OBJECTIVE: Our aim was to assess the usefulness of cranberry extract in multiple sclerosis (MS) patients suffering from urinary disorders.
METHODS: In total, 171 adult MS outpatients with urinary disorders presenting at eight centers were randomized (stratification according to center and use of clean intermittent self-catheterization) to cranberry versus placebo in a 1-year,
prospective, double-blind study that was analyzed using a sequential method on an intent-to-treat basis. An independent monitoring board analyzed the results of the analyses each time 40 patients were assessed on the main endpoint. Cranberry extract (36 mg proanthocyanidins per day) or a matching placebo was taken by participants twice daily for 1 year. The primary endpoint was the time to first symptomatic urinary tract infection (UTI), subject to validation by a validation committee.
RESULTS: The second sequential analyses allowed us to accept the null hypothesis (no difference between cranberry and placebo). There was no difference in time to first symptomatic UTI distribution across 1 year, with an estimated hazard ratio
of 0.99, 95% CI [0.61, 1.60] (p = 0.97). Secondary endpoints and tolerance did not differ between groups.
CONCLUSION: Taking cranberry extract versus placebo twice a day did not prevent UTI occurrence in MS patients with urinary disorders. Trial Registration NCT00280592.

BACKGROUND: Urinary tract infections (UTIs) are the most common bacterial infection in women. Most UTIs are acute uncomplicated cystitis caused by Escherichia coli (86%). This study was undertaken to assess the effectiveness of an association of a cranberry dry extract, D-mannose, a gelling complex composed of the exopolysaccharides produced by Streptococcus thermophilus ST10 (DSM 25246) and tara gum, as well as the 2 microorganisms Lactobacillus plantarum LP01 (LMG P-21021) and Lactobacillus paracasei LPC09 (DSM 24243) in women affected by acute uncomplicated cystitis.
MATERIALS AND METHODS: Thirty-three premenopausal, nonpregnant women diagnosed with acute uncomplicated cystitis were enrolled in a pilot prospective study and
completed the treatment protocol. Subjects were instructed to take 2 doses per day during the first month, and then to continue with 1 sachet per day until the sixtieth day. Nitrites and leukocyte esterase on urine dipstick testing were used
as indicators of cystitis, with analysis performed at enrollment, after 30 and 60 days, and after 1 month of follow-up. Typical UTI symptoms, namely dysuria, frequent voiding of small volumes, urinary urgency, suprapubic pain, and gross
hematuria were scored 0 to 3 and evaluated at each visit.
RESULTS: Positive results for the presence of nitrites and leukocyte esterase were found in 14 and 20 subjects after 30 days and in 9 and 14 women after 60 days, respectively (P0.001). At the end of the follow-up period, positive
results for nitrites and leukocyte esterase were recorded in only 4 and 3 of 24 and 19 subjects (16.7%, P=0.103; 15.8%, P=0.325, respectively), with negative results after 60 days. Typical symptoms of cystitis, specifically dysuria, frequent voiding, urgency, and suprapubic pain were significantly improved as well. No significant differences were recorded in the incidence and severity of hematuria at any visit.
CONCLUSION: The long-term ability of an association of cranberry, D-mannose, an innovative gelling complex, and the 2 microorganisms tested to significantly improve the uncomfortable symptoms reported by women with acute cystitis has been suggested.

Urinary tract infections (UTIs) are among the most common bacterial infections affecting women. UTIs are primarily caused by Escherichia coli, which increases the likelihood of a recurrent infection. We encountered two cases of recurrent
UTIs (rUTIs) with a positive E. coli culture, not improving with antibiotics due to the development of antibiotic resistance. An alternative therapeutic regimen based on parsley and garlic, L-arginine, probiotics, and cranberry tablets has been given. This regimen showed a significant health improvement and symptoms relief without recurrence for more than 12 months. In conclusion, the case supports the concept of using alternative medicine in treating rUTI and as a prophylaxis or in patients who had developed antibiotic resistance.

The purpose of this research was to correlate daily consumption of cranberry juice and symptoms of a diagnosed UTI among 26 volunteer adult female patients

Pseudomonas aeruginosa colonizes the lungs in cystic fibrosis (CF) and mechanically ventilated patients by binding to the cellular receptors on the surface of the lung epithelium. Studies have shown that blocking this interaction could be achieved with sub-minimum inhibitory concentrations of antibiotics such as ciprofloxacin. The development of bacterial resistance is a probable drawback of such an intervention. The use of natural extracts to interfere with bacterial adhesion and invasion has recently gained substantial attention and is
hypothesized to inhibit bacterial binding and consequently prevent or reduce pathogenicity. This study used an A549 lung epithelial cell infection model, and the results revealed that a combination of aqueous cranberry extract with ciprofloxacin could completely prevent the adhesion and invasion of P. aeruginosa PAO1 compared to the untreated control. All of the natural extracts (cranberry, dextran, and soybean extracts) and ciprofloxacin showed a significant reduction (P0.0001) in P. aeruginosa PAO1 adhesion to and invasion of lung epithelial
cells relative to the control. The cranberry, dextran, and soybean extracts could substantially increase the anti-adhesion and anti-invasion effects of ciprofloxacin to the averages of 100% (P0.0001), 80% (P0.0001), and 60%
(P0.0001), respectively. Those extracts might result in a lower rate of the development of bacterial resistance; they are relatively safe and inexpensive agents, and utilizing such extracts, alone or in combination with ciprofloxacin,
as potential anti-adhesion and anti-invasion remedies, could be valuable in preventing or reducing P. aeruginosa lung infections.

SCOPE: A major portion of ingested procyanidins is degraded by human microbiota in the colon into various phenolic compounds. These microbial metabolites are thought to contribute to the health benefits of procyanidins in vivo. The
objective of this study was to identify and quantify the microbial metabolites of procyanidins after anaerobic fermentation with human microbiota.
METHODS AND RESULTS: (-)-Epicatechin, (+)-catechin, procyanidin B2, procyanidin A2, partially purified apple and cranberry procyanidins were incubated with human
microbiota at a concentration equivalent to 0.5 mM epicatechin. GC-MS analysis showed that common metabolites of all six substrates were benzoic acid, 2-phenylacetic acid, 3-phenylpropionic acid, 2-(3'-hydroxyphenyl)acetic acid,
2-(4'-hydroxyphenyl)acetic acid, 3-(3'-hydroxyphenyl)propionic acid, and hydroxyphenylvaleric acid. 5-(3',4'-Dihydroxyphenyl)-γ-valerolactones and 5-(3'-hydroxyphenyl)-γ-valerolactones were identified as the microbial metabolites of epicatechin, catechin, procyanidin B2, and apple procyanidins but not from the procyanidin A2 or cranberry procyanidin ferments. 2-(3',4'-Dihydroxyphenyl)acetic acid was only found in the fermented broth of procyanidin B2, A2, apple, and cranberry procyanidins. The mass recoveries of microbial metabolites range from 20.0 to 56.9% for the six substrates after 24 h
of fermentation.
CONCLUSION: Procyanidins, both B-type and A-type can be degraded by human gut microbiota. The microbial metabolites may contribute to the bioactivities of procyanidins.

In the present study, the efficacy of generally recognised as safe (GRAS) antimicrobial plant metabolites in regulating the growth of Staphylococcus aureus and S. epidermidis was investigated. Thymol, carvacrol and eugenol showed the
strongest antibacterial action against these microorganisms, at a subinhibitory concentration (SIC) of ≤ 50 μg ml(-1). Genistein, hydroquinone and resveratrol showed antimicrobial effects but with a wide concentration range (SIC = 50-1,000 μg ml(-1)), while catechin, gallic acid, protocatechuic acid, p-hydroxybenzoic acid and cranberry extract were the most biologically compatible molecules (SIC ≥ 1000 μg ml(-1)). Genistein, protocatechuic acid, cranberry extract, p-hydroxybenzoic acid and resveratrol also showed anti-biofilm activity against S. aureus, but not against S. epidermidis in which, surprisingly, these metabolites stimulated biofilm formation (between 35% and 1,200%). Binary combinations of cranberry extract and resveratrol with genistein, protocatechuic or p-hydroxibenzoic acid enhanced the stimulatory effect on S. epidermidis biofilm formation and maintained or even increased S. aureus anti-biofilm
activity.

Despite considerable controversy about their effects, cranberries in various forms have been used widely for several decades to prevent as well as treat urinary tract infections (UTIs). The purpose of this article is to present a review of research-based information regarding the ability of cranberries to prevent UTIs in adults at risk for UTIs. Current evidence suggests that cranberries decrease bacterial adherence to uroepithelial cells and thus decrease
the incidence of UTIs without adverse effects in most individuals. Thus clinicians may safely advise patients that cranberries are helpful in preventing UTIs. Cranberries may be a viable adjunct to antibiotics for patients with repeated UTIs.

Urinary tract infections (UTIs) are relatively common in women and may be classified as uncomplicated or complicated, depending upon the urinary tract anatomy and physiology. Acute uncomplicated cystitis (AUC) occurs when urinary pathogens from the bowel or vagina colonize the periurethral mucosa and reach the bladder. The vast majority of episodes in healthy women involving the same bacterial strain that caused the initial infection are thought to be reinfections. About 90% of AUC are caused by uropathogenic Escherichia coli (UPEC), but Proteus mirabilis also plays an important role. Several studies support the importance of cranberry (Vaccinium macrocarpon) proanthocyanidins in preventing adhesion of P-fimbriated UPEC to uroepithelial cells. In this study, we evaluated the in vitro anti-adhesion activity of A2-linked proanthocyanidins from cranberry on a UPEC and Proteus mirabilis strains and their possible influence on urease activity of the latter. A significant reduction of UPEC adhesion (up to 75%) on the HT1376 cell line was observed vs. control. For the strains of P. mirabilis there was also a reduction of adhesion (up to 75%) compared to controls, as well as a reduction in motility and urease activity. These results suggest that A2-type cranberry proanthocyanidins could aid in maintaining urinary tract health.

BACKGROUND & OBJECTIVES: Emergence of antimicrobial resistance in Pseudomonas aeruginosa has led to the search for alternative agents for infections control. Natural products have been a good alternative to present antibiotics. The present study was undertaken to evaluate the effectiveness of cranberry in attenuation of virulence of P. aeruginosa in experimental urinary tract infection (UTI) in mouse model. Efforts were also directed to explore the action of cranberry towards virulence of P. aeruginosa through quorum sensing (QS) inhibition.

METHODS: Efficacy of cranberry was evaluated in an experimental UTI mouse model and on production of QS signals, alginate, pyochelin, haemolysin, phospholipase-C, cell-surface hydrophobicity, uroepithelial cell-adhesion assay and biofilm formation by already standardized methods.

RESULTS: Presence of cranberry showed significant decline in the production of QS signals, biofilm formation and virulence factors of P. aeruginosa in vitro (P<0.001). Further, cranberry was found to be useful in prevention of experimental UTI in mouse model as indicated by reduced renal bacterial colonization and kidney tissues destruction.

INTERPRETATION & CONCLUSIONS: The findings of the present study indicated that cranberry inhibited QS and hence elaboration of virulence factors of P. aeruginosa. It also affected the adherence ability of this pathogen. This approach can lead to the discovery of new category of safe anti-bacterial drugs from dietary sources such as cranberry with reduced toxicity without the risk of antibiotic resistance.