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Background: The AnTIC trial linked continuous low-dose antibiotic prophylaxis treatments to a lower incidence of symptomatic urinary tract infections (UTIs) among individuals performing clean intermittent self-catheterisation (CISC). Objective: To explore potential mechanisms underlying the protective effects of low-dose antibiotic prophylaxis treatments, blood and urine samples and uro-associated Escherichia coli isolates from AnTIC participants were analysed. Design, setting, and participants: Blood samples (n = 204) were analysed for TLR gene polymorphisms associated with UTI susceptibility and multiple urine samples (n = 558) were analysed for host urogenital responses. E.coli sequence data for 45 temporal isolates recovered from the urine samples of 16 trial participants in the prophylaxis (n = 9) and no-prophylaxis (n = 7) study arms, and characterised by multidrug resistance (MDR), were used to classify individual strains. Outcome measurements and statistical analysis: TLR polymorphism data were analysed using Poisson regression. Concentrations of urine host defence markers were analysed using linear mixed-effects models, which accounted for repeated urine samples. Results and limitations: Urine samples from CISC users, irrespective of antibiotic treatment regimens, were associated with robust urothelial innate responses. No links were identified between TLR genotype and CISC user susceptibility to recurrent UTIs. Microbiological study data were limited to the predominant MDR E. coli population; participants prescribed low-dose prophylactic antibiotics were predominantly colonised by a single uro-associated E. coli strain, while participants given acute antibiotic treatments were each colonised by more than one E. coli strain. Conclusions: Antibiotic treatments did not impact urogenital responses to infection in CISC users. Host genetics in terms of TLR polymorphisms played no role in determining CISC user susceptibility to or protection from recurrent UTIs. Prophylactic antibiotic treatments associated with MDR E. coli were associated with colonisation by stable uro-associated E. coli genotypes. Patient summary: Our findings show that the natural urogenital defences of clean intermittent self-catheterisation (CISC) users were not impacted by antibiotic treatments. For some CISC users, prophylaxis with low-dose antibiotics selected for a stable, predominantly, Esherichia coli rich uromicrobiota.

Uropathogenic Escherichia coli is a major cause of urinary tract infections. Analysis of the innate immune response in immortalized urothelial cells suggests that the bacterial flagellar subunit, flagellin, is key in inducing host defenses. A panel of 48 clinical uro-associated E. coli isolates recovered from either cystitis, pyelonephritis asymptomatic bacteriuria (ABU) or UTI-associated bacteraemia infections were characterized for motility and their ability to induce an innate response in urothelial cells stably transfected with a NF-κB luciferase reporter. Thirty-two isolates (67%) were identified as motile with strains recovered from cystitis patients exhibiting an uneven motility distribution pattern; seven of the cystitis isolates were associated with a > 5-fold increase in NF-κB signaling. To explore whether the NF-κB signaling response reflected antigenic variation, flagellin was purified from 14 different isolates. Purified flagellin filaments generated comparable NF-κB signaling responses, irrespective of either the source of the isolate or H-serotype. These data argued against any variability between isolates being related to flagellin itself. Investigations also argued that neither TLR4 dependent recognition of bacterial lipopolysaccharide nor growth fitness of the isolates played key roles in leading to the variable host response. To determine the roles, if any, of flagellar abundance in inducing these variable responses, flagellar hook numbers of a range of cystitis and ABU isolates were quantified. Images suggested that up to 60% of the isolate population exhibited flagella with the numbers averaging between 1 and 2 flagella per bacterial cell. These data suggest that selective pressures exist in the urinary tract that allow uro-associated E. coli strains to maintain motility, but exploit population heterogeneity, which together function to prevent host TLR5 recognition and bacterial killing.

Abstract Background Age is a significant risk factor for recurrent urinary tract (rUTI) infections, but the clinical picture is often confused in older patients who also present with asymptomatic bacteriuria (ASB). Yet, how bacteriuria establishes in such patients and the factors underpinning and/or driving symptomatic UTI episodes are still not understood. To explore this further a pilot study was completed in which 30 male and female community based older patients (mean age 75y) presenting clinically with ASB / rUTIs and 15 control volunteers (72y) were recruited and monitored for up to 6 months. During this period symptomatic UTI episodes were recorded and urines collected for urinary cytokine and uropathogenic Escherichia coli (UPEC) analyses. Results Eighty-six per cent of patients carried E. coli (102 ≥ 105 CFU/ml urine) at some point throughout the study and molecular typing identified 26 different E. coli strains in total. Analyses of urine samples for ten different cytokines identified substantial patient variability. However, when examined longitudinally the pro-inflammatory markers, IL-1 and IL-8, and the anti-inflammatory markers, IL-5 and IL-10, were significantly different in the patient urines compared to those of the controls (P

Objectives To determine whether there are differences in pressure and flow measurements between conventional cystometry (CONV) and ambulatory urodynamic monitoring (AMB) in women with overactive bladder syndrome and urinary incontinence. Materials and Methods Retrospective study which included female subjects who underwent both CONV (with saline filling medium) and AMB, separated by less than 24 months, not using medication active on the lower urinary tract and without history of prior pelvic surgery. Both tests were carried out in compliance with the International Continence Society standards. The paired Student’s t test was used to compare continuous variables. Bland-Altman statistics were used to assess the agreement of each variable between both studies. Results Thirty women with a median (range) age of 50 (14 - 73) years met the inclusion criteria. AMB was carried out at a mean (SD) of 11 (6) months after CONV. Measurements of pves and pabd at the end of filling, and Qmax were significantly higher from AMB recordings. There were no differences in pdet at the end of filling, pdetQmax or pdetmax during voiding, nor significant difference in Vvoid. Conclusions We provide previously undocumented comparative voiding data between CONV and AMB for patients who most commonly require both investigations. Our findings show higher values of Qmax but similar values of pdetQmax measured by AMB which may partly reflect an overall lower catheter caliber, physiological filling but perhaps also more ‘normal’ voiding conditions.

Objectives: To summarize the development of a novel non-invasive test to categorize voiding dysfunction in men complaining of lower urinary tract symptoms (LUTS) - the penile cuff test. Methods: The test involves the controlled inflation of a penile cuff during micturition to interrupt voiding and hence estimate isovolumetric bladder pressure (p ves.isv ). The validity, reliability, and clinical usefulness of the test were determined in a number of studies in men with LUTS. Results: The penile cuff test can be successfully performed in over 90% of men with LUTS. The reading of cuff pressure at flow interruption (p cuff.int ) gives a valid and reliable estimate of invasively-measured p ves.isv and when combined with the reading for maximum flow rate obtained during the test (Q max ) produces an accurate categorization of bladder outlet obstruction (BOO). Use of this categorization prior to treatment allows improved prediction of outcome from prostatectomy. Conclusion: The penile cuff test fulfils the criteria as a useful clinical measurement technique applicable to the diagnosis and treatment planning of men with LUTS.

Objective: To evaluate the accuracy and diagnostic usefulness of a disposable flowmeter consisting of a plastic funnel with a spout divided into three chambers. Materials and Methods: Men with lower urinary tract symptoms (LUTS) voided sequentially into a standard flowmeter and the funnel device recording maximum flow rate (Q max ) and voided volume (V void ). The device was precalibrated such that filling of the bottom, middle and top chambers categorized maximum input flows as < 10, 10-15 and > 15 ml s -1 respectively. Subjects who agreed to use the funnel device at home obtained readings of flow category and V void twice daily for seven days. Results: A single office reading in 46 men using the device showed good agreement with standard measurement of Q max for V void > 150 ml (Kappa = 0.68). All 14 men whose void reached the top chamber had standard Q max > 15 ml s -1 (PPV = 100%, NPV = 72%) whilst eight of 12 men whose void remained in the bottom chamber had standard Q max < 10 ml s -1 (PPV = 70%, NPV = 94%). During multiple home use by 14 men the device showed moderate repeatability (Kappa = 0.58) and correctly categorized Q max in comparison to standard measurement for 12 (87%) men. Conclusions: This study suggests that the device has sufficient accuracy and reliability for initial flow rate assessment in men with LUTS. The device can provide a single measurement or alternatively multiple home measurements to categorize men with Q max < 15 ml s -1 .