Efficacy and safety of preventing catheter-associated urinary tract infection by inhibiting catheter bacterial biofilm formation: a multicenter randomized controlled trial.

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) remains the most significant challenge among hospital-acquired infections (HAIs), yet still unresolved. The present study aims to evaluate the preventive effectiveness of JUC Spray Dressing (name of U.S. FDA and CE certifications, while the medical device name in China is Long-acting Antimicrobial Material) alone for CAUTI without combining with antibiotics and to evaluate the impact of bacterial biofilm formation on CAUTI results on the inserted catheters of patients. METHODS: In this multicenter, randomized, double-blind study, we enrolled adults who suffered from acute urinary retention (AUR) and required catheterization in 6 hospitals in China. Participants were randomly allocated 1:1 according to a random number table to receive JUC Spray Dressing (JUC group) or normal saline (placebo group). The catheters were pretreated with JUC Spray Dressing or normal saline respectively before catheterization. Urine samples and catheter samples were collected after catheterization by trial staff for further investigation. RESULTS: From April 2012 to April 2020, we enrolled 264 patients and randomly assigned them to the JUC group (n = 132) and the placebo group (n = 132). Clinical symptoms and urine bacterial cultures showed the incidence of CAUTI of the JUC group was significantly lower than the placebo group (P < 0.01). In addition, another 30 patients were enrolled to evaluate the biofilm formation on catheters after catheter insertion in the patients' urethra (10 groups, 3 each). The results of scanning electron microscopy (SEM) showed that bacterial biofilm formed on the 5th day in the placebo group, while no bacterial biofilm formed on the 5th day in the JUC group. In addition, no adverse reactions were reported using JUC Spray Dressing. CONCLUSION: Continued indwelling urinary catheters for 5 days resulted in bacterial biofilm formation, and pretreatment of urethral catheters with JUC Spray Dressing can prevent bacterial biofilm formation by forming a physical antimicrobial film, and significantly reduce the incidence of CAUTI. This is the first report of a study on inhibiting bacterial biofilm formation on the catheters in CAUTI patients.

The bacterial displacement test: an in vitro microbiological test for the evaluation of intermittent catheters and urinary tract infection.

AIMS: Intermittent catheters (ICs) are commonly used in bladder management, but catheter-associated urinary tract infections (CAUTIs) remain challenging. Insertion tips may reduce the risk of CAUTIs by minimizing bacterial transfer along the urinary tract. However, there are few laboratory tests to evaluate such technologies. We describe the use of an adapted in vitro urethra agar model to assess bacterial displacement by ICs. METHODS AND RESULTS: Simulated urethra agar channels (UACs) were prepared with catheter-specific sized channels in selective media specific to the challenge organisms. UACs were inoculated with Escherichia coli and Enterococcus faecalis before insertion of ICs, and enumeration of UAC sections was performed following insertion. Four ICs were evaluated: Cure Catheter® Closed System (CCS), VaPro Plus Pocket™, Bard® Touchless® Plus, and SpeediCath® Flex Set. CCS demonstrated significantly reduced bacterial displacement along the UACs compared to the other ICs and was also the only IC with undetectable levels of bacteria toward the end of the UAC (representing the proximal urethra). CONCLUSION: The bacterial displacement test demonstrated significant differences in bacterial transfer between the test ICs with insertion tips, which may reflect their different designs. This method is useful for evaluating CAUTI prevention technology and may help guide future technology innovations.

Mucus Mimic Hydrogel Coating for Lubricous, Antibiofouling, and Anti-Inflammatory Urinary Catheters.

Silicone is a common elastomer used in indwelling urinary catheters, and catheters are widely used in various medical applications due to their exceptional biocompatibility, hypoallergenic properties, and flexibility. However, silicones exhibit hydrophobic characteristics, lack inherent biolubrication, and are susceptible to nonspecific biosubstance adsorption, resulting in complications including but not limited to tissue trauma, postoperative pain, and urinary tract infections (UTIs). The development of effective surface designs for biomedical catheters to mitigate invasive damage and UITs has been a longstanding challenge. Herein, we present a novel approach to prepare a mucus mimic hydrogel coating. A thin layer of hydrogel containing xylitol is fabricated via photopolymerization. The surface modification technique and the interface-initiated hydrogel polymerization method ensure robust interfacial coherence. The resultant coating exhibits a low friction coefficient (CoF ≈ 0.1) for urinary catheter applications. Benefiting from the hydration layer and the antifouling of the xylitol unit, the xylitol hydrogel-coated surfaces (pAAAMXA) demonstrate outstanding antibiofouling properties against proteins (98.9% reduction relative to pristine polydimethylsiloxane (PDMS)). Furthermore, the pAAAMXA shows general adhesion resistance against bacteria primarily responsible for UITs (Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Methicillin-resistant strains of Staphylococcus aureus (MRSA), and Staphylococcus epidermidis (S. epidermidis)) without compromising biotoxicity (cell viability 98%). In vivo, catheters coated with the mucus mimic hydrogel displayed excellent biocompatibility, resistance to adhesion of bio substance, and anti-inflammatory characteristics. This work describes a promising alternative to conventional silicone catheters, offering potential for clinical interventional procedures with minimized complications.

Materials-based incidence of urinary catheter associated urinary tract infections and the causative micro-organisms: systematic review and meta-analysis.

BACKGROUND: Both long (> 30 days) and short-term (≤ 30 days) catheterisation has been associated with urinary tract infections (UTIs) due to the invasive nature of device insertion through the urethra. Catheter associated Urinary Tract Infections (CAUTIs) are common (prevalence of ~ 8.5%) infections which can be treated with antibiotics; however, CAUTIs are both expensive to treat and contributes to the antibiotic usage crisis. As catheters are unlikely be replaced for the management of patients' urination, ways of reducing CAUTIs are sought out, using the catheter device itself. The aim of this review is to assess the incidence of CAUTI and the causative micro-organisms when different urinary catheter devices have been used by humans, as reported in published research articles. METHODS: A Systematic Literature Review was conducted in Ovid Medline, Web of Science and PubMed, to identify studies which investigated the incidence of UTI and the causative micro-organisms, in patients with different urinary catheter devices. The articles were selected based on a strict set of inclusion and exclusion criteria. The data regarding UTI incidence was extracted and calculated odds ratio were compared across studies and pooled when types of catheters were compared. CAUTI causative micro-organisms, if stated within the research pieces, were also gathered. RESULTS: A total of 890 articles were identified, but only 26 unique articles met the inclusion/exclusion criteria for this review. Amongst the large cohort there were catheters of materials silicone, latex and PVC and catheter modifications of silver nanoparticles and nitrofurantoin antibiotics. The meta-analysis did not provide a clear choice towards a single catheter against another although silver-based catheters, and silver alloy, appeared to statistically reduce the OR of developing CAUTIs. At genus level the three commonest bacteria identified across the cohort were E. coli, Enterococcus spp. and Pseudomonas spp. whilst considering only at the genus level, with E. coli, Klebsiella pneumonia and Enterococcus faecalis most common at the species-specific level. CONCLUSIONS: There does not appear to be a catheter type, which can significantly reduce the incidence of CAUTI's in patients requiring catheterisation. Ultimately, this warrants further research to identify and develop a catheter device material that will reduce the incidence for CAUTIs.

An in-vitro model for bacteria-related catheter encrustations.

PURPOSE: About 50% of individuals with long-term indwelling catheters are affected by catheter encrustations and bladder stone formation. Therefore, prophylaxis of catheter encrustations is important. Currently, however, neither an established prophylaxis nor a standardized in-vitro model to test different measures exist. We have therefore developed and qualitatively evaluated an in-vitro model of catheter encrustation. METHODS: Size 14 French suprapubic catheters were incubated under sterile conditions at 37 degrees Celsius in five different media: (1) sterile artificial urine (n = 16), (2) artificial urine with E. coli (n = 8), (3) with Pseudomonas aeruginosa (n = 8), (4) with Proteus mirabilis (n = 8), and (5) with a mix of these three strains (n = 8). Catheter balloons were inflated either a glycerine or a bactericidal solution. After 6 weeks, the catheters were removed from the solution, dried, and weighed, and a photometric determination of the retrieved encrustations was performed. RESULTS: Most frequently and pronounced encrustations were detected in the Pseudomonas group. The median weight of these encrustations (50% struvite and brushite) was 84.4 mg (47.7 mg / 127.3 mg). Even on catheters stored in sterile urine, encrustations (69.2% struvite) were found. Bacterial growth was not affected by the medium used for catheter blockage. CONCLUSION: Although in-vitro models appear to be limited because they lack "the human factor", they are valuable for systematically assessing physico-chemical factors affecting encrustations. Therefore, our model, being reliable and cost-effective, may foster further research despite its limitations.

Antibiofilm activity of promethazine against ESBL-producing strains of Escherichia coli in urinary catheters.

The bacterium Escherichia coli is one of the main causes of urinary tract infections. The formation of bacterial biofilms, especially associated with the use of urinary catheters, contributes to the establishment of recurrent infections and the development of resistance to treatment. Strains of E. coli that produce extended-spectrum beta-lactamases (ESBL) have a greater ability to form biofilms. In addition, there is a lack of drugs available in the market with antibiofilm activity. Promethazine (PMZ) is an antihistamine known to have antimicrobial activity against different pathogens, including in the form of biofilms, but there are still few studies of its activity against ESBL E. coli biofilms. The aim of this study was to evaluate the antimicrobial activity of PMZ against ESBL E. coli biofilms, as well as to assess the application of this drug as a biofilm prevention agent in urinary catheters. To this end, the minimum inhibitory concentration and minimum bactericidal concentration of PMZ in ESBL E. coli strains were determined using the broth microdilution assay and tolerance level measurement. The activity of PMZ against the cell viability of the in vitro biofilm formation of ESBL E. coli was analyzed by the MTT colorimetric assay and its ability to prevent biofilm formation when impregnated in a urinary catheter was investigated by counting colony-forming units (CFU) and confirmed by scanning electron microscopy (SEM). PMZ showed bactericidal activity and significantly reduced (p < 0.05) the viability of the biofilm being formed by ESBL E. coli at concentrations of 256 and 512 µg/ml, as well as preventing the formation of biofilm on urinary catheters at concentrations starting at 512 µg/ml by reducing the number of CFUs, as also observed by SEM. Thus, PMZ is a promising candidate to prevent the formation of ESBL E. coli biofilms on abiotic surfaces.

Enzymatically Built Nanoenabled Antimicrobial Coating on Urinary Catheters.

Catheter-associated urinary tract infections represent a major share of nosocomial infections, and are associated with longer periods of hospitalization and a huge financial burden. Currently, there are only a handful of commercial materials that reduce biofilm formation on urinary catheters, mostly relying on silver alloys. Therefore, we combined silver-phenolated lignin nanoparticles with poly(carboxybetaine) zwitterions to build a composite antibiotic-free coating with bactericidal and antifouling properties. Importantly, the versatile lignin chemistry enabled the formation of the coating in situ, enabling both the nanoparticle grafting and the radical polymerization by using only the oxidative activity of laccase. The resulting surface efficiently prevented nonspecific protein adsorption and reduced the bacterial viability on the catheter surface by more than 2 logs under hydrodynamic flow, without exhibiting any apparent signs of cytotoxicity. Moreover, the said functionality was maintained over a week both in vitro and in vivo, whereby the animal models showed excellent biocompatibility.

Assessment of Biofilm Forming Capability and Antibiotic Resistance in Proteus mirabilis Colonizing Indwelling Catheter.

<b>Background and Objective:</b> Urinary tract infections from the use of an indwelling urinary catheter are one of the most common infections caused by <i>Proteus mirabilis</i>. Due to their biofilm-producing capacity and the increasing antimicrobial resistance in this microorganism, this study aimed to determine the prevalence, biofilm-producing capacity, antimicrobial resistance patterns, multidrug resistance and plasmid mediated resistance of the recovered isolates. <b>Materials and Methods:</b> A total of 50 urinary samples were collected from May to August, 2018 from patients on indwelling urinary catheters. Using routine microbiological and biochemical methods, 37 <i>P. mirabilis</i> were isolated. Biofilm forming capability was determined among the isolates using the tube method while antimicrobial susceptibility and plasmid curing were also performed. <b>Results:</b> All isolates were biofilm producers with 17(46%) being moderate producers while 20(54%) were strong biofilm formers. The study isolates exhibited a high resistance rate to empiric antibiotics, including ceftazidime (75.8%), cefuroxime (54.5%), ampicillin (69.7%) and amoxicillin-clavulanic acid (51.5%). Low resistance was seen in the fluoroquinolones, gentamicin and nitrofurantoin. Plasmid curing experiment revealed that most isolates lost their resistance indicating that resistance was borne on plasmids. Plasmid carriage is likely the reason for the high MDR rate of 56.8% observed. <b>Conclusion:</b> These findings necessitate the provision of infection control programs which will guide and implement policies.

Mussel-Inspired Sonochemical Nanocomposite Coating on Catheters for Prevention of Urinary Infections.

Catheter-associated urinary tract infections are the most common hospital-acquired infections and cause patient discomfort, increased morbidity, and prolonged stays, altogether posing a huge burden on healthcare services. Colonization occurs upon insertion, or later by ascending microbes from the rich periurethral flora, and is therefore virtually unavoidable by medical procedures. Importantly, the dwell time is a significant risk factor for bacteriuria because it gives biofilms time to develop and mature. This is why we engineer antibacterial and antibiofilm coating through ultrasound- and nanoparticle-assisted self-assembly on silicone surfaces and validate it thoroughly in vitro and in vivo. To this end, we combine bimetallic silver/gold nanoparticles, which exercise both biocidal and structural roles, with dopamine-modified gelatin in a facile and substrate-independent sonochemical coating process. The latter mussel-inspired bioadhesive potentiates the activity and durability of the coating while attenuating the intrinsic toxicity of silver. As a result, our approach effectively reduces biofilm formation in a hydrodynamic model of the human bladder and prevents bacteriuria in catheterized rabbits during a week of placement, outperforming conventional silicone catheters. These results substantiate the practical use of nanoparticle-biopolymer composites in combination with ultrasound for the antimicrobial functionalization of indwelling medical devices.

Antimicrobial nanocomposite coatings for rapid intervention against catheter-associated urinary tract infections.

Catheter-associated urinary tract infections (CAUTIs) pose a significant challenge in hospital settings. Current solutions available on the market involve incorporating antimicrobials and antiseptics into catheters. However, challenges such as uncontrolled release leading to undesirable toxicity, as well as the prevalence of antimicrobial resistance reduce the effectiveness of these solutions. Additionally, conventional antibiotics fail to effectively eradicate entrenched bacteria and metabolically suppressed bacteria present in the biofilm, necessitating the exploration of alternative strategies. Here, we introduce a novel polymer-nanocomposite coating that imparts rapid antimicrobial and anti-biofilm properties to coated urinary catheters. We have coated silicone-based urinary catheters with an organo-soluble antimicrobial polymer nanocomposite (APN), containing hydrophobic quaternized polyethyleneimine and zinc oxide nanoparticles, in a single step coating process. The coated surfaces exhibited rapid eradication of drug-resistant bacteria within 10-15 min, including E. coli, K. pneumoniae, MRSA, and S. epidermidis, as well as drug-resistant C. albicans fungi. APN coated catheters exhibited potent bactericidal activity against uropathogenic strains of E. coli, even when incubated in human urine. Furthermore, the stability of the coating and retention of antimicrobial activity was validated even after multiple washes. More importantly, this coating deterred biofilm formation on the catheter surface, and displayed rapid inactivation of metabolically repressed stationary phase and persister cells. The ability of the coated surfaces to disrupt bacterial membranes and induce the generation of intracellular reactive oxygen species (ROS) was assessed through different techniques, such as electron microscopy imaging, flow cytometry as well as fluorescence spectroscopy and microscopy. The surface coatings were found to be biocompatible in an in vivo mice model. Our simple one-step coating approach for catheters holds significant potential owing to its ability to tackle multidrug resistant bacteria and fungi, and the challenge of biofilm formation. This work brings us one step closer to enhancing patient care and safety in hospitals.

Long-term antifouling surfaces for urinary catheters.

The presence of a variety of bacteria is an inevitable/indispensable part of human life. In particular, for patients, the existence and spreading of bacteria lead to prolonged treatment period with many more complications. The widespread use of urinary catheters is one of the main causes for the prevalence of infections. The necessity of long-term use of indwelling catheters is unavoidable in terms of the development of bacteriuria and blockage. As is known, since a permanent solution to this problem has not yet been found, research and development activities continue actively. Herein, polyethylene glycol (PEG)-like thin films were synthesized by a custom designed plasma enhanced chemical vapor deposition (PE-CVD) method and the long-term effect of antifouling properties of PEG-like coated catheters was investigated against Escherichia coli and Proteus mirabilis. The contact angle measurements have revealed the increase of wettability with the increase of plasma exposure time. The antifouling activity of surface-coated catheters was analyzed against the Gram-negative/positive bacteria over a long-term period (up to 30 days). The results revealed that PE-CVD coated PEG-like thin films are highly capable of eliminating bacterial attachment on surfaces with relatively reduced protein attachment without having any toxic effect. Previous statements were supported with SEM, XPS, FTIR spectroscopy, and contact angle analysis.

AI-aided geometric design of anti-infection catheters.

Bacteria can swim upstream in a narrow tube and pose a clinical threat of urinary tract infection to patients implanted with catheters. Coatings and structured surfaces have been proposed to repel bacteria, but no such approach thoroughly addresses the contamination problem in catheters. Here, on the basis of the physical mechanism of upstream swimming, we propose a novel geometric design, optimized by an artificial intelligence model. Using Escherichia coli, we demonstrate the anti-infection mechanism in microfluidic experiments and evaluate the effectiveness of the design in three-dimensionally printed prototype catheters under clinical flow rates. Our catheter design shows that one to two orders of magnitude improved suppression of bacterial contamination at the upstream end, potentially prolonging the in-dwelling time for catheter use and reducing the overall risk of catheter-associated urinary tract infection.

Comparison of Superhydrophilic, Liquid-Like, Liquid-Infused, and Superhydrophobic Surfaces in Preventing Catheter-Associated Urinary Tract Infection and Encrustation.

Over the past decade, superhydrophilic zwitterionic surfaces, slippery liquid-infused porous surfaces, covalently attached liquid-like surfaces, and superhydrophobic surfaces have emerged as the most promising strategies to prevent biofouling on biomedical devices. Despite working through different mechanisms, they have demonstrated superior efficacy in preventing the adhesion of biomolecules (e.g., proteins and bacteria) compared with conventional material surfaces. However, their potential in combating catheter-associated urinary tract infection (CAUTI) remains uncertain. In this research, we present the fabrication of these four coatings for urinary catheters and conduct a comparative assessment of their antifouling properties through a stepwise approach. Notably, the superhydrophilic zwitterionic coating demonstrated the highest antifouling activity, reducing 72.3% of fibrinogen deposition and over 75% of bacterial adhesion (Escherichia coli and Staphylococcus aureus) when compared with an uncoated polyvinyl chloride (PVC) surface. The zwitterionic coating also exhibited robust repellence against blood and improved surface lubricity, decreasing the dynamic coefficient of friction from 0.63 to 0.35 as compared with the PVC surface. Despite the fact that the superhydrophilic zwitterionic and hydrophobic liquid-like surfaces showed great promise in retarding crystalline biofilm formation in the presence of Proteus mirabilis, it is worth noting that their long-term antifouling efficacy may be compromised by the proliferation and migration of colonized bacteria as they are unable to kill them or inhibit their swarming. These findings underscore both the potential and limitations of these ultralow fouling materials as urinary catheter coatings for preventing CAUTI.

A comprehensive status update on modification of foley catheter to combat catheter-associated urinary tract infections and microbial biofilms.

Present-day healthcare employs several types of invasive devices, including urinary catheters, to improve medical wellness, the clinical outcome of disease, and the quality of patient life. Among urinary catheters, the Foley catheter is most commonly used in patients for bladder drainage and collection of urine. Although such devices are very useful for patients who cannot empty their bladder for various reasons, they also expose patients to catheter-associated urinary tract infections (CAUTIs). Catheter provides an ideal surface for bacterial colonization and biofilm formation, resulting in persistent bacterial infection and severe complications. Hence, rigorous efforts have been made to develop catheters that harbour antimicrobial and anti-fouling properties to resist colonization by bacterial pathogens. In this regard, catheter modification by surface functionalization, impregnation, blending, or coating with antibiotics, bioactive compounds, and nanoformulations have proved to be effective in controlling biofilm formation. This review attempts to illustrate the complications associated with indwelling Foley catheters, primarily focussing on challenges in fighting CAUTI, catheter colonization, and biofilm formation. In this review, we also collate scientific literature on catheter modification using antibiotics, plant bioactive components, bacteriophages, nanoparticles, and studies demonstrating their efficacy through in vitro and in vivo testing.

Development of an anti-infective urinary catheter composed of polyvinyl alcohol/sodium alginate/methylcellulose/polyethylene glycol by using a pressure-assisted 3D-printing technique.

Catheter-associated urinary tract infections (CAUTI) are a common complication associated with catheterization, leading to urosepsis, bacteriuria, and septicaemia. The present work focuses on 3D printing a urinary catheter with anti-infective properties using various concentrations of polyvinyl alcohol (PVA, e.g., 6-8 %), sodium alginate (NaAlg, e.g. 1-4 %), methylcellulose (MC, 5 %), polyethylene glycol (PEG, 5 %) impregnated with secnidazole, an antibiotic acting against Gram-negative bacteria. To produce suitable polymer ink for Pressure Assisted Microsyringe (PAM) 3D printing, the cross-linked between NaAlg and calcium chloride is necessary to prepare the catheter. The optimised catheter was found to have an outer diameter of 5 mm, an inner diameter of 3.5 mm, and a length of the catheter of 50 mm. The analysis by various methods confirms the successful incorporation of secnidazole in the 3D-printed catheter. A drug-loaded/coated catheter showed an initial drug release of 79 % following a sustained release to reach 100 % within 5 h. Weibull model fits well with the drug release data. The release models suggest the Quasi-Fickian diffusion mechanism from the system. Moreover, the secnidazole 3D printed catheter disrupted biofilms and suppressed all the Quorum sensing mediated virulence factors of two important keystone pathogens causing urinary tract infections.

Deposition of Daldinia starbaeckii (ELF) functionalized silver nanoparticles on urinary catheter tube using chitosan polymer to prevent microbial biofilms formation during UTI infection.

Catheter-associated urinary tract infections (CAUTI) are the most common healthcare problem in hospitals. In this study, we isolated the Daldinia starbaeckii (An endolichenic fungus from Roccella montagnie) and its biomass extract were used to simultaneously synthesize and deposit DSFAgNPs on the inner and outer surfaces of the catheter tube using chitosan biopolymer via In-situ deposition method. Perfectly designed D. starbaeckii extract functionalized DSFAgNPs were characterized by UV spectroscopy, FTIR, SEM, EDS, TEM, and XRD. The microbial efficacy of DSFAgNPs & DSFAgNPs coated catheter (CTH3) was evaluated against eight human pathogenic gram (+ / -) ive strains and Candida albicans. Results indicated DSFAgNPs showed significant biological activity against both gram (+ / -) ive bacteria with an average MIC90 of 4 µl/ml. The most promising activity was observed against Helicobacter pylori. When bacteria strains allow to grow with CTH3 we reported significant reduction in colony formation unit (CFU/ml) in broth culture assay with an average 70% inhibition. Further, antibiofilm activity of CTH3 against P. aeruginosa showed strong inhibition of biofilm formation (85%). The study explored an alternate approach for significantly prevent CAUTI among hospital patients. We isolated an endolichenic fungus from lichen Roccella montagnei. The molecular characterization of fungus identified as Daldinia starbaeckii (DSF). The DSF was cultured and its fungal biomass exudes were used to simultaneously construct DSF-AgNPs and its deposition on the catheter surface using biopolymer chitosan via In-situ deposition method. Further, antimicrobial and antibiofilm efficacy of DSF-AgNPs was checked against urinary catheter contaminating and human pathogenic bacterial strains. Based on our research, we determined that DSF-AgNPs coating on a urinary catheter through this method is a cost-effective, eco-friendly approach to prevent catheter contamination.

Development and Characterization of Lactobacillus rhamnosus-Containing Bioprints for Application to Catheter-Associated Urinary Tract Infections.

Catheter-associated urinary tract infections (CAUTI) are a significant healthcare burden affecting millions of patients annually. CAUTI are characterized by infection of the bladder and pathogen colonization of the catheter surface, making them especially difficult to treat. Various catheter modifications have been employed to reduce pathogen colonization, including infusion of antibiotics and antimicrobial compounds, altering the surface architecture of the catheter, or coating it with nonpathogenic bacteria. Lactobacilli probiotics offer promise for a "bacterial interference" approach because they not only compete for adhesion to the catheter surface but also produce and secrete antimicrobial compounds effective against uropathogens. Three-dimensional (3D) bioprinting has enabled fabrication of well-defined, cell-laden architectures with tailored release of active agents, thereby offering a novel means for sustained probiotic delivery. Silicone has shown to be a promising biomaterial for catheter applications due to mechanical strength, biocompatibility, and its ability to mitigate encrustation on the catheter. Additionally, silicone, as a bioink, provides an optimum matrix for bioprinting lactobacilli. This study formulates and characterizes novel 3D-bioprinted Lactobacillus rhamnosus (L. rhamnosus)-containing silicone scaffolds for future urinary tract catheterization applications. Weight-to-weight (w/w) ratio of silicone/L. rhamnosus was bioprinted and cured with relative catheter dimensions in diameter. Scaffolds were analyzed in vitro for mechanical integrity, recovery of L. rhamnosus, antimicrobial production, and antibacterial effect against uropathogenic Escherichia coli, the leading cause of CAUTI. The results show that L. rhamnosus-containing scaffolds are capable of sustained recovery of live bacteria over 14 days, with sustained production of lactic acid and hydrogen peroxide. Through the use of 3D bioprinting, this study presents a potential alternative strategy to incorporate probiotics into urinary catheters, with the ultimate goal of preventing and treating CAUTI.

Multifunctional hydrogel coatings with high antimicrobial loading efficiency and pH-responsive properties for urinary catheter applications.

Catheter-associated urinary tract infections are one of the most common hospital-acquired infections. Encrustation formation results from infection of urease-producing bacteria and further complicates the situation. A typical sign of the initial onset of encrustation formation is the alkalization of the urine (pH up to 9-10). However, effective antibacterial strategies with high antimicrobial loading efficiency and pH-responsiveness of antimicrobial release are still lacking. In this study, we developed a poly(sulfobetaine methacrylate)-tannic acid (polySBMA-TA) hydrogel coating, which served as a universal, efficient, and responsive carrier for antimicrobials on urinary catheters. Common antimicrobials, including poly(vinylpyrrolidone)-iodine, copper ions, and nitrofurazone were loaded into the polySBMA-TA coating in high efficiency (several fold higher than that of the polySBMA coating), via the formation of multiple non-covalent interactions between the antimicrobials and hydrogel coating. The hydrogel coatings maintained good antibacterial properties under neutral conditions. More importantly, the pH-responsive release of antibacterial agents under alkaline conditions further enhanced the antibacterial activity of the coatings, which was advantageous for killing the urease-producing bacteria and preventing encrustation. In vitro and in vivo tests confirmed that the hydrogel coating has good biocompatibility, and could effectively inhibit bacterial colonization and encrustation formation. This study offers new opportunities for the utilization of a simple and universal antimicrobial-loaded hydrogel coating with smart pH-responsive properties to combat bacterial colonization and encrustation formation in urinary catheters.

Discovery of a polymer resistant to bacterial biofilm, swarming, and encrustation.

Innovative approaches to prevent catheter-associated urinary tract infections (CAUTIs) are urgently required. Here, we describe the discovery of an acrylate copolymer capable of resisting single- and multispecies bacterial biofilm formation, swarming, encrustation, and host protein deposition, which are major challenges associated with preventing CAUTIs. After screening ~400 acrylate polymers, poly(tert-butyl cyclohexyl acrylate) was selected for its biofilm- and encrustation-resistant properties. When combined with the swarming inhibitory poly(2-hydroxy-3-phenoxypropyl acrylate), the copolymer retained the bioinstructive properties of the respective homopolymers when challenged with Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. Urinary tract catheterization causes the release of host proteins that are exploited by pathogens to colonize catheters. After preconditioning the copolymer with urine collected from patients before and after catheterization, reduced host fibrinogen deposition was observed, and resistance to diverse uropathogens was maintained. These data highlight the potential of the copolymer as a urinary catheter coating for preventing CAUTIs.

Fibrinogen Deposition on Silicone Oil-Infused Silver-Releasing Urinary Catheters Compromises Antibiofilm and Anti-Encrustation Properties.

Slippery silicone-oil-infused (SOI) surfaces have recently emerged as a promising alternative to conventional anti-infection coatings for urinary catheters to combat biofilm and encrustation formation. Benefiting from the ultralow low hysteresis and slippery behavior, the liquid-like SOI coatings have been found to effectively reduce bacterial adhesion under both static and flow conditions. However, in real clinical settings, the use of catheters may also trigger local inflammation, leading to release of host-secreted proteins, such as fibrinogen (Fgn) that deposits on the catheter surfaces, creating a niche that can be exploited by uropathogens to cause infections. In this work, we report on the fabrication of a silicone oil-infused silver-releasing catheter which exhibited superior durability and robust antibacterial activity in aqueous conditions, reducing biofilm formation of two key uropathogens Escherichia coli and Proteus mirabilis by ∼99%, when compared with commercial all-silicone catheters after 7 days while remaining noncytotoxic toward L929 mouse fibroblasts. After exposure to Fgn, the oil-infused surfaces induced conformational changes in the protein which accelerated adsorption onto the surfaces. The deposited Fgn blocked the interaction of silver with the bacteria and served as a scaffold, which promoted bacterial colonization, resulting in a compromised antibiofilm activity. Fgn binding also facilitated the migration of Proteus mirabilis over the catheter surfaces and accelerated the deposition and spread of crystalline biofilm. Our findings suggest that the use of silicone oil-infused silver-releasing urinary catheters may not be a feasible strategy to combat infections and associated complications arising from severe inflammation.