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Urinary Tract Health and Antibacterial Benefits: Human

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Effectiveness of cranberry capsules to prevent urinary tract infections in vulnerable older persons: a double-blind randomized placebo-controlled trial in long-term care facilities.

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Authors
Caljouw MAA, Hout WB van den, Putter H, Achterberg WP, Cools HJM, Gussekloo J
Journal
J Am Geriatr Soc 62(1):103-10
Abstract

OBJECTIVES: To determine whether cranberry capsules prevent urinary tract infection (UTI) in long-term care facility (LTCF) residents. DESIGN: Double-blind randomized placebo-controlled multicenter trial. SETTING: Long-term care facilities (LTCFs). PARTICIPANTS: LTCF residents (N=928; 703 women, median age 84). MEASUREMENTS: Cranberry and placebo capsules were taken twice daily for 12 months. Participants were stratified according to UTI risk (risk factors included long-term catheterization, diabetes mellitus, >=1 UTI in preceding year). Main outcomes were incidence of UTI according to a clinical definition and a strict definition. RESULTS: In participants with high UTI risk at baseline (n=516), the incidence of clinically defined UTI was lower with cranberry capsules than with placebo (62.8 vs 84.8 per 100 person-years at risk, P=.04); the treatment effect was 0.74 (95% confidence interval (CI)=0.57-0.97). For the strict definition, the treatment effect was 1.02 (95% CI=0.68-1.55). No difference in UTI incidence between cranberry and placebo was found in participants with low UTI risk (n=412). CONCLUSION: In LTCF residents with high UTI risk at baseline, taking cranberry capsules twice daily reduces the incidence of clinically defined UTI, although it does not reduce the incidence of strictly defined UTI. No difference in incidence of UTI was found in residents with low UTI risk.

Recurrent urinary tract infections among women: comparative effectiveness of 5 prevention and management strategies using a Markov chain Monte Carlo model.

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Authors
Eells SJ, Bharadwa K, McKinnell JA, Miller LG
Journal
Clin Infect Dis 58(2):147-60
Abstract

BACKGROUND: Recurrent urinary tract infections (UTIs) are a common problem among women. However, comparative effectiveness strategies for managing recurrent UTIs are lacking.

METHODS: We performed a systematic literature review of management of women experiencing >3 UTIs per year. We then developed a Markov chain Monte Carlo model of recurrent UTI for each management strategy with >2 adequate trials published. We simulated a cohort that experienced 3 UTIs/year and a secondary cohort that experienced 8 UTIs/year. Model outcomes were treatment efficacy, patient and payer cost, and health-related quality of life.

RESULTS: Five strategies had >2 clinical trials published: (1) daily antibiotic (nitrofurantoin) prophylaxis; (2) daily estrogen prophylaxis; (3) daily cranberry prophylaxis; (4) acupuncture prophylaxis; and (5) symptomatic self-treatment. In the 3 UTIs/year model, nitrofurantoin prophylaxis was most effective, reducing the UTI rate to 0.4 UTIs/year, and the most expensive to the payer ($821/year). All other strategies resulted in payer cost savings but were less efficacious. Symptomatic self-treatment was the only strategy that resulted in patient cost savings, and was the most favorable strategy in term of cost per quality-adjusted life-year (QALY) gained.

CONCLUSIONS: Daily antibiotic use is the most effective strategy for recurrent UTI prevention compared to daily cranberry pills, daily estrogen therapy, and acupuncture. Cost savings to payers and patients were seen for most regimens, and improvement in QALYs were seen with all. Our findings provide clinically meaningful data to guide the physician-patient partnership in determining a preferred method of prevention for this common clinical problem.

Solidago, orthosiphon, birch and cranberry extracts can decrease microbial colonization and biofilm development in indwelling urinary catheter: a microbiologic and ultrastructural pilot study.

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Authors
Cai T, Caola I, Tessarolo F, Piccoli F, D'Elia C, Caciagli P, Nollo G, Malossini G, Nesi G, Mazzoli S, Bartoletti R
Journal
World J Urol 32(4):1007-14
Abstract

"PURPOSE: Plants extracts are used in urology to manage urinary tract infections. We aimed to evaluate the efficacy of a preparation with solidago, orthosiphon, birch and cranberry extracts (CISTIMEV PLUS()) in reducing microbial colonization and biofilm development in patients with indwelling urinary catheters.

METHODS: All consecutive outpatients attending our department between January and June 2010 for the substitution of indwelling catheters were considered for this single-blinded, randomized and controlled pilot study to test superiority of the preventative management (CISTIMEV PLUS(), 1 tablet daily for 30 days) in respect to no treatment. A sample size of 10-40 participants per group was considered adequate. All patients underwent urine culture the same day of the catheter substitution and were then randomized into test group (n = 48) and control group (n = 35). Ultrastructural analysis was also performed. After 30 days, the catheter was replaced and the analysis repeated. The primary outcome was the rate of positive urinary culture at the end of the entire study period.

RESULTS: Ten patients abandoned the study. At 30 days, according to per-protocol analysis, the groups statistically differed regarding the rate of positive urine cultures: test group 10/43 and control group 16/30 (p = 0.013) (-30.1 % [95 % CI -51.94 to -8.21]). The most common isolated bacteria were Escherichia coli and Enterococcus faecalis.

CONCLUSIONS: The use of solidago, orthosiphon, birch and cranberry extracts resulted in a significant reduction of microbial colonization in patients with indwelling urinary catheters. Larger clinical trials are needed to demonstrate that the effects here reported are sufficient to reduce symptomatic catheter-associated urinary tract infections."

Consumption of sweetened, dried cranberries may reduce urinary tract infection incidence in susceptible women--a modified observational study.

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Authors
Burleigh AE, Benck SM, McAchran SE, Reed JD, Krueger CG, Hopkins WJ
Journal
Nutr J 12(1):139
Abstract

BACKGROUND: Urinary tract infections (UTIs) are one of the most common bacterial infections, and over 50% of women will have a UTI during their lifetimes. Antibiotics are used for prophylaxis of recurrent UTIs but can lead to emergence of drug-resistant bacteria. Therefore, it is reasonable to investigate nutritional strategies for prevention of UTIs. Cranberry juices and supplements have been used for UTI prophylaxis, but with variable efficacy. Because dried cranberries may contain a different spectrum of polyphenolics than juice, consuming berries may or may not be more beneficial than juice in decreasing the incidence of UTIs in susceptible women. The primary objectives of this study were to determine if consumption of sweetened, dried cranberries (SDC) decreases recurrent UTIs and whether this intervention would alter the heterogeneity, virulence factor (VF) profiles, or numbers of intestinal E. coli.

METHODS: Twenty women with recurrent UTIs were enrolled in the trial and consumed one serving of SDC daily for two weeks. Clinical efficacy was determined by two criteria, a decrease in the six-month UTI rates pre- and post-consumption and increased time until the first UTI since beginning the study. Strain heterogeneity and virulence factor profiles of intestinal E. coli isolated from rectal swabs were determined by DNA fingerprinting and muliplex PCR, respectively. The numbers of intestinal E. coli eluted from rectal swabs pre- and post-consumption were also quantified.

RESULTS: Over one-half of the patients did not experience a UTI within six months of SDC consumption, and the mean UTI rate per six months decreased significantly. Kaplan-Meier analysis of infection incidence in women consuming SDC compared to patients in a previous control group showed a significant reduction in time until first UTI within six months. The heterogeneity, VF profiles, and prevalence of intestinal E. coli strains were not significantly different after cranberry consumption.

CONCLUSIONS: Results of this study indicate a beneficial effect from consuming SDC to reduce the number of UTIs in susceptible women. Because there were no changes in the heterogeneity or VF profiles of E. coli, additional studies are needed to determine the mechanism of action of SDC for reduction of UTIs.

Cysticlean a highly pac standardized content in the prevention of recurrent urinary tract infections: an observational, prospective cohort study.

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Authors
Sanchez Ballester F, Ruiz Vidal V, Lopez Alcina E, Domenech Perez C, Escudero Fontano E, Oltra Benavent A, Montoliu Garcia A, Sobron Bustamante M
Journal
BMC Urol 13:28
Abstract

BACKGROUND: The present study was aimed at determining the prophylactic efficacy of American cranberry (AC) extract (Cysticlean) in women with recurrent symptomatic postcoital urinary tract infections (PCUTI), non-consumer of AC extract in the past 3 months before inclusion, and to determine changes in their quality of life (QoL).

METHODS: This was a single center, observational, prospective study in a total of 20 women (mean age 35.2 years; 50.0% were married). Patients were followed up for 3 and 6 months during treatment.

RESULTS: The number of PCUTIs in the previous 3 months prior to start the treatment with Cysticlean was 2.8+1.3 and it was reduced to 0.2+0.5 at Month 6 (P0.0001), which represent a 93% improvement. At baseline, the mean score on the VAS scale (range from 0 to 100) for assessing the QoL was 62.4+19.1, increasing to 78.2+12.4 at Month 6 (P=0.0002), which represents a 20% improvement. All patients had an infection with positive urine culture at baseline, after 6 months there were only 3 symptomatic infections (P0.001). The most common bacterium was Escherichia coli.

CONCLUSIONS: Prophylaxis with American cranberry extract (Cysticlean) could be an alternative to classical therapies with antibiotics. Further studies are needed to confirm results obtained in this pilot study.

A randomized clinical trial to evaluate the preventive effect of cranberry juice (UR65) for patients with recurrent urinary tract infection

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Authors
Takahashi S. Hamasuna R. Yasuda M. Arakawa S. Tanaka K. Ishikawa K. Kiyota H. Hayami H. Yamamoto S. Kubo T. Matsumoto T.
Journal
J Infect Chemother 19(1):112-7
Abstract

We examined the rate of relapse, as a variable index, in patients with urinary tract infection (UTI) who suffered from multiple relapses when using cranberry juice (UR65). A randomized, placebo-controlled, double-blind study was conducted from October 2007 to September 2009 in Japan. The subjects were outpatients aged 20 to 79 years who were randomly divided into two groups. One group received cranberry juice (group A) and the other a placebo beverage (group P). To keep the conditions blind, the color and taste of the beverages were adjusted. The subjects drank 1 bottle (125 mL) of cranberry juice or the placebo beverage once daily, before going to sleep, for 24 weeks. The primary endpoint was relapse of UTI. In the group of females aged 50 years or more, there was a significant difference in the rate of relapse of UTI between groups A and P (log-rank test; p = 0.0425). In this subgroup analysis, relapse of UTI was observed in 16 of 55 (29.1 %) patients in group A and 31 of 63 (49.2 %) in group P. In this study, cranberry juice prevented the recurrence of UTI in a limited female population with 24-week intake of the beverage.

Identification of polyphenols and their metabolites in human urine after cranberry-syrup consumption

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Authors
Iswaldi I, Arraez-Roman D, Gomez-Caravaca AM, Contreras Mdel M, Uberos J, Segura-Carretero A, Fernandez-Gutierrez A
Journal
Food Chem Toxicol 55:484-92
Abstract

As the beneficial effects of American cranberry (Vaccinium macrocarpon) can be partly attributed to its phenolic composition, the evaluation of the physiological behaviour of this fraction is crucial. A rapid and sensitive method by ultra-performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) has been used to identify phenolic metabolites in human urine after a single dose of cranberry syrup. Prior to the analysis, metabolites were extracted using an optimised solid-phase extraction procedure. All possible metabolites were investigated based on retention time, accurate mass data and isotope and fragmentation patterns. Free coumaroyl hexose (isomer 1 and 2), dihydroxybenzoic acid, caffeoyl glucose, dihydroferulic acid 4-O--d-glucuronide, methoxyquercetin 3-O-galactoside, scopoletin, myricetin and quercetin, together with other 23 phase-I and phase-II metabolites, including various isomers, could be tentatively identified in the urine. Afterwards, the metabolites were simultaneously screened in the urine of different subjects at 0, 2, 4, and 6h after the ingestion of cranberry syrup by Target Analysis(TM) software.

Prophylaxis of recurrent urinary tract infection after renal transplantation by cranberry juice and L-methionine

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Authors
Pagonas N, Horstrup J, Schmidt D, Benz P, Schindler R, Reinke P, van der Giet M, Zidek W, Westhoff TH
Journal
Transplant Proc 44(10):3017-21
Abstract

BACKGROUND: Recurrent urinary tract infections (UTIs) increase mortality and reduce graft survival after renal transplantation. Strategies to prevent recurrent UTIs include L-methionine, cranberry juice, and antibiotics. Data on the efficacy of cranberry and L-methionine, however, are controversial in the general population; there are few data in renal transplant recipients.
METHODS: We performed a retrospective analysis of 82 transplant recipients with recurrent UTIs, who underwent prophylaxis with cranberry juice (2 x 50 mL/d, n = 39, 47.6%), or L-methionine (3 x 500 mg/d, n = 25, 30.5%), or both modalities (n = 18, 21.9%). Thirty patients without prophylaxis served as controls. We analyzed symptoms, pyuria/nitrituria, and incidence of UTI events during 1 year before versus after initiation of prophylaxis.
RESULTS: Prophylaxis highly significantly decreased the annual UTI incidence by 58.3% (P .001) in the study population with no change in the control group (P = .85); in addition, 53.7% of symptomatic patients reported relief of symptoms and pyuria/nitrituria disappeared in 42.4% of the dipstick-positive patients (P .001 each). Cranberry reduced the annual number of UTI episodes by 63.9% from 3.6 +/- 1.4 to 1.3 +/- 1.3/year (P .001) and L-methionine by 48.7% from 3.9 +/- 1.8 to 2.0 +/- 1.3/year (P .001).
CONCLUSION: Cranberry juice and L-methionine successfully reduced the incidence of UTI after renal transplantation.

Cranberry Juice for the Prevention of Pediatric Urinary Tract Infection: A Randoomized Controlled Trial

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Authors
Afshar K, Stothers L, Scott H, MacNeily AE
Journal
J Urol
Abstract

Purpose: Proanthocyanidins found in cranberry have been reported to have in vitro and in vivo antibacterial activity. We determined the effectiveness of cranberry juice for the prevention of urinary tract infections in children.
Materials and Methods: A total of 40 children were randomized to receive daily cranberry juice with high concentrations of proanthocyanidin vs cranberry
juice with no proanthocyanidin for a 1-year period. The study was powered to detect a 30% decrease in the rate of symptomatic urinary tract infection with type I and II errors of 0.05 and 0.2, respectively. Toilet trained children up to age 18 years were eligible if they had at least 2 culture
documented nonfebrile urinary tract infections in the calendar year before enrollment. Patients with anatomical abnormalities (except for primary vesicoureteral
reflux) were excluded from study. Subjects were followed for 12 months. The participants, clinicians, outcome assessor and statistician were all blinded to treatment allocation.
Results: Of the children 39 girls and 1 boy were recruited. Mean and median patient age was 9.5 and 7 years, respectively (range 5 to 18). There were 20 patients with comparable baseline characteristics randomized to each group. After 12 months of followup the average incidence of urinary tract infection in the treatment group was 0.4 per patient per year and 1.15 in the placebo group
(p 0.045), representing a 65% reduction in the risk of urinary tract infection.
Conclusions: Cranberry juice with high concentrations of proanthocyanidin appears to be effective in the prevention of pediatric nonfebrile urinary tract infections. Further studies are required to determine the cost-effectiveness of this approach.

Enteric-coated, highly standardized cranberry extract reduces risk of UTIs and urinary symptoms during radiotherapy for prostate carcinoma

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Authors
Bonetta A, Di Pierro F
Journal
Cancer Manag Res
Abstract

Background: Cranberry (Vaccinium macrocarpon) proanthocyanidins can interfere with adhesion of bacteria to uroepithelial cells, potentially preventing lower urinary tract infections (LUTIs). Because LUTIs are a common side effect of external beam radiotherapy (EBRT) for prostate cancer, we evaluated the clinical efficacy of enteric-coated tablets containing highly standardized V. msacrocarpon (ecVM) in this condition.
Methods: A total of 370 consecutive patients were entered into this study. All patients received intensity-modulated radiotherapy for prostate cancer; 184 patients were also treated with ecVM while 186 served as controls. Cranberry extract therapy started on the simulation day, at which time a bladder catheterization was performed. During EBRT (over 6–7 weeks), all patients underwent weekly examination for urinary tract symptoms, including regular urine cultures during the treatment period.
Results: Compliance was excellent, with no adverse effects or allergic reactions being observed, apart from gastric pain in two patients. In the cranberry cohort (n = 184), 16 LUTIs (8.7%) were observed, while in the control group (n = 186) 45 LUTIs (24.2%) were recorded. This difference was statistically significant. Furthermore, lower rates of nocturia, urgency, micturition frequency, and dysuria were observed in the group that received cranberry extract.
Conclusion: Cranberry extracts have been reported to reduce the incidence of LUTIs significantly in women and children. Our data extend these results to patients with prostate cancer undergoing irradiation to the pelvis, who had a significant reduction in LUTIs compared with controls. These results were accompanied by a statistically significant reduction in urinary tract symptoms (dysuria, nocturia, urinary frequency, urgency), suggesting a generally protective effect of cranberry extract on the bladder mucosa.