Persistent Urinary Tract Infection Research Articles

High efficacy treatment of murine Pseudomonas aeruginosa catheter-associated urinary tract infections using the c-di-GMP modulating anti-biofilm compound Disperazol in combination with ciprofloxacin.

Persistent urinary tract infections (UTIs) in hospitalized patients constitute an important medical problem. It is estimated that 75% of nosocomial UTIs are associated with urinary tract catheters with P. aeruginosa being a species that forms biofilms on these catheters. These infections are highly resistant to standard-of-care antibiotics, and the effects of the host immune defenses, which allows for development of persistent infections. With antibiotics losing their efficacy, new treatment options against resilient infections, such as catheter-associated urinary tract infections (CAUTIs), are critically needed. Central to our anti-biofilm approach is the manipulation of the c-di-GMP signaling pathway in P. aeruginosa to switch bacteria from the protective biofilm to the unprotected planktonic mode of life. We recently identified a compound (H6-335-P1), that stimulates the c-di-GMP degrading activity of the P. aeruginosa BifA protein which plummets the intracellular c-di-GMP content and induces dispersal of P. aeruginosa biofilm bacteria into the planktonic state. In the present study, we formulated H6-335-P1 as a hydrochloride salt (Disperazol), which is water-soluble and facilitates delivery via injection or oral administration. Disperazol can work as a monotherapy, but we observed a 100-fold improvement in efficacy when treating murine P. aeruginosa CAUTIs with a Disperazol/ciprofloxacin combination. Biologically active Disperazol reached the bladder 30 min after oral administration. Our study provides proof of concept that Disperazol can be used in combination with a relevant antibiotic for effective treatment of CAUTIs.

Herbal Solutions for Urinary Tract Infections: A Literature Review

If treatment is not received, Urinary Tract Infections (UTIs), which are frequent microbial illnesses affecting the urinary system, can lead to discomfort and problems. Because they have antibacterial qualities and can potentially reduce UTI symptoms, natural treatments have been used. Supplements or juice made from cranberries are one popular natural treatment. Proanthocyanidins, which are found in cranberries, have the potential to inhibit bacteria, especially E. coli, from adhering to the lining of the urinary tract, hence decreasing the risk of infection. Its efficacy is still up for discussion, though, and certain drinks’ high sugar content may make UTI symptoms worse. D-mannose, a kind of sugar included in fruits like peaches and cranberries, is another commonly utilised treatment. D-mannose inhibits germs from sticking to the walls of the urinary system, in a manner akin to that of cranberries. It’s believed to be effective against E. coli, a common UTI-causing bacterium, but it’s ideal dosage and long-term effects require further research. Probiotics are thought to be helpful for UTIs, particularly those that contain lactobacilli strains. They may lessen the chance of infection by assisting in the maintenance of a balanced population of bacteria in the urinary tract and gut. There is, however, little data to support their direct influence on UTI treatment. Herbal treatments with possible antibacterial effects, such as buchu, goldenseal, and bearberry (uva-ursi), have been used historically. These herbs have ingredients that may aid in the battle against germs in the urinary system, but further research is needed to determine how safe and effective they are. Increasing water consumption is a simple yet effective treatment. Drinking enough water dilutes urine, which lowers the quantity of bacteria that could lead to an illness, and aids in the removal of bacteria from the urinary system. Even while these natural treatments seem promising for treating UTIs, it is important to see a doctor before using them, particularly if you think the illness may be serious. Certain medical issues may prevent the use of natural therapies, or they may interact negatively with medicines. When used as the only treatment for acute UTIs, they are frequently less successful than when used as preventative measures or in conjunction with traditional medicines. The main line of treatment for severe or persistent UTIs is still medical intervention with antibiotics to avoid complications and recurrent infections.

Воспаление парауретральных протоков и желез у женщин: проблема с 350-летней историей.

Introduction. Inflammation of the Skene glands is one of the common causes of persistent dysuria and recurrent lower urinary tract infections. Lack of awareness about this pathology can lead to diagnostic errors and inadequate treatment. This pathology is not sufficiently covered in the literature, which was the reason for preparing this lecture. Results. The lecture review covers the history of studying the anatomy of the paraurethral glands in women, the first attempts to diagnose and treat various diseases. The issues of homology of the paraurethral ducts and glands in women with the prostate gland in men are considered, the anatomy, morphology and immunohistochemical properties of the Skene glands are described, as well as modern ideas about their function. The historical background, nomenclature and classification are presented. The role of inflammation in these structures as a cause of persistent dysuria and a source of persistent lower urinary tract infections has been demonstrated. The need to standardize the methodology for examining patients with skineitis and the search for a specialized instrument for an adequate examination of the female urethra is substantiated. An analysis of the effectiveness of electrical resection of Skene's glands was carried out. Conclusions. One of the main factors behind unsatisfactory treatment results for lower urinary tract infections is inflammation of the paraurethral ducts and glands. Their insufficient visualization and assessment are the reasons for frequent relapses of the disease and repeated surgical interventions.

High antipersister activity of a promising new quinolone drug candidate in eradicating uropathogenic Escherichia coli persisters and persistent infection in mice.

To develop more potent drugs that eradicate persister bacteria and cure persistent urinary tract infections (rUTIs). We synthesized eight novel clinifloxacin analogs and measured minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), the time-kill curves in uropathogenic Escherichia coli (UPEC) UTI89, and applied the candidate drugs and combinations against biofilm bacteria in vitro and in mice. Transcriptomic analysis was performed for UPEC after candidate drug treatment to shed light on potential mechanism of action. We identified Compound 2, named Qingdafloxacin (QDF), which was more potent than clinafloxacin and clinically used levofloxacin and moxifloxacin, with an MIC of<0.04μg ml-1 and an MBC of 0.08∼0.16μg ml-1. In drug combination studies, QDF+gentamicin+nitrofuran combination but not single drugs completely eradicated all stationary phase bacteria containing persisters and biofilm bacteria, and all bacteria in a persistent UTI mouse model. Transcriptome analysis revealed that the unique antipersister activity of QDF was associated with downregulation of genes involved in bacterial stress response, DNA repair, protein misfolding repair, pyrimidine metabolism, glutamate, and glutathione metabolism, and efflux. QDF has high antipersister activity and its drug combinations proved highly effective against biofilm bacteria in vitro and persistent UTIs in mice, which may have implications for treating rUTIs.

Incidence of biofilms among the multidrug resistant E. coli, isolated from urinary tract infections in the Nilgiris district, South India.

Multidrug resistant uropathogenic Escherichia coli (MDRUPEC) significantly correlates with recurrent, complicated, and persistent urinary tract infection (UTI). The leading cause of multidrug resistance is the ability of E. coli to form biofilms. The physiological heterogeneity, genetic incontinency, and putative events in gene expression of biofilms render them resistant to antimicrobials and the host immune system. Understanding the determinants of antimicrobial resistance and its correlation with biofilm formations will, therefore, help the development of a better strategy for treating biofilm-associated UTIs. The present study reports on the in vitro detection of biofilm formation among multidrug resistant E. coli strains isolated from urine, the major cause of communal, nosocomial, and food-borne uropathogenic UTI. This is a cross-sectional study conducted in and around Ooty, Nilgiris, India. From the 869 urine samples analyzed for UTI, 29.34% were found to be caused by E. coli. Among this about 23.92% were found to be multidrug resistant. Among the multidrug resistant E. coli isolates, 36.06% of them were potent biofilm producers. E. coli biofilms (n = 22) were resistant to the antibiotics used to treat UTI, namely, amikacin, amoxicillin, ampicillin, cefepime, cefoperazone, cefotaxime, ceftriaxone, cefuroxime, cephalotin, ciprofloxacin, co-trimoxazole, gentamicin, levofloxacin, and nalidixic acid, but sensitive to imipenem and meropenem. All the biofilm producers exhibited motility and hemaggultination but none were positive for hemolysin production. The isolated E. coli biofilms were confirmed by VITEK R2 Compact (bioMerieux, France) and 16S rRNA gene sequencing.

Progress in the Research of Reflux Nephropathy

Reflux nephropathy (RN) is a renal disease caused by Vesicoureteral Reflux (VUR) and Intrarenal Reflux (IRR), resulting in renal cortical scar (localized atrophy) and focal glomerulosclerosis. RN is one of the important causes of end-stage renal diseases (ESRD). The most basic pathological feature of RN is kidney scarring. Common clinical manifestations are persistent or recurrent urinary tract infection, albuminuria, hypertension, nocturia, polyuria, lumbago, urinary calculi, etc. Due to the hidden condition of RN, doctors in various departments, especially in pediatrics, nephrology and urology, must strengthen their understanding and understanding of this disease, so as to facilitate the early detection and diagnosis of this disease. Correct conservative treatment of Western medicine, surgical treatment when necessary, and reasonable integrated treatment of Chinese and Western medicine are of great significance for the prevention and treatment of the progression from RN to ESRD.

Uterus Masculinus with a Patent Urethral Communication Documented with Positive Contrast Computed Tomography.

A 9 mo old male Labrador retriever presented for investigation into persistent urinary incontinence. Abdominal ultrasound and retrograde urethrocystogram with computed tomography documented a uterus masculinus (UM), which was confirmed on histopathology after surgical removal. A connection between the UM and the urethra was present, documented by positive contrast retrograde urethrocystography and confirmed with surgery. Typically, in the literature, UM are blind ending, and there are only a few case reports that demonstrate an assumed connection. This case has demonstrated a patent connection between the UM and the urethra, which should be considered a differential diagnosis for persistent urinary incontinence and urinary tract infection in juvenile male dogs.

Complete perforated bladder from intrauterine devices: A case series report from a nationwide monitoring system.

Complete perforation of the bladder caused by an intrauterine device (IUD) is rare. This study examined the characteristics of patients associated with IUD-related bladder perforation and evaluated the relationship between mislocated IUDs and their potential complications. From October 2005 to December 2021, 13 reports regarding complete perforations to the bladder by IUDs were retrieved from the National Contraceptives Adverse Reaction Monitoring System of China. The clinical features of these cases were analyzed. The median patient age was 30 (range, 27-46) years. There were four cases (4/13, 30.8%) with IUDs placed during lactation, one case (1/13, 7.7%) with an IUD placed after medical abortion, and eight cases (8/13, 61.5%) placed after menstruation. Seven cases (7/13, 53.9%) were first-time IUD users. The median duration of IUD placement was 47 (range, 1-145) months. Unexpected pregnancy was reported in five cases (5/13, 38.5%). Six cases (6/13, 46.2%) reported bladder stones with varying degrees of abdominal pain or urinary tract infection. Removal methods included laparotomy (four cases), cystoscopy (four cases), laparoscopy (two cases), laparoscopy combined with cystoscopy (two cases), and laparotomy after cystoscopy (one case). All IUDs were successfully removed. Complete perforation to the bladder by IUDs is a rare adverse event. Regular follow-up is required after the placement of IUDs. The possibility of uterine perforation should be investigated if IUD users encounter persistent lower abdominal pain or urinary tract infection.

HF01-10 EVOLUTION TO EXTINCTION?: THE SAGA OF FEMALE URETHRAL DILATION

You have accessJournal of UrologyCME1 Apr 2023HF01-10 EVOLUTION TO EXTINCTION?: THE SAGA OF FEMALE URETHRAL DILATION Jasmine Kashkoush and Brant Fulmer Jasmine KashkoushJasmine Kashkoush More articles by this author and Brant FulmerBrant Fulmer More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003243.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Historically, many women have reported bothersome urinary symptoms and recurrent urinary tract infections (UTIs). The challenge in managing these symptoms led to the practice of urethral dilation in the 1920s, despite the rarity of a female urethral stricture. With little scientific data to support its efficacy, this practice should have gone to extinction; however, it is still very common. This represents a historical review of urethral dilation in women and its penetration in modern day practice patterns. METHODS: A literature review was performed to evaluate the history of female urethral dilation. RESULTS: In 1923, Stevens theorized the culprit behind bothersome urinary symptoms was a narrow urethral meatus, initially presenting the idea of urethral dilation/incision. He advocated for urethral meatotomy with a scalpel up to 30 Fr. This was refined by Davis in the 1950s with the use of an Otis urethrotome to incise the urethra up to 45 Fr. This was popularized in the 1960s when Keitzer, Lyon, and Kerr thought persistent UTIs were due to a “contraction ring in the distal urethra of little girls.” They used sounds and Otis urethrotomes in infants to dilate and/or incise the entire urethra. Eventually, this practice lost scientific backing due to complications of urinary incontinence as well as favorable outcomes with less invasive options. In fact, the last reference to using urethral dilation without a urethral stricture was in 1970. Interestingly, despite the lack of data to support its use, Medicare reimbursement still shows high utilization and cost expenditures. Almost $70 million was spent in 2000 despite only ∼40 documented cases of female urethral stricture. Furthermore, when surveying urologists, those who completed residency after 1989 rarely performed urethral dilation when compared to their predecessors who find it a useful practice. CONCLUSIONS: A wide variety of treatment modalities have been used to manage recurrent UTIs and irritative lower urinary tract symptoms. Female urethral dilation was common despite the rarity of a female urethral stricture. Urinary incontinence and a better understanding of bladder function have decreased the data in favor of female urethral dilation, putting into question its practice. Evidence based medicine supports medical management, vaginal estrogen, and pelvic floor physical therapy more favorably. One would hope that this practice would go into extinction; however, Medicare data still shows high utilization. Perhaps updated guideline statements and better education of patients that have had prior dilations will help in debunking this practice. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e259 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jasmine Kashkoush More articles by this author Brant Fulmer More articles by this author Expand All Advertisement PDF downloadLoading ...

In silico design and in vivo evaluation of two multi-epitope vaccines containing build-in adjuvant with chitosan nanoparticles against uropathogenic Escherichia coli.

Urinary pathogenic Escherichia coli (UPEC) is one of the most important bacterial causes of urinary tract infections (UTIs). Rising antimicrobial resistance and serious clinical challenges such as persistent and recurrent UTIs make it a serious public health concern. Therefore, preventative approaches such as vaccinations are required. In this study, we selected three conserve and protective antigens (FdeC, Hma and UpaB) and also subunit B of cholera toxin (as build-in adjuvant) to design two multi-epitope vaccines (construct B containing B cell epitopes and construct T containing T epitopes) using different bioinformatics methods. The expression of the recombinant protein was performed using the BL21(DE3)/pET28 expression system and purified through a Ni-NTA column. Vaccine proteins were encapsulated in chitosan nanoparticles (CNP) based on ionic gelation via a microfluidic system. Mice were immunized intranasally with different vaccine formulations. Antibody responses and also cytokine expression (IFN-γ and IL-4) were measured by ELISA and real-time PCR respectively. The effectiveness of immune responses was assessed by bladder challenge. Based on the in silico study, construct B and construct T have high confidence value and stable structure in vivo. High yield expression of both constructs was confirmed by SDS-PAGE and western blot assay. Immunization of mice with construct B induced strong Th2 (IgG1 and IL4) responses and construct T shift immune responses to Th1 (IFNγ and IgG2a). Vaccine protein-encapsulated CNP elicited higher levels of antibodies and cell-mediated responses than the vaccine proteins alone. The results of this study suggest that intranasal administration of the construct B has the potential to enhance humoral immunity and construct T has the potential to stimulate cellular immunity. In addition, the combination of CTB as a build-in adjuvant and CNP can be proposed as a potent adjuvant for the development of a novel vaccine against UTI.

More than a Persistent Urinary Tract Infection: The Usefulness of Ultrasound in the Emergency Department in a Clinical Case

A 65-year-old male, hypertensive and non-insulin-dependent type 2 diabetes mellitus as the only personal history of interest, who came to the Emergency Department of our hospital with micturition symptoms consisting of dysuria and pollakiuria associated with mild hematuria and hypogastric pain of 14 days of evolution. The patient did not report fever or any other associated symptoms.

Effect of pH, Norepinephrine and Glucose on Metabolic and Biofilm Activity of Uropathogenic Microorganisms.

Urinary tract infection (UTIs) aremainly caused by a number of anatomical and physiological dysfunctions, but there are also some iatrogenic factors, including the use of certain medications, that contribute to the development of UTIs. The virulence of bacteria that colonize the urinary tract may be modified by pH and by the presence of soluble substances in urine, such as norepinephrine (NE) and glucose. In this work, we studied the influence of NE and glucose across a range of pHs (5, 7, 8) on the biomass, matrix production and metabolism of uropathogenic strains of Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecalis. We used Congo red and gentian violet to stain the extracellular matrix and biomass, respectively, of biofilms. The optical density of staining of the biofilms was measured using a multichannel spectrophotometer. The metabolic activity was analyzed by MTT assay. It was shown that NE and glucose stimulate biomass production both in the Gram-negative and Gram-positive uropathogens. The metabolic activity in the presence of glucose was higher at pH 5 for E. coli (in 4.0 ± 0.1 times), Ps. aeruginosa (in 8.2 ± 0.2 times) and Kl. pneumoniae (in 4.1 ± 0.2 times). Matrix production of Kl. pneumoniae increased under NE (in 8.2 ± 0.2 times) and in the presence of glucose (in 1.5 ± 0.3 times). Thus, NE and glucose in urine may lead to persistent UTI under patient stress and in the case of metabolic glucose disorders.

Кистозно-железистая метаплазия мочевого пузыря.

Introduction. Cystic-glandular cystitis is one of the varieties of metaplasia of the bladder wall, which, in rare cases, can manifest itself in the form of voluminous polypoid growths. Clinical study. This article presents a case of polypoid changes in the bladder wall due to cystic glandular cystitis in a 74-year-old man against the background of a chronic inflammatory process and achalasia of the upper urinary tract. This observation confirms the theory of the etiological significance for the development of urothelial metaplasia of a long-term persistent urinary tract infection. The only reliable method for diagnosing cystic glandular cystitis and differential diagnosis of pseudotumor changes from urothelial carcinoma is morphological, after transurethral resection. Conclusion. The observation presented in this article showed that the clinical manifestations of cystic glandular cystitis can be variable and require an integrated approach to diagnosis and treatment.

Staphylococcus aureus ST1 promotes persistent urinary tract infection by highly expressing the urease.

Staphylococcus aureus (SA) is a relatively uncommon cause of urinary tract infections (UTIs) in the general population. Although rare, S. aureus-induced UTIs are prone to potentially life-threatening invasive infections such as bacteremia. To investigate the molecular epidemiology, phenotypic characteristics, and pathophysiology of S. aureus-induced UTIs, we analyzed non-repetitive 4,405 S. aureus isolates collected from various clinical sources from 2008 to 2020 from a general hospital in Shanghai, China. Among these, 193 isolates (4.38%) were cultivated from the midstream urine specimens. Epidemiological analysis showed UTI-derived ST1 (UTI-ST1) and UTI-ST5 are the primary sequence types of UTI-SA. Furthermore, we randomly selected 10 isolates from each of the UTI-ST1, non-UTI-ST1 (nUTI-ST1), and UTI-ST5 groups to characterize their in vitro and in vivo phenotypes. The in vitro phenotypic assays revealed that UTI-ST1 exhibits an obvious decline in hemolysis of human red blood cells and increased biofilm and adhesion in the urea-supplemented medium, compared to the medium without urea, while UTI-ST5 and nUTI-ST1 did not show significant differences between the biofilm-forming and adhesion abilities. In addition, the UTI-ST1 displayed intense urease activities by highly expressing urease genes, indicating the potential role of urease in UTI-ST1 survival and persistence. Furthermore, in vitro virulence assays using the UTI-ST1 ureC mutant showed no significant difference in the hemolytic and biofilm-forming phenotypes in the presence or absence of urea in the tryptic soy broth (TSB) medium. The in vivo UTI model also showed that the CFU of the UTI-ST1 ureC mutant rapidly reduced during UTI pathogenesis 72 h post-infection, while UTI-ST1 and UTI-ST5 persisted in the urine of the infected mice. Furthermore, the phenotypes and the urease expression of UTI-ST1 were found to be potentially regulated by the Agr system with the change in environmental pH. In summary, our results provide important insights into the role of urease in S. aureus-induced UTI pathogenesis in promoting bacterial persistence in the nutrient-limiting urinary microenvironment.

Persistent Urinary Tract Infection in Association with Community-Acquired NDM-5 Escherichia coli Clonal Group Following COVID-19 Infection - Beijing Municipality, China, 2023.

The hospital-acquired infections caused by New Delhi metallo-beta-lactamase (NDM)-producing strains are typically attributed to a single clonal lineage. In this study, we encountered a unique case of community-acquired NDM-5 Escherichia coli urinary tract infection (UTI) following coronavirus disease 2019 (COVID-19). The UTI persisted for a duration of at least 45 days. Genomic analyses revealed the presence of two NDM-5 strains, both sharing an identical chromosomal background but distinct, homologous, and recombined plasmids. This case suggests that a diverse range of resistance genes may be present within the human body, with drug-resistant strains undergoing continuous evolution during infection. The intestinal tract may have been its drug-resistant gene pool. The observations presented in this case indicate that the endogenous acquisition of drug-resistant genes may also be an issue in managing multidrug-resistant organisms (MDRO). It is possible for continuous recombination to occur within carbapenem-resistant Enterobacteriaceae (CRE) during infection. In contrast to exogenously-acquired resistance, greater attention should be placed on the endogenous factors that contribute to the development of CRE within healthcare settings.

Urinary pH: its regulation and relevance in urolithiasis metaphylaxis

Urolithiasis is a common multifactorial disease characterized by a high recurrence rate. This review is devoted to the urine pH as one of the main factors determining its lithogenic properties. It affects the excretion of lithogenic substances and stone formation inhibitors, the solubility, and the crystallization of substances involved in stone formation. The urine pH significantly affects the solubility of uric acid in urine, which decreases at a pH &lt; 5.5. This explains the high incidence of uric acid concretions in patients with metabolic syndrome. Their insulin resistance leads to a decrease in the excretion of ammonium ions in the proximal tubules, leading to persistent urine acidification. The activity of many transport processes involved in the processing of calcium, citrates and phosphates is sensitive to changes in systemic or local pH. The data on the effect of urine pH on the solubility of calcium oxalate remain contradictory. At the same time, there is no doubt about the determining role of urine pH in the excretion of citrate, the most important stone formation inhibitor. The alkaline urine pH promotes the formation of concretions containing calcium phosphates. In conditions of constantly elevated urine pH in patients with persistent urease-producing urinary tract infection, a rapid growth of "infectious" concretions occurs. The review summarizes information on the causes of the decrease and increase in the urine pH, as well as the possibilities of medicinal and non-medicinal methods of modifying the urine pH during the prevention of stone formation recurrence.

Interaction of Neutrophils and Biofilm Formed by Uropathogenic Escherichia coli Strains with Different Pathogenic Potential.

The biofilm formation by uropathogenic E. coli (UPEC) allows bacteria to avoid the influence of the host immune system that determines the pathogenesis of persistent urinary tract infections. The purpose of this work was to evaluate the mutual influence of neutrophils and biofilms formed by UPEC with different set of virulence-associated genes (VAGs). E. coli R11 and R32 strains with a wide range of virulence factors were characterized by low biofilm biomass that did not change after interaction with neutrophils. The biomass index decreased after interaction with neutrophils for strains with a limited set of pathogenicity factors (R33, R36, R45, and R44) and a "thick" biofilm. Bacterial cells and biofilm supernatants of all UPEC strains reduced viability (DiOC6(3)+/PI-) and stimulated early apoptosis (DiOC6(3)-/PI-) of neutrophils. The number of viable neutrophils was higher, while the number of apoptotic and necrotic (DiOC6(3)-/PI+) cells was lower under the action of supernatants of strains R44, R36, R45 in comparison with bacterial cells. Thus, modulation of the innate cell functions depends on the realization of the pathogenic potential of UPEC bacteria in urinary tract biofilms that determines the development of recurrent urinary tract infections.

P13.06: Valve Bladder Diversion, Making Possible a Kidney Transplant

Introduction: The late diagnosis in a patient with posterior urethral valve (PUV) and end-stage kidney disease is a challenging scenario which may need renal replacement therapy and reconstruction of the urinary tract. Reducing recurrent urinary tract infections (UTI) is the main urologic objective in these patients in order to offer them a kidney transplantation (KT). Many factors must be considered to define the best moment to perform the reconstruction, that could be done prior, during or after kidney transplantation. Patient and Method: This is a 5-year-old boy who was admitted for febrile urinary tract infection. During the admission end-stage kidney disease and PUV were diagnosed. The first step was to perform a cystoscopy and valvular ablation. Videourodynamyc studies after surgery showed a bladder’s capacity of 50 ml, low compliance, incomplete emptying associated with high grade bilateral vesicoureteral reflux. Hemodialysis began as renal replacement therapy, antibiotic prophylaxis and anticholinergics were indicated. Four months later, an open vesicostomy was performed due to persistent febrile urinary tract infections. Eleven months after diagnosis, the patient was transplanted using a graft from a deceased donor. At the same time of transplant surgery, the right kidney and ureter were resected through a right hockey stick incision. Two months after transplantation another endoscopic residual valve ablation was done. After seventeen months from kidney transplant, the left kidney and ureter were resected by laparoscopy. Urodynamic studies continued showing high voiding detrusor pressure. While patient kept his bladder diverted, incontinence was managed with five diapers a day and maintained scholar and physical activities. At two years of follow-up, a third valvular endoscopic revision and ablation was performed associated with circumcision and replacing the open vesicostomy with a suprapubic tube. Intermittent opening was indicated and after three months, the tube was removed. Six months after the last surgery, bladder’s capacity improved from 100 ml to 250 ml, bladder emptying has no residual volume and no incontinence. Kidney ultrasonography did not present hydronephrosis and cystography showed no VUR. Twenty nine months after KT the patient remained urinary tract infections free, creatinine level was 0.68 mg/dL and clearance 102 ml/min/1.73 m2. Conclusion: Open vesicostomy is a simple and safe procedure to manage UTI and allows kidney transplant in PUV valve bladders. Urological surveillance after transplant involves clinical assessment, urodynamic studies, endoscopic and reconstructive surgeries. Bladder cycling after transplant improves storage and augmentation procedures may not be needed.

Probiotics: Lactic Acid Bacteria have Antibacterial Activity and Downregulate Biofilm Genes of Uropathogenic E. coli

Urinary tract infections (UTIs) are regarded as one of the most serious infections worldwide. Uro Pathogenic E. coli (UPEC) accounts for nearly 80% of UTI infections in females. This study investigated the antibacterial and antibiofilm effects of Lactobacillus acidophilus (l. acidophilus) and Lactobacillus plantarum (lb. plantarum) on multidrug-resistant E. coli obtained from urine samples. Complete bacteriological identification was conducted on 45 E. coli isolated from 80 urine samples of females with UTIs. Antibiotic susceptibility test was performed on all isolates by nine antibiotics. Ten out of the 45 isolates exhibited multidrug resistance (MDR). L. acidophilus and Lb. plantarum showed marked inhibition of MDR E. coli isolates on agar by a diffusion method (16 ± 0.04: 23 ± 0.05 mm). Moreover, L. acidophilus and Lb. plantarum strains inhibited the ability of UPEC to form a biofilm by 56.3% and 39.63%, respectively. The expression of biofilm genes of E. coli are as follows: csgA, crl, csgD showed remarkable downregulation after treatment with probiotics suspension: 0.00364: 0.19078 fold, 0.0005: 0.1894 fold, and 0.0490: 0.0883 for L. acidophilus, respectively. On the other hand, downregulation of biofilm gene expression for csgA, crl, csgD after treatment with Lb. plantarum suspension were expressed by fold changes as follows: 0.0769: 0.3535 fold, 0.05440: 0.12940 fold, and 0.06745: 0.4146, respectively. These findings show that L. acidophilus and Lb. plantarum exhibit potent antibacterial and antibiofilm action against MDR UPEC at both genotypic and phenotypic levels, and appear to be a promising solution in therapeutic applications for recurrent and persistent UTIs.

Basement membrane defects in CD151-associated glomerular disease

BackgroundCD151 is a cell-surface molecule of the tetraspanin family. Its lateral interaction with laminin-binding integrin ɑ3β1 is important for podocyte adhesion to the glomerular basement membrane (GBM). Deletion of Cd151 in mice induces glomerular dysfunction, with proteinuria and associated focal glomerulosclerosis, disorganisation of GBM and tubular cystic dilation. Despite this, CD151 is not routinely screened for in patients with nephrotic-range proteinuria. We aimed to better understand the relevance of CD151 in human kidney disease.MethodsNext-generation sequencing (NGS) was used to detect the variant in CD151. Electron and light microscopy were used to visualise the filtration barrier in the patient kidney biopsy, and immunoreactivity of patient red blood cells to anti-CD151/MER2 antibodies was performed. Further validation of the CD151 variant as disease-causing was performed in zebrafish using CRISPR-Cas9.ResultsWe report a young child with nail dystrophy and persistent urinary tract infections who was incidentally found to have nephrotic-range proteinuria. Through targeted NGS, a novel, homozygous truncating variant was identified in CD151, a gene rarely reported in patients with nephrotic syndrome. Electron microscopy imaging of patient kidney tissue showed thickening of GBM and podocyte effacement. Immunofluorescence of patient kidney tissue demonstrated that CD151 was significantly reduced, and we did not detect immunoreactivity to CD151/MER2 on patient red blood cells. CRISPR-Cas9 depletion of cd151 in zebrafish caused proteinuria, which was rescued by injection of wild-type CD151 mRNA, but not CD151 mRNA containing the variant sequence.ConclusionsOur results indicate that a novel variant in CD151 is associated with nephrotic-range proteinuria and microscopic haematuria and provides further evidence for a role of CD151 in glomerular disease. Our work highlights a functional testing pipeline for future analysis of patient genetic variants.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information