OBJECTIVE: Despite conflicting evidence, it is common practice to use continuous antibiotic prophylaxis (CAP) in patients with indwelling double-J (DJ) stents. Cranberry extracts and d-mannose have been shown to prevent colonization of the urinary tract. We evaluated their role in this setting.METHODS: We conducted a prospective randomized study to evaluate patients with indwelling DJ stents following urological procedures. They were randomized into three groups. Group A (n=46) received CAP (nitrofurantoin 100 mg once daily [OD]). Group B (n=48) received cranberry extract 300 mg and d-mannose 600 mg twice daily (BD). Group C (n=40) received no prophylaxis. The stents were removed between 15 days and 45 days after surgery. Three groups were compared in terms of colonization of stent and urine, stent related symptoms and febrile urinary tract infections (UTIs) during the period of indwelling stent and until 1 week after removal.RESULTS: In Group A, 9 (19.5%) patients had significant bacterial growth on the stents. This was 8 (16.7%) in the Group B and 5 (12.5%) in Group C (p-value: 0.743). However, the culture positivity rate of urine specimens showed a significant difference (p-value: 0.023) with Group B showing least colonization of urine compared to groups A and C. There was no statistically significant difference in the frequency of stent related symptoms (p-value: 0.242) or febrile UTIs (p-value: 0.399) among the groups.CONCLUSION: Prophylactic agents have no role in altering bacterial growth on temporary indwelling DJ stent, stent related symptoms or febrile UTIs. Cranberry extract may reduce the colonization of urinary tract, but its clinical significance needs further evaluation.

In this preliminary pilot registry study, we investigated the effects of the oral supplementation of a standardized cranberry extract (Anthocran R Phytosome R, Indena) delivered by a lecithin-based system, for the prophylactic management of recurrent-urinary tract infections (R-UTIs). We included 64 otherwise healthy subjects who underwent a surgical procedure and required post-surgical urinary catheterization for high-risk UTIs or a previous history of R-UTIs. Patients were given supplementation with the standardized cranberry extract at the dose of either 120 mg/day (n = 12) or 240 mg/day (n = 12) or assigned to a control group consisting of standard management (SM; n = 18) or nitrofurantoin administration (n = 22) for 4 weeks. After 4 weeks, patients receiving the standardized cranberry supplementation reported to have a more effective reduction in UTI symptoms, as assessed on the visual analogue scale, compared with patients in the SM or nitrofurantoin groups. The occurrence of hematuria and urine bacterial contamination were decreased among patients treated with the supplement compared with controls (p < 0.05). The cranberry extract was also superior to the control management in terms of recurrence of signs/symptoms, with none of the patients in this group suffering from a R-UTI in the 3 months following the study end (p < 0.05). The supplementation showed an optimal safety profile, with no significant adverse events and no drop-outs in the supplement group. This registry shows that this cranberry extract is effective as a supplementary, preventive management in preventing post-operative, post-catheter UTIs; the product has a good tolerability profile.

In this paper, an A-type procyanidin (PAC)-rich cranberry extract (CB-B) was obtained mixing different extracts and was formulated with D-mannose and ascorbic acid to obtain a novel nutraceutical (URO-F) aimed at preventing non-complicated bacterial urinary tract infections (UTIs). To assess the bioactivity of CB-B and URO-F, urine samples collected from six healthy volunteers undergoing a 2-days oral consumption of 0.41 g/day of CB-B or 10 g/day of URO-F (corresponding to 72 mg/day of PACs) were tested against uropathogenic E. coli (UPEC) incubated on urinary bladder epithelial cells (T24). Urinary markers of CB-B and URO-F consumption were assessed in the same urine output by UPLC-QTOF-based untargeted metabolomics approach. CB-B and URO-F were evaluated for their ability to promote the intestinal barrier function by restoring the trans-epithelial electrical resistance (TEER) and to inhibit the production of inflammatory cytokines in intestinal epithelial Caco2 cells. CB-B was characterized by a high PAC-A content (70% of total PACs) and a broad distribution of different PACs polymers (dimers-hexamers). Urine from subjects consuming CB-B and URO-F showed a significant effect in reducing the adhesion of UPEC to urothelium in vitro, supporting their efficacy as anti-adhesive agents after oral intake. CB-B inhibited the release of cytokine IL-8, and both products were effective in restoring the TEER. Overall, our results show that the beneficial effects of CB-B and URO-F on UTIs are not only due to the antiadhesive activity of cranberry on UPEC in the urothelium, but also to a multi-target activity involving anti-inflammatory and permeability-enhancing effects on intestinal epithelium.

Objectives: To determine the feasibility of conducting a randomised trial of the effectiveness of cranberry extract in reducing antibiotic use by women with symptoms of acute, uncomplicated urinary tract infection (UTI).Design: Open-label feasibility randomised parallel group trial. Setting: Four general practices in Oxfordshire.Participants: Women aged 18 years and above presenting to general practice with symptoms of acute, uncomplicated UTI.Interventions: Women were randomly assigned using Research Electronic Data Capture in a 1:1:1 ratio to: (1) immediate antibiotics alone (n=15); (2) immediate antibiotics and immediate cranberry capsules for up to 7 days (n=15); or (3) immediate cranberry capsules and delayed antibiotics for self-initiation in case of non-improvement or worsening of symptoms (n=16).Primary and secondary outcome measures: The primary outcome measures were: rate of recruitment of participants; numbers lost to follow-up; proportion of electronic diaries completed by participants; and acceptability of the intervention and study procedures to participants and recruiters. Secondary outcomes included an exploration of differences in symptom burden and antibiotic use between groups. Results: Four general practitioner practices (100%) were opened and recruited participants between 1 July and 2 December 2019, with nine study participants recruited per month on average. 68.7% (46/67) of eligible participants were randomised (target 45) with a mean age of 48.4 years (SD 19.9, range 18-81). 89.1% (41/46) of diaries contained some participant entered data and 69.6% (32/46) were fully complete. Three participants (6.5%) were lost to follow-up and two (4.4%) withdrew. Of women randomly assigned to take antibiotics alone (controls), one-third of respondents reported consuming cranberry products (33.3%, 4/12). There were no serious adverse events.Conclusions: It appears feasible to conduct a randomised trial of the use of cranberry extract in the treatment of acute, uncomplicated UTI in general practice

BACKGROUND: Most women experience a urinary tract infection (UTI) at least once in their lifetime. The present study determined the efficacy and safety of a combination of Lactobacillus paracasei LC11, cranberry and D-mannose (Lactoflorene Cist R) in the prophylaxis of recurrent uncomplicated UTIs in premenopausal women.METHODS: This single-centre study enrolled premenopausal women aged 18-50 years with an acute UTI and a history of recurrent uncomplicated UTIs. Patients were first treated with fosfomycin (3 g once a day for 2 days) to eliminate any underlying infection, followed by treatment with Lactoflorene Cist R once a day for 10 days/month for 90 days (Group 1), Lactoflorene Cist R once daily for 90 days (Group 2) or no treatment (Group 3; control). The main study endpoint was the rate of UTI recurrence during the study period. Any adverse events with treatment were also recorded.RESULTS: A total of 55 women (mean age 39.3 years; range: 20-46) were enrolled in the study. A significantly higher proportion of patients in the control group experienced UTIs during the study period compared with the two treatment groups (52.9% vs 16.0% in Group 1 and 15.5% in group 2; p < 0.01). Similarly, a higher proportion of patients in Group 1 (65.8%) and Group 2 (68.7%) remained UTI-free during the study versus the control group. No adverse events were reported in the treated patients.CONCLUSION: Prophylactic treatment with Lactoflorene Cist R was effective and safe in the management of recurrent uncomplicated UTIs in premenopausal women.

PURPOSE: Our objective was to assess the efficacy of a high dose cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection.MATERIAL AND METHODS: We recruited 145 healthy, adult women with a history of recurrent urinary tract infection, defined as >= 2 in the past 6 months or >= 3 in the past 12 months in this randomized, controlled, double-blind clinical trial. Participants were randomized to receive a high dose of standardized, commercially available cranberry proanthocyanidins (2 x 18.5 mg daily, n = 72) or a control low dose (2 x 1 mg daily, n = 73) for a 24-week period. During follow-up, symptomatic women provided urine samples for detection of pyuria and/or bacteriuria and received an appropriate antibiotic prescription. The primary outcome for the trial was the mean number of new symptomatic urinary tract infections during a 24-week intervention period. Secondary outcomes included symptomatic urinary tract infection with pyuria or bacteriuria.RESULTS: In response to the intervention, a non-significant 24% decrease in the number of symptomatic urinary tract infections was observed between groups (Incidence rate ratio 0.76, 95%CI 0.51-1.11). Post-hoc analyses indicated that among 97 women who experienced less than 5 infections in the year preceding enrolment, the high dose was associated with a significant decrease in the number of symptomatic urinary tract infections reported compared to the low dose (age-adjusted incidence rate ratio 0.57, 95%CI 0.33-0.99). No major side effects were reported.CONCLUSION: High dose twice daily proanthocyanidin extract was not associated with a reduction in the number of symptomatic urinary tract infections when compared to a low dose proanthocyanidin extract. Our post-hoc results reveal that this high dose of proanthocyanidins may have a preventive impact on symptomatic urinary tract infection recurrence in women who experienced less than 5 infections per year.TRIAL

Cranberries have long been purported to provide protection against urinary tract infections.There is a line of evidence suggesting that causal pathogens might be seeded from the bacteria reservoirs in the intestinal and vaginal tracts.We tested the hypothesis whether cranberry intake would reshape bacteria taxa in the gut, as well as the vaginal ecosystem.A total of 25 postmenopausal women were enrolled into a randomized, double-blind, placebo-controlled study.Stool samples and vaginal swabs were collected at baseline and after 15 days of consumption of placebo or cranberry beverages, microbiota analyses were performed by Illumina Miseq sequencing following a double-index 16S rRNA gene amplicon.All baseline stool samples generally fell in the Bacteroides enterotype.Significant increases of Prevotella (P = 0.04), Clostridium XIVa members (P = 0.04), Eggerthella (P = 0.03), and Bifidobacterium (P = 0.02) were shown following the cranberry juice intervention; this indicates modulation of the gut microbiota by cranberry components.Baseline vaginal microbiotas fell in three distinct patterns—Lactobacillus dominant, diversified microbiome, and Streptococcus dysbiosis.Compared with the placebo, the cranberry intervention significantly reduced the abundance of pathogenic Streptococcus (P = 0.04) in the dysbiosis group and increased commensal bacteria Anaerococcus, Finegoldia, Actinomyces, and Corynebacterium in the diversified microbiome and dysbiosis groups. Overall, these data suggest that cranberry consumption may improve vaginal microbiota composition in individuals with dysbiosis.Gut-borne taxa stimulation by the combination of cranberry oligosaccharides and polyphenols present in the cranberry product potentially mediates these beneficial properties.

Background: Urinary tract infections (UTIs) affect 15 million women each year in the United States, with >20% experiencing frequent recurrent UTIs. A recent placebo-controlled clinical trial found a 39% reduction in UTI symptoms among recurrent UTI sufferers who consumed a daily cranberry beverage for 24 weeks. Using metagenomic sequencing of stool from a subset of these trial participants, we assessed the impact of cranberry consumption on the gut microbiota, a reservoir for UTI-causing pathogens such as Escherichia coli, which causes >80% of UTIs. Results: The overall taxonomic composition, community diversity, carriage of functional pathways and gene families, and relative abundances of the vast majority of observed bacterial taxa, including E. coli, were not changed significantly by cranberry consumption. However, one unnamed Flavonifractor species (OTU41), which represented 1% of the overall metagenome, was significantly less abundant in cranberry consumers compared to placebo at trial completion. Given Flavonifractor's association with negative human health effects, we sought to determine OTU41 characteristic genes that may explain its differential abundance and/or relationship to key host functions. Using comparative genomic and metagenomic techniques, we identified genes in OTU41 related to transport and metabolism of various compounds, including tryptophan and cobalamin, which have been shown to play roles in host-microbe interactions. Conclusion: While our results indicated that cranberry juice consumption had little impact on global measures of the microbiome, we found one unnamed Flavonifractor species differed significantly between study arms. This suggests further studies are needed to assess the role of cranberry consumption and Flavonifractor in health and wellbeing in the context of recurrent UTI..

Purpose: Extensive inter-individual variability exists in the production of flavan-3-ol metabolites. Preliminary metabolic phenotypes (metabotypes) have been defined, but there is no consensus on the existence of metabotypes associated with the catabolism of catechins and proanthocyanidins. This study aims at elucidating the presence of different metabotypes in the urinary excretion of main flavan-3-ol colonic metabolites after consumption of cranberry products and at assessing the impact of the statistical technique used for metabotyping. Methods: Data on urinary concentrations of phenyl-P-valerolactones and 3-(hydroxyphenyl)propanoic acid derivatives from two human interventions has been used. Different multivariate statistics, principal component analysis (PCA), cluster analysis, and partial least square-discriminant analysis (PLS-DA), have been considered. Results: Data pre-treatment plays a major role on resulting PCA models. Cluster analysis based on k-means and a final consensus algorithm lead to quantitative-based models, while the expectation-maximization algorithm and clustering according to principal component scores yield metabotypes characterized by quali-quantitative differences in the excretion of colonic metabolites. PLS-DA, together with univariate analyses, has served to validate the urinary metabotypes in the production of flavan-3-ol metabolites and to confirm the robustness of the methodological approach.Conclusions: This work proposes a methodological workflow for metabotype definition and highlights the importance of data pre-treatment and clustering methods on the final outcomes for a given dataset. It represents an additional step toward the understanding of the inter-individual variability in flavan-3-ol metabolism.

This open pilot registry study aimed to evaluate and compare the prophylactic effects of PycnogenolR or cranberry extract in subjects with previous, recurrent urinary tract infections (UTI) or interstitial cystitis (IC). Methods: Inclusion criteria were recurrent UTI or IC. One subject group was supplemented with 150 mg/day PycnogenolR, another with 400 mg/day cranberry extract, and a group served as a control in a 2-month open follow-up. Results: 64 subjects with recurrent UTI/IC completed the study. The 3 groups of subjects were comparable at baseline. All subjects had significant symptoms (minor pain, stranguria, repeated need for urination, and lower, anterior abdominal pain) at inclusion. In the course of the study, the subjects reported no tolerability problems or side effects. The incidence of UTI symptoms, in comparison with the period before inclusion in the standard management (SM) group, decreased significantly; there was a more pronounced decrease in the rate of recurrent infections in the PycnogenolR group (p < 0.05). The improvement in patients supplemented with PycnogenolR was significantly superior to the effects of cranberry. At the end of the study, all subjects in the PycnogenolR group were infection-free (p < 0.05vs. cranberry). Significantly, more subjects were completely symptom-free after 2 months of management with PycnogenolR (20/22) than with SM (18/22) and cranberry (16/20). Conclusions: This pilot registry suggests that 60 days of PycnogenolR supplementation possibly decrease the occurrence of UTIs and IC without side effects and with an efficacy superior to cranberry.