PURPOSE: This review provides practicing urologists with important basic information about urinary tract infections (UTIs) that can be applied to everyday clinical problems.

MATERIALS AND METHODS: A review is presented of provocative and controversial concepts in the current literature.

RESULTS: Bacterial virulence mechanisms are critical for overcoming the normal host defenses. Increasing antimicrobial resistance of uropathogens has led to reconsideration of traditional treatment recommendations in many areas. For effective patient management the first issue is to define complicating urological factors. Managing complicated urinary tract infections, particularly in urology, is determined by clinical experience to define the pertinent anatomy and to determine the optimal interventions. New clinical data are summarized on UTIs in long-term care patients, behavioral risks for UTI in healthy women and anatomical differences associated with an increased risk for UTI. The rationale is presented for UTI prophylaxis using cranberry juice, immunization and bacterial interference. Current treatment trends for UTI include empiric therapy (without urine culture and sensitivity testing), short-course therapy, patient-administered (self-start) therapy and outpatient therapy for uncomplicated pyelonephritis.

CONCLUSIONS: Recommendations for treating patients with UTIs have changed based on basic science and clinical experience.

In this review we assess the effectiveness of cranberry and blueberry products in preventing symptomatic urinary tract infections (UTIs). Selection criteria were randomised or quasi-randomised controlled trials of cranberry or blueberry juice/products for the prevention of symptomatic UTIs. A comprehensive search was undertaken in November 2006 whereupon two reviewers independently assessed and extracted data. Quality was assessed using Cochrane criteria. Relative risks (RR) were calculated where appropriate; otherwise a narrative synthesis was undertaken. No relevant trials of blueberry products were identified. Nine trials of cranberry products met the inclusion criteria. In four good quality randomised controlled trials (RCTs), cranberry products significantly reduced the incidence of symptomatic UTIs in 12 months (overall RR 0.65, 95% CI: 0.46-0.90) compared with placebo/control. Five trials were not included in the meta-analyses due to the lack of appropriate data. However, only one reported a significant result. Side effects were common, and losses to followup/withdrawals in several of the trials were high (> 40%). There is some evidence from four good quality RCTs that cranberry juice may decrease the number of symptomatic UTIs over a 12-month period, particularly in women with recurrent UTIs. It is uncertain whether it is effective in other susceptible groups.

Studies were undertaken to investigate the antiviral effects of comestible juices, especially cranberry juice, on non-related viral species. After exposure of bacteriophage T2 to a commercially available cranberry (Vaccinium macrocarpon) juice cocktail (CJ), virus infectivity titer was no longer detectible. After a 60-min exposure to orange (OJ) and grapefruit juices (GJ), phage infectivity was reduced to 25-35% of control, respectively. Similar data were observed for the bacteriophage T4. CJ inactivation of phage T4 was rapid, dose-dependent, and occurred at either 4 or 23 degrees C. Neither pH nor differences in sugar/carbohydrate levels among the juices may be ascribed to the recognized antiviral effects. Further studies were performed to identify the occurrence of antiviral activity by CJ to a mammalian enteric virus. The treatment of the simian rotavirus SA-11 with a 20% CJ suspension was sufficient to inhibit hemagglutination. Under scanning and transmission electron microscopy, CJ was observed to inhibit the adsorption of phage T4 to its bacterial host cells and prevented the replication of rotavirus in its monkey kidney (MA-104) host cells, respectively. The data suggest, for the first time, a non-specific antiviral effect towards unrelated viral species (viz., bacteriophages T2 and T4 and the simian rotavirus SA-11) by a commercially available cranberry fruit juice drink.

Cranberry (Vaccinium macrocarpon Ait.) ingestion has long been associated with prevention of urinary tract infections. The beneficial mechanism was historically thought to be due to the fruit acids causing a bacteriostatic effect in the urine. However, recently, a group of proanthocyanidins (PACs) with A-type linkages were isolated from cranberry which exhibit bacterial antiadhesion activity against both antibiotic susceptible and resistant strains of uropathogenic P-fimbriated Escherichia coli bacteria. The link between cranberry ingestion and maintenance of urinary tract health as well as the structural diversity, pharmacokinetics, quantification, and bacterial antiadhesion bioactivity of the A-linked cranberry PACs are reviewed.

The anti-adhesive effects of cranberry have been attributed to both interactions of its components with the surface of bacterial cells and to inhibition of p-fimbriae expression. Previous reports also suggested that the presence of cranberry juice changed the Gram stain characteristics of Escherichia coli. Here, we show that the morphology of E. coli is changed when grown in the presence of juice or extract from Vaccinium macrocarpon (cranberry). Gene expression analysis indicates the down regulation of flagellar basal body rod and motor proteins. Consistent with this finding and previous reports, the SEM images indicate a decrease in the visible p-fimbriae. The iodine used in Gram-staining protocols was found to interact differently with the bacterial membrane when cells were cultured in spiked media. Slight alterations in the Gram stain protocol demonstrated that culturing in the presence of cranberry juice does not change the Gram stain characteristics contradicting other reports.

This study evaluated the antibacterial efficacy of the consumption of cranberry capsules vs. placebo in the urine of healthy volunteers. A first double-blind, randomised, crossover trial involved eight volunteers who had followed three regimens, with or without cranberry, with a wash-out period of at least 6 days between each regimen. Twelve hours after consumption of cranberry or placebo hard capsules, the first urine of the morning was collected. Different Escherichia coli strains were cultured in the urine samples. Urinary antibacterial adhesion activity was measured in vitro using the human T24 epithelial cell-line, and in vivo using the Caenorhabditis elegans killing model. With the in-vitro model, 108 mg of cranberry induced a significant reduction in bacterial adherence to T24 cells as compared with placebo (p 0.001). A significant dose-dependent decrease in bacterial adherence in vitro was noted after the consumption of 108 and 36 mg of cranberry (p 0.001). The in-vivo model confirmed that E. coli strains had a reduced ability to kill C. elegans after growth in the urine of patients who consumed cranberry capsules. Overall, these in-vivo and in-vitro studies suggested that consumption of cranberry juice represents an interesting new strategy to prevent recurrent urinary tract infection.

OBJECTIVE: To determine whether Methenamine Hippurate (MH) or cranberry tablets prevent urinary tract infections (UTI) in people with neuropathic bladder following spinal cord injury (SCI).

STUDY DESIGN: Double-blind factorial-design randomized controlled trial (RCT) with 2 year recruitment period from November 2000 and 6 month follow-up.

SETTING: In total, 543 eligible predominantly community dwelling patients were invited to participate in the study, of whom 305 (56%) agreed.

METHODS: Eligible participants were people with SCI with neurogenic bladder and stable bladder management. All regimens were indistinguishable in appearance and taste. The dose of MH used was 1 g twice-daily. The dose of cranberry used was 800 mg twice-daily. The main outcome measure was the time to occurrence of a symptomatic UTI.

RESULTS: Multivariate analysis revealed that patients randomized to MH did not have a significantly longer UTI-free period compared to placebo (HR 0.96, 95% CI: 0.68-1.35, P=0.75). Patients randomized to cranberry likewise did not have significantly longer UTI-free period compared to placebo (HR 0.93, 95% CI: 0.67-1.31, P=0.70).

CONCLUSION: There is no benefit in the prevention of UTI from the addition of MH or cranberry tablets to the usual regimen of patients with neuropathic bladder following SCI.

PURPOSE: To determine, from a societal perspective, the effectiveness and cost effectiveness of concentrated cranberry tablets, versus cranberry juice, versus placebo used as prophylaxis against lower urinary tract infection (UTI) in adult women.MATERIALS AND METHODS: One hundred fifty sexually active women aged 21 through 72 years were randomized for one year to one of three groups of prophylaxis: placebo juice + placebo tablets versus placebo juice + cranberry tablets, versus cranberry juice + placebo tablets. Tablets were taken twice daily, juice 250 ml three times daily. Outcome measures were: (1) a >50% decrease in symptomatic UTI's per year (symptoms + >or= 100 000 single organisms/ml) and (2) a >50% decrease in annual antibiotic consumption. Cost effectiveness was calculated as dollar cost per urinary tract infection prevented. Stochastic tree decision analytic modeling was used to identify specific clinical scenarios for cost savings.RESULTS: Both cranberry juice and cranberry tablets statistically significantly decreased the number of patients experiencing at least 1 symptomatic UTI/year (to 20% and 18% respectively) compared with placebo (to 32%) (p0.05). The mean annual cost of prophylaxis was $624 and $1400 for cranberry tablets and juice respectively. Cost savings were greatest when patients experienced >2 symptomatic UTI's per year (assuming 3 days antibiotic coverage) and had >2 days of missed work or required protective undergarments for urgency incontinence. Total antibiotic consumption was less annually in both treatment groups compared with placebo. Cost effectiveness ratios demonstrated cranberry tablets were twice as cost effective as organic juice for prevention.CONCLUSIONS: Cranberry tablets provided the most cost-effective prevention for UTI.

In a previous investigation it was demonstrated that cranberry juice cocktail was able to inhibit adherence in 77 clinical isolates of Escherichia coli obtained from patients with diagnosed urinary tract infections. This work has been extended to include clinical isolates of E. coli, Proteus, Klebsiella, Enterobacter and Pseudomonas isolated from urine, sputum, wound and stool. Bacterial strains isolated from urine adhere in greater numbers to urinary tract epithelial cells than organisms isolated from sputum, stool and wound sources. E. coli, isolated from urine, adheres to urinary epithelial cells, in numbers three times greater than E. coli isolated from other clinical sources, and thus appears to represent a unique population of cells in terms of adherence. Cranberry juice cocktail and urine and urinary epithelial cells obtained after drinking the cocktail all demonstrate antiadherence activity against Gram-negative rods isolated from urine and other clinical sources. Drinking the cocktail may be useful in managing urinary tract infections in certain patients.

Cranberries have been suggested to decrease the attachment of bacteria to uroepithelial cells (UC), thus preventing urinary tract infections, although the mechanisms are not well understood. A thermodynamic approach was used to calculate the Gibbs free energy of adhesion changes (DeltaG(adh)) for bacteria-UC interactions, based on measuring contact angles with three probe liquids. Interfacial tensions and DeltaG(adh) values were calculated for Escherichia coli HB101pDC1 (P-fimbriated) and HB101 (non-fimbriated) exposed to cranberry juice (0-27 wt.%). HB101pDC1 can form strong bonds with the Gal-Gal disaccharide receptor on uroepithelial cells, while HB101-UC interactions are only non-specific. For HB101 interacting with UC, DeltaG(adh) was always negative, suggesting favorable adhesion, and the values were insensitive to cranberry juice concentration. For the HB101pDC1-UC system, DeltaG(adh) became positive at 27wt.% cranberry juice, suggesting that adhesion was unfavorable. Acid-base (AB) interactions dominated the interfacial tensions, compared to Lifshitz-van der Waals (LW) interactions. Exposure to cranberry juice increased the AB component of the interfacial tension of HB101pDC1. LW interactions were small and insensitive to cranberry juice concentration. The number of bacteria attached to UC was quantified in batch adhesion assays and quantitatively correlated with DeltaG(adh). Since the thermodynamic approach should not agree with the experimental results when specific interactions are present, such as HB101pDC-UC ligand-receptor bonds, our results may suggest that cranberry juice disrupts bacterial ligand-UC receptor binding. These results help form the mechanistic explanation of how cranberry products can be used to prevent bacterial attachment to host tissue, and may lead to the development of better therapies based on natural products.