metals and polymeric substrates. The uHMW PDMA is stabilized in the coating via supramolecular interactions with PDA and generated a surface that is highly enriched with PDMA in aqueous conditions. Based on the surface analyses data, we also propose a mechanism for the stable coating formation. The molecular weight of PDMA is a crucial factor, and only uHMW polymers generate this property. An attractive feature of the coating is that it does not contain any antimicrobial agents and has the potential to prevent biofilm formation for diverse applications both short-and long-term.

Bacterial infection associated with indwelling medical devices and implants is a major clinical issue, and the prevention or treatment of such infections is challenging. Antimicrobial coatings offer a significant step toward addressing this important clinical problem. Antimicrobial coatings based on tethered antimicrobial peptides (AMPs) on hydrophilic polymer brushes have been shown to be one of the most promising strategies to avoid bacterial colonization and have demonstrated broad spectrum activity. Optimal combinations of the functionality of the polymer-brush-tethered AMPs are essential to maintaining long-term AMP activity on the surface. However, there is limited knowledge currently available on this topic. Here we report the development of potent antimicrobial coatings on implant surfaces by elucidating the roles of polymer brush chemistry and peptide structure on the overall antimicrobial activity of the coatings. We screened several combinations of polymer brush coatings and AMPs constructed on nanoparticles, titanium surfaces, and quartz slides on their antimicrobial activity and bacterial adhesion against Gram-positive and Gram-negative bacteria. Highly efficient killing of planktonic bacteria by the antimicrobial coatings on nanoparticle surfaces, as well as potent killing of adhered bacteria in the case of coatings on titanium surfaces, was observed. Remarkably, the antimicrobial activity of AMP-conjugated brush coatings demonstrated a clear dependence on the polymer brush chemistry and peptide structure, and optimization of these parameters is critical to achieving infection-resistant surfaces. By analyzing the interaction of polymer-brush-tethered AMPs with model lipid membranes using circular dichroism spectroscopy, we determined that the polymer brush chemistry has an influence on the extent of secondary structure change of tethered peptides before and after interaction with biomembranes. The peptide structure also has an influence on the density of conjugated peptides on polymer brush coatings and the resultant wettability of the coatings, and both of these factors contributed to the antimicrobial activity and bacterial adhesion of the coatings. Overall, this work highlights the importance of optimizing the functionality of the polymer brush to achieve infection-resistant surfaces and presents important insight into the design criteria for the selection of polymers and AMPs toward the development of potent antimicrobial coating on implants.

Ureteral stents are commonly used devices in hospital settings. However, their usage is often complicated by associated urinary tract infections as a result of bacterial adhesion onto the indwelling implant surfaces, followed by the formation of layers of biofilm. Once formed, the biofilm is exceedingly difficult to remove, potentially leading to further morbidity and even urosepsis. Urosepsis, where pathogens from the urinary tract enter the bloodstream, has a mortality rate of up to 50% of severely infected patients. Hence, it is important to understand its pathogenesis. In this review, ureteral stent-associated urinary tract infection and urosepsis will be addressed. In particular, the bacterial mechanisms involved, as well as the prevention and treatment of these infections will be discussed. ARTICLE HISTORY

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.

Our minimally invasive, reproducible percutaneous technique is suitable for studying catheter associated urinary tract infection in each gender. Infecting urine with P. mirabilis generates a preclinical model of catheter encrustation within 3 days. The progression of encrustation can be monitored in vivo by ultrasound, making this image based model suitable for assessing novel antibacterial and anti-encrustation therapies.

The aim of the study was to investigate whether xylitol-wipe use in young children prevented caries by affecting bacterial virulence. In a double-blinded randomized controlled clinical trial, 44 mother-child pairs were randomized to xylitol-wipe or placebo-wipe groups. Salivary mutans streptococci levels were enumerated at baseline, 6 months, and one year. Ten mutans streptococci colonies were isolated and genotyped from each saliva sample. Genotype-colonization stability, xylitol sensitivity, and biofilm formation of these isolates were studied. Despite a significant reduction in new caries at one year in the xylitol-wipe group, no significant differences were found between the two groups in levels of mutans streptococci. Children in the xylitol-wipe group had significantly fewer retained genotypes (p = 0.06) and more transient genotypes of mutans streptococci (p = 0.05) than those in the placebo-wipe group. At one year, there was no significant difference in the prevalence of xylitol-resistant genotypes or in biofilm formation ability of mutans streptococci isolates between the two groups. The mechanism of the caries-preventive effect of xylitol-wipe use may be related to the stability of mutans streptococci colonization. Further studies with genomic characterization methods are needed to determine specific gene(s) that account for the caries-preventive effect of xylitol.