Introduction: Urinary tract infection (UTI) is a commonly acquired bacterial infection mostly in young, healthy women. Cranberry (Vaccinium macrocarpon) has historically been used for the treatment and prevention of UTIs; however, research has found conflicting evidence regarding its effectiveness for the prophylaxis of UTIs. The aim of this work is to evaluate the effectiveness of cranberry on the risk of UTI occurrences in women. Methods: A systematic review with meta-analysis of randomized controlled clinical trials (RCTs) evaluating the efficacy of cranberry as prophylaxis for recurrent UTIs in women was performed. RCTs published until January 2022 comparing any cranberry product interventions with placebo in adult women were considered eligible. All statistical analyses were conducted using the random effect model (Mantel-Haenszel method). Outcomes were reported as number of participants developing a UTI. Statistical significance was defined as P < 0.05. Results: Nine clinical trials were included in the meta-analysis. The study concluded that cranberry products reduced the risk of UTI by 21 % in women compared with the placebo group (0.79 [CI 0.67, 0.94], I2 = 47 %, P = 0.008). Subgroups, including cranberry juice encapsulated cranberry powder, cultured confirmed UTIs; asymptomatic bacteriuria and uncomplicated UTIs, were also performed. Notably, pooling data from RCTs using cranberry as tablets/capsule showed a RR = 0.71 (P = 0.005). Conclusions: This data suggested that cranberry products may be effective in the prevention of UTIs in women. However, these results are not to be considered definitive, and more clinical trials are needed to confirm these findings.

Cranberries are a rich source of bioactive compounds that comprise a healthy diet. Cranberry is abundant in nutritional components and many bioactive compounds that have antioxidant properties. Both American (Vaccinium macrocarpon) and European (Vaccinium oxycoccus) cranberry species are rich in polyphenols such as phenolic acids, anthocyanins and flavonoids, and is one of the few fruits that is high in proanthocyanidins, which is linked to many health benefits. The review systematizes information on the chemical composition of cranberry, its antioxidant effect, and the beneficial impact on human health and disease prevention after cranberry consumption, and in particular, its effect against urinary tract inflammation with both adults and children, cardiovascular, oncology diseases, type 2 diabetes, metabolic syndrome, obesity, tooth decay and periodontitis, Helicobacter pylori bacteria in the stomach and other diseases. Additional research needs to study cranberry proteomics profiling, polyphenols interaction and synergism with other biologically active compounds from natural ingredients and what is important in formulation of new functional foods and supplements.

A number of clinical trials support the use of standardized cranberry supplement products for prevention of urinary tract infections; however, products that are not well-characterized for sufficient levels of bioactive components may contribute to negative clinical outcomes. Cranberry supplements for consumer use are not regulated and can be formulated different ways using cranberry juice, pomace or various combinations. This can lead to consumer confusion regarding effectiveness of individual products. The current study compared two commercial supplement products, one made from cranberry juice extract and the other from a blend of whole cranberry. The influence of formulation and proanthocyanidin (PAC) solubility on in vitro and ex vivo P-fimbriated Escherichia coli bacterial anti-adhesion activity (AAA) was determined. Both supplement products as well as whole, frozen cranberries were chromatographically separated into crude polyphenolic, sugar and acid fractions. In vitro AAA testing of all fractions confirmed that only those containing soluble PACs elicited activity. The cranberry juice extract product had higher soluble PAC content than the whole cranberry blended product, which contained mainly insoluble PACs. The influence of soluble and insoluble PAC levels in each product on the urinary (ex vivo) AAA was determined following ingestion. The juice extract product was associated with significantly higher urinary AAA than that of the whole berry blended product when consumed once daily over the 1-week intervention period.

Background: Antimicrobial resistance is a rapidly growing global issue affecting the effective treatment of infectious diseases. This provides a window of opportunity for the use and implementation of well researched effective complementary therapies such as herbal medicines. In this literature review, an overview is provided of the effectiveness of herbal medicine to control symptoms of urinary tract in-fections and reduce antibiotic use.Methods: PubMed, CAM-Quest, CORE-Hom, ScienceDirect, CAMBase, Anthromedics.org and AnthroMedLi-brary databases were searched for peer-reviewed meta-analyses, systematic reviews and randomized con-trolled trials from 2005 till 8 October 2020. Included were clinical studies on the use of herbal medicine for clinically diagnosed urinary tract infection with any control group except another herbal medicine. Study quality was assessed using the Joanna Briggs Institute critical appraisal tools.Results: Of the 408 citations identified, 23 met the inclusion criteria: 5 meta-analyses, 3 systematic re-views and 15 randomized controlled trials. Of these studies 13 involved the use of cranberry products, 4 studies concerned traditional Chinese herbal medicines, and 6 studies dealt with other herbal medicines.Conclusions: The latest published meta-analysis including 28 trials reports a clear benefit of Cranberry products for the prevention of recurrent UTIs in women. Five TCM formulas were found to be equally or more effective than antibiotics in the treatment of UTIs. Furthermore, Rosa canina seems to have the potential to prevent UTI in women undergoing a caesarean section. 'Acidif Plus Tablets' as well as 'Canephron' seem to be promising candidates for treating women with uncomplicated recurrent UTI.(c) 2022 Korea Institute of Oriental Medicine. Published by Elsevier B.V.This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Aim: Cranberries (Vaccinium macrocarpon) are traditionally used in prevention of urinary tract infections (UTIs). The authors' aim was to evaluate effects of a supplement containing cranberry extract, pumpkin seed extract, vitamin C, and vitamin B-2 on recurrent uncomplicated UTIs in women and their intestinal microbiota.Methods: A prospective, uncontrolled exploratory study was conducted in women with recurrent uncomplicated UTIs. The primary exploratory outcome was the number of UTIs in a 6-month prospective observation period compared with a 6-month retrospective period. Further outcomes included number of antibiotics, quality of life (SF-36), intestinal microbiota (assessed by 16S rRNA amplicon sequencing), and evaluation questions. Parameters were assessed at baseline and after 1, 2, and 7 months (start of intake of cranberry supplement after 1 month for 6 months). p-Values were calculated with the pairwise Wilcoxon signed-rank test for alpha diversity and permutational multivariate analysis of variance.Results: Twenty-three women (aged 52.7 +/- 12.4 years) were included in the study. Participants reported 2.2 +/- 0.8 UTIs (at baseline) in the previous 6 months. After 6 months of cranberry intake, participants reported a significant decrease to 0.5 +/- 0.9 UTIs (p < 0.001). Number of antibiotic therapies was also significantly (p < 0.001) reduced by 68% during 6 months of cranberry intake (0.14 +/- 0.35) when compared with 6 months retrospectively (1.14 +/- 0.71). The SF-36 physical component score increased from 44.9 +/- 5.5 at baseline to 45.7 +/- 4.6 at 7 months (p = 0.16). The SF-36 mental component score decreased slightly from the baseline value of 46.5 +/- 6.5 to 46.2 +/- 6.4 at 7 months (p = 0.74). No significant intragroup mean changes at genus, family, or species level for alpha and beta diversity within the intestinal microbiota were found. In the evaluation questions, participants rated the cranberry extract positively and considered it beneficial. The supplement intake was safe.Conclusions: This study shows that women with recurrent uncomplicated UTIs benefit from cranberry intake. Future larger clinical studies with further investigation of the mechanisms of action are required to determine the effects of cranberries on participants with uncomplicated UTIs.

Urinary tract infections (UTIs) are a significant clinical problem that pregnant women and children commonly experience. Escherichia coli is the primary causative organism, along with several other gram-negative and gram-positive bacteria. Antimicrobial drugs are commonly prescribed to treat UTIs in these patients. Conventional treatment can range from using broad-spectrum antimicrobial drugs for empirical or prophylactic therapy or patient-tailored therapy based on urinary cultures and sensitivity to prospective antibiotics. The ongoing emergence of multi-drug resistant pathogens has raised concerns related to commonly prescribed antimicrobial drugs such as those used routinely to treat UTIs. Consequently, several natural medicines have been explored as potential complementary therapies to improve health outcomes in patients with UTIs. This review discusses the effectiveness of commonly used natural products such as cranberry juice/extracts, ascorbic acid, hyaluronic acid, probiotics, and multi-component formulations intended to treat and prevent UTIs. The combination of natural products with prescribed antimicrobial treatments and use of formulations that contained high amounts of cranberry extracts appear to be most effective in preventing recurrent UTIs (RUTIs). The incorporation of natural products like cranberry, hyaluronic acid, ascorbic acid, probiotics, Canephron (R) N, and Cystenium II to conventional treatments of acute UTIs or as a prophylactic regimen for treatment RUTIs can benefit both pregnant women and children. Limited information is available on the safety of natural products in these patients' populations. However, based on limited historical information, these remedies appear to be safe and well-tolerated by patients.

Importance There is little consensus on an effective nonantibiotic agent for the prevention of urinary tract infection (UTI) after pelvic reconstructive surgery. Objective The aim of the study was to investigate the impact of methenamine hippurate with cranberry capsules on rates of UTI after pelvic reconstructive surgery, among patients requiring short-term catheterization. Study Design In this randomized, double-blinded placebo-controlled trial, patients discharged with a catheter after pelvic reconstructive surgery were approached to participate. Participants were randomized to receive cranberry with methenamine or cranberry with placebo. Primary outcome was number of UTIs treated within 1 week after surgery. Secondary outcomes included incidence of UTIs treated within 6 weeks postoperatively, bacterial species on culture, urinary pH, catheter duration, patient adherence, and satisfaction. A sample size of 88 participants per arm was planned. Results From June 2019 to July 2021, 185 patients were randomized and 182 analyzed; 89 received placebo and 93 received methenamine. Both groups were similar. Incidence of UTI at 1 week was significantly higher in the placebo group (79.8%) compared with the methenamine group (66.7%; odds ratio, 1.97; 95% confidence interval, 1.01-3.87; P = 0.048). This difference increased by 6 weeks postoperatively (89.9% vs 72.0%; odds ratio, 3.45; 95% confidence interval, 1.51-7.87; P = 0.003). There were fewer pseudomonal UTIs in the methenamine group (P = 0.041). Duration of catheterization and urinary pH were similar. Overall adherence and level of satisfaction was high. Conclusions In this high-risk population, methenamine was well tolerated and significantly reduced UTI rates. Methenamine with cranberry should be considered as an effective prophylactic therapy to reduce this common complication after pelvic surgery.

The use of antibiotics in the treatment of UTIs is contributing to resistance. Hence, the outcome of human clinical trials of nonantibiotic remedies for preventing or treating UTI is of significant interest. This systematic review aimed to identify, summarise and evaluate the evidence for the outcomes of different nonantibiotic options including cranberry, D-mannose and non-steroidal anti-inflammatory drugs (NSAIDs). PubMed, Embase and Scopus were searched for manuscripts relating to nonantibiotic treatment of UTI including cranberry, mannose and NSAIDs. After title and abstract screening, data were extracted from 21 papers that were published in English and related to the treatment or prevention of uncomplicated UTI in adult women. We identified twelve papers examining the effects of cranberry, two papers examining D-mannose, two papers examining combination treatments (cranberry and D-mannose) and five manuscripts investigating the effects of NSAIDs. There is low-level evidence, from a small number of studies, supporting the use of D-mannose or combination treatments for potentially preventing UTIs in adult women without producing burdening side effects. However, larger and more randomised double-blinded trials are needed to confirm this. In comparison, the multiple studies of cranberry and NSAIDs produced conflicting evidence regarding their effectiveness.

Objective: To provide a critical analysis of evidence describing the implementation and effectiveness of cranberry products for the prevention of urinary tract infections in the setting of residential aged care. Methods: A critical analysis of the literature. Results: The current evidence indicates that cranberry products decrease the occurrence of urinary tract infections in aged care residents who are likely to benefit from the use of cranberry products as a preventative measure; however, some of the results were limited and contradictory, because of gaps and insufficient research in relation to the active ingredients of cranberries - proanthocyanins. Conclusion: This critical analysis demonstrates benefits in the use of cranberry products in the prevention of urinary tract infections for residents of aged care facilities. Further research and education on preventative measures could potentially lower the use of antibiotics and the incidence of urinary tract infections in residential aged care.

Uropathogenic Escherichia coli (UPEC) are the primary cause of recurrent urinary tract infections (UTI). The poor understanding of UPEC ecology-pathophysiology from its reservoir-the gut, to its infection site-the urothelium, partly explains the inadequate and abusive use of antibiotics to treat UTI, which leads to a dramatic upsurge in antibiotic-resistance cases.Uropathogenic Escherichia coli (UPEC) ecology-pathophysiology from the gut reservoir to its urothelium infection site is poorly understood, resulting in equivocal benefits in the use of cranberry as prophylaxis against urinary tract infections. To add further understanding from the previous findings on PAC antiadhesive properties against UPEC, we assessed in this study the effects of proanthocyanidins (PAC) rich cranberry extract microbial metabolites on UTI89 virulence and fitness in contrasting ecological UPEC's environments. For this purpose, we developed an original model combining a colonic fermentation system (SHIME) with a dialysis cassette device enclosing UPEC and a 3D tissue-engineered urothelium. Two healthy fecal donors inoculated the colons. Dialysis cassettes containing 7log(10) CFU/mL UTI89 were immersed for 2h in the SHIME colons to assess the effect of untreated (7-day control diet)/treated (14-day PAC-rich extract) metabolomes on UPEC behavior. Engineered urothelium were then infected with dialysates containing UPEC for 6 h. This work demonstrated for the first time that in the control fecal microbiota condition without added PAC, the UPEC virulence genes were activated upstream the infection site, in the gut. However, PAC microbial-derived cranberry metabolites displayed a remarkable propensity to blunt activation of genes encoding toxin, adhesin/invasins in the gut and on the urothelium, in a donor-dependent manner. Variability in subjects' gut microbiota and ensuing contrasting cranberry PAC metabolism affects UPEC virulence and should be taken into consideration when designing cranberry efficacy clinical trials. IMPORTANCE Uropathogenic Escherichia coli (UPEC) are the primary cause of recurrent urinary tract infections (UTI). The poor understanding of UPEC ecology-pathophysiology from its reservoir-the gut, to its infection site-the urothelium, partly explains the inadequate and abusive use of antibiotics to treat UTI, which leads to a dramatic upsurge in antibiotic-resistance cases. In this context, we evaluated the effect of a cranberry proanthocyanidins (PAC)-rich extract on the UPEC survival and virulence in a bipartite model of a gut microbial environment and a 3D urothelium model. We demonstrated that PAC-rich cranberry extract microbial metabolites significantly blunt activation of UPEC virulence genes at an early stage in the gut reservoir. We also showed that altered virulence in the gut affects infectivity on the urothelium in a microbiota-dependent manner. Among the possible mechanisms, we surmise that specific microbial PAC metabolites may attenuate UPEC virulence, thereby explaining the preventative, yet contentious properties of cranberry against UTI.