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.

Surface-associated swarming motility is implicated in enhanced bacterial spreading and virulence, hence it follows
that anti-swarming effectors could have clinical benefits. When investigating potential applications of anti-swarming
materials it is important to consider whether the lack of swarming corresponds with an enhanced sessile biofilm
lifestyle and resistance to antibiotics. In this study, well-defined tannins present in multiple plant materials (tannic
acid (TA) and epigallocathecin gallate (EGCG)) and undefined cranberry powder (CP) were found to block swarming motility and enhance biofilm formation and resistance to tobramycin in Pseudomonas aeruginosa. In contrast, gallic acid (GA) did not completely block swarming motility and did not affect biofilm formation or tobramycin resistance. These data support the theory that nutritional conditions can elicit an inverse relationship between swarming motility and biofilm formation capacities. Although anti-swarmers exhibit the potential to yield clinical benefits, it is important to be aware of possible implications regarding biofilm formation and antibiotic resistance.

Natural chemicals have been reported to have antibacterial effects against a variety of bacteria. The present study evaluated the antibacterial effects of commercially available grape-seed extract (GSE), pomegranate polyphenols (PP), and lab-prepared cranberry proanthocyanidins (C-PAC) against two strains of methicillin-resistant Staphylococcus aureus (MRSA). GSE, PP, and C-PAC at concentrations of 2 mg/mL, 10 mg/mL, or controls were mixed with equal volumes of overnight cultures of MRSA at ~6 log10 colony-forming units (CFU)/mL and incubated for 0, 1, 2, 8, and 24 h at 37 degrees C. Treatments were neutralized/stopped using tryptic soy broth containing 3% beef extract. Serial dilutions of the treated MRSA strains and controls were spread-plated on trypticase soy agar and incubated for 24-48 h at 37 degrees C and colonies were counted. Among the three tested agents, GSE at 1 and 5 mg/mL was found to be most effective against MRSA, resulting in a 2.9-4.0 log10 CFU/mL reduction of both strains after 2 h at 37 degrees C. PP at 1 and 5 mg/mL was found to cause 1.1-2.3 log10 CFU/mL reduction, while C-PAC at 1 mg/mL caused 1 log10 CFU/mL reduction of the two MRSA strains after 2 h at 37 degrees C. All three extracts at the tested concentrations decreased the two MRSA strains to undetectable levels within 24 h, with the exception of 1 mg/mL PP for strain 33591. Scanning electron microscopy of MRSA after 2 h of treatment showed that GSE and PP caused bacterial cell wall alteration, with negligible effect observed by C-PAC treatment. However, the in vivo activity and clinical safety applications of GSE, PP, and C-PAC need to be evaluated before suggestion for use as a treatment/control measure.

The 4-(dimethylamino)cinnamaldehyde (DMAC) assay is currently used to quantify proanthocyanidin (PAC) content in cranberry products. However, this method suffers from issues of accuracy and precision in the analysis and comparison of PAC levels across a broad range of cranberry products. Current use of procyanidin A2 as a standard leads to an underestimation of PACs content in certain cranberry products, especially those containing higher molecular weight PACs. To begin to address the issue of accuracy, a method for the production of a cranberry PAC standard, derived from an extraction of cranberry (c-PAC) press cake, was developed and evaluated. Use of the c-PAC standard to quantify PAC content in cranberry samples resulted in values that were 2.2 times higher than those determined by procyanidin A2. Increased accuracy is critical for estimating PAC content in relationship to research on authenticity, efficacy, and bioactivity, especially in designing clinical trials for determination of putative health benefits.

"Aims:  Periodontitis is an inflammatory disease of polymicrobial origin that affects the tooth-supporting tissues. With the spread of antibiotic resistance among pathogenic bacteria, alternative strategies are required to better control infectious diseases such as periodontitis. The aim of our study was to investigate whether two natural compounds, A-type cranberry proanthocyanidins (AC-PACs) and licochalcone A, act in synergy against Porphyromonas gingivalis and the host inflammatory response of a macrophage model.

Methods and Results:  Using a checkerboard microtitre test, AC-PACs and licochalcone A were found to act in synergy to inhibit P. gingivalis growth and biofilm formation. Fluorescein isothiocyanate-labelled P. gingivalis adhesion to oral epithelial cells was also inhibited by a combination of the two natural compounds in a synergistic manner. Fluorometric assays showed that although AC-PACs and licochalcone A reduced both MMP-9 and P. gingivalis collagenase activities, no synergy was obtained with a combination of the compounds. Lastly, AC-PACs and licochalcone A also acted in synergy to reduce the lipopolysaccharide (LPS)-induced secretion of the pro-inflammatory mediators IL-1β, TNF-α, IL-6 and IL-8 in a macrophage model.

Conclusions:  A-type cranberry proanthocyanidins and licochalcone A, natural compounds from cranberry and licorice, respectively, act in synergy on both P. gingivalis and the host immune response, the two principal etiological factors of periodontitis.

Significance and Impact of the Study:  The combined use of AC-PACs and licochalcone A may be a potential novel therapeutic strategy for the treatment and prevention of periodontal disease."

Objectives: The present study forms part of the ISRCTN16968287 clinical assay. The objective of this study was to determine the effectiveness of cranberry syrup in the prophylaxis of recurrent urinary tract infection (UTI).
Design: Phase III randomized clinical trial. Setting: The study was conducted at the San Cecilio Clinical Hospital (Granada, Spain). Participants: A total of 192 patients were recruited. The subjects were aged between 1 month and 13 years. Criteria for inclusion were a background of ecurrent UTI (more than two episodes of infection in the last 6 months), associated or otherwise with vesicoureteral reflux of any degree, or renal pelvic dilatation associated with UTI. Criteria for exclusion from recruitment to the study included the co-existence of UTI with other infectious diseases or with metabolic diseases, chronic renal insufficiency, and the presence of allergy or intolerance to any of the components of cranberry syrup or trimethoprim.
Primary outcome measures: The primary objective was to determine the risk of UTI associated with each intervention.
Results: Of the 198 patients initially eligible, 192 were finally included in the study to receive either cranberry syrup or trimethoprim. UTI was observed in 47 patients, 17 of whom were males and 30 females. We recruited 95 patients diagnosed with recurrent UTI on entry; during
follow-up, 26 patients had a UTI (27.4%, 95% CI: 18.4%–36.3%). Six patients (6.3%) were male and 20 (21.1%) were female. Eighteen patients (18.9% of the total, 95% CI: 11%–26.3%) receiving trimethoprim had a UTI and eight patients (8.4% of the total, 95% CI: 2.8%–13.9%) were given cranberry. Sixty-six percent of the episodes of UTI recurrence were caused by Escherichia coli, with no significant differences being found between the two
treatment branches. No differences were observed between the two treatment branches in the rate of resistance to antibiotics.Conclusion: Our study confirms that cranberry syrup is a safe treatment for the pediatric population. Cranberry prophylaxis has noninferiority with respect to trimethoprim in recurrent UTI.

BACKGROUND Urinary tract infection (UTI) is one of the most commonly acquired bacterial infections. Cranberry-containing products have long been used as a folk remedy to prevent UTIs. The aims of this study were to evaluate cranberry-containing products for the prevention of UTI and to examine the factors influencing their effectiveness. METHODS MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systemically searched from inception to November 2011 for randomized controlled trials that compared prevention of UTIs in users of cranberry-containing products vs placebo or nonplacebo controls. There were no restrictions for language, population, or publication year. RESULTS Thirteen trials, including 1616 subjects, were identified for qualitative synthesis from 414 potentially relevant references; 10 of these trials, including a total of 1494 subjects, were further analyzed in quantitative synthesis. The random-effects pooled risk ratio (RR) for cranberry users vs nonusers was 0.62 (95% CI, 0.49-0.80), with a moderate degree of heterogeneity (I2 = 43%) after the exclusion of 1 outlier study. On subgroup analysis, cranberry-containing products seemed to be more effective in several subgroups, including women with recurrent UTIs (RR, 0.53; 95% CI, 0.33-0.83) (I2 = 0%), female populations (RR, 0.49; 95% CI, 0.34-0.73) (I2 = 34%), children (RR, 0.33; 95% CI, 0.16-0.69) (I2 = 0%), cranberry juice drinkers (RR, 0.47; 95% CI, 0.30-0.72) (I2 = 2%), and subjects using cranberry-containing products more than twice daily (RR, 0.58; 95% CI, 0.40-0.84) (I2 = 18%). CONCLUSIONS Our findings indicate that cranberry-containing products are associated with protective effect against UTIs. However, this result should be interpreted in the context of substantial heterogeneity across trials.

In a randomized, double-blind, placebo-controlled clinical cross-over study with 18 subjects of both sexes (aged 21-52 years), the effect of cranberry (Vaccinium macrocarpon) and pumpkin seed extract combination (Cystorenal Cranberry plus) on the urinary tract through inhibition of Escherichia coli adherence to urothelial cells was examined. With the ingestion of Cystorenal Cranberry plus, the bacterial adherence was decreased by 33.4% compared to the placebo. The recommended amount of the preparation is sufficient to protect the healthy bladder. There was no adverse effects observed.

Biofilm producing bacteria such as Staphylococcus species and Escherichia coli are the most common cause of catheter related urinary tract infections (UTIs). The American cranberry (Vaccinium macrocarpon) is utilized widely as a prophylaxis for UTIs due to its prevention of microbial adhesion. Cranberry contains proanthocyanidins (PACs), which have been implicated as active constituents responsible for its bacterial antiadhesive properties. Despite overwhelming data supporting cranberry's beneficial effects against human pathogenic bacteria, there is limited information regarding its effects on biofilm formation. This study evaluated the effects of three proprietary PAC-standardized cranberry extracts on the inhibition of bacterial growth and biofilm production against a panel of clinically relevant pathogens: Staphylococcus epidermidis, Staphylococcus aureus, clinical methicillin-resistant S. aureus (MRSA), Staphylococcus saprophyticus and Escherichia coli. The extracts inhibited the growth of the Gram-positive bacteria (Staphylococcus spp.) but not the Gram-negative species (E. coli) with minimum inhibitory concentrations in the range 0.02–5 mg/mL. The extracts also inhibited biofilm production by the Gram-positive bacteria but did not eradicate their established biofilm. These results suggest that cranberry may have beneficial effects against the growth and biofilm producing capability of Gram-positive bacteria pathogens.

Cranberry juice contains high molecular weight non-dialyzable material (NDM) which was found to inhibit hemagglutination induced by the influenza virus (IV) as well as to neutralize the cytotoxicity of IV in cell cultures. Because influenza virus surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) are involved in viral replication and in the infectious process, we sought in the present study to examine the effect of NDM on neuraminidases which are the target of most anti-influenza drugs today. NDM inhibited the NA enzymatic activity of influenza A and B strains as well as that of Streptococcus pneumoniae. This finding is of importance considering the emergence of influenza isolates resistant to antiviral drugs, reaching 90 % in some places. The anti-NA activity of NDM, evaluated by the MUNANA method and expressed as the concentration required for 50 % inhibition (IC50), was most potent against N1 (IC50, 192 microg/mL), less active against BN and N2 (IC50, 509 microg/mL and 1128 microg/mL, respectively), and moderately active against Streptococcus pneumoniae NA (IC50, 594 microg/mL). The in vitro findings of the present study suggest that cranberry constituents may have a therapeutic potential against both A and B influenza virus infections and might also interfere with the development of secondary bacterial complications