Urinary Catheter Blockage Research Articles

Rational design and in vitro testing of new urease inhibitors to prevent urinary catheter blockage.

Catheter associated urinary tract infections (CAUTI) caused by urease-positive organisms can lead to catheter blockage: urease metabolizes urea in urine to ammonia causing an increase in pH and hence precipitation of struvite and apatite salts into the catheter lumen and bladder leading to blockage. Acetohydroxamic acid (AHA) is the only urease inhibitor currently approved for patient use, however, it is rarely used owing to its side effects. Here, we report the identification and development of new urease inhibitors discovered using a rational in silico drug design approach. A series of compounds were designed, the compounds were screened and filtered to identify three compounds which were tested in in vitro urease activity assays. N,N'-Bis(3-pyridinylmethyl)thiourea (Bis-TU) outperformed AHA in activity assays and was tested in an in vitro bladder model, where it significantly extended the lifetime of the catheter compared to AHA. Bis-TU was delivered via a diffusible balloon catheter directly to the site of activity, thus demonstrating localized drug delivery. This cost-effective drug design approach allowed the identification of a potent urease inhibitor, which could be improved through iterative repeats of the method, and the process of design could be utilized to target other diseases.

Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia (2021 Edition)

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline “2018 Standard Edition”. However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons’ surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons’ skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

Optimisation of a lozenge-based sensor for detecting impending blockage of urinary catheters

Catheter-associated urinary tract infections resulting from urease-positive microorganisms are more likely to cause a urinary catheter blockage owing to the urease activity of the microbes. Catheter blockage can be dangerous and increases the risk of severe infections, such as sepsis. Ureases, a virulence factor in Proteus mirabilis, cause an increase in urine pH - leading to blockage. An optimised biosensor “lozenge” is presented here, which is able to detect impending catheter blockage. This lozenge has been optimised to allow easy manufacture and commercialisation. It functions as a sensor in a physiologically representative model of a catheterised urinary tract, providing 6.7 h warning prior to catheter blockage. The lozenge is stable in healthy human urine and can be sterilized for clinical use by ethylene oxide. Clinically, the lozenge will provide a visible indication of impending catheter blockage, enabling quicker clinical intervention and thus reducing the morbidity and mortality associated with blockage.

A small-molecular inhibitor against Proteus mirabilis urease to treat catheter-associated urinary tract infections

Infection and blockage of indwelling urinary catheters is significant owing to its high incidence rate and severe medical consequences. Bacterial enzymes are employed as targets for small molecular intervention in human bacterial infections. Urease is a metalloenzyme known to play a crucial role in the pathogenesis and virulence of catheter-associated Proteus mirabilis infection. Targeting urease as a therapeutic candidate facilitates the disarming of bacterial virulence without affecting bacterial fitness, thereby limiting the selective pressure placed on the invading population and lowering the rate at which it will acquire resistance. We describe the design, synthesis, and in vitro evaluation of the small molecular enzyme inhibitor 2-mercaptoacetamide (2-MA), which can prevent encrustation and blockage of urinary catheters in a physiologically representative in vitro model of the catheterized urinary tract. 2-MA is a structural analogue of urea, showing promising competitive activity against urease. In silico docking experiments demonstrated 2-MA’s competitive inhibition, whilst further quantum level modelling suggests two possible binding mechanisms.

Issues Related to the use of a Mobile Application of the Protocol for Preventing and Managing Urinary Catheter Blockage Among Long-term Indwelling Urinary Catheter Users for Visiting Nurses: An Interview Study of Visiting Nurses in Japan

Background: We developed a mobile application of the protocol for preventing and managing catheter blockage among long-term indwelling catheter users for visiting nurses. We conducted meetings at four visiting nurse stations in Japan from May to June 2017 to explain the application to visiting nurses. Objective: The purpose of the present study was to clarify issues related to the full-scale use of this protocol application, using data from focus group interviews with visiting nurses. Methods: We conducted focus group interviews with the meeting participants. The focus group interviews were conducted at four different venues. Three focus groups had eight participants, and the fourth had two participants, for a total of 26 study participants. Specifically, the group interviews covered (1) the application’s structure and content; (2) operability; (3) portability; (4) possibilities for use, effects, and expectations; and (5) concerns about use. Results: The results of the group interviews were classified into five categories: possibilities for the use of the mobile application, possibilities for further use of the application by nurses, suggestions for the use of the application by caregivers and nursing care workers, the burden associated with the use of the mobile application, and opinions and desires for improvements in the mobile application. Conclusion: The results suggested that visiting nurses would use the mobile application. However, for full-scale use, it would be necessary to add the ability to use accumulated data, increase the number of learning screens, and take safety management measures for the transmission of medical information.

Theranostic Infection‐Responsive Coating to In Situ Detect and Prevent Urinary Catheter Blockage

AbstractBiofilm formation induced by urease‐producing species can cause the increase of urine pH, and eventually lead to the blockage of catheters. In this study, a novel theranostic multilayer coating which combines both early visual warning of catheter blockage and antibacterial efficacy is described. The proposed coating comprised multilayered polymeric architecture using electrostatic self‐assembly (ESA) technique. In such a system, an inner layer of hydrogel PAA (poly (acrylic acid)) and middle layer of CS (chitosan) are employed to encapsulate an antibiotic delivery system that has sensitive colorimetric transition response upon pH elevation. The two layers are sealed and capped by a pH‐response layer of EUDRAGITS 100. The proposed coating sensor hydrogel exhibits chromatic color transitions (blue–purple–red) upon bacterial infection and provides an indication for both initial bacterial infection and subsequent blockage. Meanwhile, encapsulation of antimicrobials increases the amount of antibiotic resident in the vicinity of bacteria in residual urine solution and thus inhibiting bacterial growth.

Development of an Infection-Responsive Fluorescent Sensor for the Early Detection of Urinary Catheter Blockage.

Formation of crystalline biofilms following infection by Proteus mirabilis can lead to encrustation and blockage of long-term indwelling catheters, with serious clinical consequences. We describe a simple sensor, placed within the catheter drainage bag, to alert of impending blockage via a urinary color change. The pH-responsive sensor is a dual-layered polymeric "lozenge", able to release the self-quenching dye 5(6)-carboxyfluorescein in response to the alkaline urine generated by the expression of bacterial urease. Sensor performance was evaluated within a laboratory model of the catheterized urinary tract, infected with both urease positive and negative bacterial strains under conditions of established infection, achieving an average "early warning" of catheter blockage of 14.5 h. Signaling only occurred following infection with urease positive bacteria. Translation of these sensors into a clinical environment would allow appropriate intervention before the occurrence of catheter blockage, a problem for which there is currently no effective control method.

Prevention of encrustation and blockage of urinary catheters by Proteus mirabilis via pH-triggered release of bacteriophage.

The crystalline biofilms of Proteus mirabilis can seriously complicate the care of patients undergoing long-term indwelling urinary catheterisation. Expression of bacterial urease causes a significant increase in urinary pH, leading to the supersaturation and precipitation of struvite and apatite crystals. These crystals become lodged within the biofilm, resulting in the blockage of urine flow through the catheter. Here, we describe an infection-responsive surface coating for urinary catheters, which releases a therapeutic dose of bacteriophage in response to elevated urinary pH, in order to delay catheter blockage. The coating employs a dual-layered system comprising of a lower hydrogel 'reservoir' layer impregnated with bacteriophage, capped by a 'trigger' layer of the pH-responsive polymer poly(methyl methacrylate-co-methacrylic acid) (EUDRAGIT®S 100). Evaluation of prototype coatings using a clinically reflective in vitro bladder model system showed that catheter blockage time was doubled (13 h to 26 h (P < 0.05)) under conditions of established infection (108 CFU ml-1) in response to a 'burst-release' of bacteriophage (108 PFU ml-1). Coatings were stable both in the absence of infection, and in the presence of urease-negative bacteria. Quantitative and visual analysis of crystalline biofilm reduction show that bacteriophage constitute a promising strategy for the prevention of catheter blockage, a clinical problem for which there is currently no effective control method.

Catheter blockage factors in patients cared for in their own home requiring long‐term urinary catheterisation

ABSTRACTEarly urinary catheter removal from patients cared for in their own home is often difficult because of incontinence and care burdens, resulting in long duration of catheterization. Urinary tract infection and catheter blockage are major complications associated with long‐term catheterization. Preventing these complications is important for patients who require long‐term catheterization in their own home.This study aimed to examine the occurrence characteristics of urinary catheter blockage and to identify the causative factors of catheter blockage in patients cared for in their own home requiring long‐term urinary catheterization.The study targeted 154 patients cared for in their own home requiring long‐term urinary catheterization. Patient data were collected by questionnaire by the nurse manager.Catheter blockage occurred in 33·8% of patients requiring long‐term catheterization within the first 6 months, and the mean frequency in these patients was 3·0, indicating that catheter blockage occurs repeatedly. The following management factors significantly correlated with the frequency of catheter blockage: ‘check urine volume’, ‘check for flexion and distortion of the catheter’ and ‘check urinary tract infection symptoms’ for catheter management by caregivers. Symptoms correlated with catheter blockage included ‘cloudiness of the urine’, ‘decreased urine volume’, ‘abdominal pain’ and ‘duration of catheterization’. In the future, we would like to prepare the protocol to help visiting nurses improve their abilities to manage catheter blockage in patients requiring long‐term catheterization, by incorporating the findings from this study.

Bacteriophage Can Prevent Encrustation and Blockage of Urinary Catheters by Proteus mirabilis.

Proteus mirabilis forms dense crystalline biofilms on catheter surfaces that occlude urine flow, leading to serious clinical complications in long-term catheterized patients, but there are presently no truly effective approaches to control catheter blockage by this organism. This study evaluated the potential for bacteriophage therapy to control P. mirabilis infection and prevent catheter blockage. Representative in vitro models of the catheterized urinary tract, simulating a complete closed drainage system as used in clinical practice, were employed to evaluate the performance of phage therapy in preventing blockage. Models mimicking either an established infection or early colonization of the catheterized urinary tract were treated with a single dose of a 3-phage cocktail, and the impact on time taken for catheters to block, as well as levels of crystalline biofilm formation, was measured. In models of established infection, phage treatment significantly increased time taken for catheters to block (∼ 3-fold) compared to untreated controls. However, in models simulating early-stage infection, phage treatment eradicated P. mirabilis and prevented blockage entirely. Analysis of catheters from models of established infection 10 h after phage application demonstrated that phage significantly reduced crystalline biofilm formation but did not significantly reduce the level of planktonic cells in the residual bladder urine. Taken together, these results show that bacteriophage constitute a promising strategy for the prevention of catheter blockage but that methods to deliver phage in sufficient numbers and within a key therapeutic window (early infection) will also be important to the successful application of phage to this problem.

BiotecVisions 2012, March

BiotecVisions 2012, March

Development of an “early warning” sensor for encrustation of urinary catheters following Proteus infection

Biofilm formation in long-term urinary catheterized patients can lead to encrustation and blockage of urinary catheters with serious clinical complication. Catheter encrustation stems from infection with urease-producing bacteria, particularly Proteus mirabilis. Urease generates ammonia from urea, and the elevated pH of the urine results in crystallization of calcium and magnesium phosphates, which block the flow of urine. The aim of this research is to develop an "early warning" silicone sensor for catheter encrustation following bacterial infection of an in vitro bladder model system. The in vitro bladder model was infected with a range of urease positive and negative bacterial strains. Developed sensors enabled catheter blockage to be predicted ~17-24 h in advance of its occurrence. Signaling only occurred following infection with urease positive bacteria and only when catheter blockage followed. In summary, sensors were developed that could predict urinary catheter blockage in in vitro infection models. Translation of these sensors to a clinical environment will allow the timely and appropriate management of catheter blockage in long-term catheterized patients.

In Vitro Multicompartmental Bladder Model for Assessing Blockage of Urinary Catheters: Effect of Hydrogel Coating on Dynamics of Proteus mirabilis Growth

To investigate the effect of a hydrogel coating on the dynamics of bacterial growth in laboratory models of the catheterized bladder. Infection of the urinary tract by Proteus mirabilis can result in catheter blockage by crystalline biofilm, a common complication in patients undergoing long-term bladder catheterization. Two series of catheters were tested in the infected bladder models: test series 1, silicone catheters impregnated with triclosan (0.5%, 1%, 4%), or silicone catheters with 0% triclosan impregnated with pure solvents and hydrogel coated (based on polyvinylpyrrolidone); and test series 2, silicone catheters, hydrogel-coated with hydrogel plus iodine (polyvinylpyrrolidone plus iodine) or hydrogel plus polyhexamethylene biguanide. Test series 1 was used to detect the influence of triclosan, solvents, impregnation time, and the presence of hydrogel coating on the interval to catheter blockage by P. mirabilis biofilm. The experiments with test series 2 focused on the dynamic interaction of the hydrogel coating and biofilm formation. The division of the catheterized bladder model into 3 sampling zones brought more information about the spatial segregation of the bacterial population. The bacteriostatic efficiency of the water-soluble polyhexamethylene biguanide and polyvinylpyrrolidone iodine complex was limited to the first hours after catheterization. Only catheters containing triclosan resisted encrustation for significantly longer (up to >7 days). In contrast, the uncoated and hydrogel-coated catheters were occluded by day 2. The hydrogel layer can increase aggregation of the planktonic cells and newly nucleated crystals, leading to even faster catheter blockage than in the case of uncoated silicone. However, the addition of active agents were able to suppress this negative effect.

Use of quorum sensing antagonists to deter the formation of crystalline Proteus mirabilis biofilms

Proteus mirabilis biofilms are a major cause of urinary catheter blockage. Antibiotic-impregnated catheters used to prevent catheter blockage have achieved limited success. Research has examined the efficacy of quorum sensing inhibitors against Pseudomonas aeruginosa biofilms, but there are few reports of the effects of these compounds against crystalline P. mirabilis biofilms. This study examined the effect of two quorum sensing antagonists, p-nitrophenyl glycerol (PNPG) and tannic acid, against crystalline P. mirabilis biofilms. Tannic acid and PNPG were observed to inhibit the quorum sensing system and the formation of P. mirabilis biofilms grown in artificial urine. The success of these compounds provides a possible means of preventing urinary catheter encrustation.

Managing recurrent urinary catheter blockage

Journal of Wound, Ostomy and Continence Nursing: September 2004 - Volume 31 - Issue 5 - p 313

Managing Recurrent Urinary Catheter Blockage

Managing Recurrent Urinary Catheter Blockage

Managing recurrent urinary catheter blockage: Problems, promises, and practicalities

Long-term urinary catheterization is rarely completely free of complications, and encrustation by mineral salts leading to catheter blockage is common in around 40% to 50% of long-term catheterized patients. Recurrent blockage is a problem, which is both distressing to patients and caregivers and costly to health services in terms of time and resources. This article addresses the causes of recurrent urinary catheter blockage, proactive approaches to care, and the evidence for use of catheter maintenance solutions to reduce buildup of mineral deposits. (J WOCN 2003;30:146-51.)

Chronic urinary catheter blockage

Catheter blockage is a common complication of long-term urinary catheterisation which causes distress to the patient and presents management problems for both nursing and medical practitioners. Jennifer Kohler-Ockmore's study aimed to investigate some of the factors which may cause catheter blockage and how they may be overcome. Fifty-four patients, resident in the community, were monitored over a period of six months. The findings revealed that patients were divided into two groups, those with and those without catheter blockage. The only factors identified which differentiated these patients were urinary pH and the incidence of proteus organisms in the urine. The presence or history of bladder stones was also noted among patients who presented with chronic episodes of blockage.

Blockage of urinary catheters: Role of microorganisms and constituents of the urine on formation of encrustations

Long-term indwelling urinary catheters may become blocked in some patients by formation of encrustations made up of aggregated struvite crystals while other patients rarely develop blocked catheters. We have designated these groups as “blockers”, “intermediates” or “non-blockers”. To further understand this phenomenon we followed 32 catheterized elderly women in a nursing home. Catheters were changed six times at 2 week intervals. Patients tended to remain as “blockers”, “intermediates” or “non-blockers” consistently over time. There were no significant differences in use of antibiotics, clinical manifestations of urinary infection or fever among the groups. “Blockers” were significantly more often colonized with Proteus mirabilis and Providencia stuartii than “non-blockers”, and significantly less often with Klebsiella pneumoniae. However, there was no evidence of interference among the organisms. “Blockers” excreted a significantly more alkaline urine, and lesser amounts of magnesium, urea and phosphate in their urine. Two “blockers” in whom Proteus sp. were eliminated by coincidental antimicrobial therapy converted to “non-blockers”. These findings support the concept that “blockers” are patients who have prolonged colonization with urease producing Proteus mirabilis and Providencia stuartii.