Primary lymphoma of mucosa associated lymphoid tissue (MALT lymphoma) in the urinary bladder mimicking recurrent urinary tract infection: a case report and literature review.

We report the case of a 79-year-old woman with primary lymphoma of mucosa-associated lymphoid tissue (MALT) in the urinary bladder. The patient, with urinary frequency, urgency and suprapubic pain had several emergency room visits due to recurrent urinary tract infection. Both sonogram and cystoscopy identified bladder tumors near the bladder neck. An abdominal contrast-enhanced computed tomography scan revealed a polypoid lesion on the anterior bladder wall without enlarged lymph nodes. Transurethral resection of the bladder tumor was conducted. The pathology report confirmed extranodal marginal zone MALT lymphoma. The clinical stage was IEA. Follow-up imaging reported residual bladder tumors, prompting adjuvant radiotherapy. The patient was treated successfully and was disease-free at the 9-month follow-up visit. Primary lymphoma is an uncommon pathological subtype. Its clinical and radiological differentiation from urothelial carcinoma (UC) can be challenging, but treatment strategies differ significantly. A definitive diagnosis relies on histopathology and immunohistochemistry. Typically, bladder lymphoma has a favorable prognosis, but further research is required to identify the optimal treatment.

Evaluation of the diagnostic accuracy of lower urinary tract symptoms (LUTS) in uncomplicated UTI in Pakistani women.

OBJECTIVE: To evaluate the diagnostic accuracy of lower urinary tract symptoms in uncomplicated urinary tract infection in women. Methods: The cross-sectional study was conducted from September 2020 to December 2021 after approval from the ethics review board of Jinnah Postgraduate Medical Centre, Karachi, and comprised data of women aged at least 16 years from 8 institutions across Pakistan. Data included menstruation status, symptoms, urinalysis and organisms found in urine samples. The association of urinalysis variables with symptoms among culture-positive patients was measured to assess the certainty of positive diagnosis. Data was analysed using SPSS 23. RESULTS: Of the 457 women with mean age 37.87±13.9 years, 182(39.8%) had a positive urine culture. Dysuria was the most significant symptom 120(65.9%), followed by daytime frequency 114(62.6%) amongst culture-positive patients. On urinalysis, 139(76.3%) had white blood cells, and 66(36.2%) had haematuria. Dysuria along with the presence of leucocyte esterase had the highest diagnostic utility (p=0.002). Urgency along with haematuria was strongly predictive of urinary tract infection (p=0.058). Conclusion: The diagnosis of uncomplicated urinary tract infection in women could be reliably made based on a combination of symptoms along with urine analysis without urine culture.

[When should shortterm antibiotic therapy be chosen?] / Quand choisir une antibiothérapie de courte durée ?

WHEN SHOULD SHORT-TERM ANTIBIOTIC THERAPY BE CHOSEN? Reducing antibiotic exposure by shortening treatment duration is a public health priority that could mitigate the emergence of bacterial resistance, minimize adverse effects, and lower costs. Additionally, a short yet effective antibiotic regimen is associated with improved patient compliance and satisfaction. Several trials in recent years have confirmed the efficacy of shorter treatment durations. For instance, five days of antibiotics are sufficient for uncomplicated pyelonephritis, while seven days suffice for non-febrile urinary tract infections in males. However, a 14-day regimen appears necessary for febrile urinary tract infections in men. A study examining a five-day treatment period found no difference compared to a 10-day regimen for skin and soft tissue infections. In acute community-acquired pneumonia, two randomized trials found three days of beta-lactam therapy to be effective. In intra-abdominal infections, durations ranging from four to eight days were found to be non-inferior to 15-day courses in two trials. Regarding osteoarticular infections, six weeks are adequate for spondylodiscitis, whereas 12 weeks are required for prosthetic joint infections. These findings validate shorter treatment durations across many clinical scenarios. However, in rare conditions such as febrile male urinary tract infections and prosthetic joint infections, shortening the duration may not be feasible. It is imperative to prescribe the shortest effective antibiotic duration possible in routine medical practice to combat antibiotic resistance.

QUAND CHOISIR UNE ANTIBIOTHÉRAPIE DE COURTE DURÉE ? Réduire l'exposition antibiotique en diminuant la durée de traitement est un enjeu de santé publique qui permettrait de limiter l'émergence des résistances bactériennes, réduire les effets indésirables, les coûts. En outre, une durée courte et efficace de traitement antibiotique est associée à une meilleure observance et satisfaction du patient. Ces dernières années, plusieurs essais ont permis de valider l'efficacité de durées de traitement court. Cinq jours d'antibiotique suffisent au cours des pyélonéphrites simples et sept jours au cours des infections urinaires masculines non fébriles. En revanche, un traitement de quatorze jours semble nécessaire au cours des infections urinaires fébriles de l'homme. Une étude portant sur cinq jours de traitement n'a pas retrouvé de différence avec un traitement de dix jours au cours des infections de la peau et des tissus mous. Dans les pneumonies aiguës communautaires, deux essais randomisés ont prouvé l'efficacité d'un traitement de trois jours par bêtalactamines. Au cours des infections intra- abdominales, deux essais ont montré que des durées d'antibiothérapie de quatre à huit jours étaient non inférieures à des traitements de quinze jours. Concernant les infections ostéoarticulaires, une durée de six semaines suffit au cours des spondylodiscites alors que douze semaines restent nécessaires lors des infections sur prothèse ostéoarticulaire. Ces données permettent de valider des durées de traitement courtes dans un grand nombre de situations cliniques. Cependant, dans de rares pathologies comme les infections urinaires masculines fébriles et les infections sur prothèses ostéoarticulaires, la durée ne semble pas pouvoir être raccourcie. Il convient de prescrire la durée de traitement antibiotique efficace la plus courte possible en pratique médicale courante afin de lutter contre l'antibiorésistance.

Cumulative rabbit anti-human thymocyte globulin dose to recipient weight during the peri-operative period is an independent risk factor for early postoperative urinary tract infection after kidney transplantation.

Anti-human thymocyte globulin-Fresenius (ATG-F) is frequently utilized to achieve successful induction for kidney transplantation recipients. This study aimed to examine the association between the ATG-F dose-to-recipient-weight ratio (ADR) and the risk of developing urinary tract infections (UTIs) following kidney transplantation. Data of kidney transplant recipients who underwent ATG-F-induction peri-operatively in a medical center were retrospectively collected, and the incidence of UTIs during the first postoperative year was also recorded. The risk of UTI associated with ADR was analyzed, and receiver operating characteristic curves were drawn to determine the optimal ADR, followed by Cox regression models. In total, 131 recipients were included, with an UTI incidence of 19.08% and a mean interval of 3.08 months. The optimal ADR was 6.34, involving 41 and 90 patients in the low ADR and high ADR groups, respectively. The UTI-free rate in the low ADR group was significantly higher than that in the high ADR group (p = 0.007). Cox regression analysis indicated that a high ADR independently increased the risk of UTI following kidney transplantation (hazard ratio: 5.306, 95% confidence interval: 1.243-22.660, p = 0.024). There was no significant difference in rejection rate between the high ADR and low ADR groups. In conclusion, a high ADR increased the incidence of early postoperative UTI among kidney transplant recipients.

Suppression of virulence factors of uropathogenic Escherichia coli by Trans-resveratrol and design of nanoemulgel.

BACKGROUND: Development of multidrug resistance in Uropathogenic Escherichia coli (UPEC) makes treatment of Urinary Tract Infections (UTIs) a major challenge. This study was conducted to investigate the effect of trans-resveratrol (t-RSV) at a subinhibitory concentration (sub-MIC-t-RSV) on phenotypic and genotypic expression of virulence factors of clinical isolates of UPEC and develop a nanoformulation of t-RSV. Fifty-five clinical UPEC strains were investigated for the presence of virulence factors by phenotypic methods and PCR detection of virulence genes. The effect of sub-MIC-t-RSV was studied on the phenotypic and genotypic expression of virulence factors. t-RSV-loaded nanoemulgel formulation was prepared and characterized. RESULTS: Out of the 55 tested isolates, 50.9% were biofilm producers, 23.6% showed both mannose-sensitive and mannose-resistant hemagglutination, 21.8% were serum-resistant, 18.2% were hemolysin producers, while 36.4% showed cytotoxic effect on HEp-2 cells. A total of 25.5% of the isolates harbor one or more of hly-A, cnf-1 and papC genes, while 54.5% were positive for one or more of fimH, iss and BssS genes. A concentration of 100 µg/mL of t-RSV effectively downregulates the phenotypic and genotypic expression of the virulence factors in positive isolates. A stable t-RSV-nanaoemulgel with droplet size of 180.3 nm and Zetapotential of -46.9 mV was obtained. CONCLUSION: The study proves the effective role of t-RSV as an antivirulence agent against clinical UPEC isolates in vitro and develops a stable t-RSV-nanoemulgel formulation to be assessed in vivo. The promising antibacterial and antivirulence properties of t-RSV place this natural compound to be a better alternative in the treatment of persistent UTIs.

Economic Burden of Community-Acquired Antibiotic-Resistant Urinary Tract Infections: Systematic Review and Meta-Analysis.

Background: Antibiotic resistance (ABR) poses a major burden to global health and economic systems. ABR in community-acquired urinary tract infections (CA-UTIs) has become increasingly prevalent. Accurate estimates of ABR's clinical and economic burden are needed to support medical resource prioritization and cost-effectiveness evaluations of urinary tract infection (UTI) interventions. Objective: This study aims to systematically synthesize the evidence on the economic costs associated with ABR in CA-UTIs, using published studies comparing the costs of antibiotic-susceptible and antibiotic-resistant cases. Methods: We searched the PubMed, Ovid MEDLINE and Embase, Cochrane Review Library, and Scopus databases. Studies published in English from January 1, 2008, to January 31, 2023, reporting the economic costs of ABR in CA-UTI of any microbe were included. Independent screening of titles/abstracts and full texts was performed based on prespecified criteria. A quality assessment was performed using the Integrated Quality Criteria for Review of Multiple Study Designs (ICROMS) tool. Data in UTI diagnosis criteria, patient characteristics, perspectives, resource costs, and patient and health economic outcomes, including mortality, hospital length of stay (LOS), and costs, were extracted and analyzed. Monetary costs were converted into 2023 US dollars. Results: This review included 15 studies with a total of 57,251 CA-UTI cases. All studies were from high- or upper-middle-income countries. A total of 14 (93%) studies took a health system perspective, 13 (87%) focused on hospitalized patients, and 14 (93%) reported UTI pathogens. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa are the most prevalent organisms. A total of 12 (80%) studies reported mortality, of which, 7 reported increased mortality in the ABR group. Random effects meta-analyses estimated an odds ratio of 1.50 (95% CI 1.29-1.74) in the ABR CA-UTI cases. All 13 hospital-based studies reported LOS, of which, 11 reported significantly higher LOS in the ABR group. The meta-analysis of the reported median LOS estimated a pooled excess LOS ranging from 1.50 days (95% CI 0.71-4.00) to 2.00 days (95% CI 0.85-3.15). The meta-analysis of the reported mean LOS estimated a pooled excess LOS of 2.45 days (95% CI 0.51-4.39). A total of 8 (53%) studies reported costs in monetary terms-none discounted the costs. All 8 studies reported higher medical costs spent treating patients with ABR CA-UTI in hospitals. The highest excess cost was observed in UTIs caused by carbapenem-resistant Enterobacterales. No meta-analysis was performed for monetary costs due to heterogeneity. Conclusions: ABR was attributed to increased mortality, hospital LOS, and economic costs among patients with CA-UTI. The findings of this review highlighted the scarcity of research in this area, particularly in patient morbidity and chronic sequelae and costs incurred in community health care. Future research calls for a cost-of-illness analysis of infections, standardizing therapy-pathogen combination comparators, medical resources, productivity loss, intangible costs to be captured, and data from community sectors and low-resource settings and countries.

Clean intermittent catheterisation determinants and caregiver adherence in paediatric patients with spinal dysraphism and spinal cord injury in a paediatric spinal differences clinic: a mixed methods study protocol.

INTRODUCTION: Clean intermittent catheterisation (CIC) is the standard of care for treating neurogenic lower urinary tract dysfunction (NLUTD), the most common bladder dysfunction in children diagnosed with spinal dysraphism (SD) and spinal cord injury (SCI). Failure to follow the prescribed CIC regimen results in urinary tract infections, incontinence and renal insufficiency. Adherence to CIC is suboptimal, with reported non-adherence rates of 18%-66%. Despite the efficacy of CIC, the research on CIC adherence is not well defined in the literature and even less for caregivers of children on CIC protocols. METHODS: This proposed study aims to identify caregiver CIC adherence and determinants while exploring the personal experiences of performing CIC from the perspective of caregivers of children with NLUTD due to SD and SCI. This cross-sectional, correlational, convergent mixed methods study design in which qualitative and quantitative data will be collected simultaneously will be used to study the level of adherence and the relationship of caregiver determinants to CIC in children with SD and SCI and adherence to the CIC protocol. Convenience sampling will be used to identify 60 adult caregivers who can read and write English or Spanish and have a child diagnosed with SD and SCI who is currently prescribed CIC by a urology provider. ANALYSIS: The adherence data will be reported as frequency and percentages. A correlation analysis will be computed to assess the association between determinants measured by the Clean Intermittent Catheterization-Caregiver Questionnaire and adherence levels measured with the Intermittent Catheterization Adherence Scale. Thematic analysis will be used to analyse and interpret the interview data. A comparison joint display will be developed to compare quantitative and qualitative data results. ETHICAL AND DISSEMINATION: Institutional review board approval was obtained from the Children's Mercy Kansas City (Study00003003) and the University of Missouri-Kansas City (#2100185). The study's main results will be disseminated to caregiver participants, published in peer-reviewed journals and presented at conferences.

Estrogen-stimulated uropathogenic E. coli mediate enhanced neutrophil responses.

Urinary tract infection (UTI) is one of the most common bacterial infections worldwide and the most common cause is uropathogenic Escherichia coli (UPEC). Current research is mostly focused on how UPEC affects host factors, whereas the effect of host factors on UPEC is less studied. Our previous studies have shown that estrogen alters UPEC virulence. However, the effect of this altered UPEC virulence on neutrophils is unknown. The aim of the present study was to investigate how the altered UPEC virulence mediated by estrogen modulates neutrophil responses. We found that estradiol-stimulated CFT073 increased neutrophil phagocytosis, NETs formation and intracellular ROS production. We observed that the total ROS production from neutrophils was reduced by estradiol-stimulated CFT073. We also found that estradiol-stimulated CFT073 induced less cytotoxicity in neutrophils. Additionally, we found that several cytokines and chemokines like IL-8, IL-1ß, CXCL6, MCP-1 and MCP-4 were increased upon estradiol-stimulated CFT073 infection. In conclusion, this study demonstrates that the estrogen-mediated alterations to UPEC virulence modulates neutrophil responses, most likely in a host-beneficial manner.

Efficacy of a pharmacist care protocol to manage uncomplicated female cystitis in community pharmacies: an open-label, multicenter, randomized, controlled, cluster study: the PharmaCyst' protocol.

BACKGROUND: Urinary tract infections are common affections, especially for women. Difficult access to a general practitioner to obtain a prescription has led France to offer dispensing under protocol by community pharmacists. The primary objective of this study is to evaluate the effectiveness of a pharmacist care protocol provided to manage women with urinary tract infection symptoms. This objective will be assessed using the Acute Cystitis Symptom Score. METHODS: PharmaCyst' is an open-label, multicenter, controlled, cluster-randomized study conducted in the Loire region, France. Women aged between 18 and 65 years presenting to a pharmacy complaining of at least one symptom of an uncomplicated urinary tract infection present over the last 3 days (including burning pain during micturition, dysuria, pollakiuria, urgent urination) will be considered for inclusion. All patients will be contacted on day 3, 10, and month 3. A total of 480 patients need to be recruited for the 24 clusters participating in the research. The quantitative data will be described using means and standard deviations and compared using Student's t-test. The qualitative data will be described using numbers and percentages and compared using chi2 test (or Fisher's exact test if necessary). The primary and secondary outcomes analyses will consider the intention-to-treat population. DISCUSSION: PharmaCyst' is the first clinical trial conducted in France only by community pharmacists. Its results could lead to an extension of the protocol. TRIAL REGISTRATION: The protocol has been approved by the French ethics committee on 2022/12/02 and is registered under the number 49RC22_0240 on ClinicalTrials.gov.

Investigating urinary characteristics and optimal urine white blood cell threshold in paediatric urinary tract infection: A prospective observational study.

Introduction: While the definitive diagnosis of urinary tract infection (UTI) requires a positive urine culture, the likelihood of UTI can be determined by urinalysis that includes white blood cell (WBC) count. We aimed to determine the optimal urine WBC threshold in urinalysis to predict UTIs in children presenting at the emergency department (ED). Method: We performed a prospective observational study in the ED at KK Women's and Children's Hospital for children below 18 years old who underwent both urine microscopy and urine cultures, between 10 January and 7 November 2022. We assessed the various urine WBC thresholds associated with culture-proven UTIs using sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and area under receiver operating characteristic curve. Results: We found a culture-proven UTI rate of 460/1188 (38.7%) among all patients analysed, and 278/998 (27.9%) among those with nitrite-negative urine samples. Among all patients, a urinalysis WBC threshold of 100/µL had a sensitivity of 82.2% (95% confidence interval [CI] 78.4-85.5) and negative predictive value of 86.2% (95% CI 83.6-88.4). Among those who were nitrite-negative, a WBC threshold of ≥100/µL resulted in a potential missed rate of 48/278 (17.3%). By lowering the WBC threshold to ≥10/µL, the potential missed cases reduced to 6/278 (2.2%), with an estimated increase in 419 urine cultures annually. Conclusion: A urine microscopy WBC threshold of ≥100/µL results in a clinically significant number of missed UTIs. Implementation of various thresholds should consider both the potential missed UTI rate and the required resource utilisation.

Comprehensive insights into UTIs: from pathophysiology to precision diagnosis and management.

Urinary tract infections (UTIs) are the second most common infectious disease, predominantly impacting women with 150 million individuals affected globally. It increases the socio-economic burden of society and is mainly caused by Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter spp., and Staphylococcus spp. The severity of the infection correlates with the host factors varying from acute to chronic infections. Even with a high incidence rate, the diagnosis is mainly based on the symptoms, dipstick analysis, and culture analysis, which are time-consuming, labour-intensive, and lacking sensitivity and specificity. During this period, medical professionals prescribe empirical antibiotics, which may increase the antimicrobial resistance rate. Timely and precise UTI diagnosis is essential for addressing antibiotic resistance and improving overall quality of life. In response to these challenges, new techniques are emerging. The review provides a comprehensive overview of the global burden of UTIs, associated risk factors, implicated organisms, traditional and innovative diagnostic methods, and approaches to UTI treatment and prevention.

Elucidation of the mechanisms of fluconazole resistance and repurposing treatment options against urinary Candida spp. isolated from hospitalized patients in Alexandria, Egypt.

BACKGROUND: The incidence of fungal urinary tract infections (UTIs) has dramatically increased in the past decades, with Candida arising as the predominant etiological agent. Managing these infections poses a serious challenge to clinicians, especially with the emergence of fluconazole-resistant (FLC-R) Candida species. In this study, we aimed to determine the mechanisms of fluconazole resistance in urinary Candida spp. isolated from hospitalized patients in Alexandria, Egypt, assess the correlation between fluconazole resistance and virulence, and explore potential treatment options for UTIs caused by FLC-R Candida strains. RESULTS: Fluconazole susceptibility testing of 34 urinary Candida isolates indicated that 76.5% were FLC-R, with a higher prevalence of resistance recorded in non-albicans Candida spp. (88.9%) than in Candida albicans (62.5%). The calculated Spearman's correlation coefficients implied significant positive correlations between fluconazole minimum inhibitory concentrations and both biofilm formation and phospholipase production. Real-time PCR results revealed that most FLC-R isolates (60%) significantly overexpressed at least one efflux pump gene, while 42.3% significantly upregulated the ERG11 gene. The most prevalent mutation detected upon ERG11 sequencing was G464S, which is conclusively linked to fluconazole resistance. The five repurposed agents: amikacin, colistin, dexamethasone, ketorolac, and sulfamethoxazole demonstrated variable fluconazole-sensitizing activities in vitro, with amikacin, dexamethasone, and colistin being the most effective. However, the fluconazole/colistin combination produced a notable reduction (49.1%) in bladder bioburden, a 50% decrease in the inflammatory response, and tripled the median survival span relative to the untreated murine models. CONCLUSIONS: The fluconazole/colistin combination offers a promising treatment option for UTIs caused by FLC-R Candida, providing an alternative to the high-cost, tedious process of novel antifungal drug discovery in the battle against antifungal resistance.

Primary vesicoureteral reflux.

Primary vesicoureteral reflux (VUR) is one of the most common urological abnormalities in infants and children. The association of VUR, urinary tract infection (UTI) and renal parenchymal damage is well established. The most serious complications of VUR-associated reflux nephropathy are hypertension and proteinuria with chronic kidney disease. Over the past two decades, our understanding of the natural history of VUR has improved, which has helped to identify patients at increased risk of both VUR and VUR-associated renal injury. The main goals in the treatment of paediatric patients with VUR are the prevention of recurrent UTIs and minimizing the risk of renal scarring and long-term renal impairment. Currently, there are four options for managing primary VUR in infants and children: surveillance or intermittent treatment of UTIs with management of bladder and bowel dysfunction; continuous antibiotic prophylaxis; endoscopic subureteral injection of tissue-augmenting substances; and ureteral reimplantation via open, laparoscopic or robotic-assisted surgery. Current debates regarding key aspects of management include when to perform diagnostic imaging and how to best identify the paediatric patients that will benefit from continuous antibiotic prophylaxis or surgical intervention, including endoscopic injection therapy and minimally invasive ureteral reimplantation. Evolving technologies, such as artificial intelligence, have the potential to assist clinicians in the decision-making process and in the individualization of diagnostic imaging and treatment of infants and children with VUR in the future.

At a glance: urinary catheterisation in males and females.

Urinary catheterisation is a crucial procedure in healthcare, requiring a thorough understanding of the anatomical and physiological differences between males and females to ensure safe and effective care. This guide explores the anatomy of the urinary system, detailing the kidneys, ureters, bladder, and urethra, and highlights key differences in catheterisation techniques for men and women. Emphasising evidence-based practices, it discusses recent advancements, such as antimicrobial catheters, and underscores the importance of comprehensive training and competency assessments for healthcare providers. Additionally, the guide advocates for patient-centred approaches, multidisciplinary collaboration, and adherence to updated policies to reduce complications such as catheter-associated urinary tract infections (CAUTIs). By integrating these critical evaluations and best practices, health professionals can enhance patient outcomes and maintain high standards of care in urinary catheterisation.

[A 49-year-old woman with long-standing urinary symptoms. Histological and immunohistochemical study of a case of bladder mullerianosis]. / Mujer de 49 años con clínica urinaria de larga evolución. Estudio histológico e inmunohistoquímico de un caso de mullerianosis vesical.

Bladder müllerianosis is defined by the presence of Müllerian epithelium (endometrial, endocervical or endosalpinx) in the bladder. It is a rare benign disease that affects women and presents a non-specific clinical presentation that poses a broad differential diagnosis. We present the case of a 49-year-old woman who presented with recurrent urinary tract infections, urinary discomfort and abdominal pain. The approach is carried out by ultrasound and urethrocystoscopy that reveal the presence of a 5mm polypoid lesion that is removed. The histological study revealed bladder müllerianosis together with the complementary finding of glandular cystitis and cystic cystitis.

Strategies for older people living in care homes to prevent urinary tract infection: the StOP UTI realist synthesis.

Background: Urinary tract infection is the most diagnosed infection in older people. It accounts for more than 50% of antibiotic prescriptions in care homes and is a frequent reason for care home residents being hospitalised. Objective: This realist review developed and refined programme theories for preventing and recognising urinary tract infection, exploring what works, for whom and in what circumstances. Design: The review used realist synthesis to explore existing literature on the detection and prevention of urinary tract infection, complemented by stakeholder consultation. It applies to the UK context, although other healthcare systems may identify synergies in our findings. Data sources: Bibliographic databases searched included MEDLINE, CINAHL, EMBASE, Cochrane Library, Web of Science Core Collection (including the Social Sciences Citation Index), Sociological Abstracts, Bibliomap and National Institute for Health and Care Research Journals Library. Data selection and extraction: Title and abstract screening were undertaken by two researchers independently of each other. Selection and assessment were based on relevance and rigour and cross-checked by a second researcher. Data extracted from the included studies were explored for explanations about how the interventions were considered to work (or not). Evidence tables were constructed to enable identification of patterns across studies that offered insight about the features of successful interventions. Data analysis and synthesis: Programme theories were constructed through a four-stage process involving scoping workshops, examination of relevant extant theory, analysis and synthesis of primary research, teacher-learner interviews and a cross-system stakeholder event. A process of abductive and retroductive reasoning was used to construct context-mechanism-outcome configurations to inform programme theory. Results: The scoping review and stakeholder engagement identified three theory areas that address the prevention and recognition of urinary tract infection and show what is needed to implement best practice. Nine context-mechanism-outcome configurations provided an explanation of how interventions to prevent and recognise urinary tract infection might work in care homes. These were (1) recognition of urinary tract infection is informed by skills in clinical reasoning, (2) decision-support tools enable a whole care team approach to communication, (3) active monitoring is recognised as a legitimate care routine, (4) hydration is recognised as a care priority for all residents, (5) systems are in place to drive action that helps residents to drink more, (6) good infection prevention practice is applied to indwelling urinary catheters, (7) proactive strategies are in place to prevent recurrent urinary tract infection, (8) care home leadership and culture fosters safe fundamental care and (9) developing knowledgeable care teams. Limitations: We adapted our approach and work to online interactions with stakeholders and as a research team because of COVID-19. This also had an impact on bringing stakeholders together at a face-to-face event at the end of the project. Studies focusing on the prevention of urinary tract infection in care home settings were predominantly from the USA and Europe where the regulatory and funding systems for the long-term care of the elderly have some differences, particularly in the USA where national reporting plays a significant role in driving improvements in care. Conclusions: Care home staff have a vital role in the prevention and recognition of urinary tract infection, which can be enabled through integration and prioritisation within the systems and routines of care homes and delivery of person-centred care. Promoting fundamental care as a means of facilitating a holistic approach to prevention and recognition of urinary tract infection helps staff to recognise how they can contribute to antimicrobial stewardship and recognition of sepsis. Challenging assumptions made by staff about the presentation of urinary tract infection is complex and requires education that facilitates 'unlearning' and questioning of low-value practices. Programmes to prevent urinary tract infection need to be co-designed and supported through active and visible leadership by care home managers with support from specialist practitioners. Future work: We will focus on co-designing tools that facilitate implementation of our findings to ensure they fit with the care home context and address some of the challenges faced by care home leaders. This will underpin action at care home and system levels. Further research is needed to better understand the perspectives of residents and family carers, the effectiveness of non-pharmacological, pharmacological and specialist practitioner interventions and non-traditional approaches to training and educating the workforce in care home settings. Study registration: This study is registered as PROSPERO CRD42020201782. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR130396) and is published in full in Health Technology Assessment; Vol. 28, No. 68. See the NIHR Funding and Awards website for further award information.

This study was about how interventions to prevent and recognise urinary tract infections might work in care homes to reduce urinary tract infection in older people. We used an approach called realist synthesis. This aims to understand everything that influences how care is delivered to find out what works in particular situations and settings. We did this by talking to care home staff, residents, family carers and other experts about how to reduce urinary tract infection in older people living in care homes. We combined their experiences and ideas with the evidence from the research literature. From this, we developed three areas of focus: care approaches to support accurate recognition of urinary tract infection care approaches to prevent urinary tract infection/catheter-associated urinary tract infection making best practice happen. Our research shows that care staff are best placed to recognise subtle changes in a resident's behaviour or well-being which might indicate an infection. There are several things care staff can do to proactively help residents from developing a urinary tract infection such as prioritising residents' hydration needs and addressing poor fluid intake. Putting in place infection prevention measures such as caring for, or where possible, removing a urinary catheter can also help. Actively monitoring residents to determine reasons for changes in behaviour can increase the focus on preventative activities and help avoid inappropriate treatment. The detection and prevention of urinary tract infection in older people could be improved in several ways, including: education tailored to the roles and work of care home staff leaders of care homes providing a culture of safety and improvement where urinary tract infection is recognised as something preventable rather than unavoidable having a safe and supportive environment where staff are confident to communicate their concerns all care team members, residents and their families and other professionals linked with the home having a common language and shared goals in the recognition, prevention and diagnosis of urinary tract infection. The COVID-19 pandemic required us to adapt our approach and work mainly online both in our interactions with stakeholders and as a research team. While this provided opportunities to extend our reach to a wider group of stakeholders, it also limited some of our engagement work.

Implementation of a tailored multifaceted antibiotic stewardship intervention to improve antibiotic prescribing for urinary tract infections in frail older adults (ImpresU) in four European countries: a process evaluation alongside a pragmatic cluster randomized controlled trial.

BACKGROUND: We previously performed a pragmatic cluster randomized controlled trial (RCT) in general practices and older adult care organizations in Poland, the Netherlands, Norway, and Sweden. We found that a multifaceted antibiotic stewardship intervention (ASI) substantially reduced antibiotic use for suspected urinary tract infections (UTIs) in frail older adults compared with usual care. We aimed to evaluate the implementation process of the ASI to provide recommendations for clinical practice. METHODS: We conducted a process evaluation alongside the cluster RCT. The ASI consisted of a decision-tool and a toolbox, which were implemented using a participatory-action-research (PAR) approach with sessions for education and evaluation. We documented the implementation process of the intervention and administered a questionnaire to health care professionals (HCPs) from participating organizations in the intervention and usual care clusters. We evaluated the multiple components of the intervention and its implementation following a structured framework. RESULTS: The questionnaire was completed by 254 HCPs from the 38 participating clusters. All components were largely delivered according to plan and evaluated as useful. The decision-tool and toolbox materials were reported to facilitate decision-making on UTIs. Regarding the PAR approach, educational sessions focusing on the distinction between UTIs and asymptomatic bacteriuria were held in all 19 intervention clusters. In 17 out of these 19 clusters, evaluation sessions took place, which were reported to help remind HCPs to implement the ASI. During both sessions, HCPs valued the reflection that took place and the resulting awareness of their behavior. It allowed them to explore implementation barriers and to tailor their local implementation process to overcome these. For example, HCPs organized extra educational sessions or revised local policies to incorporate the use of the decision-tool. Various HCPs took key roles in implementation. Staff changes and the COVID-19 pandemic were important contextual barriers. CONCLUSIONS: We found each component of the multifaceted ASI and its implementation to have added value in the process to improve antibiotic prescribing for suspected UTIs in a heterogeneous older adult care setting. We recommend using a multifaceted, multidisciplinary approach that enables HCPs to reflect on their current practice and accordingly tailor local implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT03970356. Registered on May 31, 2019.

Value of Urinary Neutrophil Gelatinase-Associated Lipocalin in Diagnosing Urinary Tract Infections in Children: A Systematic Review and Meta-Analysis.

This study presents a comprehensive review of the literature regarding the use of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a diagnostic tool for urinary tract infection (UTI) in children. Meta-analysis was conducted to evaluate the effectiveness of uNGAL in diagnosing UTI and differentiating acute pyelonephritis (APN) from other sites infection in pediatric patients. We searched PubMed, Web of Science, the Cochrane Library and EMBASE for reports published up to January 2023. We only included published literature that addressed the diagnosis of UTI and APN with the use of uNGAL in children aged 0-18 years. Two authors independently reviewed the included studies and extracted the corresponding data according to the inclusion and exclusion criteria. The sensitivity, specificity and area under the curve for each study were pooled by using a bivariate mixed-effects model. A total of 13 studies met the inclusion criteria for this review: 8 reported on uNGAL diagnosis of UTI, 2 on uNGAL diagnosis of APN, and 3 on both UTI and APN. Among all included studies, uNGAL had good sensitivity (0.88, 95% CI 0.79-0.94) and good specificity (0.86, 95% CI 0.78-0.92) for the diagnosis of UTI. The sensitivity and specificity of uNGAL for the diagnosis of APN were 0.79 (95% CI 0.72-0.85) and 0.78 (95% CI 0.50-0.93), respectively. uNGAL has good sensitivity and specificity in the diagnosis of UTI in children and is a promising marker. However, the use of uNGAL still does not provide significant advantages in the diagnosis of APN in children. Consequently, there is a need to optimize and further explore the assay for improved diagnostic accuracy.

Outpatient parenteral antimicrobial therapy with carbapenems: A systematic review.

OBJECTIVE: To review the literature on parenteral carbapenems in OPAT and present comprehensive evidence on their safety, efficacy, and stability. METHODS: A systematic review following PRISMA guidelines was conducted through 17 January 2024, using PubMed, Embase, Web of Science, Scopus, and the Cochrane Library to find relevant articles. RESULTS: Ertapenem (1 g QD) in OPAT showed high clinical (81-97%) and microbiological (67-90.9%) success rates. Ertapenem (1 g QD) was also comparable to piperacillin/tazobactam (3.375 g every 6 h) for complicated skin infections and superior to cefazolin (2 g every 8 h) and oxacillin (2 g every 4-6 h) for various infections. Ertapenem monotherapy, once daily, achieved an 81% clinical cure rate for urinary tract infections. Additionally, subcutaneous ertapenem in OPAT showed outcomes comparable to parenteral routes. Meropenem continuous infusion (CI) may also be considered safe and effective in selected patient populations; however, its use in OPAT as a CI is limited due to stability concerns. CONCLUSION: Parenteral carbapenems are effective, and well-tolerated OPAT treatment options; nonetheless, further studies are warranted to optimize the stability and/or dosing regimens of meropenem and enable its wider use.