Urinary Tract Infection In People Research Articles

Skip The Dip For Urinary Tract Infection in over 65s. A National Initiative To Reduce Antibiotic Prescribing In Older Persons

Abstract Background Urinary tract infection (UTI) is the most common reason for antibiotic use in older persons in residential care. Dipstick urinalysis for UTI is an ingrained practice. Inappropriate use of dipstick urinalysis can lead to inappropriate antibiotic prescribing, contributing to adverse effects and antimicrobial resistance. The ‘Skip the Dip for UTI in over 65s’ quality improvement initiative (QI) aims to raise awareness of best practice for diagnosis and management of suspected UTI to reduce unnecessary antibiotic use. It supports implementation of national guidance stating dipstick urinalysis is not recommended for assessment of evidence of UTI in people 65 years and over. Methods Focus groups with nursing staff in older persons residential care facilities (OPRCFs) identified barriers and facilitators for implementing national guidance on dipstick urinalysis for UTI. Supporting resources developed included a resident leaflet on UTI, staff handbook and webinar recording, hosted on www.antibioticprescribing.ie. Antimicrobial pharmacists delivered workshops on improving assessment of suspected UTI in the HSE OPRCFs from September 2023 to March 2024. Monthly monitoring of antibiotic use for UTI was established in all 119 HSE OPRCFs. Surveys to establish dipstick urinalysis practice in the OPRCFs were administered in March 2023 and March 2024. Results A baseline survey in 2020/21 indicated 98% HSE OPRCFs (133/135) performed dipstick urinalysis for residents with symptoms of UTI, reducing to 53% (57/107) in March 2023, and 24% (25/103) in March 2024 following this QI. Prevalence of antibiotics for treatment of UTI in the HSE OPRCFs decreased by 38%, from a baseline of 2.6% (114/4,446 residents) in 2020/21, to 1.6% (66/4,222 residents) in March 2024. Conclusion The ‘Skip the Dip for UTI in over 65s’ QI has resulted in a change in practice, with the majority of HSE OPRCFs now reporting dipstick urinalysis is not performed for UTI assessment, with a considerable reduction in antibiotics prescribed for UTIs.

Population incidence and associated mortality of urinary tract infection in people living with dementia

OBJECTIVESUrinary tract infections (UTIs) frequently cause hospitalisation and death in people living with dementia (PLWD). We examine UTI incidence and associated mortality among PLWD relative to matched controls and people with diabetes and investigate whether delayed or withheld treatment further impacts mortality. METHODSData were extracted for n=2,449,814 people aged ≥ 50 in Wales from 2000-2021, with groups matched by age, sex, and multimorbidity. Poisson regression was used to estimate incidences of UTI and mortality. Cox regression was used to study the effects of treatment timing. RESULTSUTIs in dementia (HR=2.18, 95%CI [1.88-2.53], p<.0) and diabetes (1.21[1.01-1.45], p=.035) were associated with high mortality, with the highest risk in individuals with diabetes and dementia (both) (2.83[2.40-3.34], p<.0) compared to matched individuals with neither dementia nor diabetes. 5.4% of untreated PLWD died within 60 days of GP diagnosis—increasing to 5.9% in PLWD with diabetes. CONCLUSIONSIncidences of UTI and associated mortality are high in PLWD, especially in those with diabetes and dementia. Delayed treatment for UTI is further associated with high mortality.

Diabetes, SGLT-2 Inhibitors, and Urinary Tract Infection: a Review.

The aim of this review is to focus on epidemiology, pathogenesis, risk factors, management, and complications of UTI in people with diabetes as well as reviewing the association of SGLT-2 inhibitors with genitourinary infections. Individuals diagnosed with T2DM are more prone to experiencing UTIs and recurrent UTIs compared to individuals without T2DM. T2DM is associated with an increased risk of any genitourinary infections (GUI), urinary tract infections (UTIs), and genital infections (GIs) across all age categories. SGLT2 inhibitors are a relatively new class of anti-hyperglycemic agents, and studies suggest that they are associated with an increased risk of genitourinary infections. The management of diabetes and lifestyle modifications with a patient-centric approach are the most recognized methods for preventing critical long-term complications including genitourinary manifestations of diabetes. The available data regarding the association of SGLT-2 inhibitors with genitourinary infections is more comprehensive compared to that with UTIs. Further research is needed to better understand the mechanisms underlining the association between SGLT-2 inhibitors and genital infections and UTIs.

A simple and successful solution to issues relating to urinary tract infections in people with MS

The coronavirus pandemic prompted one of the authors to develop a simple yet innovative solution to detecting urinary tract infections in people with multiple sclerosis, in order to improve their wellbeing and reduce hospital admissions. The initiative has been longer lasting, wider reaching and has had better outcomes than expected. The authors discuss the initiative, how and why it was developed, patient outcomes and limitations.

Complications of different methods of urological management in people with neurogenic bladder secondary to spinal cord injury

Objective To investigate the association between multiple types of urological management and urological complications in patients with spinal cord injury (SCI). Design A retrospective cohort study. Setting Single medical center. Methods Medical records of SCI patients with regular follow-up of more than two years were reviewed. Urological management was classified into five groups: indwelling urethral catheter (IUC), clean intermittent catheterization (CIC), reflex voiding, suprapubic catheter (SPC), and self-voiding. We analyzed the incidence of urinary tract infection (UTI), epididymitis, hydronephrosis, and renal stone across the different urological-management groups. Results Of 207 individuals with SCI, the most common management type was self-voiding (n = 65, 31%) followed by CIC (n = 47, 23%). The IUC and SPC groups included more people with complete SCI than the other management groups. Compared with the IUC group, the SPC and self-voiding groups had lower risks of developing UTI (relative risk [RR] = 0.76, 95% CI, 0.59-0.97 and RR = 0.39, 95% CI, 0.28-0.55, respectively). The SPC group tended to have a lower risk of epididymitis than the IUC group (RR = 0.55, 95% CI, 0.18-1.63). Conclusion Long-term IUC use was associated with a higher incidence of UTI in people with SCI. As compared to those with IUC, a lower risk of UTI was found in persons with SPC. These findings may have implications for shared clinical decision-making.

Urinary Tract Infections Among Gender Diverse People Assigned Female at Birth on Testosterone.

The current literature lacks evidence to support the relationship between gender-affirming testosterone use and urinary tract infections (UTIs). The aims of the study are to compare UTI rates among gender diverse people assigned female at birth on testosterone (GDT) to cisgender women (CW) and to identify factors associated with UTI. This is a retrospective cohort study of GDT and age-matched CW over a 5-year period. The primary outcome was based on the International Classification of Diseases, Ninth/Tenth Revisions, Clinical Modification, UTI diagnosis codes with a filled pharmacy order for antibiotics within 7 days of the diagnosis. The study included 2,401 GDT who were then age matched to 2,401 CW. The mean rates of UTI among GDT and CW were not significantly different at 0.09 and 0.10 UTIs per year, respectively. During the study period, 6.9% of GDT and 7.5% of CW had at least 1 UTI. Diabetes mellitus type 1 or 2 was significantly associated with UTI frequency among CW (P = 0.04) but not GDT (P = 0.96). The rate of UTIs among our young cohort of GDT and CW was similarly low. Diabetes mellitus type 1 or 2 was significantly associated with UTIs among CW but not GDT. These findings suggest that testosterone-induced vaginal atrophy may not be associated with a higher a UTI risk. A deeper understanding of the pathogenesis of UTI in people assigned female at birth and more data on the relationship between testosterone and UTIs are needed before recommending vaginal estrogen to all GDT with recurrent UTI.

The frequency of UTIs in people who undertake intermittent catheterization: A systematic review

Abstract Background Intermittent Catheterization (IC) is a common procedure used for the management of incomplete bladder emptying in various diseases such as spinal cord injury, multiple sclerosis and benign prostatic hypertrophy. Catheterization is associated with several complications and particularly with an increased risk of developing urinary tract infections (UTIs) responsible for high morbidity worldwide and significant costs to health systems and society.Today, this health problem is still underestimated. Therefore, the aim of this study was to summarize the available evidence on the clinical and epidemiological burden of UTIs among patients performing IC. Methods A systematic literature review was performed querying two online database (PubMed,Web of Science) from January 2012 to January 2022. All studies in English language and focused on the clinical-epidemiological burden of UTIs related to IC in the adult population were included. Results Overall, 43 studies were considered. It was described a range of UTIs from 26% to 63%, with an increased number of hospital admissions and length of stay. UTIs were more common in patients with spinal cord injuries (about 40%) and with multiple sclerosis (24-34%).The main risk factors associated with UTIs were catheter reuse, type of catheter and catheterization procedure adopted. Conclusions Data on IC-associated UTIs are still limited. Estimating the UTIs load in patients with IC could support healthcare professionals to identify the most appropriate type of catheter to reduce the risk of this important complication. Proper management of catheterization could improve patients’ quality of life and also reduce the impact of diseases associated with this procedure on health systems and society. Key messages

Diagnosing, managing and preventing urinary tract infections in older people with dementia in hospital.

Urinary tract infections (UTIs) are common in older people and are frequently more complicated to diagnose than in younger adults. There are often challenges associated with distinguishing symptomatic UTIs from asymptomatic bacteriuria, particularly in people with cognitive impairment. Older people with dementia are at increased risk of developing a UTI because dementia can lead to voiding issues, impede personal hygiene and increase the need for urinary catheterisation. Furthermore, while a UTI is usually diagnosed based on an individual's physical signs and symptoms, people with dementia may only exhibit signs of sudden altered mental status such as increased confusion, agitation or withdrawal, making diagnosis challenging. This article discusses the main considerations regarding UTIs in people with dementia in hospital and outlines prevention strategies that nurses can implement in their practice.

A Real-world Data Analysis of Intermittent Catheterization, Showing the Impact of Prelubricated Versus Hydrophilic Catheter Use on the Occurrence of Symptoms Suggestive of Urinary Tract Infections

BackgroundSystematic reviews have highlighted the lack of evidence on choosing the type of intermittent urinary catheter (IUC) with regard to the occurrence of urinary tract infections (UTIs). ObjectiveTo describe the incidence and frequency of symptoms suggestive of UTIs (ssUTIs) for prelubricated versus hydrophilic IUCs. Design, setting, and participantsAn observational study of a patient database compiled by UK general practitioners was conducted. Outcome measurements and statistical analysisThe primary outcome measures were the proportion of patients with at least one ssUTI (prescription of a nonspecific antibiotic with a UTI-related diagnosis, or prescription of a UTI-specific antibiotic) and the mean number of ssUTIs per affected patient in the 12 mo following the index IUC prescription. Comparable prelubricated (“PRELUBE”) and hydrophilic (“HYDRO”) catheter groups were obtained with 1:1 propensity score matching (PSM). Results and limitationsA total of 5296 patients were included (prelubricated: n = 458; hydrophilic: n = 4838). After PSM, the two groups had similar proportions of patients with ssUTIs at baseline. The proportion of patients with ssUTIs during exposure was similar in the PRELUBE (36.9%) and HYDRO groups (41.5%; p = 0.155). However, among patients having used the same type of catheter throughout the exposure period, the proportion with ssUTIs was significantly lower in the PRELUBE group (44.6%, vs 55.0% for HYDRO; p = 0.015), as was the number of ssUTIs per patient (1.3 vs 1.8; p = 0.036). ConclusionsWhen choosing a coated IUC, physicians and patients should not rule out PRELUBE IUCs for safety reasons alone. Patient summaryUsing real-world data compiled by UK general practitioners, we described the incidence and frequency of symptoms suggestive of urinary tract infection in people who were using various types of intermittent urinary catheters. When the same type of prelubricated catheter was used throughout the study period, the incidence of these symptoms was lower than for hydrophilic catheters.

A Semi-Supervised Machine Learning Model for Risk Analysis of Urinary Tract Infections in People with Dementia

Background: Urinary Tract Infections (UTIs) are common conditions in the elderly population and one of the key causes of hospital admissions in people with dementia. One of the key challenges in dealing with UTIs is that the condition often remains undiagnosed until it advances and shows severe symptoms which can lead to hospitalisation. Method: This study presents a new system for detecting UTI in people with dementia. The system relies on low-cost in-home sensory monitoring combined with a novel machine learning algorithm. Environmental and physiological monitoring devices provide continuous data collection from homes, and the proposed machine learning model is trained to extract and identify the risk of UTIs. In conditions such as UTI, collecting sufficient training data to train machine learning models is a challenging task. The limited access to labelled data and examples creates the risk that learning models can become overfitted or biased. We propose a semi-supervised learning model to process a large unlabelled data set in combination with a smaller labelled dataset. We use an unsupervised learning technique which trains a model by extracting the underlying features from a set of unlabelled data and use the probabilistic neural network to estimate the density distribution. We use the unsupervised model for feature extraction and use these features from the smaller dataset to train a supervised classifier. The proposed approach is tested in real-world application and within a healthcare monitoring system with 110 participants. Finding: The proposed system can record the environmental and clinical data in an integrated framework. This provides information for the proposed machine learning model to identify the risks of UTIs by processing the patterns and changes in vital signs and activity patterns. The evaluation results show that the proposed model can detect the risk of UITs with an F1-score of 84%, which outperforms the baseline methods by 10% on average. Interpretation: The proposed model uses continuous environmental monitoring data and vital signs to detect early symptoms and the risk of UTIs. This is a first study using deep learning and semi-supervised models to analyse in-home sensory data in remote healthcare monitoring scenarios. The model provides a new approach to analyse and interpret continuous observation and measurement data for dementia care. Funding: The UK Dementia Research Institute, Medical Research Council (MRC), Alzheimer's Society and Alzheimer's Research UK. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study protocol for this work has been reviewed and approved by the South East Coast Surrey NHS Research Ethics Committee and all the research has been performed in accordance with relevant guidelines and regulations. We obtained informed consent from all the study participants.

Canagliflozin and Risk of Genital Infections and Urinary Tract Infections in People with Diabetes Mellitus and Kidney Disease in the CREDENCE Trial

Canagliflozin and Risk of Genital Infections and Urinary Tract Infections in People with Diabetes Mellitus and Kidney Disease in the CREDENCE Trial

Immunotherapy to reduce frequency of urinary tract infections in people with neurogenic bladder dysfunction; a pilot randomised, placebo-controlled trial

Objective: To establish the feasibility of a randomized, placebo-controlled trial to investigate the effect of a specific immunotherapy bacterial lysate OM-89 (Uro-Vaxom®) in reducing the frequency of urinary tract infections in people with neurogenic bladder dysfunction. Design: A parallel-group, double-blind, randomized, placebo-controlled trial. Setting: Patients at home, recruited through out-patient contact, social media and patient support groups. Subjects: People with a spinal cord injury, multiple sclerosis, transverse myelitis or cauda equina syndrome who had suffered three or more clinically diagnosed urinary tract infections treated with antibiotics over the preceding 12 months. Interventions: All participants took one capsule of oral OM-89 immunotherapy (6 mg) or matching Placebo (randomisation ratio 1:1), once daily in the morning for 3 months. Main measures: The primary outcome was occurrence of a symptomatic urinary tract infection treated with an antibiotic, assessed at 3 and 6 months. Feasibility measures included recruitment, retention and practical difficulties. Results: Of 115 patients screened, 49 were recruited, one withdrew before randomization, and 23 were allocated to the control group receiving matching placebo. Six participants, all in the control group, discontinued the intervention; all participants provided full data at both follow-up times. Over 6 months, 18/25 active group patients had 55 infections, and 18/23 control group patients had 47 infections. Most research and clinical procedures were practical, and acceptable to participants. Conclusion: It is feasible to undertake a larger trial. We recommend broader inclusion criteria to increase eligibility and generalizability.

The prevalence and utility of screening for urinary tract infection at the time of presumed multiple sclerosis relapse

BackgroundMethods of screening for infections at the time of suspected relapse in people with multiple sclerosis (MS) vary across physicians. People with multiple sclerosis (MS) are at an increased risk of urinary tract infection (UTI). Data evaluating the utility of screening for potential UTI at the time of suspected relapse and whether there are key subgroups of patients in which screening would be most effective are sparse. ObjectivesTo evaluate demographic and clinical predictors of UTI in the context of a suspected acute relapse in (1) a retrospective hospital admission cohort and (2) a prospectively-enrolled, ambulatory care-based cohort, and to determine an approximate number needed to screen to detect one UTI in both healthcare settings. MethodsFor the hospital admissions cohort, we included individuals with a known or new diagnosis of MS or clinically isolated syndrome who were admitted at least once to the Johns Hopkins Neurology Inpatient Service (March 2012 to December 2014). We considered those screened via urinalysis. Possible UTI was defined as leukocyte esterase OR nitrite positive. For the ambulatory population, we enrolled a cohort of RRMS patients aged 18–65 who were suspected of suffering from an acute MS relapse who either called or came into clinic. Participants were screened via urinalysis; possible UTI was similarly defined. Participants also completed questionnaires (disability, history of Uhthoff's-type phenomenon, recent sexual intercourse, and new urologic symptoms). For both cohorts, we calculated an approximate number needed to screen, and tested if demographic and patient characteristics were associated with possible UTI using logistic regression models. ResultsFor the hospital admissions cohort, we included 158 individuals; 48 (30.4%) were identified as possibly having a UTI. For possible UTI, the approximate number needed to screen in order to detect 1 possible UTI is 3 (95% CI: 2, 6). Female sex was the only factor associated with increased odds of UTI (odds ratio [OR]: 3.90; 95% CI: 1.59–9.61; p = 0.003). For the ambulatory cohort, we included 50 participants; 10 (20.0%) with possible UTI. The approximate number needed to screen in order to detect 1 possible UTI was 5 (95% CI: 3, 11) in this cohort. Foul-smelling urine was positively associated with UTI (OR: 5.36; 95% CI: 1.10, 26.17; p = 0.04); no men had a possible UTI in this cohort, so we could not estimate odds ratios associated with sex. ConclusionUTIs at the time of a suspected MS relapse are relatively uncommon. Female sex is a strong risk factor for UTI in people with MS; foul-smelling urine is a potential predictor of UTI in people with MS. Larger studies are needed to comprehensively evaluate the utility of screening and risk factors for UTI at the time of suspected MS relapse.

Diagnosis of Urinary Tract Infection in the Neuropathic Bladder: Changing the Paradigm to Include the Microbiome.

Bacteriuria, a non-specific term that refers to the presence of bacteria in the urine, is common in people with neuropathic bladders. However, accurately determining when bacteriuria represents a urinary tract infection (UTI) as opposed to asymptomatic bacteriuria is difficult. There is currently no widely accepted definition of what constitutes a UTI in people with neuropathic bladders. As a result, there is significant variation in care, which likely leads to unnecessary use of antibiotics for bacteriuria. To improve the clinical management of people with neuropathic bladders, it is important to be able to accurately diagnose and treat UTIs. In this article, we review the difficulties associated with accurately diagnosing UTIs and then review proposed definitions. Finally, we discuss the emerging literature of the urinary microbiome and how this may assist in accurately diagnosing UTIs in people with neuropathic bladders.

Cefiderocol in context

New antibiotics reaching clinical development are scarce, although bacterial plasmids encoding antibiotic resistance genes seem to be everywhere. 1 Madec JY Haenni M Ponsin C et al. Sequence type 48 Escherichia coli carrying the blaCTX-M-1 IncI1/ST3 plasmid in drinking water in France. Antimicrob Agents Chemother. 2016; 60: 6430-6432 Crossref PubMed Scopus (28) Google Scholar Thus, the first clinical trial of cefiderocol, a siderophore cephalosporin active against multidrug-resistant Gram-negative pathogens, 2 Kohira N West J Ito A et al. In vitro antimicrobial activity of a siderophore cephalosporin, S-649266, against Enterobacteriaceae clinical isolates, including carbapenem-resistant strains. Antimicrob Agents Chemother. 2016; 60: 729-734 Crossref PubMed Scopus (172) Google Scholar reported by Simon Portsmouth and colleagues in The Lancet Infectious Diseases, 3 Portsmouth S van Veenhuyzen D Echols R et al. Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial. Lancet Infect Diseases. 2018; (published online Oct 25.)http://dx.doi.org/10.1016/S1473-3099(18)30554-1 Summary Full Text Full Text PDF PubMed Scopus (198) Google Scholar represents an eagerly-awaited development in the field. The definitive mechanism of action of cefiderocol is not novel; once inside the bacterial cell, it interrupts the synthesis of peptidoglycan, a key component of the bacterial cell wall. What is novel is its manner of getting inside to do the job—no easy task in the era of increasing efflux pump overproduction and porin mutations. Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trialIntravenous infusion of cefiderocol (2 g) three times daily was non-inferior compared with imipenem-cilastatin (1 g each) for the treatment of complicated urinary tract infection in people with multidrug-resistant Gram-negative infections. The results of this study will provide the basis for submission of a New Drug Application to the US Food and Drug Administration. Clinical trials of hospital-acquired pneumonia and carbapenem-resistant infections are ongoing. Full-Text PDF Cefiderocol for treatment of complicated urinary tract infections – Author's replyThe enormous efforts of investigators and trial participants in the premarket development of cefiderocol should be neither disregarded nor underestimated: thanks to their work,1 this drug might soon be accessible to patients who might benefit from it. Nonetheless, a drug tested on only a few hundred people and for a few narrow indications will always require additional, postmarket development. As I have stated,2 because we, the public, have demanded an accelerated path to approval, novel antibiotics are now entering the market on the basis of very thin clinical experience. Full-Text PDF Cefiderocol for treatment of complicated urinary tract infectionsWe were pleased to read the generally positive Comment1 regarding our Article,2 published in The Lancet Infectious Diseases. However, we would like to respond to some of the points raised. Full-Text PDF

Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial

Carbapenem-resistant Gram-negative bacteria represent the highest priority for addressing global antibiotic resistance. Cefiderocol (S-649266), a new siderophore cephalosporin, has broad activity against Enterobacteriaceae and non-fermenting bacteria, such as Pseudomonas aeruginosa and Acinetobacter baumannii, including carbapenem-resistant strains. We assessed the efficacy and safety of cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infection in patients at risk of multidrug-resistant Gram-negative infections. We did a phase 2, multicentre, double-blind, parallel-group non-inferiority trial at 67 hospitals in 15 countries. Adults (≥18 years) admitted to hospital with a clinical diagnosis of complicated urinary tract infection with or without pyelonephritis or those with acute uncomplicated pyelonephritis were randomly assigned (2:1) by an interactive web or voice response system to receive 1 h intravenous infusions of cefiderocol (2 g) or imipenem-cilastatin (1 g each) three times daily, every 8 h for 7-14 days. Patients were excluded if they had a baseline urine culture with more than two uropathogens, a fungal urinary tract infection, or pathogens known to be carbapenem resistant. The primary endpoint was the composite of clinical and microbiological outcomes at test of cure (ie, 7 days after treatment cessation), which was used to establish non-inferiority (15% and 20% margins) of cefiderocol versus imipenem-cilastatin. The primary efficacy analysis was done on a modified intention-to-treat population, which included all randomly assigned individuals who received at least one dose of study drug and had a qualifying Gram-negative uropathogen (≥1 × 105 colony-forming units [CFU]/mL). Safety was assessed in all randomly assigned individuals who received at least one dose of study drug, according to the treatment they received. This study is registered with ClinicalTrials.gov, number NCT02321800. Between Feb 5, 2015, and Aug 16, 2016, 452 patients were randomly assigned to cefiderocol (n=303) or imipenem-cilastatin (n=149), of whom 448 patients (n=300 in the cefiderocol group; n=148 in the imipenem-cilastatin group) received treatment. 371 patients (n=252 patients in the cefiderocol group; n=119 patients in the imipenem-cilastatin group) had qualifying Gram-negative uropathogen (≥1 × 105 CFU/mL) and were included in the primary efficacy analysis. At test of cure, the primary efficacy endpoint was achieved by 183 (73%) of 252 patients in the cefiderocol group and 65 (55%) of 119 patients in the imipenem-cilastatin group, with an adjusted treatment difference of 18·58% (95% CI 8·23-28·92; p=0·0004), establishing the non-inferiority of cefiderocol. Cefiderocol was well tolerated. Adverse events occurred in 122 (41%) of 300 patients in the cefiderocol group and 76 (51%) of 148 patients in the imipenem-cilastatin group, with gastrointestinal disorders (ie, diarrhoea, constipation, nausea, vomiting, and abdominal pain) the most common adverse events for both treatment groups (35 [12%] patients in the cefiderocol group and 27 [18%] patients in the imipenem-cilastatin group). Intravenous infusion of cefiderocol (2 g) three times daily was non-inferior compared with imipenem-cilastatin (1 g each) for the treatment of complicated urinary tract infection in people with multidrug-resistant Gram-negative infections. The results of this study will provide the basis for submission of a New Drug Application to the US Food and Drug Administration. Clinical trials of hospital-acquired pneumonia and carbapenem-resistant infections are ongoing. Shionogi & Co Ltd, Shionogi Inc.

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

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. To assess the benefit, harms and cost-effectiveness of antibiotic prophylaxis to prevent UTIs in people who perform CISC. Parallel-group, open-label, patient-randomised 12-month trial of allocated intervention with 3-monthly follow-up. Outcome assessors were blind to allocation. UK NHS, with recruitment of patients from 51 sites. 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. 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. 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. 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. Lack of blinding may have led participants in each group to use different thresholds to trigger reporting and treatment-seeking for UTI. 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. Current Controlled Trials ISRCTN67145101 and EudraCT 2013-002556-32. 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.

Stigma and self-management: an Interpretative Phenomenological Analysis of the impact of chronic recurrent urinary tract infections after spinal cord injury

Study designQualitative, phenomenological design.ObjectivesNeurogenic bladder dysfunction and urinary tract infection (UTI) are common secondary consequences to neurological damage to the spinal cord. This study sought to establish the impact of chronic, recurrent UTIs on people with spinal cord injury (SCI).SettingCommunity sample, United Kingdom.MethodsTwelve participants with SCI, aged between 28 and 68 years, who had experienced at least three recurrent UTI events within the previous 12 months were recruited. Detailed qualitative information was obtained from semi-structured interviews, which lasted between 30 and 60 min. Interpretative Phenomenological Analysis was performed to explore the lived experience of UTIs.ResultsInterview findings identified a range of factors related to the experience of recurrent UTIs in people with SCI. These were classified into the following themes: (1) Symptom Management Precedence, (2) Stigma-Motivated Risk Management and (3) Exhaustive Exploration of Treatment Options. Participants discussed management of acute exacerbations. Distress arose from perceptions of UTIs as potentially stigmatizing and fear of relying on antibiotics. Arising from this fear, many participants sought alternative prevention and management strategies.ConclusionsThese results suggest that chronic recurrent UTIs act as major barriers to social participation, with adverse effects on quality of life of people with a neurogenic bladder after SCI. People with SCI would benefit from additional assessment of the impact of recurrent UTIs, so that healthcare professionals can address specific concerns, such as the psychosocial impact of urinary incontinence and stigmatizing views. Additional support to enhance self-management and facilitate social participation should be provided.

Probiotics for preventing urinary tract infection in people with neuropathic bladder.

Neuropathic or neurogenic bladder describes a process of dysfunctional voiding as the result of injury in the brain, spinal cord or nerves innervating the bladder. People with neuropathic bladder, such as from spinal cord injury (SCI), are at significant risk of morbidity from urinary tract infections (UTI). Effective methods to prevent UTI in people with SCI have been sought for many years. Probiotics (micro-organisms that exert beneficial health effects in the host) have been recommended for bacterial interference of the urological tract to reduce colonisation by uropathogen and to manage the dual problems of infection and antibiotic resistance. This review looked at the benefits and harms of probiotics in preventing symptomatic UTI in people with neuropathic bladder compared with placebo, no therapy, or non-antibiotic prophylaxis (cranberry juice, methenamine hippurate, topical oestrogen). We searched the Cochrane Kidney and Transplant Specialised Register up to 10 March 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. All randomised controlled trials (RCTs), quasi-RCTs and cross-over RCTs looking at the use of probiotics for the prophylaxis of UTI in people with neuropathic bladders was considered for inclusion. Men, women and children of all ages with neuropathic bladders from neurological injury such as suprapontine, supra sacral and sacral aetiologies was included. All bladder management types, including reflex voiding, time voiding, indwelling and intermittent catheterization were eligible for this review.Studies comparing probiotics to placebo, no treatment or other non-antibiotic prophylaxis was included. Studies comparing probiotics with antibiotics or in combination with antibiotics were excluded. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) or standardised mean difference (SMD) and 95% CI were planned for continuous outcomes. This review includes a total of three studies (one cross-over and two parallel RCTs) which involved 110 participants. All three studies looked at intravesical instillation of a low virulent Escherichia coli (E. coli) strain in reducing the risk of symptomatic UTI in participants with neuropathic bladder, predominantly from SCI. Two studies used the E. coli 83972 strain and one study used the E. coli HU2117 strain.We did not find any RCTs involving other probiotics or other routes of administration for preventing UTI in people with neuropathic bladder.There was consistency in definition of symptomatic UTI in all three studies. Symptoms that all studies considered were relevant to diagnose UTI were adequately defined. All three studies defined microbiological diagnosis of symptomatic UTI.Asymptomatic bacteriuria was not considered an outcome measure in any of the included studies; however it was defined in two studies to establish successful inoculation.It is uncertain if the risk of symptomatic UTI is reduced with bladder inoculation using E. coli because the certainty of the evidence is very low (3 studies, 110 participants: RR 0.32, 95% CI 0.08 to 1.19; I2 = 82%).Two studies reported adverse events. One study reported one episode of autonomic dysreflexia. One study reported three symptomatic UTI occurring in two patients, and two studies mentioned the absence of septicaemia and pyelonephritis. Intravesical instillation was reported as "generally safe". One study reported high attrition rates in participants due to the need to adhere to strict instillation protocols.The overall quality of the studies was poor. All three studies had high risk of attrition bias due to failure of an intention-to-treat analysis which undermines the randomisation process and weakened the results of the studies. All three studies also had high risk of reporting bias. In this review, there were no studies identified addressing oral probiotics in preventing UTI in people with neuropathic bladder. It is uncertain if the risk of symptomatic UTI is reduced in people with neuropathic bladders via intravesical instillation of non-pathogenic E. coli as data were derived from small studies with high risk of bias.Although very minimal levels of harm was reported with this procedure, due to variable success rates, the need for strict adherence to instillation protocols together with high attrition rates in these studies, it is doubtful bladder instillation will be a widely accepted intervention in its current form.It is recommended that further appropriately powered RCTs with more robust methodological reporting be carried out.

Urinary tract infections attributed to diverse ExPEC strains in food animals: evidence and data gaps.

Between 70 and 95% of urinary tract infections (UTI) are caused by strains of Escherichia coli. These strains, often termed Extraintestinal Pathogenic E. coli (ExPEC), possess specific virulence traits allowing them to colonize more inhospitable environments, such as the urogenital tract. Some ExPEC isolates from humans have similar virulence factor profiles to ExPEC isolates from animals, and because of the potential for these strains to cause UTI in people, these infections have been referred to as foodborne UTI, or FUTI. Finding similarities in ExPEC in animals and humans is not necessarily proof of transmission, particularly a unidirectional pathway from animals to humans; similarities in virulence factor profiles should be expected given the specific bacterial requirements for colonizing physiological compartments with similar characteristics in all animals. Many of the most important strains of human ExPEC globally, such as ST131, are highly virulent and clonal implying routes of transmission other than food. Documenting routes of transmission is particularly difficult due to the wide range of potential ExPEC sources, including the human intestinal tract, and non-human reservoirs such as food animals and retail meat products, sewage and other environmental sources, and companion animals. The significant environmental reservoir of ExPEC, including strains such as ST131, could potentially explain much more completely the global dissemination of virulent ExPEC clones and the rapid dissemination of new strains within the community. Taken in its totality, the link between ExPEC in animals and UTI in humans might exist, but studies conducted to date do not enable an estimation of the relative importance of this route of transmission. To reduce the burden of illness associated with ExPEC, the scientific community needs to push forward with ecologically-based, scientifically-sound study designs that can address the plethora of ways in which E. coli can spread.