Catechol-modified chitosan hydrogel containing PLGA microspheres loaded with triclosan and chlorhexidine: a sustained-release antibacterial system for urinary catheters.

Blockage and infection are common in hospitals, especially with long-term indwelling catheters, due to bacterial adhesion, colonization, and other reasons. A drug-sustained-release antibacterial coating for urinary catheters was described in this paper. Chlorhexidine (CHX) and triclosan (TCS) were encapsulated in poly(lactic-co-glycolic acid) microspheres and mixed with a modified chitosan hydrogel deposited on the surface of silicone rubber. The results showed that drugs can be released continuously more than 35 days. Catechol-modified chitosan (Chi-C) hydrogel was successful synthesized according to FT-IR and UV spectrophotometry, as well as 1H NMR. Furthermore, the coating with CHX and TCS presented stable antibacterial ability compared to the other groups. The results of CCK-8 revealed that the coating was cytotoxic-free and had a wide range of applications. The findings could provide a new drug sustained-release system and hydrogel-microsphere assembly for urinary catheters. HighlightsThe microspheres presented a sustained release more than 40 days with a remarkable initial burst release.The microspheres/catechol-modified chitosan (Chi-C)/silicon rubber system emerged stable binding ability in liquid environment more than 14 days.The Chi-C/chlorhexidine (CHX)+triclosan (TCS) microspheres system presented better antimicrobial property for entire experiment period.The coated samples showed no significant difference for relative growth rate (RGR) compared to different groups.

Intraluminal diamond-like carbon coating with anti-adhesion and anti-biofilm effects for uropathogens: A novel technology applicable to urinary catheters.

OBJECTIVES: To examine anti-adhesion and anti-biofilm effects of a diamond-like carbon coating deposited via a novel technique on the inner surface of a thin silicon tube. METHODS: Diamond-like carbon coatings were deposited into the lumen of a silicon tube with inner diameters of 2 mm. The surface of the diamond-like carbon was evaluated using physicochemical methods. We used three clinical isolates including green fluorescent protein-expressing Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus. We employed a continuous flow system for evaluation of both bacterial adhesion and biofilm formation. Bacterial adhesion assays consisted of counting the number of colony-forming units and visualization of adhered bacterial cells by scanning electron microscope to evaluate the diamond-like carbon-coated/uncoated samples. The biofilm structure was analyzed by confocal laser scanning microscopy on days 3, 5, 7 and 14 for green fluorescent protein-expressing Pseudomonas aeruginosa. RESULTS: The smooth and carbon-rich structure of the intraluminal diamond-like carbon film remained unchanged after the experiments. The numbers of colony-forming units suggested lower adherence of green fluorescent protein-expressing Pseudomonas aeruginosa and Escherichia coli in the diamond-like carbon-coated samples compared with the uncoated samples. The scanning electron microscope images showed adhered green fluorescent protein-expressing Pseudomonas aeruginosa cells without formation of microcolonies on the diamond-like carbon-coated samples. Finally, biofilm formation on the diamond-like carbon-coated samples was lower until at least day 14 compared with the uncoated samples. CONCLUSIONS: Intraluminal diamond-like carbon coating on a silicone tube has anti-adhesion and anti-biofilm effects. This technology can be applied to urinary catheters made from various materials.

Natural Cyanobacterial Polymer-Based Coating as a Preventive Strategy to Avoid Catheter-Associated Urinary Tract Infections.

Catheter-associated urinary tract infections (CAUTIs) represent about 40% of all healthcare-associated infections. Herein, the authors report the further development of an infection preventive anti-adhesive coating (CyanoCoating) meant for urinary catheters, and based on a natural polymer released by a marine cyanobacterium. CyanoCoating performance was assessed against relevant CAUTI etiological agents, namely Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, methicillin resistant Staphylococcus aureus (MRSA), and Candida albicans in the presence of culture medium or artificial urine, and under biofilm promoting settings. CyanoCoating displayed a broad anti-adhesive efficiency against all the uropathogens tested (68-95%), even in the presence of artificial urine (58-100%) with exception of P. mirabilis in the latter condition. Under biofilm-promoting settings, CyanoCoating reduced biofilm formation by E. coli, P. mirabilis, and C. albicans (30-60%). In addition, CyanoCoating prevented large crystals encrustation, and its sterilization with ethylene oxide did not impact the coating stability. Therefore, CyanoCoating constitutes a step forward for the implementation of antibiotic-free alternative strategies to fight CAUTIs.

Randomized Clinical Trial Using Sterile Single Use and Reused Polyvinylchloride Catheters for Intermittent Catheterization with a Clean Technique in Spina Bifida Cases: Short-Term Urinary Tract Infection Outcomes.

PURPOSE: Urinary tract infections are common and severe complications in patients with spina bifida. Management includes intermittent bladder catheterization with single use or reused sterile catheters. There is insufficient evidence to set a standard among the different techniques. We determined whether single use polyvinylchloride catheters would reduce urinary tract infections compared to reused polyvinylchloride catheters in patients with neurogenic bladder due to spina bifida. MATERIALS AND METHODS: We performed a 2-arm randomized parallel clinical trial from 2015 to 2016 with an 8-week followup at our center in patients with neurogenic bladder caused by spina bifida. Patients were divided into single use and reused polyvinylchloride catheter groups. Evaluations were done on days 0, 7, 14, 28, 42 and 56. Participants reported symptoms and urine cultures were obtained. The primary outcome was urinary tract infection frequency, defined as positive urine culture plus fever, flank pain, malaise, or cloudy or odorous urine. Study eligibility criteria were age 2 years or greater, spina bifida diagnosis with regular clean intermittent bladder catheterization and no urinary tract infection at initial evaluation. RESULTS: The calculated sample size was 75. Of the patients 135 were screened, 83 were randomized and 75 completed followup. Mean age was 12.7 years (range 2-56) and there were 29 males and 46 females. No statistical difference was found between the single use vs reused catheter groups in the frequency of asymptomatic bacteriuria (32.4% vs 23.7%, p = 0.398) or urinary tract infections (35.2% vs 36.8%, p = 0.877). CONCLUSIONS: Single use polyvinylchloride catheters for intermittent bladder catheterization did not decrease the incidence of urinary tract infections in our patients with neurogenic bladder compared to reused polyvinylchloride catheters. These results are consistent with the 2014 Cochrane Review.

A randomized clinical trial comparing Nitrofurazone-coated and uncoated urinary catheters in kidney transplant recipients: Results from a pilot study.

BACKGROUND: Urinary tract infections are frequent complications early after kidney transplantation, and the use of antimicrobial coated catheters in settings other than transplantation has shown promising results for infection prevention. The purpose of this study was to compare the efficacy of Nitrofurazone-coated silicone urinary catheters with non-impregnated silicone urinary catheters in reducing bacteriuria and urinary tract infections in kidney transplant recipients. METHODS: This single-center study, randomized controlled trial at the Hospital do Rim, a tertiary referral center in kidney transplantation, located in São Paulo, Brazil. Subjects involved living donor kidney transplant recipients, and were randomized 1:1 ratio with a computer-generated system to a Nitrofurazone-coated silicone urinary catheter and non-impregnated silicone urinary catheter from March 2013 to December 2014. Patients with asymptomatic bacteriuria or urinary tract infection at baseline, deceased kidney transplant donors, patients with known hypersensitivity to nitrofurantoin, pregnancy, and those refusing to sign the informed consent form were excluded from the study. RESULTS: Two hundred fourteen subjects were randomized and one hundred seventy-six completed the study. There were no differences in the rates of asymptomatic bacteriuria (12.5% in the Nitrofurazone group and 11.4% in the control group, P = 0.99) and urinary tract infection (8% and 6.8%, P = 0.99) and the incidence of side effects was more frequent in the Nitrofurazone-impregnated silicone urinary catheter group (46.6% and 26.1%, P = 0.007). CONCLUSION: The study suggests that there is no beneficial effect of the employment of Nitrofurazone-coated urinary catheter. TRIAL REGISTRATION NUMBER: ISRCTN57888785.

The Construction of Alkaline Phosphatase-Responsive Biomaterial and Its Application for In Vivo Urinary Tract Infection Therapy.

Urinary tract infections caused by urinary catheter implantations are becoming more serious. Therefore, the construction of a responsive antibacterial biomaterial that can not only provide biocompatible conditions, but also effectively prevent the growth and metabolism of bacteria, is urgently needed. In this work, a benzophenone-derived phosphatase light-triggered antibacterial agent is designed and synthesized, which is tethered to the biological materials using a one-step method for in vivo antibacterial therapy. This surface could kill gram-positive bacteria (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli). More importantly, because this material exhibited a zwitterion structure, it does not damage blood cells and tissue cells. When the bacteria interact with this surface, the initial fouling of the bacteria is reduced by zwitterion hydration. When the bacteria actively accumulate and metabolize to produce a certain amount of alkaline phosphatase, the surface immediately started the sterilization performance, and the bactericidal effect is achieved by destroying the bacterial cell membrane. In summary, an antibacterial biomaterial that shows biocompatibility with mammalian cells is successfully constructed, providing new ideas for the development of intelligent urinary catheters.

Silicone Foley catheters impregnated with microbial indole derivatives inhibit crystalline biofilm formation by Proteus mirabilis.

Proteus mirabilis is a common causative agent for catheter-associated urinary tract infections (CAUTI). The crystalline biofilm formation by P. mirabilis causes catheter encrustation and blockage leading to antibiotic treatment resistance. Thus, biofilm formation inhibition on catheters becomes a promising alternative for conventional antimicrobial-based treatment that is associated with rapid resistance development. Our previous work has demonstrated the in vitro antibiofilm activity of microbial indole derivatives against clinical isolates of P. mirabilis. Accordingly, we aim to evaluate the capacity of silicone Foley catheters (SFC) impregnated with these indole derivatives to resist biofilm formation by P. mirabilis both phenotypically and on the gene expression level. Silicon Foley catheter was impregnated with indole extract recovered from the supernatant of the rhizobacterium Enterobacter sp. Zch127 and the antibiofilm activity was determined against P. mirabilis (ATCC 12435) and clinical isolate P8 cultured in artificial urine. The indole extract at sub-minimum inhibitory concentration (sub-MIC=0.5X MIC) caused a reduction in biofilm formation as exhibited by a 60-70% reduction in biomass and three log10 in adhered bacteria. Results were confirmed by visualization by scanning electron microscope. Moreover, changes in the relative gene expression of the virulence genes confirmed the antibiofilm activity of the indole extract against P. mirabilis. Differential gene expression analysis showed that extract Zch127 at its sub-MIC concentration significantly down-regulated genes associated with swarming activity: umoC, flhC, flhD, flhDC, and mrpA (p< 0.001). In addition, Zch127 extract significantly down-regulated genes associated with polyamine synthesis: speB and glnA (p< 0.001), as well as the luxS gene associated with quorum sensing. Regulatory genes for capsular polysaccharide formation; rcsB and rcsD were not significantly affected by the presence of the indole derivatives. Furthermore, the impregnated catheters and the indole extract showed minimal or no cytotoxic effect against human fibroblast cell lines indicating the safety of this intervention. Thus, the indole-impregnated catheter is proposed to act as a suitable and safe strategy for reducing P. mirabilis CAUTIs.

[The use of urokinase in urinary catheter obstructed by clots.] / El uso de urocinasa en catéteres urinarios obstruidos por coágulos.

OBJECTIVE: The objective of thisstudy is to review three cases using urokinase in patientswith urinary catheter obstructed by clots, aswell to carry out a review of the published literature. METHODS: It was done a review of three casesfrom 2019 to 2020 who required urokinase due tourinary catheters obstructed by clots in our department.In addition, a reference search was performedin Pubmed. RESULTS: The first case was a woman with metastaticbreast carcinoma who required nephrostomyplacement. The second case was a renal trauma thatrequired bladder catheterization. The third case wasa male with a benign ureteric obstruction who requirednephrostomy placement due to sepsis. After instillationswith urokinase, the first two cases respondedadequately, while the third was unsuccessful. CONCLUSIONS: Urokinase may be an effectiveand well-tolerated therapy in the treatment of coagulatedurinary catheters that does not respond toother measures.

OBJETIVO: Reportar tres casos acercadel uso de la urocinasa en pacientes portadores decatéteres urinarios obstruidos por coágulos y realizaruna revisión de la literatura publicada. MATERIAL Y MÉTODOS: Revisión de casos quehan precisado de urocinasa en nuestro servicio de2019 a 2020 en relación a pacientes con catéteresurinarios obstruidos por coágulos. Además, se realizóbúsqueda de referencias en Pubmed. RESULTADOS: El primer caso fue una mujer concarcinoma de mama metástasico que precisó colocaciónde nefrostomías. El segundo fue un paciente pediátricocon traumatismo renal que requirió sondajevesical. El último enfermo fue un varón con obstrucciónbenigna de uréter que precisó de nefrostomía porsepsis. Tras instilaciones con urocinasa, los dos primerospacientes respondieron adecuadamente, mientrasque no hubo éxito en el tercero. CONCLUSIONES: La urocinasa puede ser unaterapia eficaz y bien tolerada en el tratamiento decatéteres urinarios coagulados que no responden aotras medidas.

Biofilm Development on Urinary Catheters Promotes the Appearance of Viable but Nonculturable Bacteria.

Catheter-associated urinary tract infections have serious consequences, for both patients and health care resources. Much work has been carried out to develop an antimicrobial catheter. Although such developments have shown promise under laboratory conditions, none have demonstrated a clear advantage in clinical trials. Using a range of microbiological and advanced microscopy techniques, a detailed laboratory study comparing biofilm development on silicone, hydrogel latex, and silver alloy-coated hydrogel latex catheters was carried out. Biofilm development by Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis on three commercially available catheters was tracked over time. Samples were examined with episcopic differential interference contrast (EDIC) microscopy, culture analysis, and staining techniques to quantify viable but nonculturable (VBNC) bacteria. Both qualitative and quantitative assessments found biofilms to develop rapidly on all three materials. EDIC microscopy revealed the rough surface topography of the materials. Differences between culture counts and quantification of total and dead cells demonstrated the presence of VBNC populations, where bacteria retain viability but are not metabolically active. The use of nonculture-based techniques showed the development of widespread VBNC populations. These VBNC populations were more evident on silver alloy-coated hydrogel latex catheters, indicating a bacteriostatic effect at best. The laboratory tests reported here, which detect VBNC bacteria, allow more rigorous assessment of antimicrobial catheters, explaining why there is often minimal benefit to patients.IMPORTANCE Several antimicrobial urinary catheter materials have been developed, but, although laboratory studies may show a benefit, none have significantly improved clinical outcomes. The use of poorly designed laboratory testing and lack of consideration of the impact of VBNC populations may be responsible. While the presence of VBNC populations is becoming more widely reported, there remains a lack of understanding of the clinical impact or influence of exposure to antimicrobial products. This is the first study to investigate the impact of antimicrobial surface materials and the appearance of VBNC populations. This demonstrates how improved testing is needed before clinical trials are initiated.

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.

Controversies in the management of vesicovaginal fistula.

Achieving 100% closure and continence rate in the management of vesicovaginal fistulas remains a challenge. There is still debate about several aspects of the care including the following.

A novel method to cease traumatic urethral bleeding.

Urethral bleeding due to trauma is a well-studied and often self-limiting condition. However, existing evidence regarding effective management of massive hemorrhage is limited. Intermittent penile compression and continuous perineal pressure are methods commonly used to control urethral bleeding. Nevertheless, these methods are not mentioned in the literature as specific treatment for this condition, and are rather learned by physicians via word of mouth. Sometimes these methods are ineffective and difficult for the patient to tolerate. This paper explains a new method implemented on a young man with massive urethral bleeding due to iatrogenic trauma, which was unresponsive to standard management. For this patient, the bleeding was controlled by gradually inflating the balloon of the catheter up to 4 mL. Given its safety and efficiency in controlling bleeding in this patient, it seems this new technique should be considered in cases of massive hemorrhage unresponsive to routine treatment.

Chitosans as new tools against biofilms formation on the surface of silicone urinary catheters.

Urinary catheters contamination by microorganisms is a major cause of hospital acquired infections and represents a limitation for long-term use. In this work, biofilms of Klebsiella pneumoniae and Escherichia coli clinical isolates were developed on urinary catheters for 48 and 72 h in artificial urine medium (AUM) with different molecular weight chitosans (AUM-CS solutions) at pH 5.0. The number of viable bacteria was determined by standard plate count agar while crystal violet (CV) staining was carried out to assess biomass production (optical density at 570 nm) in the mentioned conditions. Re-growth of each strain was also evaluated after 24 h re-incubation of the treated catheters. Significant decreases of log CFU/catheter and biomass production were observed for all the biofilms developed in AUM-CS compared with the controls in AUM. The percentages of biofilm removal were slightly higher for E. coli biofilms (up to 90.4%) than those of K. pneumoniae (89.7%); in most cases, the complete inhibition of bacterial re-growth on treated catheter pieces was observed. Contact time influenced chitosan efficacy rather than its molecular weight or the biofilms age. The results confirmed the potentiality of chitosans as a biomacromolecule tool to contrast biofilm formation and reduce bacterial re-growth on urinary catheters.

A review of the recent advances in antimicrobial coatings for urinary catheters.

More than 75% of hospital-acquired or nosocomial urinary tract infections are initiated by urinary catheters, which are used during the treatment of 15-25% of hospitalized patients. Among other purposes, urinary catheters are primarily used for draining urine after surgeries and for urinary incontinence. During catheter-associated urinary tract infections, bacteria travel up to the bladder and cause infection. A major cause of catheter-associated urinary tract infection is attributed to the use of non-ideal materials in the fabrication of urinary catheters. Such materials allow for the colonization of microorganisms, leading to bacteriuria and infection, depending on the severity of symptoms. The ideal urinary catheter is made out of materials that are biocompatible, antimicrobial, and antifouling. Although an abundance of research has been conducted over the last forty-five years on the subject, the ideal biomaterial, especially for long-term catheterization of more than a month, has yet to be developed. The aim of this review is to highlight the recent advances (over the past 10years) in developing antimicrobial materials for urinary catheters and to outline future requirements and prospects that guide catheter materials selection and design. STATEMENT OF SIGNIFICANCE: This review article intends to provide an expansive insight into the various antimicrobial agents currently being researched for urinary catheter coatings. According to CDC, approximately 75% of urinary tract infections are caused by urinary catheters and 15-25% of hospitalized patients undergo catheterization. In addition to these alarming statistics, the increasing cost and health related complications associated with catheter associated UTIs make the research for antimicrobial urinary catheter coatings even more pertinent. This review provides a comprehensive summary of the history, the latest progress in development of the coatings and a brief conjecture on what the future entails for each of the antimicrobial agents discussed.

Efficacy and safety of urinary catheters with silver alloy coating in patients with spinal cord injury: a multicentric pragmatic randomized controlled trial. The ESCALE trial.

BACKGROUND: Patients with spinal cord injury (SCI) who carry indwelling urinary catheters have an increased risk of urinary tract infection (UTI). Antiseptic silver alloy-coated (SAC) silicone urinary catheters prove to be a promising intervention to reduce UTIs; however, current evidence cannot be extrapolated to patients with SCI. PURPOSE: This study aimed to assess the efficacy of SAC urinary catheters for preventing catheter-associated urinary tract infections. DESIGN/SETTING: This is an open-label, multicenter (developed in Spain, Portugal, Chile, Turkey, and Italy), randomized clinical trial conducted in 14 hospitals from November 2012 to December 2015. PATIENT SAMPLE: Eligible patients were men or women with traumatic or medical SCI, aged ≥18 years, requiring an indwelling urinary catheter for at least 7 days. OUTCOME MEASURES: The primary outcome was the incidence of symptomatic UTIs. The secondary outcome included bacteremia in the urinary tract and adverse events. MATERIALS AND METHODS: Patients were randomized to receive a SAC urinary catheter (experimental group) or a standard catheter (control group) for at least 7 days. Data were compared using chi-squared test and also calculating the absolute risk difference with a 95% confidence interval. An adjusted analysis including different risk factors of UTI was performed. This study was mainly funded by La Marató de TV3 Foundation (grant number # 112210) and the European Clinical Research Infrastructures Network organization. The funders had no role in the interpretation or reporting of results. RESULTS: A total of 489 patients were included in the study, aged 55 years in the experimental group and aged 57 in the control group (p=.870); 72% were men; 43% were hospitalized patients, and 57% were outpatients (p=1.0). The most frequent cause of SCI was traumatic (73.75%), and the localization was mainly the cervical spine (42.74%). Most of the patients had an A score (complete spinal injury and no motor and sensory is preserved) on the ASIA scale (62.37%). The median time of urethral catheterization was 27 days in the experimental group and 28 days in the control group (p=.202). Eighteen patients (7.41%) in the experimental group and 19 in the control (7.72%) group had a symptomatic UTI (odds ratio [OR] 0.96 [0.49-1.87]). The adjusted analysis revealed no change in the results. Only three patients in the experimental group had bacteremia within the urinary tract. The experimental group presented more adverse events related to the use of a catheter than the control group (OR 0.03 [0.00-0.06]). CONCLUSIONS: The results of this study do not support the routine use of indwelling antiseptic SAC silicone urinary catheters in patients with SCI. However, UTIs associated to long-term urinary catheter use remain a challenge and further investigations are still needed.

Antifungal activity of a ß-peptide in synthetic urine media: Toward materials-based approaches to reducing catheter-associated urinary tract fungal infections.

UNLABELLED: Catheter-associated urinary tract infections (CAUTI) are the most common type of hospital-acquired infection, with more than 30 million catheters placed annually in the US and a 10-30% incidence of infection. Candida albicans forms fungal biofilms on the surfaces of urinary catheters and is the leading cause of fungal urinary tract infections. As a step toward new strategies that could prevent or reduce the occurrence of C. albicans-based CAUTI, we investigated the ability of antifungal ß-peptide-based mimetics of antimicrobial peptides (AMPs) to kill C. albicans and prevent biofilm formation in synthetic urine. Many α-peptide-based AMPs exhibit antifungal activities, but are unstable in high ionic strength media and are easily degraded by proteases-features that limit their use in urinary catheter applications. Here, we demonstrate that ß-peptides designed to mimic the amphiphilic helical structures of AMPs retain 100% of their structural stability and exhibit antifungal and anti-biofilm activity against C. albicans in a synthetic medium that mimics the composition of urine. We demonstrate further that these agents can be loaded into and released from polymer-based multilayer coatings applied to polyurethane, polyethylene, and silicone tubing commonly used as urinary catheters. Our results reveal catheters coated with ß-peptide-loaded multilayers to kill planktonic fungal cells for up to 21days of intermittent challenges with C. albicans and prevent biofilm formation on catheter walls for at least 48h. These new materials and approaches could lead to advances that reduce the occurrence of fungal CAUTI. STATEMENT OF SIGNIFICANCE: Catheter-associated urinary tract infections are the most common type of hospital-acquired infection. The human pathogen Candida albicans is the leading cause of fungal urinary tract infections, and forms difficult to remove 'biofilms' on the surfaces of urinary catheters. We investigated synthetic ß-peptide mimics of natural antimicrobial peptides as an approach to kill C. albicans and prevent biofilm formation in media that mimics the composition of urine. Our results reveal these mimics to retain structural stability and activity against C. albicans in synthetic urine. We also report polymer-based approaches to the local release of these agents within urinary catheter tubes. With further development, these materials-based approaches could lead to advances that reduce the occurrence of fungal urinary tract infections.

Cellobiose dehydrogenase functionalized urinary catheter as novel antibiofilm system.

Urinary catheters expose patients to a high risk of acquiring nosocomial infections. To prevent this risk of infection, cellobiose dehydrogenase (CDH), an antimicrobial enzyme able to use various oligosaccharides as electron donors to produce hydrogen peroxide using oxygen as an electron acceptor, was covalently grafted onto plasma-activated urinary polydimethylsiloxane (PDMS) catheter surfaces. Successful immobilization of CDH on PDMS was confirmed by Fourier transformed-infrared spectrometry and production of H2 O2 . The CDH functionalized PDMS surfaces reduced the amount of viable Staphylococcus aureus by 60%, total biomass deposited on the surface by 30% and 70% of biofilm formation. The immobilized CDH was relatively stable in artificial urine over 16 days, retaining 20% of its initial activity. The CDH coated PDMS surface did not affect the growth and physiology of HEK 239 and RAW 264,7 mammalian cells. Therefore this new CDH functionalized catheter system shows great potential for solving the current problems associated with urinary catheters. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1448-1456, 2016.

Singly and binary grafted poly(vinyl chloride) urinary catheters that elute ciprofloxacin and prevent bacteria adhesion.

Acrylic acid (AAc) and poly(ethylene glycol) methacrylate (PEGMA) were singly and dually grafted onto poly(vinyl chloride) (PVC) urinary catheters with the aim of preventing biofouling by endowing the catheters with the ability to load and release antimicrobial agents and to avoid bacteria adhesion. The polymers were grafted applying an oxidative pre-irradiation ((60)Co source) method in two steps. Grafting percentage and kinetics were evaluated by varying the absorbed pre-irradiation dose, reaction time, monomer concentration, and reaction temperature. Catheters with grafting percentages ranging from 8 to 207% were characterized regarding thermal stability, surface hydrophilicity, mechanical properties, swelling, and lubricity. The modified catheters proved to have better compatibility with fibroblast cells than PVC after long exposure times. Furthermore, grafted catheters were able to load ciprofloxacin and sustained its release in urine medium for several hours. Ciprofloxacin-loaded catheters inhibited the growth of Escherichia coli and Staphylococcus aureus in the catheter surroundings and prevented bacteria adhesion.

Quorum-Quenching and Matrix-Degrading Enzymes in Multilayer Coatings Synergistically Prevent Bacterial Biofilm Formation on Urinary Catheters.

Bacteria often colonize in-dwelling medical devices and grow as complex biofilm communities of cells embedded in a self-produced extracellular polymeric matrix, which increases their resistance to antibiotics and the host immune system. During biofilm growth, bacterial cells cooperate through specific quorum-sensing (QS) signals. Taking advantage of this mechanism of biofilm formation, we hypothesized that interrupting the communication among bacteria and simultaneously degrading the extracellular matrix would inhibit biofilm growth. To this end, coatings composed of the enzymes acylase and α-amylase, able to degrade bacterial QS molecules and polysaccharides, respectively, were built on silicone urinary catheters using a layer-by-layer deposition technique. Multilayer coatings of either acylase or amylase alone suppressed the biofilm formation of corresponding Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus. Further assembly of both enzymes in hybrid nanocoatings resulted in stronger biofilm inhibition as a function of acylase or amylase position in the layers. Hybrid coatings, with the QS-signal-degrading acylase as outermost layer, demonstrated 30% higher antibiofilm efficiency against medically relevant Gram-negative bacteria compared to that of the other assemblies. These nanocoatings significantly reduced the occurrence of single-species (P. aeruginosa) and mixed-species (P. aeruginosa and Escherichia coli) biofilms on silicone catheters under both static and dynamic conditions. Moreover, in an in vivo animal model, the quorum quenching and matrix degrading enzyme assemblies delayed the biofilm growth up to 7 days.

Soft robotic concepts in catheter design: an on-demand fouling-release urinary catheter.

Infectious biofilms are problematic in many healthcare-related devices and are especially challenging and ubiquitous in urinary catheters. This report presents an on-demand fouling-release methodology to mechanically disrupt and remove biofilms, and proposes this method for the active removal of infectious biofilms from the previously inaccessible main drainage lumen of urinary catheters. Mature Proteus mirabilis crystalline biofilms detach from silicone elastomer substrates upon application of strain to the substrate, and increasing the strain rate increases biofilm detachment. The study presents a quantitative relationship between applied strain rate and biofilm debonding through an analysis of biofilm segment length and the driving force for debonding. Based on this mechanism, hydraulic and pneumatic elastomer actuation is used to achieve surface strain selectively within the lumen of prototypes of sections of a fouling-release urinary catheter. Proof-of-concept prototypes of sections of active, fouling-release catheters are constructed using techniques typical to soft robotics including 3D printing and replica molding, and those prototypes demonstrate release of mature P. mirabilis crystalline biofilms (e.g., ≈90%) from strained surfaces. These results provide a basis for the development of a new urinary catheter technology in which infectious biofilms are effectively managed through new methods that are entirely complementary to existing approaches.