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Urinary Tract Health and Antibacterial Benefits

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Corrected: Cranberry Supplements for Urinary Tract Infection Prophylaxis in Pregnant Women: A Systematic Review of Clinical Trials and Observational Studies on Efficacy, Acceptability, Outcomes Measurement Methods, and Studies' Feasibility

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Authors
Bolgarina, Zoryana; Gonzalez-Gonzalez, Luis Fernando; Rodroiguez, Guillermo Villamizar; Camacho, Alejandro
Journal
CUREUS JOURNAL OF MEDICAL SCIENCE 10.7759/cureus.46738
Abstract

Cranberry supplements are commonly used to prevent urinary tract infections (UTIs). However, their usefulness is uncertain in pregnant women. We aimed to comprehensively summarize the current knowledge on cranberry supplements' efficacy and acceptability during pregnancy in addition to the outcome's measurement methods and studies' feasibility. To achieve it, we searched PubMed, PMC, and Europe PMC databases plus screened citations followed by critical appraisal of included eligible English written primary studies that (1) focused on pregnant women supplemented with any cranberry supplements; (2) provided data on cranberry supplements' efficacy, acceptability, outcomes measurement methods, and studies' feasibility; (3) included human subjects; and (4) published worldwide. Two randomized clinical trials (RCTs) and one nested cohort study, including 1156 pregnant women in total, contributed to our analysis. A tendency toward UTI reduction was demonstrated, although the results' validity was impacted by significant juice-induced gastrointestinal intolerance (23%; 44 of 188 subjects). Changing the form of supplementation from cranberry juice to capsules reduced the issue, causing side effects in one of 49 subjects (2%). Nevertheless, both RCTs still experienced significant recruitment and retention problems, which were at 33% and 59% on average, respectively. Newly acquired safety data on 919 more subjects suggests no increased risks of all malformations, vaginal bleeding, and neonatal complications. Investigating cranberry capsules' efficacy as a non-antibacterial option for UTI prevention in pregnant women has become a feasible and important direction with the current advancement in understanding cranberry supplements' actions, recommended doses plus regimens, and their safety in the population. We reviewed the challenges and discovered knowledge gaps and the implementation strategies for future studies.

Cranberries for treating urinary tract infections

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Authors
Jepson, Ruth G.; Mihaljevic, Lara; Craig, Jonathan C.
Journal
COCHRANE DATABASE OF SYSTEMATIC REVIEWS 10.1002/14651858.CD001322.pub2
Abstract

Background: Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). The aim of this review is to assess the effectiveness of cranberries in treating such infections.

Objectives: To assess the effectiveness of cranberries for the treatment of UTIs.

Search methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 1 August 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Portal (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria: All randomised controlled trials (RCTs) or quasi-RCTs of cranberry juice or cranberry products for the treatment of UTIs. Studies of men, women or children were to be included.Data collection and analysisTitles and abstracts of studies that were potentially relevant to the review were screened and studies that were clearly ineligible were discarded. Further information was sought from the authors where papers contained insufficient information to make a decision about eligibility.Main resultsNo studies were found that fulfilled all of our inclusion criteria. Seven studies were excluded because they were the wrong study design, mixed interventions or did not report any relevant outcomes. One study is ongoing; however, its current status is unknown.

Authors' conclusions: After a thorough search, no RCTs which assessed the effectiveness of cranberry juice for the treatment of UTIs were found. Therefore, at the present time, there is no good quality evidence to suggest that it is effective for the treatment of UTIs. Well-designed parallel-group, double-blind studies comparing cranberry juice and other cranberry products versus placebo to assess the effectiveness of cranberry juice in treating UTIs are needed. Outcomes should include a reduction in symptoms, sterilisation of the urine, side effects and adherence to therapy. The dosage (amount and concentration) and duration of therapy should also be assessed. Consumers and clinicians will welcome the evidence from these studies.

PLAIN LANGUAGE SUMMARY: Still waiting for evidence about whether cranberries are useful for treating urinary tract infectionsCranberries contain a substance that can prevent bacteria from sticking to the walls of the bladder. This may help reduce bladder and other urinary tract infections (UTIs). Cranberries (usually as cranberry juice) have been used to try and treat UTIs, particularly in high-risk groups such as older people. Cranberries have few adverse effects. This review found no studies reporting the effects of cranberry juice or other cranberry products on the treatment of UTIs.

Cranberry Juice, Cranberry Tablets, or Liquid Therapies for Urinary Tract Infection: A Systematic Review and Network Meta-analysis.

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Authors
Moro, Christian; Phelps, Charlotte; Veer, Vineesha; Jones, Mark; Glasziou, Paul; Clark, Justin; Tikkinen, Kari A O; Scott, Anna Mae
Journal
European urology focus 10.1016/j.euf.2024.07.002
Abstract

BACKGROUND AND OBJECTIVE: With over 50% of women suffering from at least one episode of urinary tract infection (UTI) each year and an increasing prevalence of antimicrobial resistance, efforts need to be made to clearly identify the evidence supporting potential non-drug interventions. This study aims to compare the effects of cranberry juice, cranberry tablets, and increased liquids for the management of UTIs.

METHODS: PubMed, Embase, and Cochrane CENTRAL were searched for randomised controlled trials. The primary outcome was the number of UTIs, and the secondary outcomes were UTI symptoms and antimicrobial consumption. A risk of bias assessment was performed using the Cochrane risk of bias tool, and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation.

KEY FINDINGS AND LIMITATIONS: A total of 20 trials (3091 participants) were included, with 18 studies highlighting a 54% lower rate of UTIs with cranberry juice consumption than no treatment and a 27% lower rate than placebo liquid. Cranberry juice also resulted in a 49% lower rate of antibiotic use than placebo liquid and a 59% lower rate than no treatment, based on a network meta-analysis of six studies. The use of cranberry compounds also reduced the prevalence of symptoms associated with UTIs.

CONCLUSIONS AND CLINICAL IMPLICATIONS: With moderate to low certainty, the evidence supports the use of cranberry juice for the prevention of UTIs. While increased liquids reduce the rate of UTIs compared with no treatment, cranberry in liquid form provides even better clinical outcomes in terms of reduction in UTIs and antibiotic use and should be considered for the management of UTIs.

PATIENT SUMMARY: With the increasing prevalence of antimicrobial-resistant UTIs, alternate non-drug treatment options for its management are required. Available evidence supports the use of cranberry compounds and increases in fluid intake for managing UTIs.

Cranberry-lingonberry juice affects the gut and urinary microbiome in children - a randomized controlled trial

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Authors
Hakkola, Mikael; Vehvilaeinen, Pekka; Muotka, Janita; Tejesvi, Mysore V.; Pokka, Tytti; Vaehaesarja, Paeivi; Hanni, Anna-Maija; Renko, Marjo; Uhari, Matti; Salo, Jarmo; Tapiainen, Terhi
Journal
APMIS 10.1111/apm.13292
Abstract

The mechanism by which cranberry-lingonberry juice (CLJ) prevents urinary tract infections (UTI) in children remains unknown. We hypothesized that it alters the composition of the gut or urinary microbiome. Altogether, 113 children with UTIs were randomly allocated to drink either CLJ or a placebo juice for 6 months. We collected urinary samples at 3 months and fecal samples at 3, 6 and 12 months and used next-generation sequencing of the bacterial 16S gene. The children who consumed CLJ had a lower abundance of Proteobacteria (p = 0.03) and a higher abundance of Firmicutes phylum (p = 0.04) in their urinary microbiome at 3 months than did those in the placebo group. The abundance of Escherichia coli in the urinary microbiome was 6% in the CLJ group and 13% in the placebo group (p = 0.42). In the gut microbiome the abundance of Actinobacteria at 3 and 12 months was higher in the children receiving CLJ. The diversity of the urinary and gut microbiome did not differ between the groups. The children drinking CLJ had a different urinary and gut microbiome from those receiving a placebo juice. A healthy urinary microbiome may be important in preventing UTIs in children.

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.

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.