Recurrent urinary tract infection (rUTI) continues to challenge pediatric care providers. The diagnosis of an rUTI can be difficult, especially in young febrile children. Antibiotic resistance rates continue to rise, which limits oral treatment options. Prophylactic antibiotics are used commonly to manage rUTI, but their use increases the risk of rUTI with antibiotic-resistant strains without significantly reducing renal scarring. Alternative therapies for rUTI include probiotics and anthocyanidins (eg, cranberry extract) to reduce gut colonization by uropathogens and prevent bacterial adhesion to uroepithelia, but efficacy data for these treatments are sparse. The future of rUTI care rests in addressing the following contemporary issues: best diagnostic practices, risk factors associated with rUTI, and the prevention of recurrent infection. In this review, we summarize the state of the art for each of these issues and highlight future studies that will aim to take an alternative approach to managing rUTI.

INTRODUCTION:Urinary tract infections (UTIs) represent a common and costly public health issue. The bacterium Escherichia coli is mainly responsible for most uncomplicated UTIs. Cranberry antibacterial effects have extensively been studied in order to understand the molecular mechanisms of action of its bioactive components and their clinical benefits against UTIs. In this respect, the present review aims to critically analyze the current clinical studies that have evaluated the efficacy of supplementing cranberry products against UTIs in different subpopulations.METHODS:PubMed database was comprehensively searched, using relative keywords in order to identify clinical trials exploring the efficacy of cranberry supplementation against UTIs.RESULTS:Current clinical evidence clearly indicates a possible benefit overall from the use of cranberries against UTIs. Cranberry consumption may prevent bacterial adherence to uroepithelial cells, reducing UTI related symptoms. Cranberry consumption could also decrease UTI related symptoms by suppressing inflammatory cascades as an immunologic response to bacterial invasion. The existing clinical trials have supported substantial evidence that the beneficial effects of cranberry against UTIs seem to be prophylactic by preventing infections recurrence; however, they exert low effectiveness in populations at increased risk for contracting UTIs. Moreover, a lack of cost-effectiveness for cranberry supplementation has been highlighted.CONCLUSIONS:Additional well-designed, double-blind, placebo-controlled clinical trials that use standardized cranberry products for long study periods are strongly recommended in order to determine the efficiency of cranberry on the prevention of UTIs in susceptible populations. At present, cranberry supplementation can safely be suggested as complementary therapy in women with recurrent UTIs.

We conducted a prospective study with the aim to evaluate the efficacy and safety of standardized cranberry capsules as prophylaxis in children with recurrent Urinary Tract Infections (UTIs). Therefore, children and adolescents, aged 2-18 years, with history of recurrent UTIs, were recruited for the study and randomized to receive cranberry in a standardized dose of cranberry extract 125 mg (proanthocyanidins 7.2%), vitamin C 7.5 mg and vitamin E 2.5 mg or not. They were followed for 1 year during which compliance, side-effects and UTI episodes were recorded. Children on cranberry compared to control group presented significantly lower percentage of UTIs, fewer days/year on antibiotic treatment and lower percentage of initiation of antimicrobial prophylaxis (p<0.05) due to UTIs recurrences. In addition, in the subgroup of children with vesicoureteral reflux we observe a significant difference between the cranberry and the controls group in the number of UTIs (p<0.05). No side effects in cranberry group were reported. Escherichia coli, Klebsiella and Proteus spp. in this order were the predominant species isolated in both groups in the beginning and also in the end of the study. A trend of decrease of E. coli episodes in the cranberry group before and after the treatment was documented (83.3% vs. 66.6%), however, this was not significant (p=0.28). It seems that the use of standardized dose of cranberry seems to be a secure and effective treatment for children with recurrent episodes of UTIs

LC-MS characterized cranberry extract from the fruits of Vaccinium macrocarpon inhibited under in vitro conditions the bacterial adhesion of Escherichia coli strain 2980 uropathogenic E. coli (UPEC strains UTI89, NU14) to T24 bladder cells and adhesion of UPEC strain CFT073 to A498 kidney cells in a concentration-dependent manner. Within a biomedical study, urine samples from 16 volunteers (8 male, 8 female) consuming cranberry extract for 7 d (900 mg/d) were analyzed for potential antiadhesive activity against UPEC by ex vivo experiments. Results indicated inhibition of adhesion of UPEC strain UTI89 to human T24 bladder cells. Subgroup analysis proved significant inhibition of bacterial adhesion in case of urine samples obtained from male volunteers while female urine did not influence the bacterial attachment. Differences between antiadhesive capacity of urine samples from male/female volunteers were significant. Protein analysis of the urinesamples indicated increased amounts of Tamm-Horsfall protein (THP, syn. uromodulin) in the active samples. Inhibition of bacterial adhesion by the urine samples was correlated to the respective amount of THP. As it is known that THP, a highly mannosylated glycoprotein, strongly interacts with FimH of UPEC, this will lead to a decreased interaction with uroplakin, a FimH-binding transmembrane protein of urothelial lining cells. From these data it can be concluded that the antiadhesive effect of cranberry after oral intake is not only related to the direct inhibition of bacterial adhesins by extract compounds but is additionally due to an induction of antiadhesive THP in the kidney.

Dark-colored fruit berries are a rich source of polyphenols that could provide innovative bioactive molecules as natural weapons against dental caries. High-quality extracts of cranberry, blueberry, and strawberry, and a combination of the three berry extracts (Orophenol), were used to treat 24-h-old Streptococcus mutans biofilms. The grown biofilms were treated with the berry extracts at concentrations ranging from 62.5 to 500 μg ml-1 . Treated biofilms were assessed for metabolic activity, acidogenicity, biovolumes, structural organization, and bacterial viability. The biofilms treated with the cranberry and Orophenol extracts exhibited the most significant reductions in metabolic activity, acid production, and bacterial/exopolysaccharide (EPS) biovolumes, while their structural architecture appeared less compact than the control-treated biofilms. The blueberry extract produced significant reductions in metabolic activity and acidogenicity only at the highest concentration tested, without significantly affecting bacterial/EPS biovolumes or biofilm architecture. Strawberry extracts had no significant effects on S. mutans biofilms. None of the berry extracts were bactericidal for S. mutans. The results indicate that cranberry extract was the most effective extract in disrupting S. mutans virulence properties without significantly affecting bacterial viability. This suggests a potential ecological role for cranberry phenols as non-bactericidal agents capable of modulating pathogenicity of cariogenic biofilms.

Quorum sensing (QS) and nucleotide-based second messengers are vital signaling systems that regulate bacterial physiology in response to changing environments. Disrupting bacterial signal transduction is a promising direction to combat infectious diseases, and QS and the second messengers are undoubtedly potential targets. In Vibrio cholerae, both QS and the second messenger 3', 5' - cyclic diguanylate (c-di-GMP) play a central role in controlling motility, motile-to-sessile life transition, and virulence. In this study, we found that water-soluble extract from the North American cranberry could significantly inhibit V. cholerae biofilm formation during the development/maturation stage by reducing the biofilm matrix production and secretion. The anti-biofilm effect by water-soluble cranberry extract was possibly through modulating the intracellular c-di-GMP level and was independent of QS and the QS master regulator HapR. Our results suggest an opportunity to explore more functional foods to fight stubborn infections through interference with the bacterial signaling systems.

Urinary tract infections (UTIs) are one the of the most common types of infections in adults older than 65 years of age. Preventing UTIs with prophylactic antibiotics increases the risk of side effects and microbial resistance, and is costly. Cranberry fruit and juices contain the compound proanthrocyanidins (PACs), specifically proanthrocyanidin-A, which exerts antiadhesion characteristics against bacteria. Cranberry products therefore have been an attractive, nonantibiotic preventative option for UTIs; however, the current literature supporting cranberry use in older adults is controversial. This could be multifactorial owing to the heterogeneity of the older population as well as inconsistencies in the recommended dose of PAC in the current literature. Evidence supports that cranberry may be beneficial in preventing UTIs in specific populations such as catheterassociated UTI and postradiotherapy prostate cancer. The cost of daily capsules versus the cost of preventing a UTI in older adults is an important consideration for initiating therapy.

BACKGROUND: Urinary tract infections (UTIs) are common in pregnancy and account for the highest proportion of primary care antibiotic prescriptions issued to pregnant women in the UK. It is well known that antibiotic use is associated with increased antimicrobial resistance and therefore measures to minimise antibiotic use for UTI prevention have been studied. The efficacy and safety of these measures in pregnancy have not been addressed and therefore the aim of this study was to systematically review the literature to identify and evaluate potential measures to prevent UTIs in pregnant women. METHODS: Ten databases (EMBASE, AMED, BNI, CINAHL, Medline, PubMed, PsycINFO, Cochrane Trials, Scopus and Science Direct) were systematically searched in July 2017 for studies reporting non-antibiotic measures to prevent UTIs in pregnancy. The terms ("urinary tract infection" or UTI or bacteriuria or cystitis) AND (prevention) AND (pregnan*) were used. The quality of the publications was appraised using the Critical Appraisal Skills Programme (CASP) checklists for cohort study, case-control study and randomised controlled trial. The results were synthesised using a textual narrative approach. RESULTS: Search results yielded 3276 publications and after reviewing titles and removing duplicates, 57 full text articles were assessed for eligibility and eight were included in the review. Five different approaches (hygiene measures, cranberry juice, immunisation, ascorbic acid and Canephron N) have been identified, all of which are reported to be safe in pregnancy. CONCLUSION: The quality of the evidence varied considerably and only hygiene measures were supported by evidence to be recommended in practice. Future work needs to concentrate on strengthening the evidence base through improved design and reporting of studies with a focus on immunisation, ascorbic acid and Canephron N.

This article describes the chemical composition, efficacy and risks of using cranberries for the treatment of cystitis in cats and dogs.

The American cranberry (Vaccinium macrocarpon) is one of the fruits containing antioxidants in great quantity and of high quality. From recent research, it is evident that both cranberry and its products, when consumed chronically or acutely, boost the antioxidant effect. Likewise, most studies revealed the anti-inflammatory potential of the cranberry polyphenols. Both effects exert direct action mechanisms, revealed by the ability of the polyphenols to remove the reactive oxygen species, as well as indirect effects, represented by the action of these phytochemicals on the cell signaling pathways and genetic expression. A limited number of articles that evaluated the effects of cranberry on mitochondrial damages are available. However, an enhancement in the functions of this organelle was confirmed by the increased production of adenosine triphosphate (ATP). Therefore, further studies are required to demonstrate the benefits credited to the use of cranberry, as well as to describe the action mechanisms of the polyphenols.