Cranberry products are a nonantimicrobial
method for prevention of urinary tract infection
(UTI). Cranberry proanthocyanidin (PAC), a type of condensed tannin, is the active ingredient in cranberry that
inhibits adherence of P-fimbriated Escherichia coli to
uroepithelial cells. Previous cranberry studies for UTI
prevention yielded conflicting results, probably because
of variability of PAC dose and clinical populations studied. In a clinical trial of 300 mL of cranberry juice beverage daily (36 mg PAC), older women (mean age 78.5) had 58% lower odds of having bacteriuria and pyuria than controls, but nursing home residents have difficulty ingesting the volume of juice necessary to prevent bacteriuria. Cranberry capsules are feasible to administer to nursing home residents, but their efficacy has not been demonstrated. In vitro, 36–108 mg of PAC is efficacious at inhibiting bacterial adherence to uroepithelial cells, but the most efficacious dose for older nursing home residents has not been identified. The goal of this study was to identify the optimal dose of cranberry capsules that reduced the incidence of bacteriuria plus pyuria over 1 month.

Objectives. The aim of this randomized controlled prospective study is to evaluate the efficacy of cranberry capsules for prevention of UTI in children with neurogenic bladder caused by myelomeningocele. Patients and Methods. To be eligible for this study, patients had to be diagnosed as neurogenic bladder caused by myelomeningocele, evaluated urodynamically, followed up with clean intermittent catheterization and anticholinergic drugs. Intervention. Six months of treatment with placebo; after a week of wash-out period treatment of cranberry extract tablets (1 capsule/day) for an additional 6 months. Randomization was performed sequentially. Patients and care givers were blinded to drug assignment. Main outcome measure was infection rate. Group comparisons were performed with Wilcoxon test. Results. The study population included 20 (F/M: 13/7) patients with neurogenic bladder with the mean age of 7.25 ± 3.49 (4, 18) years. The median UTI rate was 0.5/year during placebo usage whereas 0/year during cranberry capsule usage. Decrease in infection rate was significant with cranberry capsule usage (P = 0.012). Decrease in the percentage of the pyuria was also recorded as significant (P = 0.000). Any adverse events or side effects were not recorded. Conclusion. We concluded that cranberry capsules could be an encouraging option for the prevention of recurrent UTI in children with neurogenic bladder caused by myelomeningocele.

AIMS:
Radical pelvic radiotherapy is one of the main treatment modalities for cancers of the bladder and cervix. The side-effects of pelvic radiotherapy include urinary symptoms, such as urinary frequency and cystitis. The therapeutic effects of cranberry juice in the prevention and treatment of urinary tract infections in general are well documented. The purpose of this study was to evaluate the effectiveness of cranberry juice on the incidence of urinary tract infections and urinary symptoms in patients undergoing pelvic radiotherapy for cancer of the bladder or cervix.
MATERIALS AND METHODS:
The study was a placebo-controlled, double-blind design. Participants were randomised to receive cranberry juice, twice a day (morning and night) for the duration of their radiotherapy treatment and for 2 weeks after treatment (6 weeks in total) or a placebo beverage, for the same duration.
RESULTS:
The incidence of increased urinary symptoms or urinary tract infections was 82.5% on cranberry and 89.3% on placebo (P=0.240, adjusted odds ratio [cranberry/placebo] 0.48, 95% confidence interval 0.14-1.63).
CONCLUSIONS:
The power of the study to detect differences was limited by the below target sample size and poor compliance. Further research is recommended, taking cognisance of the factors contributing to the limitations of this study.

Cranberry-lingonberry juice (CLJ) was effective in preventing urinary tract infections (UTIs) in our earlier randomized clinical trial. We aimed to test whether consumption of CLJ at a similar dose to earlier reduces the biofilm formation and virulence of uropathogenic Escherichia coli in urine. Twenty healthy women drank 100 ml of CLJ daily for two weeks. Urine samples were obtained 2–4 hours after the last dose. Control samples were taken after a one-week period without berry consumption. Biofilm formation of 20 E. coli strains was measured at 72 hours by the polystyrene microtitre plate method. Quantitative real-time PCR analyses were performed for selected genes. Four of the 20 clinical strains produced more biofilm in urine after CLJ consumption (P  0.05) and one produced less. Expression levels of the pga, cpxA, fimA and papF genes did not differ between bacteria grown in control urine and urine obtained after CLJ consumption, except for pga gene expression, which was reduced in one strain after CLJ (P = 0.04). It appears that the effect of CLJ in preventing UTIs is not explained by mechanisms that reduce biofilm formation or the expression of selected virulence genes of Escherichia coli in urine.

OBJECTIVE:
To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice daily.
PATIENTS AND METHODS:
Premenopausal women with a history of recent UTI were enrolled from November 16, 2005, through December 31, 2008, at 2 centers and randomized to 1 of 3 arms: 4 oz of cranberry juice daily, 8 oz of cranberry juice daily, or placebo juice. Time to UTI (symptoms plus pyuria) was the main outcome. Asymptomatic bacteriuria, adherence, and adverse effects were assessed at monthly visits.
RESULTS:
A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days. The cumulative rate of UTI was 0.29 in the cranberry juice group and 0.37 in the placebo group (P=.82). The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 0.68 (95% confidence interval, 0.33-1.39; P=.29). The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (43.5%) in the cranberry juice group and 8 of 10 (80.0%) in the placebo group (P=.07). The mean dose adherence was 91.8% and 90.3% in the cranberry juice group vs the placebo group. Minor adverse effects were reported by 24.2% of those in the cranberry juice group and 12.5% in the placebo group (P=.07).
CONCLUSION:
Cranberry juice did not significantly reduce UTI risk compared with placebo. The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger, well-powered studies of women with recurrent UTI. The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity.
TRIAL REGISTRATION:
clinicaltrials.gov Identifier: NCT00128128.

Urinary tract infections (UTIs) represent a recurrent health problem especially for women. More than 50% of women will suffer from a UTI at least once in their lifetime. Cranberries have long been used for their beneficial effects in preventing symptomatic UTIs in several published studies. However, cranberry products used in these clinical studies do not indicate the amount of active ingredients delivered that help to prevent UTIs. Therefore, a dose-dependent study was designed to understand the impact and safety profile of a standardized cranberry product (Proanthocyanidins Standardized Whole Cranberry Powder,PS-WCP) on reducing the recurrences of symptomatic UTI in culture-positive subjects. A 90- day randomized clinical trial including an untreated control group with a total of 60 female subjects between 18-40 years of age was conducted. Study subjects were randomly selected and assigned to three groups including an untreated control group (n=16), a low dose (500 mg daily, n=21) and a high dose (1000 mg daily, n=23) treatment group. The safety of PSWCP was assessed by evaluation of biochemical and hematological parameters on days 10, 30, 60 and 90 during the study, comparing the values with those at the baseline. Occurrence of UTI at baseline and during the follow-up period was characterized by the presence of symptoms and Escherichia coli in the culture of urine samples. The statistical analysis used was ANOVA. At the end of the 90-day treatment period, no significant changes were observed in the hematological and serum biochemical parameters. At the end of the study, change in the presence of E. coli in the untreated control group was not significant (p=0.7234), whereas, there was significant reduction (p0.05) in the subjects positive for E. coli in both the high dose and low dose treatment groups, compared to baseline evaluation. Symptomatic relief was also reported in the low and high dose treatment groups, while none was reported by subjects in the untreated control group. In conclusion, PS-WCP was effective in safely reducing the number of E. coli positive subjects at both the 500 mg and 1000 mg dose levels and in ameliorating the symptoms of UTI in these subjects. Therefore, a daily dose of 500 mg or 1000 mg of PS-WCP may be considered as an adjunct to antibiotic prophylactic therapy against recurrent UTIs.

Absorption and excretion of twenty cranberry-derived phenolics were studied following the consumption of cranberry juice, sauces, and fruits by healthy human volunteers. Plasma and urine samples were collected and analysed by gas chromatography–mass spectrometry (GC–MS). A high performance liquid chromatography (HPLC) method was employed for analysing urinary creatinine, which was used as a normalisation agent. Significant increases in the sum of plasma phenolics were observed with different concentration peaks (between 0.5 and 2 h) for individual subjects. Some of the phenolics, such as trans-cinnamic, vanillic, p-coumaric acids, and catechin showed second plasma concentration peaks. All of cranberry-derived phenolics increased significantly in urine samples after the intake of each cranberry product. The high molecular weight quercetin and myricetin, which were abundant in cranberry foodstuffs, were not found in either plasma or urine samples. This study provided the fundamental information for understanding the absorption and excretion of phenolics in the human gastrointestinal system after dietary intake of cranberry products.

Background. Cranberry juice prevents recurrences of urinary tract infections (UTIs) in adult women. The objective of this study was to evaluate whether cranberry juice is effective in preventing UTI recurrences in children.
Methods. A double-blind randomized placebo-controlled trial was performed in 7 hospitals in Finland. A total of 263 children treated for UTI were randomized to receive either cranberry juice (n = 129) or placebo (n = 134) for 6 months. Eight children were omitted because of protocol violations, leaving 255 children for the final analyses. The children were monitored for 1 year, and their recurrent
UTIs were recorded. Results. Twenty children (16%) in the cranberry group and 28 (22%) in the placebo group had at least 1 recurrent UTI (difference, -6%; 95% confidence interval [CI], -16 to 4%; P = .21). There were no differences in timing between these first recurrences (P = .32). Episodes of UTI totaled 27 and 47 in the cranberry and placebo groups, respectively, and the UTI incidence density per person-year at risk was 0.16 episodes lower in the cranberry group (95% CI, -.31 to -.01; P = .035). The children in the cranberry group had significantly fewer days on antimicrobials (-6 days per patient-year; 95% CI, -7 to -5; P .001). Conclusions. The intervention did not significantly reduce the number of children who experienced a recurrence of UTI, but it was effective in
reducing the actual number of recurrences and related antimicrobial use.

Cranberry juice cocktail (CJC) has been shown to inhibit the formation of biofilm by uropathogenic Escherichia coli. In order to investigate whether the anti-adhesive components could reach the urinary tract after oral consumption of CJC, a volunteer was given 16 oz of either water or CJC. Urine samples were collected at 0, 2, 4, 6, and 8 hours after consumption of a single dose. The ability of compounds in the urine to influence bacterial adhesion was tested for six clinical uropathogenic E. coli strains, including four P-fimbriated strains (B37, CFT073, BF1023, and J96) and two strains not expressing P-fimbriae but exhibiting mannose-resistant hemagglutination (B73 and B78). A non-fimbriated strain, HB101, was used as a control. Atomic force microscopy (AFM) was used to measure the adhesion force between a silicon nitride probe and bacteria treated with urine samples. Within 2 hours after CJC consumption, bacteria of the clinical strains treated with the corresponding urine sample demonstrated lower adhesion forces than those treated with urine collected before CJC consumption. The adhesion forces continued decreasing with time after CJC consumption over the 8-hour measurement period. The adhesion forces of bacteria after exposure to urine collected following water consumption did not change. HB101 showed low adhesion forces following both water and CJC consumption, and these did not change over time. The AFM adhesion force measurements were consistent with the results of a hemagglutination assay, confirming that oral consumption of CJC could act against adhesion of uropathogenic E. coli.

Background: The increasing prevalence of uropathogens resistant to antimicrobial agents has stimulated interest in cranberries to prevent recurrent urinary tract infections (UTIs). Methods: In a double-blind, double-dummy noninferiority trial, 221 premenopausal women with recurrent UTIs were randomized to 12-month prophylaxis use of trimethoprim-sulfamethoxazole (TMP-SMX), 480 mg once daily, or cranberry capsules, 500 mg twice daily. Primary end points were the mean number of symptomatic UTIs over 12 months, the proportion of patients with at least 1 symptomatic UTI, the median time to first UTI, and development of antibiotic resistance in indigenous Escherichia coli. Results: After 12 months, the mean number of patients with at least 1 symptomatic UTI was higher in the cranberry than in the TMP-SMX group (4.0 vs 1.8; P=.02), and the proportion of patients with at least 1 symptomatic UTI was higher in the cranberry than in the TMP-SMX group (78.2% vs 71.1%). Median time to the first symptomatic UTI was 4 months for the cranberry and 8 months for the TMP-SMX group. After 1 month, in the cranberry group, 23.7% of fecal and 28.1% of asymptomatic bacteriuria E. coli isolates were TMP-SMX resistant, whereas in the TMP-SMX group, 86.3% of fecal and 90.5% of asymptomatic bacteriuria E. coli isolates were TMP-SMX resistant. Similarly, we found increased resistance rates for trimethoprim, amoxicillin, and ciprofloxacin in these E. coli isolates after 1 month in the TMP-SMX group. After discontinuation of TMP-SMX, resistance reached baseline levels after 3 months. Antibiotic resistance did not increase in the cranberry group. Cranberries and TMP-SMX were equally well tolerated. Conclusion: In premenopausal women, TMP-SMX, 480 mg once daily, is more effective than cranberry capsules, 500 mg twice daily, to prevent recurrent UTIs, at the expense of emerging antibiotic resistance.