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Urinary Tract Health and Antibacterial Benefits

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Cranberry, but not D-mannose and ibuprofen, prevents against uropathogenic Escherichia coli-induced cell damage and cell death in MDCK cells

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Authors
Konesan, Jenane; Wang, Jenny; Moore, Kate H.; Mansfield, Kylie J.; Liu, Lu
Journal
FRONTIERS IN MICROBIOLOGY 10.3389/fmicb.2023.1319785
Abstract

Introduction: The main function of the urinary tract is to form an impermeable barrier against urinary solutes and bacteria. However, this barrier can be compromised by urinary tract infections, most commonly caused by uropathogenic Escherichia coli (UPEC). This can result in damage to the epithelial barrier, leading to decreased epithelial thickness, loss of tight junctions, loss of epithelial integrity, and apoptosis. Due to the rise in antimicrobial resistance, there is worldwide interest in exploring non-antibiotic agents as alternative therapy. 

Methods: Using the Madin-Darby canine kidney (MDCK) cell line, a widely accepted epithelial cell model for the urinary tract, and the UPEC strain UTI89, this paper aimed to investigate the impact of UPEC on cell integrity, permeability, and barrier functions, and determine whether cranberry, D-mannose and ibuprofen could counteract the effects induced by UPEC. Furthermore, the study examined the protective potential of these agents against UPEC-induced increase in reactive oxygen species (ROS) production and programmed death-ligand 1 (PD-L1) expression.

Results: The results demonstrated that UTI89 caused a marked reduction in cell viability and monolayer integrity. Cranberry (3 mg/mL) was protective against these changes. In addition, cranberry exhibited protective effects against UPEC-induced damage to cell barrier integrity, escalation of oxidative stress, and UPEC/TNF alpha-triggered PD-L1 expression. However, no effect was observed for D-mannose and ibuprofen in alleviating UPEC-induced cell damage and changes in ROS and PD-L1 levels.

Conclusion: Overall, cranberry, but not D-mannose or ibuprofen, has a protective influence against UPEC associated damage in urinary epithelial cells. Turn on screen reader support To enable screen reader support, press Ctrl+Alt+Z To learn about keyboard shortcuts, press Ctrl+slash

Cranberry/Chondroitin Sulfate Co-precipitate as a New Method for Controlling Urinary Tract Infections

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Authors
Caglioti, Concetta; Iannitti, Rossana; Ceccarelli, Giada; Selan, Laura; Artini, Marco; Papa, Rosanna; Malvasi, Antonio; Gentile, Rosaria; Del Bianco, Diletta; Apone, Florinda; Angelini, Paola; Palazzetti, Federico; Fioretti, Bernard
Journal
ANTIBIOTICS-BASEL 10.3390/antibiotics12061053
Abstract

Urinary tract infections (UTI), which are among the most frequent cases of infectious diseases, mainly affect women. The most common treatment approach involves the use of antibiotics, although this solution is not always the most suitable, mainly because of the resistance that bacterial strains develop. Proanthocyanidins are a class of polyphenols, abundantly contained in cranberry extracts, which have shown beneficial effects in the treatment of urinary tract infections, due to their anti-adhesive properties toward bacteria, with respect to the membranes of the cells of the urothelium and intestine, thus reducing their virulence. In this work, we demonstrate via microscopy and scattering measurements how a mixture of cranberry and chondroitin sulfate can form a crosslinked structure with barrier properties. By using a design of experiment (DOE), we optimized the mass ratio to obtain a precipitate between cranberry extract and chondroitin sulfate in the presence of N-acetylcysteine and hyaluronic acid. By using transepithelial electrical resistance (TEER) chambers, we confirmed the barrier properties of the best mixture obtained with the DOE. Lastly, the antibiofilm action was investigated against five strains of Escherichia coli with different antibiotic sensitivity. The precipitate displayed a variable inhibitory effect in biofilm formation with major effects in UTI with an antibiotic resistance profile.

Differences in P-Type and Type 1 Uropathogenic Escherichia coli Urinary Anti-Adhesion Activity of Cranberry Fruit Juice Dry Extract Product and D-Mannose Dietary Supplement

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Authors
Howell, Amy B.; Dreyfus, Jean-Francois; Bosley, Scott; Krueger, Christian G.; Birmingham, Andrew; Reed, Jess D.; Chughtai, Bilal
Journal
JOURNAL OF DIETARY SUPPLEMENTS 10.1080/19390211.2024.2356592
Abstract

Background: Urinary tract infection (UTI) prevention benefits of cranberry intake are clinically validated, especially for women and children. To ensure the benefits of cranberry dietary supplement products, the anti-adhesion activity (AAA) against uropathogenic bacteria is routinely used in in vitro bioassays to determine the activity in whole product formulations, isolated compounds, and ex vivo bioassays to assess urinary activity following intake. D-mannose is another dietary supplement taken for UTI prevention, based on the anti-adhesion mechanism. 

Objective: Compare the relative AAA of cranberry and D-mannose dietary supplements against the most important bacterial types contributing to the pathogenesis of UTI, and consider how certain components potentially induce in vivo activity. 

Methods: The current study used a crossover design to determine ex vivo AAA against both P- and Type 1-fimbriated uropathogenic Escherichia coli of either D-mannose or a cranberry fruit juice dry extract product containing 36 mg of soluble proanthocyanidins (PACs), using bioassays that measure urinary activity following consumption. AAA of extracted cranberry compound fractions and D-mannose were compared in vitro and potential induction mechanisms of urinary AAA explored. 

Results: The cranberry dietary supplement exhibited both P-type and Type 1 in vitro and ex vivo AAA, while D-mannose only prevented Type 1 adhesion. Cranberry also demonstrated more robust and consistent ex vivo urinary AAA than D-mannose over each 1-week study period at different urine collection time points. The means by which the compounds with in vitro activity in each supplement product could potentially induce the AAA in urines was discussed relative to the data. 

Conclusions: Results of the current study provide consumers and healthcare professionals with additional details on the compounds and mechanisms involved in the positive, broad-spectrum AAA of cranberry against both E. coli bacterial types most important in UTIs and uncovers limitations on AAA and effectiveness of D-mannose compared to cranberry.

Emerging Non-Antibiotic Options Targeting Uropathogenic Mechanisms for Recurrent Uncomplicated Urinary Tract Infection

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Authors
Chen, Yu-Chen; Lee, Wei-Chia; Chuang, Yao-Chi
Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 10.3390/ijms24087055
Abstract

Urinary tract infections (UTIs) are the most frequent bacterial infections in the clinical setting. Even without underlying anatomic or functional abnormalities, more than 40% of women experience at least one UTI in their lifetime, of which 30% develop recurrent UTIs (rUTIs) within 6 months. Conventional management with antibiotics for rUTIs may eventually lead to the development of multidrug-resistant uropathogens. Targeting of the pathogenicity of rUTIs, the evolution of uropathogenic Escherichia coli (UPEC), and inadequate host defenses by immune responses should be explored to provide non-antibiotic solutions for the management of rUTIs. The adaptive evolution of UPEC has been observed in several aspects, including colonization, attachment, invasion, and intracellular replication to invade the urothelium and survive intracellularly. Focusing on the antivirulence of UPEC and modulating the immunity of susceptible persons, researchers have provided potential alternative solutions in four categories: antiadhesive treatments (i.e., cranberries and D-mannose), immunomodulation therapies, vaccines, and prophylaxis with topical estrogen therapy and probiotics (e.g., Lactobacillus species). Combination therapies targeting multiple pathogenic mechanisms are expected to be a future trend in UTI management, although some of these treatment options have not been well established in terms of their long-term efficacy. Additional clinical trials are warranted to validate the therapeutic efficacy and durability of these techniques.

Evidence-based review of nonantibiotic urinary tract infection prevention strategies for women: a patient-centered approach

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Authors
Stair, Sabrina L.; Palmer, Cristina J.; Lee, Una J.
Journal
CURRENT OPINION IN UROLOGY 10.1097/MOU.0000000000001082
Abstract

Purpose of review: There is a growing interest in nonantibiotic prevention strategies for recurrent urinary tract infections (rUTIs). Our objective is to provide a focused, pragmatic review of the latest evidence.

Recent findings: Vaginal estrogen is well tolerated and effective for preventing rUTI in postmenopausal women. Cranberry supplements at sufficient doses are effective in preventing uncomplicated rUTI. Methenamine, d-mannose, and increased hydration all have evidence to support their use, although the evidence is of somewhat variable quality.There is sufficient evidence to recommend vaginal estrogen and cranberry as first-line rUTI prevention strategies, particularly in postmenopausal women. Prevention strategies can be used in series or in tandem, based on patient preference and tolerance for side effects, to create effective nonantibiotic rUTI prevention strategies.

Nonantibiotic prophylaxis for urinary tract infections: a network meta-analysis of randomized controlled trials

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Authors
Han, Zeyu; Yi, Xianyanling; Li, Jin; Liao, Dazhou; Ai, Jianzhong
Journal
INFECTION 10.1007/s15010-024-02357-z
Abstract

Objective: Recent guidelines indicated that, in addition to antibiotics, nonantibiotic interventions serve as available preventive options for urinary tract infections (UTIs). This study aimed to compare the efficacy and safety of various nonantibiotic interventions in preventing UTIs. 

Methods: The authors systematically searched databases for eligible studies. The inclusion criteria encompassed randomized controlled trials (RCTs) focusing on one or more nonantibiotic interventions for UTI prevention, with the incidence of UTIs being a key outcome measure. Subgroup analyses were performed according to age, sex, and follow-up. 

Results: 50 RCTs comprising 10,495 subjects and investigating 14 interventions, were included. Nearly 80% of the RCTs utilized double-blind or triple-blind designs. In the whole group, D-mannose (risk ratio [RR] 0.34, 0.21 to 0.56), vaccine (RR 0.65, 0.52 to 0.82), probiotics (RR 0.69, 0.50 to 0.94), cranberry (RR 0.72, 0.60 to 0.87), and triple therapy (cranberry plus probiotics plus vitamin A) (RR 0.27, 0.09 to 0.87), exhibited a significant reduction in UTI incidence compared to the placebo. Probiotics (RR 0.50, 0.28 to 0.89) were the most effective in the nonadult group, while vitamin D (RR 0.46, 0.27 to 0.81) showed the highest efficacy in the long follow-up group (>= 1 year). There was no significant difference in the incidence of adverse events between the interventions and the placebo group. 

Conclusions: D-mannose, triple therapy, vaccine, probiotics, and cranberry serve as potential nonantibiotic intervention options for clinical UTI prevention.

Potential of Cranberry Jelly to Prevent Urinary Stone Formation After Cutaneous Ureterostomy: A Case Report

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Authors
Kaga, Kanya; Kaga, Mayuko
Journal
CUREUS JOURNAL OF MEDICAL SCIENCE 10.7759/cureus.54819
Abstract

One complication of cutaneous ureterostomy is urinary stone formation, which may lead to recurrent pyelonephritis. Frequent catheter changes and the prophylactic administration of antibiotics are commonly used to prevent stone formation. Cranberry products have been reported to inhibit stone formation in indwelling urethral catheters. We herein examined the inhibitory effects of a cranberry product on stone formation in a case of catheter occlusion due to stone formation after cutaneous ureterostomy. The results obtained indicate the potential of cranberry products to prevent stone formation after cutaneous ureterostomy requiring catheter placement.

Randomized, placebo-controlled, double-blinded study of prophylactic cranberries use in women with recurrent uncomplicated cystitis

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Authors
Tsiakoulias, Eleftherios; Gravas, Stavros; Hadjichristodoulou, Christos; Oikonomou, Katerina G.; Kyritsi, Maria; Dadouli, Katerina; Matziri, Alexia; Kola, Konstantina; Vacthsioli, Evangelia; Tsiakoulia, Marianna; Gianniou, Michaela; Tzortzis, Vassilios
Journal
WORLD JOURNAL OF UROLOGY 10.1007/s00345-023-04741-0
Abstract

Background:  The adherence of p-fimbriated Escherichia coli (E. coli) to urothelial cells leading to recurrent urinary tract infections (rUTIs) may be prevented by proanthocyanidins (PACs) contained in American cranberries.

Purpose: The purpose of this clinical trial was to assess the clinical utility of prophylactic use of high-dose PACs daily in women with a history of rUTIs.

Materials and methods: 172 adult women with a history of rUTIs, defined as >= 2 within a 6-month period or >= 3 within a 12-month period were enrolled and randomized in two groups to receive either Cysticlean (TM) 240 mg or placebo for a 12-month period. Urine samples, vaginal and rectal swabs were collected at initial and quarterly study visits. The primary study endpoints were the number of urinary tract infections (UTIs) and changes in Quality of Life (QoL), assessed by the 36-Item Short Form Survey (SF-36) questionnaire.

Results: 160 adult women of median age 40 years old (range 19-82) were finally analyzed in this randomized, placebo-controlled, double-blinded clinical trial. In response to intervention, the number of UTIs was significantly lower (Incidence rate ratio IRR 0.49, p < 0.001) and QoL was slightly improved. The numbers of E. coli isolates detected in vaginal (IRR 0.71, p value < 0.001) and in rectal swabs (IRR 0.87, p value < 0.001) were also significantly decreased. No adverse events were reported.

Conclusion: The daily use of Cysticlean (TM) 240 mg was associated with a reduction of UTIs and a prolongation of UTI-free survival compared to placebo treatment, supporting its use as prophylaxis in this patient population.

Reducing urinary tract infection in female pelvic surgery: A retrospective cohort study

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Authors
Mann, Gurkiran K.; Koenig, Nicole A.; Lee, Terry; Geoffrion, Roxana
Journal
INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS 10.1002/ijgo.14892
Abstract

Objective: To compare prebundle versus postbundle implementation urinary tract infection (UTI) rates among inpatients within 6 weeks of clean-contaminated pelvic reconstructive surgery. 

Methods:The authors conducted a retrospective cohort study from September 2019 to December 2021 at a tertiary hospital. The bundle strategy included the following: universal preoperative UTI check with treatment if positive, replacing prolonged postoperative voiding trials on the ward with earlier discharge and indwelling catheter removal by a nurse continence advisor the next day, and daily cranberry extract for 6 weeks postoperatively. UTI was defined as positive urine culture (>= 100 000 colony-forming unit per mL) in a symptomatic patient. Data analysis involved hypothesis testing and logistic regression. 

Results: The authors reviewed 132 postbundle inpatient charts and retained 93 for analyses. The results were compared with 204 prebundle inpatient charts. The rate of postoperative UTI decreased from 17.6% in the prebundle group to 6.5% after bundle implementation (P = 0.01). The adjusted odds ratio for postbundle versus prebundle likelihood of UTI was 0.35 (95% confidence interval, 0.13-0.98; P = 0.045). Significantly more postbundle patients compared with prebundle patients were discharged home on the first day postoperatively (76.3% vs. 37.7%, P < 0.001). 

Conclusions: A clinical bundle can significantly decrease both UTI rates and hospital stay after pelvic reconstructive surgery.

Segmental Acupuncture for Prevention of Recurrent Urinary Tract Infections. A Randomised Clinical Trial

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Authors
Ots, Thomas; Gold, Daniela; Ziller, Paul; Kuenzer, Thomas; Dalpiaz, Orietta; Pesto, Lejla; Trutnovsky, Gerda
Journal
INTERNATIONAL UROGYNECOLOGY JOURNAL 10.1007/s00192-024-05872-7
Abstract

Introduction and Hypothesis: Urinary tract infections (UTIs) are a common medical problem and prophylaxis of recurrent UTIs is an ongoing clinical challenge. In the present study we examined whether acupuncture is able to prevent recurrent UTIs in women. 

Methods: This multicentre randomised controlled trial, based at a University clinic and private acupuncture clinics, recruited women suffering from recurrent uncomplicated UTIs. Participants were randomised to the acupuncture group or control group. Acupuncture therapy consisted of 12 treatments over a period of 18 weeks, using a set of predefined body and ear acupuncture points. Cranberry products were recommended to all participants as standard of care.

Results: A total of 137 women were randomised (68 acupuncture, 69 control group) and occurrence of UTIs at 6 and 12 months could be assessed in 123 and 120 women respectively. Acupuncture combined with cranberry slightly increased the proportion of UTI-free women compared with cranberry alone at 6 months (59% vs 46%, p = 0.2). Between 6 and 12 months the proportion of UTI-free women was significantly higher in the acupuncture group (66 vs 45%, p = 0.03). The number of UTIs decreased from baseline to 12 months in both study groups. The number of UTIs at 12 months was significantly lower in the acupuncture group (median difference 1, p = 0.01).

Conclusions: Segmental acupuncture may be an effective treatment option for women with recurrent UTIs over a longer follow-up period and may limit antibiotics use. Further studies are needed.