OBJECTIVE: Cranberry prophylaxis of recurrent urinary tract infection in infants has proven effective in the experimental model of the adult. There are few data on its efficacy, safety and recommended dose in the pediatric population.
METHODS: A controlled, double-blind Phase III clinical trial was conducted on children older than 1 month of age to evaluate the efficacy and safety of cranberry in recurrent urinary tract infection. The assumption was of the non-inferiority of cranberry versus trimethoprim. Statistical analysis was performed using Kaplan Meier analysis.
RESULTS: A total of 85 patients under 1 year of age and 107 over 1 year were recruited. Trimethoprim was prescribed to 75 patients and 117 received cranberry. The cumulative rate of urinary infection associated with cranberry prophylaxis in children under 1 year was 46% (95% CI; 23-70) in children and 17% (95% CI; 0-38) in girls, effectively at doses inferior to trimethoprim. In children over 1 year-old cranberry was not inferior to trimethoprim, with a cumulative rate of urine infection of 26% (95% CI; 12-41). The cranberry was well tolerated and with no new adverse effects.
CONCLUSIONS: Our study confirms that cranberry is safe and effective in the prophylaxis of recurrent urinary tract infection in infants and children. With the doses used, their efficiency is not less than that observed for trimethoprim among those over 1 year-old. (Clinical Trials Registry ISRCTN16968287).

Background: Urinary tract infection is the most common bacterial infection in the community, mainly caused by Escherichia coli (E. coli). Due to its high incidence and recurrence, problems are faced in the treatment with antibiotics. Cranberry being herbal remedy have long been the focus of interest for their beneficial effects in preventing urinary tract infections. This study was conducted to analyse in vitro activity of cranberry (Vaccinium macrocarpon) on uropathogenic E. coli in uncomplicated urinary tract infections. Methods: In this laboratory based single group experimental study, anti-bacterial activity of Vaccinium macrocarpon concentrate on urinary tract E. coli was investigated, in vitro. Ninety-six culture positive cases of different uropathogens were identified. Vaccinium macrocarpon concentrate at different concentrations was prepared in distilled water and put in wells punched in nutrient agar. E. coli isolates were inoculated on the plates and incubated at 37 oC for 24 hours. A citric acid solution of the same pH as that of Vaccinium macrocarpon was used and put in a well on the same plate to exclude the effect of pH. Results: A total of 35 isolates of E. coli were identified out of 96 culture positive specimens of urine and found sensitive to Vaccinium macrocarpon (p<0.000). Results revealed that Vaccinium macrocarpon has antibacterial effect against E. coli. Furthermore the antibacterial activity of Vaccinium macrocarpon has dose response relationship. Acidic nature of Vaccinium macrocarpon due to its pH is not contributory towards its antibacterial effect. Conclusion: Vaccinium macrocarpon concentrate may be used in urinary tract infection caused by E. coli.

For investigation of the molecular interaction of cranberry extract with adhesins of uropathogenic Escherichia coli (UPEC), urine from four volunteers consuming standardized cranberry extract (proanthocyanidin content = 1.24%) was analyzed within ex vivo experiments, indicating time-dependent significant inhibition of 40-50% of bacterial adhesion of UPEC strain NU14 to human T24 bladder cells. Under in vitro conditions a dose-dependent increase in bacterial adhesion was observed with proanthocyanidin-enriched cranberry Vaccinium macrocarpon extract (proanthocyanidin content = 21%). Confocal laser scanning microscopy and scanning electron microscopy proved that V.m. extract led to the formation of bacterial clusters on the outer plasma membrane of the host cells without subsequent internalization. This agglomerating activity was not observed when a PAC-depleted extract (V.m. extract(PAC)) was used, which showed significant inhibition of bacterial adhesion in cases where type 1 fimbriae dominated and mannose-sensitive UPEC strain NU14 was used. V.m. extract(PAC) had no inhibitory activity against P- and F1C-fimbriae dominated strain 2980. Quantitative gene expression analysis indicated that PAC-containing as well as PAC-depleted cranberry extracts increased the fimH expression in NU14 as part of a feedback mechanism after blocking FimH. For strain 2980 the PAC-containing extract led to up-regulation of P- and F1C-fimbriae, whereas the PAC-depleted extract had no influence on gene expression. V.m. and V.m. extract(PAC) did not influence biofilm and curli formation in UPEC strains NU14 and 2980. These data lead to the conclusion that also proanthocyanidin-free cranberry extracts exert antiadhesive activity by interaction with mannose-sensitive type 1 fimbriae of UPEC.

The effectiveness of cranberry in the treatment of urinary tract infection (UTI) has been associated with its polyphenol content, particularly proanthocyanidins (PACs) and the inhibition of adherence of Escherichia coli to the uroepithelium. This paper describes a controlled, double blind, clinical trial of children aged over one month with recurrent urinary tract infection. The study aims were to evaluate the safety and efficacy of cranberry syrup in children and to investigate the relationship between the excretion of phenolic acids in urine with the antiadherent activity of cranberry syrup. In the study population, cranberry syrup was found to be similar to trimethoprim, with a rate of UTI (reinfection) of 26% (95% CI 12-41). The administration of cranberry syrup was associated with high levels of hydroxycinnamic and hydroxybenzoic acids in urine; in both cases these molecules present activity in the biofilm inhibition or reduction of surface hydrophobicity of E. coli (Clinical Trials Registry ISRCTN16968287).

OBJECTIVES: To evaluate the compliance with and tolerability of daily cranberry capsule ingestion for asymptomatic bacteriuria (ASB) prevention in pregnancy.
DESIGN: A total of 49 pregnant women from two sites were randomly assigned to cranberry or matching placebo, two doses daily, at gestational ages less than 16 weeks. Patients were followed monthly for urinary tract infection until delivery. Up to seven monthly visits were scheduled for each patient. Delivery data were evaluated.
RESULTS: Of 38 evaluable patients, the mean compliance rate over the study period was 82% (range, 20%-100%). This compliance rate and the 74% of patients achieving good (>75%) compliance were similar between those who received cranberry capsules and placebo. Compliance evaluation revealed that most patients stopped capsule consumption after 34-38 weeks of participation. Multivariate logistic regression and longitudinal analysis showed a significant interaction time effect with cranberry treatment. However, cranberry consumption was not a significant predictor of gastrointestinal intolerance or study withdrawal. Although 30% of patients withdrew for various reasons, only 1 withdrew because of intolerance to the cranberry capsules. Loss to follow-up was mostly due to provider change (9 of 49 [18%]) and therapy disinterest (4 of 49 [8%]). Seven cases of ASB occurred in 5 patients: 2 of 24 (8%) in the cranberry group and 3 of 25 (12%) in the placebo group. No cases of cystitis or pyelonephritis were observed.
CONCLUSION: One third of pregnant women could not complete the study protocol for various reasons. Compliance with and tolerability of cranberry capsule ingestion appear good; these capsules provide a potentially effective means to prevent ASB in pregnancy. Further studies with large samples are necessary to confirm the findings.

The overall metabolic changes caused by cranberry juice or apple juice consumption using a global 1H NMR-based metabolomics approach were investigated. Eighteen female college students were given either cranberry or apple juice for three days using a cross-over design. Plasma and urine samples were collected and analyzed using 1H NMR-based metabolomics followed by multivariate analyses. No metabolic difference was observed in plasma before and after juice consumption. However, metabolome in plasma and urine after cranberry juice consumption were different from those after apple juice consumption. Cranberry juice consumption caused a greater increase in urinary excretion of hippuric acid and a higher level of citric acid in the plasma. Furthermore, cranberry juice decreased the plasma level of lactate, D-glucose, and two unidentified metabolites compared to apple juice consumption. The metabolomic changes caused by cranberry juice consumption may help to explain its reported health benefits.

In this study, we examined the ex vivo urinary anti-adhesion activity of low-calorie cranberry extract beverages in both a pilot study (n = 10) and a randomized, double-blind, placebo controlled clinical trial (n = 59). In the pilot study, subjects consumed a cranberry extract beverage (CEB) or a cranberry extract and juice beverage (CEJB), compared to placebo. Both cranberry beverages utilized a standardized cranberry extract powder at a level equivalent to low-calorie cranberry juice cocktail (LCJC) on a PAC content basis. Clean-catch urine samples collected at baseline and post intervention were tested for anti-adhesion activity utilizing a mannose-resistant human red blood cell hemagglutination assay specific for P-fimbriated E. coli. Results from the pilot study indicated that ex vivo anti-adhesion activity for both cranberry treatments were higher (p < 0.05) than placebo. In the clinical trial, we compared CEJB to LCJC and a placebo beverage. Post-consumption urine from both cranberry treatment groups showed significantly higher (p < 0.05) anti-adhesion activity compared to placebo. There were no differences observed in anti-adhesion activity between CJEB and LCJC, indicating similar bioactivity. Therefore, acute beverage consumption of cranberry extract and/or juice provides ex vivo anti-adhesion activity, which may help to improve urinary tract health.

INTRODUCTION: Urinary tract infection (UTI) is among the most frequent complications after urinary tract surgical procedures, mainly when catheter placement is necessary. Although the use of American cranberry has been related with a reduced risk of UTI, there is no study reporting the value of its prevention effect against catheter-associated urinary tract infections.
MATERIAL AND METHODS: A prospective trial comparing UTI rate (positive urine culture) among 31 patients with double J catheter (JJ) and adding American cranberry (120 mg) in routine prophylactic therapy, and 31 patients with JJ catheter only receiving routine prophylactic therapy.
RESULTS: Regarding general characteristics of the populations no significant difference among groups have been found. Only significant differences have been observed when the variables ""cranberry treatment"" and ""dwell time of JJ catheter"" were related. ""Dwell time of JJ catheter"" was higher in patients with UTI (35.9 compared 28.5 days [P=.03]). UTI percentage was lower in cranberry supplemented patient group (12.9 compared to 38.7% [P=.04]).
CONCLUSIONS: We can conclude that American cranberry (120 mg) has an adjuvant effect in the prevention of UTI in patients with JJ catheter after surgery.

Cranberry consumption has shown prophylactic effects against urinary tract infections (UTI), although the mechanisms involved are not completely understood. In this paper, cranberry phenolic compounds and their potential microbial-derived metabolites (such as simple phenols and benzoic, phenylacetic and phenylpropionic acids) were tested for their capacity to inhibit the adherence of uropathogenic Escherichia coli (UPEC) ATCC53503TM to T24 epithelial bladder cells. Catechol, benzoic acid, vanillic acid, phenylacetic acid and 3,4-dihydroxyphenylacetic acid showed anti-adhesive activity against UPEC in a concentration-dependent manner from 100-500 micro M, whereas procyanidin A2, widely reported as an inhibitor of UPEC adherence on uroepithelium, was only statistically significant (p < 0.05) at 500 micro M (51.3% inhibition). The results proved for the first time the anti-adhesive activity of some cranberry-derived phenolic metabolites against UPEC in vitro, suggesting that their presence in the urine could reduce bacterial colonization and progression of UTI.

Urinary tract infection (UTI) is the most common infection
among nursing home residents, and the microorganisms pre-valent in this setting pose significant challenges for treatment. Cranberries (Vaccinium macrocarpon Aiton
) are thought to reduce UTIs; this view is supported by a placebo-controlled trial showing lower rates of bacteriuria plus pyuria with daily ingestion of 300 mL of cranberry juice cocktail (15.0% versus 28.1% in controls). However, subsequent studies of cranberries for prevention of UTI, including a large Cochrane meta-analysis, have shown mixed results. Various mechanisms of the bacteriologic effect of cranberries are postulated; however, inhibition of P fimbriae–mediated adhesion of E. coli by proanthocyanidin (PAC) remains the leading theory.
We sought to compare antibiotic susceptibility and proportions of non–E. coli Enterobacteriaceae among Gram-negative urinary isolates from participants randomized to cranberry capsules compared to placebo.