Development and first-in-human testing of FLUME urinary catheter with protected tip and relocated drainage holes.

Purpose: Evaluation of a catheter design which protects its tip with the retaining balloon when inflated, and has eyeholes at the base of the balloon to improve drainage. Materials and methods: Preclinical tests included assessment of retaining balloon performance, and microbiological blockage. Clinical testing evaluated short-term use and safety in hospital (stage 1) or the patient's usual residence (stage 2). Results: The retaining balloon supported static loads of 0.7kg, with reduced trauma when modelling forced evulsion. In vitro time to blockage with P. Mirabilis was significantly slower for FLUME compared with latex Foley catheters, but not the silicone Foley. Stage 1 testing (10 patients) confirmed balloon inflation, drainage, retention and removal, with no serious adverse events caused by catheterisation; one balloon failed to inflate, one patient could not be catheterised. Of five patients at stage 2, one had the catheter for 28 days without complication, one experienced spontaneous balloon deflation (14th day) and three needed early removal (blood clot, bypassing, difficulty connecting the drainage bag). Bacterial profiles of two FLUME catheters retained at least 2 weeks matched the Foley catheters. Acquired catheter colouration (two FLUME, one Foley) was not associated with biochemical change in the material. Conclusion: FLUME catheter performed well in preclinical blockage and balloon tests. Tests in 15 patients confirmed basic function and additional training was not needed for staff familiar with Foley catheterisation. Clinical issues commonly seen with catheters included failed catheterisation, clot blockage and bypassing. In addition, an unintended balloon deflation and a failure of bag connection occurred. Plain language summary: This article describes a new catheter design which aims to improve patient comfort and safety, and maximise bladder drainage, by protecting the bladder from the exposed catheter tip and by locating the drainage holes better. Various tests were done to check the catheter retaining balloon was safe and how well the catheter did when exposed to bacteria that could block it. The catheter was also used in people for the first time, to check it could be put in safely and functioned as intended. The results showed the FLUME catheter did well in the balloon and blockage tests. Tests in 15 patients confirmed basic function and showed placement was easy for staff familiar with conventional catheters. There were some clinical issues typical of urinary catheters and some possible improvements were identified.

Development of a more clinically relevant bladder and urethral model for catheter testing.

This paper sets out the rationale and design for a more physiologically representative bladder/urethral model than the current rigid funnel industry standard. We suggest this flexible model can better serve as a basis for evaluating new catheters. We investigated the parameters and the validation tests required to construct and test with more flexible materials. The protocol includes static and impact force tests, while measuring internal retention balloon pressure. We have designed a flexible elastomer bladder floor and urethral model and tested it with a Foley balloon catheter. The tests showed that the model could hold the catheter with static loads up to 0.7 kg, but that the catheter was pulled out by impact forces from dropped weights. The Foley catheter design and its associated standards make no provision to mitigate urethral injury in the surprisingly common event of removal with a filled balloon. Our design is a more realistic model for testing retention and extraction characteristics of a urethral catheter. Validation tests have confirmed the feasibility of measuring urethral dilation and balloon pressure, both under traction and during progressive deflation. We suggest this model improves upon the current standard tests and will enable the design of safer catheters.

An effective evidence-based cleaning method for the safe reuse of intermittent urinary catheters: In vitro testing.

AIMS: To determine a safe bactericidal cleaning method that does not damage urethral catheters used for intermittent catheterization. In some countries, single-use catheters are the norm; in others, the reuse of catheters is common depending on health insurance, personal preference, or individual concerns about the environment. However, no recent study of cleaning methods has been published to provide evidence for the safe reuse of catheters. METHODS: Using advanced microbiological methods, a laboratory study of eight cleaning methods was conducted. Sections of uncoated polyvinylchloride (PVC) catheters were exposed to bacterial uropathogens in physiologically correct artificial urine media then tested with a range of heat, chemical, and mechanical cleaning methods. Analysis of culturable and viable but nonculturable (VBNC) bacteria was done and direct microscopy was used. Descriptive statistics were used to compare values. RESULTS: Heat treatments, although effective, resulted in catheter surface breakdown and damage. Ultrasonic cleaning and vinegar showed evidence of VBNC populations indicating the methods were bacteriostatic. Detergent and water wash followed by immersion in a commercially available 0.6% sodium hypochlorite solution and 16.5% sodium chloride (diluted Milton) gave consistent bactericidal results and no visible catheter damage. CONCLUSIONS: Combined mechanical and chemical treatment of a detergent and water wash followed by immersion in diluted Milton (the "Milton Method") provided consistent and effective cleaning of uncoated PVC catheters, showing bactericidal action for all uropathogens tested after repeated exposure. If found safe in clinical testing, this method could increase the reuse of catheters, reduce plastic waste in the environment, reduce cost, and increase patient choice.

Continuous low-dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self-catheterisation: the AnTIC RCT.

BACKGROUND: People carrying out clean intermittent self-catheterisation (CISC) to empty their bladder often suffer repeated urinary tract infections (UTIs). Continuous once-daily, low-dose antibiotic treatment (antibiotic prophylaxis) is commonly advised but knowledge of its effectiveness is lacking. OBJECTIVE: To assess the benefit, harms and cost-effectiveness of antibiotic prophylaxis to prevent UTIs in people who perform CISC. DESIGN: Parallel-group, open-label, patient-randomised 12-month trial of allocated intervention with 3-monthly follow-up. Outcome assessors were blind to allocation. SETTING: UK NHS, with recruitment of patients from 51 sites. PARTICIPANTS: Four hundred and four adults performing CISC and predicted to continue for ≥ 12 months who had suffered at least two UTIs in the previous year or had been hospitalised for a UTI in the previous year. INTERVENTIONS: A central randomisation system using random block allocation set by an independent statistician allocated participants to the experimental group [once-daily oral antibiotic prophylaxis using either 50 mg of nitrofurantoin, 100 mg of trimethoprim (Kent Pharmaceuticals, Ashford, UK) or 250 mg of cefalexin (Sandoz Ltd, Holzkirchen, Germany); n = 203] or the control group of no prophylaxis (n = 201), both for 12 months. MAIN OUTCOME MEASURES: The primary clinical outcome was relative frequency of symptomatic, antibiotic-treated UTI. Cost-effectiveness was assessed by cost per UTI avoided. The secondary measures were microbiologically proven UTI, antimicrobial resistance, health status and participants' attitudes to antibiotic use. RESULTS: The frequency of symptomatic antibiotic-treated UTI was reduced by 48% using prophylaxis [incidence rate ratio (IRR) 0.52, 95% confidence interval (CI) 0.44 to 0.61; n = 361]. Reduction in microbiologically proven UTI was similar (IRR 0.49, 95% CI 0.39 to 0.60; n = 361). Absolute reduction in UTI episodes over 12 months was from a median (interquartile range) of 2 (1-4) in the no-prophylaxis group (n = 180) to 1 (0-2) in the prophylaxis group (n = 181). The results were unchanged by adjustment for days at risk of UTI and the presence of factors giving higher risk of UTI. Development of antimicrobial resistance was seen more frequently in pathogens isolated from urine and Escherichia coli from perianal swabs in participants allocated to antibiotic prophylaxis. The use of prophylaxis incurred an extra cost of £99 to prevent one UTI (not including costs related to increased antimicrobial resistance). The emotional and practical burden of CISC and UTI influenced well-being, but health status measured over 12 months was similar between groups and did not deteriorate significantly during UTI. Participants were generally unconcerned about using antibiotics, including the possible development of antimicrobial resistance. LIMITATIONS: Lack of blinding may have led participants in each group to use different thresholds to trigger reporting and treatment-seeking for UTI. CONCLUSIONS: The results of this large randomised trial, conducted in accordance with best practice, demonstrate clear benefit for antibiotic prophylaxis in terms of reducing the frequency of UTI for people carrying out CISC. Antibiotic prophylaxis use appears safe for individuals over 12 months, but the emergence of resistant urinary pathogens may prejudice longer-term management of recurrent UTI and is a public health concern. Future work includes longer-term studies of antimicrobial resistance and studies of non-antibiotic preventative strategies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67145101 and EudraCT 2013-002556-32. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 22, No. 24. See the NIHR Journals Library website for further project information.

The urinary microbiome and its contribution to lower urinary tract symptoms; ICI-RS 2015.

AIMS: The microbiome is the term used for the symbiotic microbial colonisation of healthy organs. Studies have found bacterial identifiers within voided urine which is apparently sterile on conventional laboratory culture, and accordingly there may be health and disease implications. METHODS: The International Consultation on Incontinence Research Society (ICI-RS) established a literature review and expert consensus discussion focussed on the increasing awareness of the urinary microbiome, and potential research priorities. RESULTS: The consensus considered the discrepancy between findings of conventional clinical microbiology methods, which generally rely on culture parameters predisposed towards certain "expected" organisms. Discrepancy between selective culture and RNA sequencing to study species-specific 16S ribosomal RNA is increasingly clear, and highlights the possibility that protective or harmful bacteria may be overlooked where microbiological methods are selective. There are now strong signals of the existence of a "core" urinary microbiome for the human urinary tract, particularly emerging with ageing. The consensus reviewed the potential relationship between a patient's microbiome and lower urinary tract dysfunction, whether low-count bacteriuria may be clinically significant and mechanisms which could associate micro-organisms with lower urinary tract symptoms. CONCLUSIONS: Key research priorities identified include the need to establish the scope of microbiome across the range of normality and clinical presentations, and gain consensus on testing protocols. Proteomics to study enzymatic and other functions may be necessary, since different bacteria may have overlapping phenotype. Longitudinal studies into risk factors for exposure, cumulative risk, and emergence of disease need to undertaken. Neurourol. Urodynam. 36:850-853, 2017. © 2017 Wiley Periodicals, Inc.

Antibiotic treatment for intermittent bladder catheterisation with once daily prophylaxis (the AnTIC study): Study protocol for a randomised controlled trial.

BACKGROUND: Clean intermittent self-catheterisation is an important management option for people who cannot empty their bladder effectively. Recurrent urinary tract infections are common in these patients. Data from recent studies suggest that antibiotic prophylaxis may be beneficial in reducing infection risk, but the effectiveness of this intervention remains uncertain. METHODS/DESIGN: This is a 52-site, patient randomised superiority trial set in routine care comparing an experimental strategy of once daily antibiotic prophylaxis for 12 months against a control strategy of no prophylaxis in people who carry out self-catheterisation and suffer recurrent urinary tract infections. The primary outcome is number of urinary tract infections during a 12-month treatment period. Both groups will otherwise receive usual care including on demand treatment courses of antibiotics for urinary tract infection. Participants and their clinicians will not be blinded to the allocated intervention, but central trial staff managing and analysing trial data will, as far as possible, be unaware of participant allocation. The analysis will follow intention-to-treat principles. DISCUSSION: This trial was commissioned and funded by the United Kingdom National Health Service following prioritisation of the research question by the National Institute for Health and Care Excellence. TRIAL REGISTRATION: ISRCTN67145101 EUDRACT2013-002556-32. Registered on 25 October 2013.

In vitro multicompartmental bladder model for assessing blockage of urinary catheters: effect of hydrogel coating on dynamics of Proteus mirabilis growth.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A population audit of first clinic attendance with suspected epilepsy.

OBJECTIVE: To assess the quality of clinical care at first clinic attendance in children with suspected epilepsy from a defined geographical population. METHOD: All hospital- and community-based consultant paediatricians in Nottingham City region, UK, were asked to collaborate with a retrospective clinical audit identifying children seen between January 2001 and March 2002. The British Paediatric Neurology Association (BPNA) audit tool (Appleton R, Besag F, Kennedy C, et al. An audit of children referred with suspected epilepsy. Seizure 1998;7(6):489-95) was used to analyse the initial outpatient assessment. RESULTS: All consultants agreed to participate. A total of 147 children were identified as meeting the inclusion criteria. The sequence of events during the episodes was well recorded (91%). Other aspects of the history were less well recorded. Twelve percent were given a diagnosis of epilepsy, 26% non-epileptic and 62% uncertain. Documentation of early development and school performance was low (41%). Twenty-four percent of the children had no written documentation confirming physical and neurological examination. Documentation describing referral to an epilepsy nurse or support group was seen in 11%. Drug treatment and doses and follow-up plans were recorded in nearly all cases where applicable. DISCUSSION: A managed clinical network for children with epilepsy in Nottingham and the surrounding Trent region is currently being discussed which will consider alternative models of care for children with epilepsy. A revision of the BPNA audit tool has been produced with the BPNA Audit group and is available for other centres via the BPNA website's 'clinical toolbox' (http://www.bpna.org.uk/audit).

An electrified catheter to resist encrustation by Proteus mirabilis biofilm.

PURPOSE: We investigated the effect of iontophoresis produced by passing an electric current through silver electrodes attached to catheters on catheter encrustation by crystalline Proteus mirabilis biofilm. MATERIALS AND METHODS: Four glass bladder models were catheterized with 16Fr silicone catheters, of which 3 had 0.25 mm silver wires running through and beside the lumen. Two wired catheters had the silver wires connected to a 9 V direct current source supplying a steady current of 150 microA via a self-regulating circuit. Artificial urine, which had been inoculated with a clinical strain of P. mirabilis isolated from an encrusted catheter, was instilled into the bladder model at 0.5 ml per minute. The models were operated until the test catheters became blocked. Mean blockage time was statistically analyzed by ANOVA. Bacterial colony count, silver ions and pH were assessed every 24 hours. RESULTS: The experiment was repeated 3 times. Time to blockage, colony count, pH and scanning electron microscopy was used to assess encrustation in electrified and control catheters. Time to blockage in electrified vs control catheters was 156 vs 22 hours. The difference in blockage times was statistically significant (p <0.002). The viable bacterial cell count in urine with test catheters vs that in controls was 1.12 x 10(4) vs 2.73 x 10(9) cfu/ml. The pH increased to 9 in control models, whereas it remained less than 6.5 in test models for about 100 hours. CONCLUSIONS: Electrified catheters released ions in urine that have the oligodynamic property of inhibiting bacterial growth. The application of electric current to catheters fitted with silver electrodes significantly decreased the rate at which these devices became encrusted by P. mirabilis. This principle could be used to prevent encrustation on long-term catheters.

Why are Foley catheters so vulnerable to encrustation and blockage by crystalline bacterial biofilm?

Many patients undergoing long-term bladder catheterisation experience blockage and encrustation of their catheters. The problem stems from infection by urease producing bacteria, particularly Proteus mirabilis. Bacterial biofilms colonise the catheters, the activity of urease raises the pH and induces the deposition of calcium and magnesium phosphate crystals. In this study, a laboratory model of the catheterised bladder has been used to examine the early stages in the formation of the crystalline biofilms. The results show that initial cell adhesion is to the irregular surfaces surrounding the catheter eye-holes. Microcolonies form in depressions in these surfaces and spread to cover the entire surface of the rims around the eye-holes. Crystals then form around the bacterial populations and the biofilm starts to move down the lumenal surfaces of the catheters. The encrustation develops most extensively and generally blocks the catheter at or just below the eye-hole. There is a need to improve catheter design and manufacturing procedures for the eye-holes if the problems associated with the current devices are to be reduced.