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.

2,5-Dimethyl-4-hydroxy-3(2H)-furanone as an Anti-biofilm Agent Against Non-Candida albicans Candida Species.

BACKGROUND: The predominance of non-Candida albicans Candida (NCAC) species causing healthcare-associated infections has increased over the last decade pertaining to their ability to form biofilms on medical devices. These biofilm-associated infections are challenging to treat as they are resistant to antifungal agents and evade host-immune response resulting in a high risk of device failure or biomaterial removal. Thus, to minimize the risk of biofilm-associated infections, preventing biofilm formation is the best approach which is mediated by the quorum quenching process. METHODS: The present study investigated the modulatory effect of 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) on NCAC biofilm formation and also assessed the effect of the DMHF-coated catheters on biofilm formation of NCAC. The NCAC isolates studied were Candida tropicalis, Candida glabrata and Candida krusei isolated from catheter tip, urine and blood, respectively. RESULTS: DMHF at a concentration of 30 µg/mL showed an inhibitory effect against NCAC biofilms at various stages and was statistically significant (p ≤ 0.05) against the various concentrations (50-5 µg/mL) tested and also among the three phases of experiment. The furanone content on coated catheters ranged from 170 to 750 µg and release of furanone from the coated catheter was about 15 µg for 30 days. The effect of DMHF-coated catheters on NCAC biofilm formation was observed by the scanning electron microscopy which revealed the absence of NCAC adherence on DMHF-coated catheters. DISCUSSION: This study provides a design to develop furanone-coated biomaterials which could be implemented in healthcare settings to reduce medical device-associated infections. The excellent biological performance, combined with their antimicrobial properties, suggests that 2,5-dimethyl-4-hydroxy-3(2H)-furanone could be an effective anti-infective coating for implantable devices.

Prevention of urinary tract infection using a silver alloy hydrogel-coated catheter in critically ill patients: A single-center prospective randomized controlled study.

Background: A new type of silver alloy hydrogel-coated (SAH) catheter has been shown to prevent bacterial adhesion and colonization by generating a microcurrent, and to block the retrograde infection pathway. However, these have only been confirmed in ordinary patients. This study aims to evaluate the effectiveness of a SAH catheter for preventing urinary tract infections in critically ill patients. Methods: This was a prospective single-center, single-blind, randomized, controlled study. A total of 132 patients requiring indwelling catheterization in the intensive care unit (ICU) of the First Affiliated Hospital of the University of Science and Technology of China between October 2022 and February 2023 and who met the study inclusion/exclusion criteria were randomly divided into two groups. Patients in the SAH catheter group received a SAH catheter, while patients in the conventional catheter group received a conventional siliconized latex Foley catheter. The main outcome measure was the incidence of catheter-associated urinary tract infections (CAUTIs). Secondary outcome indicators included urine positivity for white blood cells and positive urine cultures on 3 days, 7 days, 10 days, and 14 days after catheterization, number of viable bacteria in the catheter biofilm on day 14, pathogenic characteristics of positive urine cultures, length of ICU stay, overall hospital stay, ICU mortality, and 28-day mortality. All the data were compared between the two groups. Results: A total of 68 patients in the conventional catheter group and 64 patients in the SAH catheter group were included in the study. On day 7 after catheter placement, the positivity rate for urinary white blood cells was significantly higher in the conventional catheter group than in the SAH catheter group (33.8% vs. 15.6%, P=0.016). On day 10, the rates of positive urine cultures (27.9% vs. 10.9%, P=0.014) and CAUTIs (22.1% vs. 7.8%, P=0.023) were significantly higher in the conventional catheter group than in the SAH catheter group. On day 14, the numbers of viable bacteria isolated from the catheter tip ([3.21±1.91]×106 colony-forming units [cfu]/mL vs. [7.44±2.22]×104 cfu/mL, P <0.001), balloon segment ([7.30±1.99]×107 cfu/mL vs. [3.48±2.38]×105 cfu/mL, P <0.001), and tail section ([6.41±2.07]×105 cfu/mL vs. [8.50±1.46]×103 cfu/mL, P <0.001) were significantly higher in the conventional catheter group than in the SAH catheter group. The most common bacteria in the urine of patients in both groups were Escherichia coli (n=13) and Pseudomonas aeruginosa (n=6), with only one case of Candida in each group. There were no significant differences between the two groups in terms of ICU hospitalization time, total hospitalization time, ICU mortality, and 28-day mortality. Conclusion: SAH catheters can effectively inhibit the formation of catheter-related bacterial biofilms in critically ill patients and reduce the incidence of CAUTIs, compared with conventional siliconized latex Foley catheters; however, regular replacement of the catheter is still necessary.

Urinary Catheters Coated with a Novel Biofilm Preventative Agent Inhibit Biofilm Development by Diverse Bacterial Uropathogens.

Despite the implementation of stringent guidelines for the prevention of catheter-associated (CA) urinary tract infection (UTI), CAUTI remains one of the most common health care-related infections. We previously showed that an antimicrobial/antibiofilm agent inhibited biofilm development by Gram-positive and Gram-negative bacterial pathogens isolated from human infections. In this study, we examined the ability of a novel biofilm preventative agent (BPA) coating on silicone urinary catheters to inhibit biofilm formation on the catheters by six different bacterial pathogens isolated from UTIs: three Escherichia coli strains, representative of the most common bacterium isolated from UTI; one Enterobacter cloacae, a multidrug-resistant isolate; one Pseudomonas aeruginosa, common among patients with long-term catheterization; and one isolate of methicillin-resistant Staphylococcus aureus, as both a Gram-positive and a resistant organism. First, we tested the ability of these strains to form biofilms on urinary catheters made of red rubber, polyvinyl chloride (PVC), and silicone using the microtiter plate biofilm assay. When grown in artificial urine medium, which closely mimics human urine, all tested isolates formed considerable biofilms on all three catheter materials. As the biofilm biomass formed on silicone catheters was 0.5 to 1.6 logs less than that formed on rubber or PVC, respectively, we then coated the silicone catheters with BPA (benzalkonium chloride, polyacrylic acid, and glutaraldehyde), and tested the ability of the coated catheters to further inhibit biofilm development by these uropathogens. Compared with the uncoated silicone catheters, BPA-coated catheters completely prevented biofilm development by all the uropathogens, except P. aeruginosa, which showed no reduction in biofilm biomass. To explore the reason for P. aeruginosa resistance to the BPA coating, we utilized two specific lipopolysaccharide (LPS) mutants. In contrast to their parent strain, the two mutants failed to form biofilms on the BPA-coated catheters, which suggests that the composition of P. aeruginosa LPS plays a role in the resistance of wild-type P. aeruginosa to the BPA coating. Together, our results suggest that, except for P. aeruginosa, BPA-coated silicone catheters may prevent biofilm formation by both Gram-negative and Gram-positive uropathogens.

Mixed-charge pseudo-zwitterionic copolymer brush as broad spectrum antibiofilm coating.

Zwitterionic polymers are classical antifouling polymers but they require specialized monomers that have cationic and anionic charges integrated into a single monomer. Herein, we show that pseudo-zwitterionic copolymers synthesized from a mixture of 2 monomers each having a single opposite polarity has excellent antibiofilm efficacy. We have discovered a new mixed-charge copolymer brush (#1-A) synthesized from 2 oppositely charged monomers, the anionic SPM (3-Sulfopropyl methacrylate) and the cationic AMPTMA ((3-Acrylamidopropyl) trimethylammonium chloride), that achieves broad spectrum in vitro antibiofilm effect of greater than 99% reductions against all six Gram-positive and Gram-negative bacteria tested. In the murine subcutaneous wound catheter infection models, the #1-A has good long-term anti-biofilm efficacy against MRSA and Pseudomonas aeruginosa of 3.41 and 3.19 orders respectively, outperforming previous mixed-charge copolymer coatings. We discovered a new method to choose the cationic/anionic pair combination to form the best antibiofilm copolymer brush coating by exploiting the solution polymerization kinetics disparity between the cationic and anionic monomers. We also showed that #1-A is softer and has higher hydration than the classical zwitterionic polymer. This study shows the possibility of achieving potent antibiofilm efficacy by combining readily available opposite singly charged monomers.

Comparison of optical microscopy and optical coherence tomography as quality assurance methods for evaluating lubricious hydrophilic coatings surrounding catheter shafts.

Cardiac catheters are a vital tool in medicine due to their widespread use in many minimally invasive procedures. To aid in advancing the catheter within the patient's vasculature, many catheters are coated with a lubricious hydrophilic coating (HPC). Although HPCs benefit patients, their delamination during use is a serious safety concern. Adverse health effects associated with HPC delamination include pulmonary and myocardial embolism, embolic stroke, infarction, and death. In order to improve patient outcomes, more consistent manufacturing methods and improved quality assurance techniques are needed to evaluate HPC medical devices. The present work investigates the efficacy of two novel methods to image and evaluate HPCs post-manufacturing, relative to industry-standard scanning electron microscopy (SEM)-based methods. We have shown that novel evaluation approaches based on optical microscopy (OM) and optical coherence tomography (OCT) are capable of imaging HPC layers and quantifying HPC thickness, saving hours of time relative to SEM sample preparation and imaging. Additionally, the nondestructive nature of OCT avoids damage and alteration to the HPC prior to imaging, leading to more reliable HPC thickness measurements. Overall, the work demonstrated the feasibility and advantages of using OM and OCT to image and measure HPC thickness relative to industry-standard SEM methods.

Auranofin Releasing Antibacterial and Antibiofilm Polyurethane Intravascular Catheter Coatings.

Intravascular catheter related bloodstream infections (CRBSIs) are a leading cause of hospital-acquired infections worldwide, resulting not only in the burden of cost and morbidity for patients but also in the over-consumption of medical resources for hospitals and health care organizations. In this study, a novel auranofin releasing antibacterial and antibiofilm polyurethane (PU) catheter coating was developed and investigated for future use in preventing CRBSIs. Auranofin is an antirheumatic drug with recently identified antimicrobial properties. The drug carrier, PU, acts as a barrier surrounding the antibacterial agent, auranofin, to extend the drug release profile and improve its long-term antibacterial and antibiofilm efficacy and potentially the length of catheter implantation within a patient. The PU+auranofin coatings developed here were found to be highly stretchable (exhibiting ~500% percent elongation), which is important for the compliance of the material on a flexible catheter. PU+auranofin coated catheters were able to inhibit the growth of methicillin-resistant Staphylococcus aureus (MRSA) for 8 to 26 days depending on the specific drug concentration utilized during the dip coating process. The PU+auranofin coated catheters were also able to completely inhibit MRSA biofilm formation in vitro, an effect that was not observed with auranofin or PU alone. Lastly, these coatings were found to be hemocompatible with human erythrocytes and maintain liver cell viability.

Surface characteristics and antimicrobial properties of modified catheter surfaces by polypyrogallol and metal ions.

Catheter associated infections (CAIs) are the major cause of nosocomial infections leading to increased morbidity, mortality rates and economical loss. Though the antibiotic coated surface modified catheters are reported to be effective in preventing CAIs, presence of sub-lethal concentrations of antibiotics in long term instilled catheters poses a risk of development and spread of drug resistant microbial strains. Herein, we have developed an antibiotic-free alternative strategy to coat catheter surfaces using pyrogallol (PG) and metal ions (Ag+/Mg2+). Surface characteristics, antimicrobial and anti-biofilm properties with hemocompatibility of the coated catheters were studied. Structural characteristics of coated catheters were similar to the uncoated catheters with improved wettability. All the coated catheters with PG and different PG/metal ion combinations exhibited broad spectrum antibacterial activity. Catheters coated with PG/metal ions combination showed effective antibiofilm properties against MRSA strains. None of the coated catheters showed any significant hemolysis for rabbit erythrocytes. In addition, polypyrogallol (pPG) coating attenuated the hemolytic properties of silver without altering the antimicrobial properties. The inherent antimicrobial properties of the coating agent along with antimicrobial metal ions broaden the application landscape which includes coating of other medical devices, clean room construction and development of antimicrobial surfaces. The chemical formulation can also be used to design antiseptic solutions to prevent healthcare associated infections.

Brush-like polycarbonates containing dopamine, cations, and PEG providing a broad-spectrum, antibacterial, and antifouling surface via one-step coating.

An antibacterial and antifouling surface is obtained by simple one-step immersion of a catheter surface with brush-like polycarbonates containing pendent adhesive dopamine, antifouling polyethylene glycol (PEG), and antibacterial cations. This coating demonstrates excellent antibacterial and antifouling activities against both Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria, proteins, and platelets, good stability under simulated blood-flow conditions, and no toxicity.