Uropathogenic Escherichia coli (UPEC), the most prevalent bacteria isolated in urinary tract infections (UTI), is now frequently resistant to antibiotics used to treat this pathology. The antibacterial properties of cranberry and propolis could reduce the frequency of UTIs and thus the use of antibiotics, helping in the fight against the emergence of antibiotic resistance. Transcriptomic profiles of a clinical UPEC strain exposed to cranberry proanthocyanidins alone (190micro g/mL), propolis alone (102.4micro g/mL) and a combination of both were determined. Cranberry alone, but more so cranberry+propolis combined, modified the expression of genes involved in different essential pathways: down-expression of genes involved in adhesion, motility, and biofilm formation, and up-regulation of genes involved in iron metabolism and stress response. Phenotypic assays confirmed the decrease of motility (swarming and swimming) and biofilm formation (early formation and formed biofilm). This study showed for the first time that propolis potentiated the effect of cranberry proanthocyanidins on adhesion, motility, biofilm formation, iron metabolism and stress response of UPEC. Cranberry+propolis treatment could represent an interesting new strategy to prevent recurrent UTI.

Study design: This study was a double-blind, placebo-controlled trial of a concentrated PACs compound (36mg/capsule), in veterans with SCI and neurogenic lower urinary tract dysfunction (NLUTD) requiring intermittent catheterization (IC) over a 15-day period. Objectives: The objective of this study was to evaluate the acute effects of concentrated proanthocyanidins (PACs) in the cranberry supplement ellura on bacteriuria, leukocyturia, and subjective urine quality in catheter-dependent veterans with SCI. Setting: Spinal cord injury center (outpatient clinic and inpatient unit). Methods: Participants with positive urine bacterial colonization (>=50K CFU/ml) were randomized to once daily concentrated PACs or identical placebo and followed with daily (in-patients) or twice weekly (out-patients) urine cultures with colony forming units per milliliter (cfu/ml) range (bacteriuria), microscopic urine white blood cells per high-powered field (wbc/hpf) quantification (leukocyturia), and surveys assessing urine clarity, odor, color, sediment, and overall satisfaction. A repeated measure analysis of variance was used to compare treatment vs. control and evaluate serial trends. Results: A total of 13 male participants (7 randomized to concentrated PACs, 6 to placebo) completed the trial. There was no significant decrease over the study period in colony forming units per milliliter (cfu/ml) or log(wbc/hpf) in the treatment vs. the control group. Patients receiving concentrated PACs rated the clarity, odor, color, sediment, and overall satisfaction of their urine as insignificantly improved compared to placebo. Conclusions: Acutely, there was no reduction of bacteriuria and pyuria or improvement in subjective urine quality for SCI patients treated with daily concentrated PACs.

Background/Aims: Clinical trials of older adults are increasingly common, but risks of serious adverse events (SAE) may vary. We describe the incidence of SAE in two randomized trials, one community-based and one nursing home-based. Methods: We performed a secondary data analysis from two randomized clinical trials at one academic health center and 21 nursing homes involving 200 sedentary community dwellers aged 70-89 years and 185 female nursing home residents aged 65 years or older. Interventions included structured physical activity to reduce mobility disability in the Lifestyle Interventions and Independence for Elders (LIFE) study and oral cranberry capsules to reduce bacteriuria plus pyuria in nursing home residents (CRANNY) trial. We measured SAE incidence per 100 person-years and incidence of protocol-related unanticipated SAE per 100 person-years in LIFE and CRANNY trials. Results: Mean age and proportion of patients with dementia in LIFE and CRANNY trials were 79.3 years and 86.4 years and 0% and 78%, respectively. There were 179 total SAE in LIFE including 8 (4%) deaths, and 116 total SAE in CRANNY including 33 (28%) deaths. SAE incidence was 33.7 (95% CI 27.2, 41.8) events per 100 person-years in LIFE and 69.4 (95% CI 49.1, 98.1) events per 100 person-years in CRANNY. No protocol-related unanticipated SAE occurred in either trial. Conclusions: The frequency and severity of SAE vary in older adults. While SAE are common in nursing home residents, protocol-related, unanticipated SAE are rare in nursing home residents and community dwellers. This finding can inform trial monitoring protocols.

BACKGROUND: Urinary tract infections (UTIs) are amongst the most common bacterial infections affecting women. Although antibiotics are the treatment of choice for UTI, cranberry derived products have been used for many years to prevent UTIs, with limited evidence as to their efficacy. Our objective is to assess the efficacy of a cranberry extract capsule standardized in A-type linkage proanthocyanidins (PACs) for the prevention of recurrent urinary tract infection. METHODS: We will perform a 1:1 randomized, controlled, double blind clinical trial in women aged 18 years or more who present >=2 UTIs in 6 months or>=3 UTIs in 12 months. One hundred and forty-eight women will be recruited and randomized in two groups to either receive an optimal dose of cranberry extract quantified and standardized in PACs (2x18.5 mg PACs per day) or a control dose (2x1 mg PACs per day). The primary outcome for the trial is the mean number of new symptomatic UTIs in women during a 6-month intervention period. Secondary outcomes are: (1) To evaluate the mean number of new symptomatic UTIs with pyuria as demonstrated by a positive leucocyte esterase test; (2) To detect the mean number of new symptomatic culture-confirmed UTIs; (3) To quantify urinary PACs metabolites in women who take a daily dose of 37 mg PACs per day compared to women who take a daily dose of 2 mg per day for 6 months; (4) To characterize women who present recurrent UTI based on known risk factors for recurrent UTI; (5) To describe the side effects of daily intake of cranberry extract containing 37 mg PACs compared to 2 mg PACs. This report provides comprehensive methodological data for this randomized controlled trial. DISCUSSION: The results of this trial will inform urologists, gynaecologists, family physicians and other healthcare professionals caring for healthy women with recurrent UTI, as to the benefits of daily use of an optimal dose of cranberry extract for the prevention of recurrent UTI.

The defense against influenza virus (IV) infections still poses a series of challenges. The current antiviral arsenal against influenza viruses is in fact limited; therefore, the development of new anti-influenza strategies effective against antigenically different viruses is an urgent priority. Bioactive compounds derived from medicinal plants and fruits may provide a natural source of candidates for such broad-spectrum antivirals. In this regard, cranberry (Vaccinium macrocarpon Aiton) extracts on the basis of their recognized anti-adhesive activities against bacteria, may provide potential compounds able to prevent viral attachment to target cells. Nevertheless, only few studies have so far investigated the possible use of cranberry extracts as an antiviral tool. This study focuses on the suitability of a cranberry extract as a direct-acting anti-influenza compound. We show that the novel cranberry extract Oximacro inhibits influenza A and B viruses (IAV, IBV) replication in vitro because of its high content of A-type proanthocyanidins (PAC-A) dimers and trimers. Mechanistic studies revealed that Oximacro prevents attachment and entry of IAV and IBV into target cells and exerts a virucidal activity. Oximacro was observed to interact with the ectodomain of viral hemagglutinin (HA) glycoprotein, thus suggesting the interference with HA functions and a consequent loss of infectivity of IV particles. Fluorescence spectroscopy revealed a reduction in the intrinsic fluorescence of HA protein after incubation with purified dimeric PAC-A (PAC-A2), thus confirming a direct interaction between HA and Oximacro PAC-A2. In silico docking simulations further supported the in vitro results and indicated that among the different components of the Oximacro chemical profile, PAC-A2 exhibited the best binding propensity with an affinity below 10 nM. The role of PAC-A2 in the anti-IV activity of Oximacro was eventually confirmed by the observation that it prevented IAV and IVB replication and caused the loss of infectivity of IV particles, thus indicating PAC-A2 as the major active component of Oximacro. As a whole, these results suggest Oximacro as a potential candidate to create novel antiviral agents of natural origin for the prevention of IV infections.

Objective: The objective of this study was to assess relationships between clinical predictors of urinary tract infection (UTI) and effects of cranberry juice consumption on recurrence in a post hoc analysis of a 24-week, randomized, double-blind, placebo-controlled, multicenter clinical trial in women with a recent history of UTI. Methods: Participants consumed a cranberry (n=185) or placebo (n=188) beverage (240 mL) daily. Odds ratios (OR) from 20 candidate predictor variables were evaluated in univariate analyses to assess clinical UTI incidence relationships in the placebo group. A multivariate logistic regression model was developed. The effects of cranberry juice consumption were evaluated in subsets categorized by the likelihood of a UTI event based on the prediction model. Results: In the placebo group, the final multivariate regression model identified four variables associated with the odds for having >=1 UTI: intercourse frequency >=1 time during the prior 4 weeks (OR: 2.36; 95% confidence interval [CI]: 0.98, 5.71; p=0.057), use of vasectomy or hormonal methods for contraception (OR: 2.58; 95% CI: 1.20, 5.58; p=0.016), most recent UTI 90 days prior to screening (OR: 2.28; 95% CI; 1.12, 4.67; p=0.024), and living in France compared with the United States (OR: 0.17; 95% CI: 0.04, 0.79; p=0.024). Three propensity categories were investigated (24-week probability 10%, 10%-21%, and >21%). Incidence rate ratios for the cranberry vs placebo groups were 0.76 (95% CI: 0.22, 2.60; p=0.663) for those with 10% probability, 0.73 (95% CI: 0.35, 1.53; p=0.064) for those with 10% to 21% probability, and 0.58 (95% CI: 0.35, 0.97; p=0.039) for those with >21% probability. Conclusions: Results suggest that clinical predictors identify women with low and high risk of clinical UTI recurrence, which may be useful for design of clinical studies evaluating preventive therapies.

The relationship among diet, human health, and disease is an area of growing interest in biomarker research. Previous studies suggest that the consumption of cranberries (Vaccinium macrocarpon) could beneficially influence urinary and digestive health. The present study sought to determine if daily consumption of sweetened dried cranberries (SDC) changes the urinary proteome and fecal microbiome, as determined in a prospective sample of 10 healthy individuals. Baseline urine and fecal samples were collected from the subjects in the fasted (8-12h) state. The subjects then consumed one serving (42g) of SDC daily with lunch for 2 weeks. Urine and fecal samples were collected again the day after 2 weeks of SDC consumption. Orbitrap Q-Exactive mass spectrometry of urinary proteins showed that consumption of SDC resulted in changes to 22 urinary proteins. Multiplex sequencing of 16S ribosomal RNA genes in fecal samples indicated changes in relative abundance of several bacterial taxonomic units after consumption of SDC. There was a shift in the Firmicutes:Bacteroidetes ratio, increases in commensal bacteria, and decreases or the absence of bacteria associated with negative health effects. A decrease in uromodulin in all subjects and an increase in Akkermansia bacteria in most subjects were observed and warrant further investigation. Future larger clinical studies with multiomics and multitissue sampling designs are required to determine the effects of SDC consumption on nutrition and health.

PURPOSE: The study was conducted to investigate the effects of training provided by researcher and the use of cranberry capsule in preventing late term UTIs after urostomy. METHODS: The study included 60 patients who underwent ileal conduit diversion between June 2013 and November 2014. The participants were randomly divided into three groups. First group used cranberry capsule, second group received training about UTIs and the other control group. The patients were assessed for a UTI by laboratory analysis at 2, 3, and 4 months after discharge. RESULTS: When the effect of cranberry capsule use and training on the prevention of urinary tract infections were compared, we found that there was a significant difference between the group that used and didn't use cranberry capsules, favoring the cranberry capsule (log-rank test; p < 0.05). CONCLUSION: We found that the use of cranberry capsules is effective in the prevention of urinary tract infections.

OBJECTIVE: The Affordable Care Act (ACA) established the Hospital-Acquired Condition (HAC) Reduction Program. The Centers for Medicare and Medicaid Services (CMS) established a total HAC scoring methodology to rank hospitals based upon their HAC performance. Hospitals that rank in the lowest quartile based on their HAC score are subject to a 1% reduction in their total Medicare reimbursements. In FY 2017, 769 hospitals incurred payment reductions totaling $430 million. This study analyzes how improvements in the rate of catheter-associated urinary tract infections (CAUTI), based on the implementation of a cranberry-treatment regimen, impact hospitals' HAC scores and likelihood of avoiding the Medicare-reimbursement penalty. METHODS: A simulation model is developed and implemented using public data from the CMS' Hospital Compare website to determine how hospitals' unilateral and simultaneous adoption of cranberry to improve CAUTI outcomes can affect HAC scores and the likelihood of a hospital incurring the Medicare payment reduction, given results on cranberry effectiveness in preventing CAUTI based on scientific trials. The simulation framework can be adapted to consider other initiatives to improve hospitals' HAC scores. RESULTS: Nearly all simulated hospitals improved their overall HAC score by adopting cranberry as a CAUTI preventative, assuming mean effectiveness from scientific trials. Many hospitals with HAC scores in the lowest quartile of the HAC-score distribution and subject to Medicare reimbursement reductions can improve their scores sufficiently through adopting a cranberry-treatment regimen to avoid payment reduction. LIMITATIONS: The study was unable to replicate exactly the data used by CMS to establish HAC scores for FY 2018. The study assumes that hospitals subject to the Medicare payment reduction were not using cranberry as a prophylactic treatment for their catheterized patients, but is unable to confirm that this is true in all cases. The study also assumes that hospitalized catheter patients would be able to consume cranberry in either juice or capsule form, but this may not be true in 100% of cases. CONCLUSION: Most hospitals can improve their HAC scores and many can avoid Medicare reimbursement reductions if they are able to attain a percentage reduction in CAUTI comparable to that documented for cranberry-treatment regimes in the existing literature.

PURPOSE: Cranberry supplements are commonly used as a natural deterrent to urinary tract infection. However, one small study (n=5) which showed an increase in urinary oxalate levels following cranberry supplementation has led to its use with caution among patients susceptible to nephrolithiasis. Furthermore, most commonly available cranberry tablet preparations contain vitamin C, which has been independently shown to increase urinary oxalate excretion. The aim of this study is to investigate the influence of cranberry supplementation on urinary oxalate excretion. METHODS: Fifteen participants were randomised to receive cranberry tablets alone or cranberry tablets containing vitamin C. Tablets were taken at the manufacturers recommended dosage for a period of 14 days. Participants provided a 24 h urine collection at trial entry and day 14. Urinary variables were compared to assess for changes in oxalate levels. RESULTS: The median age was 27 years (21-43). There was no difference in the 24 h urine volume pre or post commencement of cranberry tablets (1.7 vs 2 L, p=0.07). An increase in median urinary oxalate excretion was observed in participants taking both cranberry-only tablets (0.10 mmol/day) and tablets containing vitamin C (1.15 mmol/day). CONCLUSION: Dietary supplementation with cranberry increases urinary oxalate excretion and should be avoided in patients at risk of urolithiasis.