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Urinary Tract Health and Antibacterial Benefits

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Antiadhesive Activity and Metabolomics Analysis of Rat Urine after Cranberry (Vaccinium macrocarpon Aiton) Administration.

Posted: 
August 15, 2017
Authors: 
Peron G, Pellizzaro A, Brun P, Schievano E, Mammi S, Sut S, Castagliuolo I, Dall'Acqua S
Journal: 
J Agric Food Chem. 65(28):5657-5667
Abstract: 

Cranberry (Vaccinium macrocarpon Aiton) is used to treat noncomplicated urinary tract infections (UTIs). A-type procyanidins (PAC-A) are considered the active constituents able to inhibit bacterial adhesion to the urinary epithelium. However, the role of PAC-A in UTIs is debated, because of their poor bioavailability, extensive metabolism, limited knowledge about urinary excretion, and contradictory clinical trials. The effects of 35-day cranberry supplementation (11 mg/kg PAC-A, 4 mg/kg PAC-B) were studied in healthy rats using a ultra performance liquid chromatography-mass spectrometry (UPLC-MS)-based metabolomics approach. Microbial PAC metabolites, such as valeric acid and valerolactone derivatives, were related to cranberry consumption. An increased urinary excretion of glucuronidated metabolites was also observed. In a further experiment, urine samples were collected at 2, 4, 8, and 24 h after cranberry intake and their antiadhesive properties were tested against uropathogenic Escherichia coli. The 8 h samples showed the highest activity. Changes in urinary composition were studied by ultra performance liquid chromatography-time-of-flight (UPLC-QTOF), observing the presence of PAC metabolites. The PAC-A2 levels were measured in all collected samples, and the highest amounts, on the order of ng/mL, were found in the samples collected after 4 h. Results indicate that the antiadhesive activity against uropathogenic bacteria observed after cranberry consumption is ascribable to PAC-A metabolites rather than to a direct PAC-A effect, as the measured PAC-A levels in urine was lower than those reported as active in the literature.

Can Cranberries Contribute to Reduce the Incidence of Urinary Tract Infections? A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Clinical Trials.

Posted: 
August 15, 2017
Authors: 
Luis A; Domingues F; Pereira L.
Journal: 
Journal of Urology https://doi.org/10.1016/j.juro.2017.03.078
Abstract: 

PURPOSE: We sought to clarify the association between cranberry intake and the prevention of urinary tract infections. MATERIALS AND METHODS: This systematic review, which complies with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statement, was done as a meta-analysis and trial sequential analysis of clinical trials. RESULTS: The findings clearly showed the potential use of cranberries for the clinical condition of urinary tract infection. Cranberry products significantly reduced the incidence of urinary tract infections as indicated by the weighted risk ratio (0.6750, 95% CI 0.5516-0.7965, p <0.0001). The results of subgroup analysis demonstrated that patients at some risk for urinary tract infections were more susceptible to the effects of cranberry ingestion. CONCLUSIONS: The results of the current study could be used by physicians to recommend cranberry ingestion to decrease the incidence of urinary tract infections, particularly in individuals with recurrent urinary tract infections. This would also reduce the administration of antibiotics, which could be beneficial since antibiotics can lead to the worldwide emergence of antibiotic resistant microorganisms.

Cranberry capsules to prevent nosocomial urinary tract bacteriuria after pelvic surgery: a randomised controlled trial.

Posted: 
August 15, 2017
Authors: 
Letouzey V; Ulrich D; Demattei C; Alonso S; Huberlant S; Lavigne JP; de Tayrac R.
Journal: 
BJOG: An International Journal of Obstetrics & Gynaecology. 124(6):912-917
Abstract: 

OBJECTIVE: To evaluate whether cranberries are able to prevent postoperative urinary bacteriuria in patients undergoing pelvic surgery and receiving transurethral catheterisation.DESIGN: Randomised, double-blind, placebo-controlled trial.SETTINGS: French tertiary Care centre, University Hospital.POPULATION: A total of 272 women undergoing pelvic surgery aged 18 or older.METHODS: Participants undergoing pelvic surgery were randomised to 36 mg cranberry (proanthocyanidins, PAC) or placebo once daily for 10 days. Statistical analysis was performed by a chi-square test.MAIN OUTCOME MEASURES: The primary and secondary outcomes were postoperative bacteriuria, defined by a positive urine culture, within the first 15 and 40 days, respectively.RESULTS: Two hundred and fifty-five participants received the intended treatment: 132 (51.8%) received PAC and 123 (48.2%) received placebo. There were no significant differences in baseline demographics, intra-operative characteristics or duration and type of catheterisation between the two groups. PAC prophylaxis did not reduce the risk of bacteriuria treatment within 15 days of surgery [27% bacteriuria with PAC compared with 25% bacteriuria with placebo: relative risk 1.05, 95% CI 0.78-1.4, P = 0.763). The same result was observed on day 40. Bacteriuria occurred more often in older women with increased length of catheterisation.CONCLUSION: Immediate postoperative prophylaxis with PAC does not reduce the risk of postoperative bacteriuria in patients receiving short-term transurethral catheterisation after pelvic surgery.

Cranberry Extract Inhibits in Vitro Adhesion of F4 and F18+ Escherichia Coli to Pig Intestinal Epithelium and Reduces in Vivo Excretion of Pigs Orally Challenged with F18+ Verotoxigenic E. Coli.

Posted: 
August 15, 2017
Authors: 
Coddens, A. Loos, M. Vanrompay, D. Remon, J. P. Cox, E.
Journal: 
Veterinary Microbiology 202:64-71
Abstract: 

F4+ E. coli and F18+ E. coli infections are an important threat for pig industry worldwide. Antibiotics are commonly used to treat infected piglets, but the emerging development of resistance against antibiotics raises major concerns. Hence, alternative therapies to prevent pigs from F4+ E. coli and F18+ E. coli infections need to be developed. Since cranberry previously showed anti-adhesive activity against uropathogenic E. coli, we aimed to investigate whether cranberry extract could also inhibit binding of F4+ E. coli and F18+ E. coli to pig intestinal epithelium. Using the in vitro villus adhesion assay, we found that low concentrations of cranberry extract (20 micro g or 100 micro g/ml) have strong inhibitory activity on F4+ E. coli (75.3%, S.D.=9.31 or 95.8%, S.D.=2.56, respectively) and F18+ E. coli adherence (100% inhibition). This effect was not due to antimicrobial activity. Moreover, cranberry extract (10 mg or 100 mg) could also abolish in vivo binding of F4 and F18 fimbriae to the pig intestinal epithelium in ligated loop experiments. Finally, two challenge experiments with F18+ E. coli were performed to address the efficacy of in-feed or water supplemented cranberry extract. No effect could be observed in piglets that received cranberry extract only in feed (1 g/kg or 10 g/kg). However, supplementation of feed (10 g/kg) and drinking water (1 g/L) significantly decreased excretion and diarrhea. The decreased infection resulted in a decreased serum antibody response indicating reduced exposure to F18+ E. coli.

Cranberry Juice and Combinations of Its Organic Acids Are Effective against Experimental Urinary Tract Infection.

Posted: 
August 15, 2017
Authors: 
Jensen HD; Struve C; Christensen SB; Krogfelt KA.
Journal: 
Frontiers in Microbiology. 8:542
Abstract: 

The antibacterial effect of cranberry juice and the organic acids therein on infection by uropathogenic Escherichia coli was studied in an experimental mouse model of urinary tract infection (UTI). Reduced bacterial counts were found in the bladder (P < 0.01) of mice drinking fresh cranberry juice. Commercially available cranberry juice cocktail also significantly reduced (P < 0.01) bacterial populations in the bladder, as did the hydrophilic fraction of cranberry juice (P < 0.05). Quinic, malic, shikimic, and citric acid, the preponderant organic acids in cranberry juice, were tested in combination and individually. The four organic acids also decreased bacterial levels in the bladder when administered together (P < 0.001), and so did the combination of malic plus citric acid (P < 0.01) and malic plus quinic acid (P < 0.05). The other tested combinations of the organic acids, and the acids administered singly, did not have any effect in the UTI model. Apparently, the antibacterial effect of the organic acids from cranberry juice on UTI can be obtained by administering a combination of malic acid and either citric or quinic acid. This study show for the first time that cranberry juice reduce E. coli colonization of the bladder in an experimental mouse model of urinary tract infection and that the organic acids are active agents.

Cranberry Juice Concentrate does not Significantly Decrease the Incidence of Acquired Bacteriuria in Female Hip Fracture Patients Receiving Urine Catheter: a Double-Blind Randomized Trial.

Posted: 
August 15, 2017
Authors: 
Gunnarsson AK; Gunningberg L; Larsson S; Jonsson KB.
Journal: 
Clinical Interventions In Aging. 12:137-143
Abstract: 

BACKGROUND: Urinary tract infection (UTI) is a common complication among patients with hip fractures. Receiving an indwelling urinary catheter is a risk factor for developing UTIs. Treatment of symptomatic UTIs with antibiotics is expensive and can result in the development of antimicrobial resistance. Cranberries are thought to prevent UTI. There is no previous research on this potential effect in patients with hip fracture who receive urinary catheters. AIM: The aim of this study is to investigate whether intake of cranberry juice concentrate pre-operatively decreases the incidence of postoperative UTIs in hip fracture patients that received a urinary catheter. DESIGN: This study employed a randomized, placebo-controlled double-blind trial. METHOD: Female patients, aged 60 years and older, with hip fracture (n=227) were randomized to receive cranberry or placebo capsules daily, from admission, until 5 days postoperatively. Urine cultures were obtained at admission, 5 and 14 days postoperatively. In addition, Euro Qual five Dimensions assessments were performed and patients were screened for UTI symptoms. RESULT: In the intention-to-treat analysis, there was no difference between the groups in the proportion of patients with hospital-acquired postoperative positive urine cultures at any time point. When limiting the analysis to patients that ingested at least 80% of the prescribed capsules, 13 of 33 (39%) in the placebo group and 13 of 47 (28%) in the cranberry group (P=0.270) had a positive urine culture at 5 days postoperatively. However, this difference was not statistically significant (P=0.270). CONCLUSION: Cranberry concentrate does not seem to effectively prevent UTIs in female patients with hip fracture and indwelling urinary catheter.

Effect of Cranberry Extract on the Frequency of Bacteriuria in Dogs with Acute Thoracolumbar Disk Herniation: A Randomized Controlled Clinical Trial.

Posted: 
August 15, 2017
Authors: 
Olby NJ; Vaden SL; Williams K; Griffith EH; Harris T; Mariani CL; Munana KR; Early PJ; Platt SR; Boozer L; Giovanella C; Longshore R.
Journal: 
Journal of Veterinary Internal Medicine. 31(1):60-68
Abstract: 

BACKGROUND: Dogs with spinal cord injury are at increased risk of developing bacteriuria due to increased residual urine volume. Cranberry extract inhibits binding of E. coli to uroepithelial cells, potentially reducing risk of bacteriuria. HYPOTHESIS: Cranberry extract reduces risk of bacteriuria in dogs after acute TL-IVDH. ANIMALS: Client-owned dogs with acute onset TL-IVDH causing nonambulatory status. METHODS: Randomized, placebo-controlled, blinded, prospective clinical trial. Dogs with acute TL-IVDH were recruited 48 hours postoperatively and randomized to receive cranberry extract or placebo in a masked fashion. Urine cultures and neurological examinations were performed 2, 4, and 6 weeks postoperatively. The number of dogs with bacteriuria (all bacterial species) and bacteriuria (E. coli) were primary and secondary outcome measures and were evaluated using chi-squared test. Urine antiadhesion activity (AAA) was measured in a subset (N = 47) and examined in a secondary analysis evaluating additional risk factors for bacteriuria. RESULTS: Bacteriuria was detected 17 times in 94 dogs (6 placebo, 11 cranberry, P = .12). There were 7 E. coli. positive cultures (1 placebo, 6 cranberry, P = .09). Dogs in both groups had positive urine AAA (14/21: placebo, 16/26: cranberry), and dogs with urine AAA had significantly fewer E. coli positive cultures (n = 1) than dogs without it (n = 4) (P = .047). CONCLUSIONS AND CLINICAL IMPORTANCE: This clinical trial did not show a benefit of oral cranberry extract but had low power. Cranberry extract supplementation did not impact urine AAA, but a possible association between urine AAA and lower risk of E. coli bacteriuria was identified. Other doses could be investigated.

Enteric-Coated and Highly Standardized Cranberry Extract Reduces Antibiotic and Nonsteroidal Anti-Inflammatory Drug Use for Urinary Tract Infections During Radiotherapy for Prostate Carcinoma.

Posted: 
August 15, 2017
Authors: 
Bonetta A; Roviello G; Generali D; Zanotti L; Cappelletti MR; Pacifico C; Di Pierro F.
Journal: 
Research & Reports in Urology. 9:65-69
Abstract: 

INTRODUCTION: Worldwide, bacterial resistance to antibiotic therapy is a major concern for the medical community. Antibiotic resistance mainly affects Gram-negative bacteria that are an important cause of lower urinary tract infections (LUTIs). Pelvic irradiation for prostate cancer is a risk factor for LUTIs. Cranberry extract is reported to reduce the incidence of LUTIs. The prophylactic role of an enteric-coated, highly standardized cranberry extract (VO370) in reducing LUTI episodes, urinary discomfort, and nonsteroidal anti-inflammatory drug (NSAID) and antibiotic use during radiotherapy for prostate carcinoma was evaluated.METHODS: A total of 924 patients with prostate carcinoma treated by radiotherapy to the prostatic and pelvic areas were randomized to receive (n=489) or not (n=435) the enteric-coated, highly standardized cranberry extract for 6-7 weeks concurrently with irradiation. Outcomes were analyzed by using Mann-Whitney U test and Pearson's chi2 test. Primary endpoint was the number of patients with LUTI; secondary endpoints were incidence of recurrence, days of treatment with antibiotics and number of subjects treated with NSAIDs, and incidence of dysuria.RESULTS: The treatment was very well tolerated, and there were no serious side effects. All enrolled patients completed the study. Urinary infections were detected in 53 of the 489 patients (10.8%) treated with enteric-coated, highly standardized cranberry extract, while 107 of the 435 patients (24.6%) in the control group developed LUTIs (p=0.0001). A clear and significant reduction in urinary discomfort of ~50% was seen in treated subjects. The treatment also resulted in ~50% reduction in the use of anti-inflammatory drugs and antibiotics. CONCLUSION: The enteric-coated, highly standardized cranberry extract could be used as a prophylactic to reduce the incidence of LUTIs and decrease antibiotic therapy in patients receiving pelvic irradiation for prostate cancer.

Evaluation of the Effects of a Natural Dietary Supplement with Cranberry, Noxamicina® and D-Mannose in Recurrent Urinary Infections in Perimenopausal Women] [Article In Italian]

Posted: 
August 15, 2017
Authors: 
De Leo V, Cappelli V, Massaro MG, Tosti C, Morgante G.
Journal: 
Minerva Ginecol. 69(4):336-341
Abstract: 

BACKGROUND:The female genital apparatus, the urinary tract and the perineal supporting tissues share a common embryological origin, whose differentiation depends on the action of estrogens. In adult women, the progressive decline of the ovarian function, with the ensuing estrogen deprivation, reduces tissue tropism causing urogenital atrophy, which makes these organs much more susceptible to traumatisms and urinary infections. The disorders associated with changes in the urogenital tract of peri- and postmenopausal women have significant clinical relevance, both on account of their chronicity and high frequency of occurrence and on account of their having major repercussions on the quality of life of the women, who often have to call their doctor seeking relief for their symptoms. In general, these patients report having a significant number of episodes of cystitis per year. With a view to verifying whether the use of a new dietary supplement (Kistinox® Forte sachets) containing cranberry (Vaccinium macrocarpon), Noxamicina® (propolis extract) and D-mannose can be of use in the treatment of cystitis, with or without bacteriuria, through the elimination of urinary symptoms, a multicenter clinical study was conducted on 150 women aged 40 to 50 suffering from recurrent episodes of cystitis as attested by at least one positive urine culture during the six months preceding their recruitment.METHODS:The subjects were randomly assigned to two groups: Group A: 100 women were given Kistinox® Forte, 1 sachet per day during the first 10 days of the month, for 3 months; Group B: 50 women did not receive any treatment to serve as a control group.RESULTS:The results of the present study show a complete remission of urinary symptoms in 92 women; a slight decrease in urinary symptoms was observed in 5 subjects, whereas 3 women who stopped the treatment after the first cycle were considered drop-outs.CONCLUSIONS:This multicenter clinical study revealed the excellent efficacy and tolerability of Kistinox® Forte sachets in the treatment and prevention of urinary disorders in peri- and postmenopausal women. The posology of a sachet a day during the first 10 days of the month for 3 months was well tolerated by the patients, who did not report any disorder arising from the product.

Highly Standardized Cranberry Extract Supplementation (Anthocran®) as Prophylaxis in Young Healthy Subjects with Recurrent Urinary Tract Infections

Posted: 
August 15, 2017
Authors: 
Ledda A, Belcaro G, Dugall M, Riva A, Togni S, Eggenhoffner R, Giacomelli L.
Journal: 
Eur Rev Med Pharmacol Sci. 21(2):389-393
Abstract: 

OBJECTIVE:Several studies have investigated the role of cranberry extract in the prevention of recurrent urinary tract infections (UTIs), on different selected subpopulations at increased risk of UTI. In this registry, we tested the prophylactic effects of an oral supplementation containing a highly standardized cranberry extract (Anthocran®) in young subjects with a previous history of recurrent UTIs, over a 2-months follow-up.PATIENTS AND METHODS:36 otherwise healthy subjects in juvenile age (between 12 and 18 years of age) suffering by recurrent UTIs were enrolled. Participants received either a standard management (SM) (control group, n=17) or SM associated with an oral daily supplementation (supplementation group, n=19). Oral supplementation consisted in one capsule containing 120 mg of cranberry extract (Anthocran®), standardized to 36 mg proanthocyanidins, for 60 days. The effectiveness in the prevention of UTIs was determined by: the number of UTIs evaluated two months before the inclusion in the registry and during the supplementation period; the number of symptom-free subjects during the registry period. Safety considerations and measurement of adherence to treatment were also performed.RESULTS:The two groups were comparable for age, gender distribution, the days of follow-up and also for the number of UTIs before inclusion. The mean number of UTIs observed during the registry in the supplemented group (0.31±0.2) was significantly lower compared to the control group (2.3±1.3) and to the mean number of UTIs assessed before inclusion (1.74±1.1) (p-value = 0.0001 for both). Moreover, 63.1% of supplemented subjects was symptom-free during the registry period, whereas 23.5% subjects were asymptomatic in the control group (p-value <0.05).CONCLUSIONS:This registry supplement study provides compelling evidence on the efficacy of an oral supplementation, based on a highly standardized cranberry extract (Anthocran®), as prophylaxis in young healthy subjects suffering by recurrent UTIs.

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