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Can Cranberries Contribute to Reduce the Incidence of Urinary Tract Infections? A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Clinical Trials
Abstract
Purpose:
To clarify the association between cranberries intake and the prevention of urinary tract infections (UTIs).
Methods:
It was performed a systematic review, complied with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statement, followed by a meta-analysis and trial sequential analysis (TSA) of clinical trials.
Results:
The results clearly show the potential use of cranberries in a clinical condition of UTI. The weighted risk ratio observed (WRR=0.6750; 95% CI:0.5516-0.7965; p-value<0.0001) indicates that the use of cranberry products significantly reduced the incidence of UTIs. The results of subgroup analysis demonstrate that the patients at some risk to develop UTIs were more susceptible to the effects of the ingestion of cranberries.
Conclusions:
The results of the present work could be used by physicians to recommend the ingestion of cranberries to reduce the incidence of UTIs, particularly in individuals with recurrent UTIs, and so to also reduce the use of antibiotics which can lead to the worldwide emergence of antibiotic resistant microorganisms.
... p < 0.0 0 01) based on 28 clinical trials with a total of 4947 patients. 18 The authors report moderate heterogeneity ( I 2 = 58%) which is in line with observations in other metaanalyses with fewer and less recent studies which has resulted in mainly negative findings. A notable one is the Cochrane review by Jepson et al. in 2012 concluding that cranberry products do not reduce the incidence of rUTI. ...
... the Barbosa-Cesnik study was suggested to be the lower threshold of 10 3 CFU/mL for including patients, compared to the common threshold of 10 5 CFU/mL. 12 The most recent meta-analysis by Luis et al. 18 shows a positive effect of cranberry on prevention of rUTI compared to placebo even though the Barbosa-Cesnik study was included. Subgroup analysis of specific populations have been performed in some of the meta-analyses. ...
... Subgroup analysis of specific populations have been performed in some of the meta-analyses. No significant effects of cranberry products were found for pregnant women, children, patient undergoing catheterization and patients with bladder or cervical cancer in the most recent meta-analysis by Luis et al. 18 Liska et al. report on differences in populations included in meta-analysis and suggests a larger effect of cranberry products for women with uncomplicated recurrent UTIs versus women with complicated UTIs. 12 Wan et al. show a reduction of UTI incidence in boys from a paediatrics clinic in Taiwan. ...
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 infections and reduce antibiotic use.
Methods
PubMed, CAM-Quest, CORE-Hom, ScienceDirect, CAMBase, Anthromedics.org and AnthroMedLibrary databases were searched for peer-reviewed meta-analyses, systematic reviews and randomized controlled 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 reviews 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.
... Microbial host-associated reservoirs at the underlying bladder tissue or gastrointestinal tract could cause reinfection, even after an intensive treatments and subsequent negative urine culture [3]. All of this means that UTIs account for several millions of outpatient hospital visits and millions of emergency room visits with a large cost for the Primary Care and Public Health systems affecting the national economy [4]. ...
... Although the consumption of cranberries (Vaccinium macrocarpon) has been extensively recommended for UTIs prophylaxis and relief of adverse symptoms, the UTIs preventive activity of cranberry has been debated in the literature and numerous clinical studies have been carried out, including some recent meta-analyses [4,12,13]. Several studies have shown a protective effect of cranberry against UTIs [14][15][16][17][18]; nevertheless, others have not found significant effects [19,20]. This current controversy about conflicting results of the clinical and cost effectiveness of cranberry supplements has been attributed to different manufactured cranberry based products and doses, as well as a lack of systematic protocol for the selection of subjects and clinical assay [13]. ...
... Apart from differences in composition and doses of the cranberry-based products used in the intervention studies [13], differences among studies have been attributed to the different susceptibility of the UPEC strains to cranberry preventive effects [54]. One of the last meta-analyses concerning this topic reported a large interindividual variability in cranberry efficiency against UTIs, also concluding that patients at some risk of these infections were more susceptible to the beneficial effects of cranberry consumption [4]. Recently, Mantzorou and Giaginis [42] critically analyse the current clinical studies that have evaluated the efficacy of supplementing cranberry products against UTIs in different subpopulations; they conclude that it seems to be prophylactic by preventing infections recurrence; however, it exerts low effectiveness in populations at an increased risk of contracting UTIs. ...
Cranberry (Vaccinium macrocarpon) is a distinctive source of polyphenols as flavonoids and phenolic acids that has been described to display beneficial effects against urinary tract infections (UTIs), the second most common type of infections worldwide. UTIs can lead to significant morbidity, especially in healthy females due to high rates of recurrence and antibiotic resistance. Strategies and therapeutic alternatives to antibiotics for prophylaxis and treatment against UTIs are continuously being sought after. Different to cranberry, which have been widely recommended in traditional medicine for UTIs prophylaxis, probiotics have emerged as a new alternative to the use of antibiotics against these infections and are the subject of new research in this area. Besides uropathogenic Escherichia coli (UPEC), the most common bacteria causing uncomplicated UTIs, other etiological agents, such as Klebsiellapneumoniae or Gram-positive bacteria of Enterococcus and Staphylococcus genera, seem to be more widespread than previously appreciated. Considerable current effort is also devoted to the still-unraveled mechanisms that are behind the UTI-protective effects of cranberry, probiotics and their new combined formulations. All these current topics in the understanding of the protective effects of cranberry against UTIs are reviewed in this paper. Further progresses expected in the coming years in these fields are also discussed.
... The role of BC in urinary tract infection (UTI) prevention and prophylaxis has not yet been studied, whereas the role of cranberry products as a preventive agent against UTI has been extensively demonstrated by six meta-analyses and many systematic reviews encompassing 82 clinical studies [54][55][56][57][58][59]. Uncertainties surrounding the effectiveness of cranberry products remain. ...
... A Cochrane review and meta-analysis discovered that cranberry products did not significantly lower the incidence of symptomatic UTI in women with recurrent UTIs compared with placebo, water, or no treatment [55]. According to five subsequent metaanalyses, cranberry-containing products may prevent UTIs in some patient populations [54,[56][57][58][59]. The clinical and methodological heterogeneity of the included studies could be a contributing factor to the disparate results across meta-analyses [60]. ...
Both in vivo and in vitro studies have shown that functional plant-based food such as fruits, vegetables, and
berries can enhance health, have preventive effects, and reduce the risk of several chronic diseases. This
review discusses blackcurrant fruit usage in humans and experimental animals and its effect on the
genitourinary system (GUS). This comprehensive review demonstrates that blackcurrants and their bioactive
compounds possess medicinal and therapeutic properties related to the GUS. Emphasis in the literature has
been placed on the bioavailability of the active blackcurrant components. Nonetheless, future clinical trials
are needed to investigate and improve the bioavailability of blackcurrant phenolic compounds, such as
anthocyanins, and to expand the evidence that active blackcurrant compounds can treat various
genitourinary diseases.
... The suggested mechanism may be related to the proanthocyanidins (PACs) in cranberry fruit which have the ability to prevent bacterial adhesion to uroepithelium. Despite the known benefit of cranberry and cranberry products on UTI prevention, dosage and ideal mode of administration have not been established as positive outcomes have been seen with ingestion of juices, capsules, tablets, and extracts all with varying levels of PACs [3,26,27]. ...
... Evidence for effectiveness in older men, women, and catheterized patients was inconclusive. An updated meta-analysis in 2017 by Luís et al. including 28 clinical trials concluded that cranberry ingestion of at least 36 mg of PACs can decrease incidence of UTIs especially in those patients with recurrent UTIs [27]. In 2019, the AUA conditionally recommended the use of cranberry for prophylaxis against rUTIs with an evidence level of Grade C based on the data available. ...
Purpose of Review
In this review, we discuss the current literature available to patients and providers regarding alternative and complementary treatments for the prevention of recurrent urinary tract infections. These therapies include cranberry products, D-mannose, hyaluronic acid, vitamins C and D, probiotics, herbal medicine, behavioral modifications, and acupuncture.
Recent Findings
Numerous non-antimicrobial as well as non-pharmacologic preventative strategies are under investigation, but studies have been largely limited to observational studies or small randomized trials. Investigations into over-the-counter nutraceuticals have raised concerns regarding product purity, contamination, and unknown interactions.
Summary
The current literature lacks sufficient evidence for a majority of these strategies to yet be a viable alternative to the current mainstay of antibiotics prophylaxis. Further investigation should target comprehensive RCTs, establish safe and standardized therapeutic dosages, and carefully document adverse effects as well as potential drug interactions.
... 4 Cranberry extracts can also reduce the administration of antibiotics, which is of utmost clinical relevance since the use of antibiotics can lead to emergence of antibiotic-resistant microorganisms. 7 Cranberries have multiple biological properties, including effects on bacterial adhesion, biofilm formation, microbial growth, and immunomodulatory and anti-inflammatory activities. 8 In particular, the cranberry oligosaccharides can contribute to many health benefits. ...
... This is in accordance with previous studies on cranberries. 4,6,7 However, the effect of cranberries on UTIs is not unambiguous. 5 It can be speculated that the use of cranberries reduced the amount of pathogenic microbes in the urine. ...
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 B2 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 α 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 α and β 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.
... Several studies have observed the beneficial role of cranberry products in reducing the frequency of R-UTIs (21,22). The complex mixture of proanthocyanidins (PACs), flavonols and hydroxycinnamic acids contained in cranberry extract seems to decrease biofilm formation and reduce inflammation. ...
... The complex mixture of proanthocyanidins (PACs), flavonols and hydroxycinnamic acids contained in cranberry extract seems to decrease biofilm formation and reduce inflammation. This activity is mainly exerted by preventing bacterial adhesion and co-aggregation rather than through a direct bactericidal activity (22)(23)(24)(25)(26)28). Thanks to its beneficial properties, cranberry use is also used as a supplementary management model for UTIs in the Merck Manual (1) and can safely be suggested as a complementary therapy (21,26). ...
a Surgical School, G D'annunzio university, pescara, italy; b irvine3 labs and San Valentino Vascular Screening project DScmedBiotec, Chieti-pescara university, Chieti, italy; c international agency for pharma Standard Supplements (iapSS), pescara, italy; d r&D indena Spa, milan, italy ABSTRACT In this preliminary pilot registry study, we investigated the effects of the oral supplementation of a standardized cranberry extract (Anthocran® Phytosome®, Indena) delivered by a lecithin-based system , for the prophylactic management of recurrent-urinary tract infections (R-UTIs). We included 64 otherwise healthy subjects who underwent a surgical procedure and required post-surgical urinary catheterization for high-risk UTIs or a previous history of R-UTIs. Patients were given supplementation with the standardized cranberry extract at the dose of either 120 mg/day (n = 12) or 240 mg/day (n = 12) or assigned to a control group consisting of standard management (SM; n = 18) or nitrofurantoin administration (n = 22) for 4 weeks. After 4 weeks, patients receiving the standardized cranberry supplementa-tion reported to have a more effective reduction in UTI symptoms, as assessed on the visual analogue scale, compared with patients in the SM or nitrofurantoin groups. The occurrence of hematuria and urine bacterial contamination were decreased among patients treated with the supplement compared with controls (p < 0.05). The cranberry extract was also superior to the control management in terms of recurrence of signs/symptoms, with none of the patients in this group suffering from a R-UTI in the 3 months following the study end (p < 0.05). The supplementation showed an optimal safety profile, with no significant adverse events and no drop-outs in the supplement group. This registry shows that this cranberry extract is effective as a supplementary, preventive management in preventing post-operative, post-catheter UTIs; the product has a good tolerability profile.
... Similar results were obtained by another meta-analysis of 28 RCTs (RR: 0.67, 95% CI 0.55-0.79, p < 0.0001) [81]. However, data on complicated UTIs prevention with cranberry remains unclear and in part contrasting as reported by four previous meta-analyses [71,[82][83][84], among which only preventing uncomplicated UTI recurrence in healthy people [74]. ...
... Similar results were obtained by another meta-analysis of 28 RCTs (RR: 0.67, 95% CI 0.55-0.79, p < 0.0001) [81]. However, data on complicated UTIs prevention with cranberry remains unclear and in part contrasting as reported by four previous meta-analyses [71,[82][83][84], among which only three reported a trend of relative risk reduction after cranberry supplementation [71,82,83]. ...
Cranberry is a fruit originally from New England and currently growing throughout the east and northeast parts of the USA and Canada. The supplementation of cranberry extracts as nutraceuticals showed to contribute to the prevention of urinary tract infections, and most likely it may help to prevent cardiovascular and gastroenteric diseases, as highlighted by several clinical trials. However, aiming to validate the efficacy and safety of clinical applications as long-term randomized clinical trials (RCTs), further investigations of the mechanisms of action are required. In addition, a real challenge for next years is the standardization of cranberry’s polyphenolic fractions. In this context, the optimization of the extraction process and downstream processing represent a key point for a reliable active principle for the formulation of a food supplement. For this reason, new non-conventional extraction methods have been developed to improve the quality of the extracts and reduce the overall costs. The aim of this survey is to describe both technologies and processes for highly active cranberry extracts as well as the effects observed in clinical studies and the respective tolerability notes.
... To this aim, we conducted a systematic review and evaluated previous meta-analysis risk of bias assessment [17][18][19]. Although it was not a meta-analysis, we also considered the systematic review of Navarrete-Opazo et al. [20], because it was focused on individuals with SCI. Figure 1 shows the four-phase diagram of meta-analysis (according to the PRISMA Statement) and the flow of the studies processed in this review. ...
... Since there were 2 studies with individuals taking both treatment and control, 1 crossover [29] and 1 longitudinal [26], 477 data from 415 participants were [19] Not reported Low Low Low analysed in this meta-analysis. Overall, 241 subjects received CB and 236 control. ...
Background:
Urinary tract infection (UTI) is common in individuals with spinal cord injury (SCI) and neurogenic lower urinary tract dysfunction (NLUTD) and in veterans with SCI who use antibiotics improperly for asymptomatic bacteriuria. Cranberry (CB) has been suggested for UTI prevention.
Methods:
We performed a systematic search up to May 2020 in the following databases: AccessMedicine, BioMed Central, CINAHL, Cochrane Library, ProQuest, and PubMed. Quality assessment was performed using a specifically designed quality score. Risk ratio was calculated with both random effect model analysis (DerSimonian-Laird method) and quality effect model analysis (Doi Thalib method).
Results:
Six studies on bacteriuria and SCI were reviewed. From the four studies available for meta-analysis, two of which with individuals taking both CB and control, 477 data from 415 participants were analysed (241 CB and 236 control). No significant differences were detected with meta-analysis. However, bias, limitations, and incompleteness were observed in the reviewed studies.
Conclusion:
Although further studies are needed, we suggest an accurate monitoring of diet and fluid intake, the evaluation of risk for potential food or nutraceutical interactions with drugs, and the inclusion of inflammatory markers among the outcomes in addition to UTI.
... Over the years there have been many systematic and critical reviews of the clinical trials, with the most recent ones concluding that there is benefit to consuming cranberry for prevention of UTIs in most populations (Chen et al. 2019;Mantzorou and Giaginis 2018;Luís et al. 2017;Fu et al. 2017). Very recently, a panel of urologists from the American Urological Association (AUA)/Canadian Urological Association (CUA)/Society of Urodynamics, and Female Pelvic Medicine & Urogenital Reconstruction (SUFU) reviewed the results of over 200 cranberry studies including clinical trials conducted prior to 2018. ...
... De Leo et al. conclusions about the efficacy of cranberry when comparing these studies. While many reviews have concluded that cranberry may help prevent infections, particularly in women with recurrent UTIs (Chen et al. 2019;Mantzorou and Giaginis 2018;Luís et al. 2017;Fu et al. 2017;Jepson and Craig 2008;Wang et al. 2012), one past review concluded that there was no benefit for cranberry (Jepson et al. 2012). Risk ratios of <1.0 (calculated relative risk of developing UTIs in the treated vs control groups) were interpreted as positive outcomes by Wang et al. (2012) but not by Jepson et al. (2012) with different confidence intervals reported in each study. ...
The juice of the fruit of the American cranberry (Vaccinium macrocarpon Ait.) is by far the most popular and widely used botanical preparation for the prevention and treatment of urinary tract infections. To date, most of the medical research on cranberry consists of observational clinical trials yielding mixed results or preclinical studies, the latter focusing on mechanisms of action, many of which are relevant to the putative benefits attributed to cranberry. Cranberry benefits are primarily linked to the presence of proanthocyanidin (PAC) oligomers, also referred to as condensed tannins or polyflavan-3-ols, and their capacity to prevent bacteria, particularly E. coli, from adhering to uroepithelial cells. In the following, we present a summary of the state of cranberry research in the context of urinary tract health with focus on data derived from clinical settings. The overall consensus from recent reviews and meta-analyses is that there are beneficial effects of cranberry consumption on reducing risk of UTI recurrence.
... It is worth mentioning that we did not expressly test the last factor since excluded all juice studies. Briefly, there have been 4 meta-analyses in the last decade to examine the effect of cranberries in this context [13][14][15]35]. Jepson et al reported a meta-analysis in 2012, predating almost two-thirds of trials included in our analysis [13]. ...
... There was no separate analysis by formulation for culture-confirmed UTI. In a larger meta-analysis, Luis et al pooled results from a broad set of studies conducted in all age groups including children, pregnant females, and those with neurogenic bladder [35]. Again, trials using both cranberry formulations and all outcome definitions were pooled, as were studies using non-placebo control (antibiotics, other probiotics, etc). ...
... 7 Recent studies have suggested that cranberry products, probiotics, the bacterial vaccine Uromune, D-mannose powder, and vitamin D have a role in preventing RUTI. [8][9][10][11][12][13] However, the evidence for these nonantibiotic products are weak, and more studies on this issue are required. ...
... 23 Treatment of E. coli with antibiotics is often ineffective because of acquisition of drug-resistant genes by the bacteria. Li et al. 8 reported that more than 45% of E. coli isolated from UTIs were resistant to wide-spectrum antibiotics. ...
Objective:
The present study aimed to examine the behavioral and dietary risk factors of recurrent urinary tract infection (RUTI) in postmenopausal patients in China.
Methods:
We performed a population-based case-control study with 193 postmenopausal women with RUTI and 193 age-matched healthy female controls with no history of RUTI. The study was conducted between January 2016 and June 2018 in Changzhou, China. Data were collected using an interviewer-based questionnaire, including information on demographics, lifestyle behavior, and habitual diet. Conditional logistic regression analysis was conducted to examine the risk factors associated with RUTI.
Results:
Wiping from back to front after toilet use, sedentary behavior >6 hours/day, delayed voiding, and chronic constipation were associated with an increased risk of RUTI. Drinking more than three cups of green tea per month showed an inverse association with RUTI. However, there was no evidence of dose dependency for overall consumption. Additionally, the three-cup association involved a small proportion of cases and may reflect statistical artifact.
Conclusions:
Wiping from back to front after toilet use, sedentary behavior, delayed voiding, and chronic constipation are associated with an increased risk of RUTI in postmenopausal women.
... A Cochrane review updated in 2012 reported that cranberries do not have significant benefits in terms of decreasing the number of UTIs, and a high dropout rate was found in the cranberry group [128]. However, recent meta-analyses and systematic reviews concluded that cranberry-containing products may protect against UTIs in certain patient populations [84,[129][130][131][132], especially in women, children (2-17 years), and middle-aged adults (36-55 years) [129]. The daily recommended dosage of PACs to decrease episodes of UTIs is reported to be at least 36 mg [129]. ...
Urinary tract infections (UTIs) are the most frequent bacterial infections in the clinical setting. Even without underlying anatomic or functional abnormalities, more than 40% of women experience at least one UTI in their lifetime, of which 30% develop recurrent UTIs (rUTIs) within 6 months. Conventional management with antibiotics for rUTIs may eventually lead to the development of multidrug-resistant uropathogens. Targeting of the pathogenicity of rUTIs, the evolution of uropathogenic Escherichia coli (UPEC), and inadequate host defenses by immune responses should be explored to provide non-antibiotic solutions for the management of rUTIs. The adaptive evolution of UPEC has been observed in several aspects, including colonization, attachment, invasion, and intracellular replication to invade the urothelium and survive intracellularly. Focusing on the antivirulence of UPEC and modulating the immunity of susceptible persons, researchers have provided potential alternative solutions in four categories: antiadhesive treatments (i.e., cranberries and D-mannose), immunomodulation therapies, vaccines, and prophylaxis with topical estrogen therapy and probiotics (e.g., Lactobacillus species). Combination therapies targeting multiple pathogenic mechanisms are expected to be a future trend in UTI management, although some of these treatment options have not been well established in terms of their long-term efficacy. Additional clinical trials are warranted to validate the therapeutic efficacy and durability of these techniques.
... In contrast, NSAIDs are better used for the symptomatic treatment of uncomplicated bacterial cystitis. There have been several previously published reviews, with or without meta-analyses, on the effectiveness of individual nonantibiotic agents including, cranberry [32][33][34][35], D-mannose [36][37][38] and NSAIDs [39,40] in preventing or treating UTIs. However, this review is distinct in applying more restrictive inclusion criteria to the comparison of the effectiveness of three different nonantibiotic agents in women over eighteen with uncomplicated UTIs (cystitis). ...
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.
... Black Chokeberry (Aronia melanocarpa) fruit is a rich source of bioactive phytochemicals, including anthocyanins, proanthocyanidins, flavonols, flavanols, and phenolic acids [74]. With a similar chemical profile as cranberry, which has been observed to reduce the risk of urinary tract infections [75,76], our scoping review reports that Black Chokeberry juice reduced the risk of developing a urinary tract infection for up to three months post-intervention [53]. ...
Background
Elderly long-term care residents (ELTCRs) face considerable burden of infection, especially evident during the COVID-19 pandemic. The nutritional status of the host can influence susceptibility to infection by altering immune system integrity, therefore, nutrition-based interventions may be a viable complement to existing infection prevention measures.
Objective
This scoping review sought to identify nutritional interventions and factors that have the strongest evidence to benefit ELTCRs, and thus best poised for rigorous clinical trial evaluation and subsequent implementation.
Methods
A database search of OVID-Medline, OVID-Embase, and Web of Science was performed from 2011 to 2021 to identify nutritional intervention studies which attribute to changes in infection in contemporary ELTCR settings. Articles were screened in duplicate and data extraction completed by a single reviewer, while a second reviewer verified the data which was fitted to identify evidence for nutritional interventions related to reducing rates of infection among ELTCRs.
Results
The search identified 1018 studies, of which 11 (nine clinical trials and two observational cohort studies) satisfied screening criteria. Interventions that significantly reduced risk of infection included whey protein (any infection), Black Chokeberry (urinary tract infection), and vitamin D (acute respiratory tract infection, skin and soft tissue infection). Both zinc and a dedicated meal-plan significantly improved lymphocyte parameters. Vitamin D deficiency was associated with the development of respiratory tract infections. Probiotic and soy-based protein interventions did not significantly affect risk of infection or lymphocyte parameters, respectively.
Conclusion
The current scoping review was effective in identifying the use of nutrition-based interventions for infection prevention among ELTCRs. In this study, some nutrition-based interventions were observed to significantly influence the risk of infection among ELTCRs. Nutritional interventions such as vitamin D (preventing deficiency/insufficiency), Black Chokeberry juice, zinc gluconate, whey protein, and varied and nutrient dense meal plans may be suitable for future rigorous clinical trial evaluation.
... At the same time, an earlier published meta-analysis includes published data from MEDLINE, EMBASE, and the Cochrane libraries [31]. Recent works only show the effective use of cranberry against UTIs [31,32]. This meta-analysis identified other agents published in the literature used against the UTIs at nursing homes. ...
This meta-analysis aims to identify urinary tract infections (UTIs) in patients with different levels of age groups. For both diagnosis and treatment of UTIs, antibiotics have been widely used in nursing home settings. We also aimed to evaluate the duration of catheterization in UTI patients to reduce catheter-associated complications. We conducted a systematic review that was performed following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines and recommendations from Cochrane Collaboration. We performed a comprehensive search for published literature in PubMed, ScienceDirect, Taylor & Francis Online, Springer, and Wiley Online databases from 2010 to June 25, 2021. We performed two meta-analysis: the first meta-analysis (meta-analysis I) was performed on data obtained from included studies that compared patients with UTIs (experimental group) and without UTIs (control group); the second meta-analysis (meta-analysis II) was performed to assess the appropriate use of a catheter in UTI patients. All statistical analyses were conducted using the Review Manager 5.4 tool. A total of 15 research articles were included in this systematic review and meta-analysis. Of these, results showed the identification of critical patients with UTIs and without UTIs from nursing resident homes (risk ratio [RR] = 0.80 95% confidence interval CI = 0.69-0.93 p < 0.0001). Risk ratio results with random effects (RE) were obtained as RR = 0.69 95% CI = 0.26-1.83, p = 0.45, along with heterogeneity I 2 (96%) values. No appropriate prescription of antibiotics in UTIs is practiced among nursing home residents. In addition, pooled results between two groups (short-duration vs. long-duration catheterization) showed RR 0.66 95% CI 0.46-0.93 p = 0.02, I 2 = 56, that reduced complications associated with CAUTIs. This systematic review and meta-analysis suggested an appropriate use of agents and catheter insertion for a short duration at nursing homes.
... Many trials of cranberry extract for UTI prevention have been conducted, with promising results. [10][11][12][13] However, many have suffered methodological problems, such as high participant drop-out attributed to difficulty drinking large volumes of cranberry juice over extended periods. 11 A systematic review found limited evidence for or against using cranberry extract to treat auUTIs. ...
Background
The views of women with acute, uncomplicated urinary tract infection (auUTI) on the acceptability of non-antibiotic treatment options are poorly understood.
Aim
To establish women’s thoughts on and experience of non-antibiotic treatment for auUTIs.
Design and setting
Qualitative interview study with primary care patients in Oxfordshire, UK, embedded within the Cranberry for Urinary Tract Infection (CUTI) feasibility trial.
Method
One-to-one, semi-structured interviews were conducted between August 2019 and January 2020 with some CUTI trial participants and some patients who were not part of the CUTI trial who had experienced at least one urinary tract infection (UTI) in the preceding 12 months in Oxfordshire, UK. Interviews were analysed using thematic analysis.
Results
In total, 26 interviews were conducted and analysed. Women expected to receive an immediate antibiotic for their UTI but were aware of the potential harms of this approach. They were keen to find a non-antibiotic, ‘natural’ alternative that could effectively manage their symptoms. In certain situations (early illness, milder illness, and with no important upcoming engagements), women indicated they would be prepared to postpone antibiotic treatment by up to 3 days, especially if offered an interim non-antibiotic option with perceived therapeutic potential.
Conclusion
Many women with auUTIs are open to trying non-antibiotic treatments first in certain situations. There is scope for more dialogue between primary care clinicians and patients with auUTI around delaying antibiotic treatment and using non-antibiotic options initially, which could reduce antibiotic consumption for this common infection.
... This is mainly due to the PACs content in cranberry [35], especially proanthocyanidin A [36]. Several studies have confirmed the positive effect of cranberry on urinary tract inflammation, not only for adults [34][35][36][37][38][39][40][41][42][43][44][45][46][47] but also for children [48][49][50]. It was found that PACs contained in cranberries prevent adherence of E. coli to uroepithelial cells in the urinary tract [44,45,56]. ...
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.
... These studies also reported a large drop-out rate of participants. Conversely, another meta-analysis of similar size (4947 participants), demonstrated that cranberry products reduced the risk of recurrent urinary tract infections (Luis et al, 2017). Owing to the conflicting evidence, the European Association of Urology (2021) does not recommend taking cranberry products to prevent the recurrence of urinary tract infections, whereas guidance from the National Institute for Health and Care Excellence (2018) suggests patients with recurrent urinary tract infections may want to consider the use of cranberry products. ...
... In 2012, Jepson et al. [6] conducted a systematic review of cranberry intake as adjuvant therapy for preventing and treating UTIs, and it was concluded that cranberry products failed to significantly reduce the occurrence of UTIs when compared with placebo or control groups. Additionally, a meta-analysis included 28 clinical studies in 2017 demonstrated that cranberry intake is associated with preventing UTIs, and that supplementing cranberry-based products provides a beneficial effect on reducing the incidence of UTIs [10]. However, few previous studies evaluated the effects of cranberry and UTIs in susceptible populations. ...
The efficacy of cranberry (Vaccinium spp.) as adjuvant therapy in preventing urinary tract infections (UTIs) remains controversial. This study aims to update and determine cranberry effects as adjuvant therapy on the recurrence rate of UTIs in susceptible groups. According to PRISMA guidelines, we conducted a literature search in Web of Science, PubMed, Embase, Scopus, and the Cochrane Library from their inception dates to June 2021. We included articles with data on the incidence of UTIs in susceptible populations using cranberry-containing products. We then conducted a trial sequential analysis to control the risk of type I and type II errors. This meta-analysis included 23 trials with 3979 participants. We found that cranberry-based products intake can significantly reduce the incidence of UTIs in susceptible populations (risk ratio (RR) = 0.70; 95% confidence interval(CI): 0.59 ~ 0.83; P<0.01). We identified a relative risk reduction of 32%, 45% and 51% in women with recurrent UTIs (RR = 0.68; 95% CI: 0.56 ~ 0.81), children (RR = 0.55; 95% CI: 0.31 ~ 0.97) and patients using indwelling catheters (RR = 0.49; 95% CI: 0.33 ~ 0.73). Meanwhile, a relative risk reduction of 35% in people who use cranberry juice compared with those who use cranberry capsule or tablet was observed in the subgroup analysis (RR = 0.65; 95% CI: 0.54 ~ 0.77). The TSA result for the effects of cranberry intake and the decreased risk of UTIs in susceptible groups indicated that the effects were conclusive. In conclusion, our meta-analysis demonstrates that cranberry supplementation significantly reduced the risk of developing UTIs in susceptible populations. Cranberry can be considered as adjuvant therapy for preventing UTIs in susceptible populations. However, given the limitations of the included studies in this meta-analysis, the conclusion should be interpreted with caution.
... However, later Howell et al. demonstrated that a daily dose of 72 mg of proanthocyanidins provided better efficacy against bacterial adhesion in the urinary tract [29]. A Cochrane review from 2012 concluded that due to low-quality evidence cranberry products cannot be recommended for the prevention of UTI [30]; however, two recent systematic reviews suggest that cranberry can be an effective alternative strategy for the prevention of UTI in the adult population [31,32]. Similar to the later reviews, pooled estimates from this meta-analysis also showed that the ingestion of cranberry products reduces UTI recurrence by 52% in children with the normal urinary tract. ...
A considerable proportion of children experience a recurrence of urinary tract infection (UTI) following the first episode. While low-dose antibiotic prophylaxis has been the mainstay for the prevention of UTI, recent evidence raised concerns over their efficacy and safety. Hence, we aim to systematically synthesize evidence on the efficacy and safety of non-antibiotic prophylactic interventions for UTI. Using keywords related to study population (children) and intervention (non-antibiotic), we searched CENTRAL, Embase, PubMed, and Web of Science for randomized controlled trials (RCTs) published until August 2020. RCTs comparing any non-antibiotic interventions with placebo/antibiotics for prevention of UTIs in children were considered eligible. We used a random-effect model to provide pooled estimates. Sixteen trials evaluating 1426 participants were included. Cranberry was as effective as antibiotic prophylaxis (RR: 0.92; 95% CI: 0.56–1.50) but better than placebo/no therapy (RR: 0.48; 95% CI: 0.28–0.80) in reducing UTI recurrence. Probiotic therapy was more effective in reducing UTI recurrence (RR: 0.52; 95% CI: 0.29–0.94) when compared with placebo. While probiotic therapy was not better than antibiotics prophylaxis in preventing UTI (RR: 0.82; 95% CI: 0.56–1.21), they have a lower risk of antibiotic resistance (RR: 0.38; 95% CI: 0.21–0.69).Conclusion: Cranberry products and probiotics are the two non-antibiotic interventions that have been chiefly evaluated, reduce the risk of UTI recurrence when compared with placebo in children with a normal urinary tract. The findings from this systematic review suggest that while cranberry and probiotics may be used, there is a definite need to identify better and more acceptable non-antibiotic interventions.
What is Known:
• Efficacy of the low-dose antibiotic is controversial in preventing UTI and it is associated with increase in the risk of antimicrobial resistance.
• Non-antibiotic interventions such as cranberry products are effective in preventing UTI recurrence in adults.
What is New:
• Cranberry products are effective in reducing the recurrence of UTI in children with normal urinary tract.
• Low-quality evidence suggests that probiotics can be a potential prophylactic measure to reduce recurrence of UTI in the pediatric population.
... Luis et al. concluded, based on a meta-analysis and sequential analysis of clinical trials, that the use of cranberry has a clear positive effect on the prevention of recurrent UTIs [39]. Thus far, few studies have assessed the potential benefit of cranberry in treating symptoms of rUTIs or whether cranberry might have a synergistic effect when combined with antibiotics [2,40,41]. If cranberry safely and effectively treats UTIs or acts synergistically with antibiotics, this could substantially help to reduce overall antibiotic exposure. ...
Due to the excessive use of antibiotic and antimycotic treatments, the risk of resistant microbes and fungi is rapidly emerging. Previous studies have demonstrated that many women with (recurrent) urinary tract infection (UTI) and/or vaginal infections (VIs) welcome alternative management approaches to reduce the use of antibiotics and antifungals and avoid short- and long-term adverse effects. This study aims to determine which complementary medicine (CM) and self-care strategies are being used by women suffering from (recurrent) UTI and VI in The Netherlands and how they perceive their effectiveness in order to define directions for future research on safety, cost-effectiveness, and implementation of best practices. A cross-sectional online survey was performed among women, ≥18 years old, with a history of UTIs; 162 respondents were included in the data analysis, with most participants aged between 50 and 64 years (36.4%). The women reported having consulted a CM practitioner for UTI-specific symptoms (23.5%) and VI-specific symptoms (13.6%). Consultations of homeopaths, acupuncturists, and herbal physicians are most often reported. Overall, 81.7% of the women suffering from UTI used complementary or self-care strategies besides regular treatment, and 68.7% reported using CM/self-care strategies to treat vaginal symptoms. UTI- related use of cranberries (51.9%), vitamin C (43.8%), and D-mannose (32.7%) were most reported. Perceived effectiveness was mostly reported for homeopathic remedies and D-mannose. The results showed a substantial burden of UTI and VI on daily and sexual activities. Besides the frequency of use, the indication of perceived effectiveness seems to be an important parameter for further and rigorously designed research to encourage nonantibiotic/antifungal treatment implementation into daily clinical practice.
... One proposed approach to combating rUTI is prophylactic consumption of cranberry products; however, the efficacy of cranberry products in preventing UTI is not clear [12][13][14][15][16][17][18][19][20][21][22][23][24]. No specific in vivo mechanism has been determined to explain cranberry's potential preventative effects, and possible mechanisms have only been described in vitro [25][26][27][28][29][30]. ...
Background
Urinary tract infections (UTIs) affect 15 million women each year in the United States, with > 20% experiencing frequent recurrent UTIs. A recent placebo-controlled clinical trial found a 39% reduction in UTI symptoms among recurrent UTI sufferers who consumed a daily cranberry beverage for 24 weeks. Using metagenomic sequencing of stool from a subset of these trial participants, we assessed the impact of cranberry consumption on the gut microbiota, a reservoir for UTI-causing pathogens such as Escherichia coli , which causes > 80% of UTIs.
Results
The overall taxonomic composition, community diversity, carriage of functional pathways and gene families, and relative abundances of the vast majority of observed bacterial taxa, including E. coli , were not changed significantly by cranberry consumption. However, one unnamed Flavonifractor species (OTU41), which represented ≤1% of the overall metagenome, was significantly less abundant in cranberry consumers compared to placebo at trial completion. Given Flavonifractor’s association with negative human health effects, we sought to determine OTU41 characteristic genes that may explain its differential abundance and/or relationship to key host functions. Using comparative genomic and metagenomic techniques, we identified genes in OTU41 related to transport and metabolism of various compounds, including tryptophan and cobalamin, which have been shown to play roles in host-microbe interactions.
Conclusion
While our results indicated that cranberry juice consumption had little impact on global measures of the microbiome, we found one unnamed Flavonifractor species differed significantly between study arms. This suggests further studies are needed to assess the role of cranberry consumption and Flavonifractor in health and wellbeing in the context of recurrent UTI.
Trial registration
Clinical trial registration number: ClinicalTrials.gov NCT01776021 .
... coli) from binding to the bladder uroepithelium [12] and thereby reducing the ability of E. coli to cause and sustain a UTI. Systematic reviews assessing the use of cranberry in the management of recurrent UTIs provide mixed evidence for benefit [13,14]. A 2012 Cochrane review of 24 trials (n = 4473) of men, women and children found that cranberry did not significantly reduce recurrent UTI compared with placebo, advice to increase water intake or no treatment. ...
Background:
Effective alternatives to antibiotics for alleviating symptoms of acute infections may be appealing to patients and enhance antimicrobial stewardship. Cranberry-based products are already in wide use for symptoms of acute urinary tract infection (UTI). The aim of this review was to identify and critically appraise the supporting evidence.
Methods:
The protocol was registered on PROSPERO. Searches were conducted of Medline, Embase, Amed, Cinahl, The Cochrane library, Clinicaltrials.gov and WHO International Clinical Trials Registry Platform. We included randomised clinical trials (RCTs) and non-randomised studies evaluating the effect of cranberry extract in the management of acute, uncomplicated UTI on symptoms, antibiotic use, microbiological assessment, biochemical assessment and adverse events. Study risk of bias assessments were made using Cochrane criteria.
Results:
We included three RCTs (n = 688) judged to be at moderate risk of bias. One RCT (n = 309) found that advice to consume cranberry juice had no statistically significant effect on UTI frequency symptoms (mean difference (MD) -0.01 (95% CI: -0.37 to 0.34), p = 0.94)), on UTI symptoms of feeling unwell (MD 0.02 (95% CI: -0.36 to 0.39), p = 0.93)) or on antibiotic use (odds ratio 1.27 (95% CI: 0.47 to 3.43), p = 0.64), when compared with promoting drinking water. One RCT (n = 319) found no symptomatic benefit from combining cranberry juice with immediate antibiotics for an acute UTI, compared with placebo juice combined with immediate antibiotics. In one RCT (n = 60), consumption of cranberry extract capsules was associated with a within-group improvement in urinary symptoms and Escherichia coli load at day 10 compared with baseline (p < 0.01), which was not found in untreated controls (p = 0.72). Two RCTs were under-powered to detect differences between groups for outcomes of interest. There were no serious adverse effects associated with cranberry consumption.
Conclusion:
The current evidence base for or against the use of cranberry extract in the management of acute, uncomplicated UTIs is inadequate; rigorous trials are needed.
Background
Two common infections in women are urinary tract infections (UTIs) and vaginal candidiasis (VC). The focus of this research project was to counter the root causes of these two infections, namely, Escherichia coli (E. coli) and Candida albicans (C. albicans).
Purpose
The purpose of this research project was to develop a dietary formulation for women’s health that inhibits both E. coli and C. albicans.
Materials & Methods
We designed a propriety blend of five strains of Bifidobacteria, ten strains of Lactobacilli, and organic cranberry powder. For the carriers, we chose a proprietary blend of organic red fruit and vegetable juices. The probiotics were added to a sterilized blend of juice and cranberry powder. Three strains of E. coli and two strains of C. albicans were used in this study.
Results
While E. coli in the control sample showed a typical growth curve for microorganisms, E. coli growth was completely inhibited in the test sample from days 1 to 5. Similarly, while C. albicans in the control sample showed overwhelming uncountable growth, C. albicans growth in the test sample was reduced by 70% on day 1 and was completely inhibited from day 2 to day 5.
Conclusion
The results of this in vitro study indicate that E. coli O157:H7 and C. albicans (the microorganisms responsible for UTI and VC) were completely inhibited by a healthy dietary formulation for women. These findings have advanced our knowledge of the inhibition of two pathogens responsible for two common medical problems in women.
Urinary Tract infection (UTI) is one of the most common infections worldwide, patients present to multiple different specialities in the community, primary and secondary care. Antibiotics are considered standard first line therapy in the treatment of urinary tract infections, however there is an alarming rise in global antibiotic resistance rates, so much so that the World Health Organisation has labelled antibiotic resistance as one of the biggest challenges to public health in our lifetime, publishing a global action plan to tackle this challenge. As a result, there is an increasing need to discover non-antibiotic alternatives, recently a number of novel therapies have been introduced into clinical practice. These are divided into oral, topical, intravesical and immunomodulation therapies. The aim of this paper is to summarise the current non-antibiotic treatments as a practical guide to utilise in patient care.
Cranberry (poly)phenols may have potential health benefits. Circulating (poly)phenol metabolites can act as mediators of these effects, but they are subjected to an extensive inter-individual variability. This study aimed to quantify both plasma and urine (poly)phenol metabolites following a 12-week intake of a cranberry powder in healthy older adults, and to investigate inter-individual differences by considering the existence of urinary metabotypes related to dietary (poly)phenols. Up to 13 and 67 metabolites were quantified in plasma and urine respectively. Cranberry consumption led to changes in plasma metabolites, mainly hydroxycinnamates and hippuric acid. Individual variability in urinary metabolites was assessed using different data sets and a combination of statistical models. Three phenolic metabotypes were identified, colonic metabolism being the main driver for subject clustering. Metabotypes were characterized by quali-quantitative differences in the excretion of some metabolites such as phenyl-γ-valerolactones, hydroxycinnamic acids, and phenylpropanoic acids. Metabotypes were further confirmed when applying a model only focused on flavan-3-ol colonic metabolites. 5-(3',4'-dihydroxyphenyl)-γ-valerolactone derivatives were the most relevant metabolites for metabotyping. Metabotype allocation was well preserved after 12-week intervention. This metabotyping approach for cranberry metabolites represents an innovative step to handle the complexity of (poly)phenol metabolism in free-living conditions, deciphering the existence of metabotypes derived from the simultaneous consumption of different classes of (poly)phenols. These results will help contribute to studying the health effects of cranberries and other (poly)phenol-rich foods, mainly considering gut microbiota-driven individual differences.
Background:
Cranberries contain proanthocyanidins (PACs), which inhibit the adherence of p-fimbriated Escherichia coli to the urothelial cells lining the bladder. Cranberry products have been used widely for several decades to prevent urinary tract infections (UTIs). This is the fifth update of a review first published in 1998 and updated in 2003, 2004, 2008, and 2012.
Objectives:
To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations.
Search methods:
We searched the Cochrane Kidney and Transplant Specialised Register up to 13 March 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal (ICTRP) and ClinicalTrials.gov.
Selection criteria:
All randomised controlled trials (RCTs) or quasi-RCTs of cranberry products compared with placebo, no specific treatment or other intervention (antibiotics, probiotics) for the prevention of UTIs were included.
Data collection and analysis:
Two authors independently assessed and extracted data. Information was collected on methods, participants, interventions and outcomes (incidence of symptomatic UTIs, positive culture results, side effects, adherence to therapy). Risk ratios (RR) with 95% confidence intervals (CI) were calculated where appropriate. Study quality was assessed using the Cochrane risk of bias assessment tool. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
Main results:
For this update 26 new studies were added, bringing the total number of included studies to 50 (8857 randomised participants). The risk of bias for sequence generation and allocation concealment was low for 29 and 28 studies, respectively. Thirty-six studies were at low risk of performance bias, and 23 studies were at low risk of detection bias. Twenty-seven, 41, and 17 studies were at low risk of attrition bias, reporting bias and other bias, respectively. Forty-five studies compared cranberry products with placebo or no specific treatment in six different groups of participants. Twenty-six of these 45 studies could be meta-analysed for the outcome of symptomatic, culture-verified UTIs. In moderate certainty evidence, cranberry products reduced the risk of UTIs (6211 participants: RR 0.70, 95% CI 0.58 to 0.84; I² = 69%). When studies were divided into groups according to the treatment indication, cranberry products probably reduced the risk of symptomatic, culture-verified UTIs in women with recurrent UTIs (8 studies, 1555 participants: RR 0.74, 95% CI 0.55 to 0.99; I² = 54%), in children (5 studies, 504 participants: RR 0.46, 95% CI 0.32 to 0.68; I² = 21%) and in people with a susceptibility to UTIs due to an intervention (6 studies, 1434 participants: RR 0.47, 95% CI 0.37 to 0.61; I² = 0%). However, in low certainty evidence, there may be little or no benefit in elderly institutionalised men and women (3 studies, 1489 participants: RR 0.93, 95% CI 0.67 to 1.30; I² = 9%), pregnant women (3 studies, 765 participants: RR 1.06, 95% CI 0.75 to 1.50; I² = 3%), or adults with neuromuscular bladder dysfunction with incomplete bladder emptying (3 studies, 464 participants: RR 0.97, 95% CI 0.78 to 1.19; I² = 0%). Other comparisons were cranberry products with probiotics (three studies) or antibiotics (six studies), cranberry tablets with cranberry liquid (one study), and different doses of PACs (two studies). Compared to antibiotics, cranberry products may make little or no difference to the risk of symptomatic, culture-verified UTIs (2 studies, 385 participants: RR 1.03, 95% CI 0.80 to 1.33; I² = 0%) or the risk of clinical symptoms without culture (2 studies, 336 participants: RR 1.30, 95% CI 0.79 to 2.14; I² = 68%). Compared to probiotics, cranberry products may reduce the risk of symptomatic, culture-verified UTIs (3 studies, 215 participants: RR 0.39, 95% CI 0.27 to 0.56; I = 0%). It is unclear whether efficacy differs between cranberry juice and tablets or between different doses of PACs as the certainty of the evidence was very low. The number of participants with gastrointestinal side effects probably does not differ between those taking cranberry products and those receiving placebo or no specific treatment (10 studies, 2166 participants: RR 1.33, 95% CI 1.00 to 1.77; I² = 0%; moderate certainty evidence). There was no clear relationship between compliance with therapy and the risk for repeat UTIs. No difference in the risk for UTIs could be demonstrated between low, moderate and high doses of PACs.
Authors' conclusions:
This update adds a further 26 studies taking the total number of studies to 50 with 8857 participants. These data support the use of cranberry products to reduce the risk of symptomatic, culture-verified UTIs in women with recurrent UTIs, in children, and in people susceptible to UTIs following interventions. The evidence currently available does not support its use in the elderly, patients with bladder emptying problems, or pregnant women.
Purpose of review:
There is a growing interest in nonantibiotic prevention strategies for recurrent urinary tract infections (rUTIs). Our objective is to provide a focused, pragmatic review of the latest evidence.
Recent findings:
Vaginal estrogen is well tolerated and effective for preventing rUTI in postmenopausal women. Cranberry supplements at sufficient doses are effective in preventing uncomplicated rUTI. Methenamine, d-mannose, and increased hydration all have evidence to support their use, although the evidence is of somewhat variable quality.
Summary:
There is sufficient evidence to recommend vaginal estrogen and cranberry as first-line rUTI prevention strategies, particularly in postmenopausal women. Prevention strategies can be used in series or in tandem, based on patient preference and tolerance for side effects, to create effective nonantibiotic rUTI prevention strategies.
Der Wildapfel ist aus Kasachstan zu uns gekommen und fühlt sich so richtig wohl hier. Er ist kulinarisch ebenso vielseitig wie in der traditionellen Heilkunde (Abb. 5.1). Beliebte Kombinationen mit Äpfeln sind Orangen, Feigen, Chili, Gewürznelken, Wacholder, Rosinen, Vanille, Zimt, Zitronenmelisse und Zitronenverbene.
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 <.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.
Objective:
This paper is a critical review examining the evidence about the prevention of urinary tract infections in aged care residents through the implementation of cranberry products. 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 review of the quantitative literature was conducted utilising a systematic search and critical review process. A critical analysis of the literature.
Results:
The current evidence suggests indicates cranberry products decrease the occurrence of urinary tract infections in aged care residents who were are likely to benefit from the use of cranberry products as a preventative measure, however, some of the findings results were limited and contradictory. Because of gaps and insufficient research in relation to the active ingredients of cranberries - proanthocyanins.
Conclusion:
The literature review identified 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.
Numerous health benefits have been reported from the consumption of cranberry-derived products, and recent studies have identified bioactive polysaccharides and oligosaccharides from cranberry pomace. This study aimed to further characterize xyloglucan and pectic oligosaccharide structures from pectinase-treated cranberry pomace and measure the growth and short-chain fatty acid production of 86 Lactobacillus strains using a cranberry oligosaccharide fraction as the carbon source. In addition to arabino-xyloglucan structures, cranberry oligosaccharides included pectic rhamnogalacturonan I which was methyl-esterified, acetylated and contained arabino-galacto-oligosaccharide side chains and a 4,5-unsaturated function at the non-reducing end. When grown on cranberry oligosaccharides, ten Lactobacillus strains reached a final culture density (ΔOD) ≥ 0.50 after 24 h incubation at 32 °C, which was comparable to L. plantarum ATCC BAA 793. All strains produced lactic, acetic, and propionic acids, and all but three strains produced butyric acid. This study demonstrated that the ability to metabolize cranberry oligosaccharides is Lactobacillus strain specific, with some strains having the potential to be probiotics, and for the first time showed these ten strains were capable of growth on this carbon source. The novel cranberry pectic and arabino-xyloglucan oligosaccharide structures reported here combined with the Lactobacillus strains that can metabolize cranberry oligosaccharides and produce short-chain fatty acids, have excellent potential as health-promoting synbiotics.
Zusammenfassung. Die zunehmende Antibiotikaresistenz verleiht der Suche nach nicht-antibiotischen Alternativen zur Behandlung und Vorbeugung vor allem von Atemwegsinfektionen und Harnwegsinfektionen entscheidende Bedeutung. Potenzielle nicht-antibiotische Ansätze umfassen Phytopharmaka (Echinacea purpurea, Pelargonium sidoides, Cranberry-Extrakt), Zink, Immunstimulanzien (OM-85 BV, OM-89) sowie Verhaltensmodifikationen. Einige dieser Ansätze sind vielversprechende Optionen; allerdings ist hochgradige Evidenz erforderlich, bevor konkrete Empfehlungen für die Anwendung abgegeben werden können.
Purpose:
To assess patient reliance on various over-the-counter (OTC) modalities used for prevention of recurrent urinary tract infection (RUTI) after electrofulguration (EF).
Patients and methods:
Following IRB approval, qualifying women were offered a short survey over the phone by a medical researcher to collect information about their use of various OTC modalities for prophylaxis of RUTI. Data was compared between two cohorts, ≥70 years old and <70 years old, using chi-squared and Student's t-tests.
Results:
From a database of 324 patients, 163 accepted the interview. 17% (28/163) reported current use of cranberry supplements, 10% (16/163) D-mannose supplements, and 42% (69/163) another non-prescription modality for RUTI prophylaxis. The non-geriatric (<70 years old) cohort spent, on average, $80 less annually on cranberry/D-mannose supplements (P=0.043) than the geriatric cohort and were more likely to use non-prescription modalities for the prevention of UTI (52% vs 30%; P=0.0061). Individuals using D-mannose were also much more likely to purchase their product online compared to those using cranberry supplements (85% vs 56%). Across all modalities, the perceived benefit difference in reducing UTI/year ranged from a median of 0 for Pyridium® (phenazopyridine hydrochloride) to four for probiotics, with D-mannose and cranberry at two/year, and those increasing daily fluid consumption at 2.5 fewer UTI/year.
Conclusion:
Continued use of non-prescription modalities for RUTI prophylaxis were common among women with an EF history, but varied based on age groups. Across both age cohorts, annual expenditure and perceived benefit also varied among different OTC prophylactic modalities. Awareness of type and method of OTC modality implementation by patients with RUTI is essential to aligning use with current field recommendations.
Antimicrobial resistance (AMR) is a global health problem and requires urgent multisectoral action to achieve Sustainable Development Goals as mandated by United Nations by 2030. According to the World Health Organization (WHO), AMR is one of the top ten global public health threats to humanity, mostly due to misuse and overuse of antimicrobials. It is the main driver in the development of drug-resistant pathogens. The emergence of life-threatening drug-resistant pathogens particularly bacteria like methicillin-resistant Staphylococcus aureus (MRSA) and some fungi have become the greatest threat to public health and have rendered the treatment of their infections ineffective. To counter the antimicrobial-resistant microbes, the discovery of novel effective antimicrobials with a new mechanism of action is the need of the hour and this has forced researchers to look upon alternative antimicrobial agents from natural sources like plants. Phenols and phenolic acids can provide a promising alternative to drug-resistant antibiotics. Polyphenols are considered as secondary metabolites generated by higher plant groups. They play diverse role, and they are very effective as antioxidant, anti-allergic, anti-inflammatory, anticancer, and antimicrobial agents. Polyphenols constitute several varieties of molecules with different polyphenol structures. They are generally divided into two groups, flavonoids and nonflavonoids. The antimicrobial activity of polyphenols has been widely examined against a broad range of pathogens including virus, bacteria, and fungi. Several plants extract rich in polyphenolic components have displayed effective anti-quorum sensing capacity and are quite effective in suppressing biofilm formation and inhibiting toxin production. The synergistic approach of combining polyphenols and conventional antimicrobial agents like antibiotics can provide hope against neutralizing multidrug-resistant microorganisms.
Prevención, abordaje y manejo de bacteriuria asintomática e infección de vías urinarias
durante el embarazo.
Guía de Práctica Clínica: Evidencias y Recomendaciones.
México, CENETEC; 2021
Recurrent urinary tract infections are a common problem faced by clinicians across many specialities. For the patient, recurrent urinary tract infections can be burdensome and detrimental to their quality of life. For the clinician, they can be challenging to manage, and the socioeconomic burden on healthcare systems can also be substantial. Investigations serve to rule out any underlying structural or pathological abnormalities. In conjunction with behavioural prevention methods, treatment strategies include antibiotic and non-antibiotic approaches and holistic management approaches. This article provides an overview of the investigation and treatment of urinary tract infections and includes algorithms which can be used in daily clinical practice.
Objectives:
To discuss optimal management of recurrent urinary tract infections (UTIs) in women. About every second woman experiences at least one UTI in her lifetime, of those 30% experience another UTI, and 3% further recurrences. Especially young healthy women without underlying anatomical deficiencies suffer from recurrent UTIs (rUTI), which are associated with significant morbidity and reduction in quality of life.
Methods:
This is a narrative review, investigating publications dealing with recurrent UTI in women. Risk factors and options for management are discussed.
Results:
The increased susceptibility of women to rUTI is based on the female anatomy in addition to behavioural, genetic, and urological factors. However, why some women are more likely than others to develop and maintain rUTI remains to be clarified. Invasive characteristics of certain uropathogenic Escherichia coli that are able to form extra- and intracellular biofilms and may therefore cause delayed release of bacteria into the bladder, may play a role in this setting. Treatment recommendations for an acute episode of rUTI do not differ from those for isolated episodes. Given the nature of rUTI, different prophylactic approaches also play an important role. Women with rUTI should first be counselled to use non-antibiotic strategies including behavioural changes, anti-adhesive treatments, antiseptics, and immunomodulation, before antibiotic prophylaxis is considered. In addition to the traditional treatment and prophylactic therapies, new experimental strategies are emerging and show promising effects, such as faecal microbiota transfer (FMT), a treatment option that transfers microorganisms and metabolites of a healthy donor's faecal matter to patients using oral capsules, enemas, or endoscopy. Initial findings suggest that FMT might be a promising treatment approach to interrupt the cycle of rUTI. Furthermore, bacteriophages, infecting and replicating in bacteria, have been clinically trialled for UTIs.
Conclusion:
Due to the limitation of available data, novel treatment options require further clinical research to objectify the potential in treating bacterial infections, particularly UTIs.
Urinary tract infections are widespread throughout the world and occupy one of the leading places among infectious diseases. Antibacterial methods are the basis of modern treatment standards. At the same time, a widespread increase in antibiotic resistance of the main uropathogens is currently observed. In clinical practice, recurrent lower urinary tract infections are increasingly common. Following this, the main task of the doctor is to maximize the recurrence-free interval. Given the obvious negative collateral effect of long-term antibiotic prophylaxis, specialists are increasingly turning to alternative methods. Non-antibacterial preventive measures are aimed at key links in the pathogenesis of the disease, such as counteracting the penetration and adhesion of uropathogens, as well as stimulating the immune system of the macroorganism. The available physicians' toolkit includes pharmacological agents (d-mannose, methenamine hippurate, estrogens, non-steroidal anti-inflammatory drugs, probiotics, intravesical glycosaminoglycans, immunostimulants and vaccines), natural uroantiseptics (medicinal herbs and cranberry products), as well as behavioural therapy. The main advantages of non-antibacterial methods for the treatment and prevention of lower urinary tract infections are environmental friendliness. It is associated with the absence of a negative effect on the commensal flora, as well as a reduction in the risk of developing antibiotic resistance. The current guidelines provide very limited information on the application of this approach to treatment. Published studies indicate the high potential of non-antibacterial methods, some of which are comparable in effectiveness to standard therapy. However, the quality of studies and the lack of drug use standards do not allow including this approach in the existing guidelines. The need for new, high-quality clinical trials is evident.
In this paper, an A-type procyanidin (PACs)-rich cranberry extract (CB-B) was obtained mixing different extracts and was formulated with D-mannose and ascorbic acid to obtain a novel nutraceutical (URO-F) aimed at preventing non-complicated bacterial urinary tract infections (UTIs). To assess the bioactivity of CB-B and URO-F, urine samples collected from six healthy volunteers undergoing a 2-days oral consumption of 0.41 g/day of CB-B or 10 g/day of URO-F (corresponding to 72 mg/day of PACs) were tested against uropathogenic E. coli (UPEC) incubated on urinary bladder epithelial cells (T24). Urinary markers of CB-B and URO-F consumption were assessed in the same urine output by UPLC-QTOF-based untargeted metabolomics approach. CB-B and URO-F were evaluated for their ability to promote the intestinal barrier function by restoring the trans-epithelial electrical resistance (TEER) and to inhibit the production of inflammatory cytokines in intestinal epithelial Caco2 cells. CB-B was characterized by a high PAC-A content (70% of total PACs) and a broad distribution of different PACs polymers (dimers-hexamers). Urine from subjects consuming CB-B and URO-F showed a significant effect in reducing the adhesion of UPEC to urothelium in vitro, supporting their efficacy as anti-adhesive agents after oral intake. CB-B inhibited the release of cytokine IL-8, and both products were effective in restoring the TEER. Overall, our results show that the beneficial effects of CB-B and URO-F on UTIs are not only due to the antiadhesive activity of cranberry on UPEC in the urothelium, but also to a multi-target activity involving anti-inflammatory and permeability-enhancing effects on intestinal epithelium.
Abstract
Polysaccharides were extracted from seven plants endemic to Gabon to study their potential immunological activities. Peripheral blood mononuclear cell (PBMC) (5 × 105 cells/mL) proliferation, cytokine and immunoglobulin G (IgG) assays were performed after stimulation with different concentrations of polysaccharide fractions compared with lipopolysaccharides (LPS) and concanavalin A (ConA) from healthy volunteers. The culture supernatants were used for cytokine and IgG detection by enzyme-linked immunosorbent assay (ELISA). The results show that pectin and hemicellulose extracts from Uvaria klainei, Petersianthus macrocarpus, Trichoscypha addonii, Aphanocalyx microphyllus, Librevillea klaineana, Neochevalierodendron stephanii and Scorodophloeus zenkeri induced production levels that were variable from one individual to another for IL-12 (3–40 pg/mL), IL-10 (6–443 pg/mL), IL-6 (7–370 pg/mL), GM-CSF (3–170 pg/mL) and IFN-? (5–80 pg/mL). Only hemicelluloses from Aphanocalyx microphyllus produce a small amount of IgG (OD = 0.034), while the proliferation of cells stimulated with these polysaccharides increased up to 318% above the proliferation of unstimulated cells. However, this proliferation of PBMCs was abolished when the pectin of some of these plants was treated with endopolygalacturonase (p < 0.05), but the trend of cytokine synthesis remained the same, both before and after enzymatic treatment or saponification. This study suggests that these polysaccharides stimulate cells in a structure-dependent manner. The rhamnogalacturonan-I (RGI) fragment alone was not able to induce the proliferation of PBMC. This study confirms the immunostimulatory properties of polysaccharides.
Keywords: Pectins hemicelluloses cytokines IgG human PBMCs endemic plants Gabon
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.
Een urineweginfectie wordt gekenmerkt door infiltratie van bacteriën in de urinewegen, leidend tot specifieke symptomen bij de patiënt, zoals dysurie, mictiedrang, toegenomen mictiefrequentie of recent ontstane/verergerde urine-incontinentie.
Purpose of Review
In this review, we examine the current literature regarding the use of cranberry and other complimentary methods for the prevention of catheter-associated urinary tract infections (CAUTIs).
Recent Findings
Some studies have suggested cranberry products may have a positive effect in reducing the incidence of CAUTIs in patients with normal bladder function receiving short-term catheterization, while other studies have failed to show the benefits of cranberry products for the reduction of CAUTIs.
Summary
While there is some data suggesting cranberry-derived products may reduce CAUTIs in specific patient populations, there is currently overall insufficient clinical data to recommend broad usage of cranberry products for the reduction of CAUTIs. Many of the studies reviewed have significant limitations in size, design, and lack standardization.
The management of small, non-obstructing renal stones in adults with recurrent lower urinary tract infections remains unclear. Whereas for larger or obstructing stones the decision to intervene becomes clearer, for stones smaller than 5 to 6 mm the decision to intervene requires consideration of multiple factors. This review describes these factors, including history, imaging, laboratory studies, as well as a comprehensive review of the literature. It remains of utmost importance that patients have additional possible etiologies appropriately evaluated and managed prior to intervention for their small renal stones.
Urinary tract infections are highly prevalent and result in significant patient morbidity as well as large financial costs to healthcare systems. Recurrent urinary tract infections can be challenging for many healthcare professionals, and the repeated use of antibiotics in this patient cohort inevitably contributes to the growing issue of antimicrobial resistance and superbugs. It is essential that these patients are appropriately diagnosed and managed to ensure rapid resolution of symptoms and the prevention of chronic or recurrent urinary tract infections. There are several antibiotic-based options available for the prophylaxis of recurrent urinary tract infections however, in the current era of rising antimicrobial resistance, an awareness of antibiotic stewardship and the use of non-antibiotic alternatives for the treatment and prevention of urinary tract infections is of critical importance. We present a case-based multidisciplinary team discussion to highlight how women with recurrent urinary tract infections should be managed, encouraging the use of non-antibiotic prophylactic measures when suitable.
Level of evidence
Level 5
Due to the high cost of the cranberry extract, there have been several reported cases of adulteration. The aim of our study was to find markers to authenticate extracts or cranberry-based food supplements. Cranberry fruits from 7 countries, 17 cranberry extracts and 10 cranberry-based food supplements were analysed by UPLC-DAD-Orbitrap MS. Procyanidins were assessed by DMAC method. Anthocyanin fingerprint and epicatechin/catechin, procyanidin A2/total procyanidin and procyanidin/anthocyanin ratios were used as markers, and PCA carried out to check for similarity. Approximately 24% and 60% of the extracts and food supplements, respectively, differed significantly from the fruits. One seemed adulterated with Morus nigra and two with Hibiscus extract. Six food supplements were non-compliant and five contained mainly cyanidin-glucoside and cyanidin-rutinoside, suggesting adulteration with M. nigra extract. Only four products contained the procyanidin amount declared on the package, and only one provided the daily dose deemed effective for treating a urinary tract infection.
L’infection urinaire (IU) est un problème majeur de Santé publique. La cystite aiguë touchant principalement les femmes est la plus fréquente des IU. La bactérie la plus fréquemment isolée au cours de ces IU est Escherichia coli. Une des particularités de la cystite est sa propension à récidiver. Le traitement préconisé pour ces infections est la prise d’antibiotiques, qui peut être fréquente en cas de cystites récidivantes. C’est dans ce contexte que de nouvelles stratégies doivent être développées afin de prévenir et traiter les IU récidivantes. Parmi ces différentes stratégies, l’utilisation de produits naturels tels que la canneberge (Vaccinium macrocarpon) apparaît comme prometteuse. En effet, des études précédentes ont montré que la canneberge a un effet négatif sur l’adhésion des bactéries aux cellules superficielles de l’épithélium vésical facilitant l’élimination des bactéries par le flux urinaire. Cette activité est portée par la proanthocyanidine de type A (PAC-A). D’autre part, une étude menée par notre équipe a montré que l’effet de la canneberge sur l’adhésion et la virulence de souches d’E. coli uropathogènes pouvait être potentialisé par l’ajout d’un autre composé naturel : la propolis. Depuis l’Antiquité ses propriétés anti-bactériennes sont reconnues et des études plus récentes ont démontré son impact sur des bactéries à Gram positif mais également sur deux bactéries à Gram négatif : E. coli et Pseudomonas aeruginosa. Ce travail de thèse a permis : i) de décrire l’impact de la canneberge, de la propolis et de leur association sur le transcriptome d’une souche clinique d’E. coli uropathogène (G50). Cette analyse transcriptomique a montré que la canneberge entrainait une sous-expression de gènes liés à l’adhésion, mais également de gènes liés à la mobilité et à la formation de biofilm. En revanche, la canneberge augmentait l’expression des gènes liés au métabolisme du fer ainsi qu’à la réponse au stress. Ces effets étaient potentialisés par l’ajout de la propolis. En parallèle, des tests phénotypiques menés sur une collection de souches d’E. coli uropathogènes sur la mobilité et la formation de biofilm ont confirmé les résultats précédents ; ii) de développer un test, basé sur les précédents travaux de transcriptomique, permettant une évaluation standardisée de l’effet de la PAC-A sur E. coli, indépendamment de sa concentration car il n’existe pas de techniques standardisées pour doser cette molécule. C’est ainsi que 4 gènes (tsr, ftnA, fecB, feoB) ont été sélectionnés, le suivi de leur expression permettant une mesure de l’activité anti-bactérienne de la canneberge; iii) de mesurer l’effet potentialisateur de la propolis sur l’activité des antibiotiques utilisés dans le traitement des IU. C’est ainsi qu’il a été montré que l’ajout de la propolis permettait d’augmenter l’activité bactéricide des antibiotiques testés et de diminuer les concentrations minimales inhibitrices de ces antibiotiques.
Purpose
To evaluate the effect of cranberry extract (PAC-A ~ proanthocyanidin-A) on the in vitro bacterial properties of uropathogenic (E. coli) and its efficacy/tolerability in patients with subclinical or uncomplicated recurrent UTI (r-UTI).
Materials and methods
After obtaining clearance from the ethics committee and administering a written informed consent, 72 patients with r-UTI were enrolled as per protocol (November 2011 to March 2013) in this prospective study, to randomly receive (PAC-A: group I, 36) or (placebo: group II, 36), for 12 weeks. Any change/reduction in the incidence of r-UTI at 12 weeks was construed to be the primary endpoint of this study.
Results
After 12 weeks, bacterial adhesion scoring decreased (0.28)/(2.14) in group I/II (p < 0.001); 32/36 (88.8 %) and 2/36 (5.5 %) in groups I and II, respectively, turned MRHA negative (p < 0.001); biofilm (p < 0.01) and bacterial growth (p < 0.001) decreased in group I; microscopic pyuria score was 0.36/2.0 in group I/II (p < 0.001); r-UTI decreased to 33.33 versus 88.89 % in group I/II (p < 0.001); mean subjective dysuria score was 0.19 versus 1.47 in group I/II (p < 0.001), while mean urine pH was 5.88 versus 6.30 in group I/II (p < 0.001). No in vitro antibacterial activity of cranberry could be demonstrated, and no adverse events were noted.
Conclusions
The overall efficacy and tolerability of standardized cranberry extract containing (PAC-A) as a food supplement were superior to placebo in terms of reduced bacterial adhesion; bacterial MRHA negativity; urine pH reduction; and in preventing r-UTI (dysuria, bacteriuria and pyuria). Larger randomized controlled trials are needed to elucidate the precise role, exact dose and optimal duration of PAC-A therapy in patients at risk of r-UTI.
Background:
Urinary tract infections (UTIs) are among the most common bacterial infections and are often treated with antibiotics. Concerns about multidrug-resistant uropathogens have pointed to the need for safe and effective UTI-prevention strategies such as cranberry consumption.
Objective:
We assessed the effects of the consumption of a cranberry beverage on episodes of clinical UTIs.
Design:
In this randomized, double-blind, placebo-controlled, multicenter clinical trial, women with a history of a recent UTI were assigned to consume one 240-mL serving of cranberry beverage/d (n = 185) or a placebo (n = 188) beverage for 24 wk. The primary outcome was the clinical UTI incidence density, which was defined as the total number of clinical UTI events (including multiple events per subject when applicable) per unit of observation time.
Results:
The dates of the random assignment of the first subject and the last subject's final visit were February 2013 and March 2015, respectively. The mean age was 40.9 y, and characteristics were similar in both groups. Compliance with study product consumption was 98%, and 86% of subjects completed the treatment period in both groups. There were 39 investigator-diagnosed episodes of clinical UTI in the cranberry group compared with 67 episodes in the placebo group (antibiotic use-adjusted incidence rate ratio: 0.61; 95% CI: 0.41, 0.91; P = 0.016). Clinical UTI with pyuria was also significantly reduced (incidence rate ratio: 0.63; 95% CI: 0.40, 0.97; P = 0.037). One clinical UTI event was prevented for every 3.2 woman-years (95% CI: 2.0, 13.1 woman-years) of the cranberry intervention. The time to UTI with culture positivity did not differ significantly between groups (HR: 0.97; 95% CI: 0.56, 1.67; P = 0.914).
Conclusion:
The consumption of a cranberry juice beverage lowered the number of clinical UTI episodes in women with a recent history of UTI. This study was registered at clinicaltrials.gov as NCT01776021.
Most research on American cranberry in the prevention of urinary tract infection (UTI) has used juices. The spectrum of components in juice is limited. This study tested whether whole cranberry fruit powder (proanthocyanidin content 0.56%) could prevent recurrent UTI in 182 women with two or more UTI episodes in the last year. Participants were randomized to a cranberry (n = 89) or a placebo group (n = 93) and received daily 500 mg of cranberry for 6 months. The number of UTI diagnoses was counted. The intent-to-treat analyses showed that in the cranberry group, the UTIs were significantly fewer [10.8% vs. 25.8%, p = 0.04, with an age-standardized 12-month UTI history (p = 0.01)]. The Kaplan-Meier survival curves showed that the cranberry group experienced a longer time to first UTI than the placebo group (p = 0.04). Biochemical parameters were normal, and there was no significant difference in urinary phenolics between the groups at baseline or on day180. The results show that cranberry fruit powder (peel, seeds, pulp) may reduce the risk of symptomatic UTI in women with a history of recurrent UTIs. Copyright © 2015 John Wiley & Sons, Ltd.
Copyright © 2015 John Wiley & Sons, Ltd.
Cranberry extracts have been tested as a nutritional supplementation in the prevention of recurrent lower-urinary tract infections (R-UTIs), with mixed results. This pilot, registry study evaluates the prophylactic effects of oral supplementation with a new well-standardized cranberry extract in patients with R-UTI, over a 2-month follow-up.
All subjects were suggested to take one capsule containing a cranberry extract (AnthocranTM) for 60 days and were also given lifestyle advice. Clinical outcomes were compared between patients on cranberry extracts and those who don't take this supplementation.
In total, 22 subjects completed the study in each of the two groups. In the cranberry group, the reduction in the frequency of UTI episodes during the study period compared with the two months before the inclusion was 73.3% (p < 0.05). This figure was 15.4% in the control group (p < 0.05; p = 0.012 vs cranberry group). Seven (31.8%) subjects in the cranberry group were symptom-free; no patient was symptom-free in the control group (p < 0.05). The mean duration of UTI episodes was 2.5±1.3 days in the cranberry group, compared with 3.6±1.7 days in subjects not on cranberry (p < 0.05). Three subjects (13.6%) in the cranberry group and 8 (36.3%) in the control group required medical consultation for UTI symptoms (p < 0.05). Urine evaluation was completely negative in 20/22 subjects in the Cranberry group (90.9%) and in 11 control subjects (50.0%; p < 0.005). No adverse events were observed.
These preliminary results, obtained in a field-practice setting, indicates the effectiveness and safety of a well-standardized cranberry extract in the prevention of R-UTI.
Objectives: To determine whether cranberry capsules prevent urinary tract infection (UTI) in long-term care facility (LTCF) residents.
Design: Double-blind randomized placebo-controlled multicenter trial.
Setting: Long-term care facilities (LTCFs).
Participants: LTCF residents (N = 928; 703 women, median age 84).
Measurements: Cranberry and placebo capsules were taken twice daily for 12 months. Participants were stratified according to UTI risk (risk factors included long-term catheterization, diabetes mellitus, ≥1 UTI in preceding year). Main outcomes were incidence of UTI according to a clinical definition and a strict definition.
Results: In participants with high UTI risk at baseline (n = 516), the incidence of clinically defined UTI was lower with cranberry capsules than with placebo (62.8 vs 84.8 per 100 person-years at risk, P = .04); the treatment effect was 0.74 (95% confidence interval (CI) = 0.57–0.97). For the strict definition, the treatment effect was 1.02 (95% CI = 0.68–1.55). No difference in UTI incidence between cranberry and placebo was found in participants with low UTI risk (n = 412).
Conclusion: In LTCF residents with high UTI risk at baseline, taking cranberry capsules twice daily reduces the incidence of clinically defined UTI, although it does not reduce the incidence of strictly defined UTI. No difference in incidence of UTI was found in residents with low UTI risk.
Cranberries have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). This is the third update of our review first published in 1998 and updated in 2004 and 2008.
To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations.
Search methods: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library) and the Internet. We contacted companies involved with the promotion and distribution of cranberry preparations and checked reference lists of review articles and relevant studies. Date of search: July 2012. Selection criteria: All randomised controlled trials (RCTs) or quasi-RCTs of cranberry products for the prevention of UTIs. Data collection and analysis: Two authors independently assessed and extracted data. Information was collected on methods, participants, interventions and outcomes (incidence of symptomatic UTIs, positive culture results, side effects, adherence to therapy). Risk ratios (RR) were calculated where appropriate, otherwise a narrative synthesis was undertaken. Quality was assessed using the Cochrane risk of bias assessment tool.
This updated review includes a total of 24 studies (six cross-over studies, 11 parallel group studies with two arms; five with three arms, and two studies with a factorial design) with a total of 4473 participants. Ten studies were included in the 2008 update, and 14 studies have been added to this update. Thirteen studies (2380 participants) evaluated only cranberry juice/concentrate; nine studies (1032 participants) evaluated only cranberry tablets/capsules; one study compared cranberry juice and tablets; and one study compared cranberry capsules and tablets. The comparison/control arms were placebo, no treatment, water, methenamine hippurate, antibiotics, or lactobacillus. Eleven studies were not included in the meta-analyses because either the design was a cross-over study and data were not reported separately for the first phase, or there was a lack of relevant data. Data included in the meta-analyses showed that, compared with placebo, water or not treatment, cranberry products did not significantly reduce the occurrence of symptomatic UTI overall (RR 0.86, 95% CI 0.71 to 1.04) or for any the subgroups: women with recurrent UTIs (RR 0.74, 95% CI 0.42 to 1.31); older people (RR 0.75, 95% CI 0.39 to 1.44); pregnant women (RR 1.04, 95% CI 0.97 to 1.17); children with recurrent UTI (RR 0.48, 95% CI 0.19 to 1.22); cancer patients (RR 1.15 95% CI 0.75 to 1.77); or people with neuropathic bladder or spinal injury (RR 0.95, 95% CI: 0.75 to 1.20). Overall heterogeneity was moderate (I² = 55%). The effectiveness of cranberry was not significantly different to antibiotics for women (RR 1.31, 95% CI 0.85, 2.02) and children (RR 0.69 95% CI 0.32 to 1.51). There was no significant difference between gastrointestinal adverse effects from cranberry product compared to those of placebo/no treatment (RR 0.83, 95% CI 0.31 to 2.27). Many studies reported low compliance and high withdrawal/dropout problems which they attributed to palatability/acceptability of the products, primarily the cranberry juice. Most studies of other cranberry products (tablets and capsules) did not report how much of the 'active' ingredient the product contained, and therefore the products may not have had enough potency to be effective.
Prior to the current update it appeared there was some evidence that cranberry juice may decrease the number of symptomatic UTIs over a 12 month period, particularly for women with recurrent UTIs. The addition of 14 further studies suggests that cranberry juice is less effective than previously indicated. Although some of small studies demonstrated a small benefit for women with recurrent UTIs, there were no statistically significant differences when the results of a much larger study were included. Cranberry products were not significantly different to antibiotics for preventing UTIs in three small studies. Given the large number of dropouts/withdrawals from studies (mainly attributed to the acceptability of consuming cranberry products particularly juice, over long periods), and the evidence that the benefit for preventing UTI is small, cranberry juice cannot currently be recommended for the prevention of UTIs. Other preparations (such as powders) need to be quantified using standardised methods to ensure the potency, and contain enough of the 'active' ingredient, before being evaluated in clinical studies or recommended for use.
Recent observational and clinical studies have raised interest in the potential health effects of cranberry consumption, an association that appears to be due to the phytochemical content of this fruit. The profile of cranberry bioactives is distinct from that of other berry fruit, being rich in A-type proanthocyanidins (PACs) in contrast to the B-type PACs present in most other fruit. Basic research has suggested a number of potential mechanisms of action of cranberry bioactives, although further molecular studies are necessary. Human studies on the health effects of cranberry products have focused principally on urinary tract and cardiovascular health, with some attention also directed to oral health and gastrointestinal epithelia. Evidence suggesting that cranberries may decrease the recurrence of urinary tract infections is important because a nutritional approach to this condition could lower the use of antibiotic treatment and the consequent development of resistance to these drugs. There is encouraging, but limited, evidence of a cardioprotective effect of cranberries mediated via actions on antioxidant capacity and lipoprotein profiles. The mixed outcomes from clinical studies with cranberry products could result from interventions testing a variety of products, often uncharacterized in their composition of bioactives, using different doses and regimens, as well as the absence of a biomarker for compliance to the protocol. Daily consumption of a variety of fruit is necessary to achieve a healthy dietary pattern, meet recommendations for micronutrient intake, and promote the intake of a diversity of phytochemicals. Berry fruit, including cranberries, represent a rich source of phenolic bioactives that may contribute to human health.
Urinary tract infections (UTIs) are one of the most common bacterial infections, and over 50% of women will have a UTI during their lifetimes. Antibiotics are used for prophylaxis of recurrent UTIs but can lead to emergence of drug-resistant bacteria. Therefore, it is reasonable to investigate nutritional strategies for prevention of UTIs. Cranberry juices and supplements have been used for UTI prophylaxis, but with variable efficacy. Because dried cranberries may contain a different spectrum of polyphenolics than juice, consuming berries may or may not be more beneficial than juice in decreasing the incidence of UTIs in susceptible women. The primary objectives of this study were to determine if consumption of sweetened, dried cranberries (SDC) decreases recurrent UTIs and whether this intervention would alter the heterogeneity, virulence factor (VF) profiles, or numbers of intestinal E. coli.
Twenty women with recurrent UTIs were enrolled in the trial and consumed one serving of SDC daily for two weeks. Clinical efficacy was determined by two criteria, a decrease in the six-month UTI rates pre- and post-consumption and increased time until the first UTI since beginning the study. Strain heterogeneity and virulence factor profiles of intestinal E. coli isolated from rectal swabs were determined by DNA fingerprinting and muliplex PCR, respectively. The numbers of intestinal E. coli eluted from rectal swabs pre- and post-consumption were also quantified.
Over one-half of the patients did not experience a UTI within six months of SDC consumption, and the mean UTI rate per six months decreased significantly. Kaplan-Meier analysis of infection incidence in women consuming SDC compared to patients in a previous control group showed a significant reduction in time until first UTI within six months. The heterogeneity, VF profiles, and prevalence of intestinal E. coli strains were not significantly different after cranberry consumption.
Results of this study indicate a beneficial effect from consuming SDC to reduce the number of UTIs in susceptible women. Because there were no changes in the heterogeneity or VF profiles of E. coli, additional studies are needed to determine the mechanism of action of SDC for reduction of UTIs.
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.
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.
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.
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.
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.
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.
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 (I(2) = 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) (I(2) = 0%), female populations (RR, 0.49; 95% CI, 0.34-0.73) (I(2) = 34%), children (RR, 0.33; 95% CI, 0.16-0.69) (I(2) = 0%), cranberry juice drinkers (RR, 0.47; 95% CI, 0.30-0.72) (I(2) = 2%), and subjects using cranberry-containing products more than twice daily (RR, 0.58; 95% CI, 0.40-0.84) (I(2) = 18%).
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.
Cranberry juice prevents recurrences of urinary tract infections (UTIs) in adult women. The objective of this study was to evaluate whether cranberry juice is effective in preventing UTI recurrences in children.
A double-blind randomized placebo-controlled trial was performed in 7 hospitals in Finland. A total of 263 children treated for UTI were randomized to receive either cranberry juice (n = 129) or placebo (n = 134) for 6 months. Eight children were omitted because of protocol violations, leaving 255 children for the final analyses. The children were monitored for 1 year, and their recurrent UTIs were recorded.
Twenty children (16%) in the cranberry group and 28 (22%) in the placebo group had at least 1 recurrent UTI (difference, -6%; 95% confidence interval [CI], -16 to 4%; P = .21). There were no differences in timing between these first recurrences (P = .32). Episodes of UTI totaled 27 and 47 in the cranberry and placebo groups, respectively, and the UTI incidence density per person-year at risk was 0.16 episodes lower in the cranberry group (95% CI, -.31 to -.01; P = .035). The children in the cranberry group had significantly fewer days on antimicrobials (-6 days per patient-year; 95% CI, -7 to -5; P < .001).
The intervention did not significantly reduce the number of children who experienced a recurrence of UTI, but it was effective in reducing the actual number of recurrences and related antimicrobial use.
This study compares the effects of daily cranberry juice to those of Lactobacillus in children with recurrent urinary tract infections (UTIs).
Eighty-four girls aged between 3 and 14 years were randomized to cranberry, Lactobacillus or control in three treatment arms: G1, cranberry juice 50 ml daily (n=28); G2, 100 ml of Lactobacillus GG drink on 5 days a month (n=27); and G3, controls (n=29). The study lasted for 6 months.
Only four subjects withdrew: 1/28 (3.5%) from G1, 1/27 (3.7%) from G2 and 2/29 (6.8%) from G3, because of poor compliance to the established protocol. There were 34 episodes of UTIs in this cohort: 5/27 (18.5%) in G1, 11/26 (42.3%) in G2 and 18/27 (48.1%) in the G3, with at least one episode of infection (p<0.05).
These data suggest that daily consumption of concentrated cranberry juice can significantly prevent the recurrence of symptomatic UTIs in children.
To determine whether recurrences of urinary tract infection can be prevented with cranberry-lingonberry juice or with Lactobacillus GG drink. Design: Open, randomised controlled 12 month follow up trial.
Health centres for university students and staff of university hospital.
150 women with urinary tract infection caused by Escherichia coli randomly allocated into three groups. Interventions: 50 ml of cranberry-lingonberry juice concentrate daily for six months or 100 ml of lactobacillus drink five days a week for one year, or no intervention. Main outcome measure: First recurrence of symptomatic urinary tract infection, defined as bacterial growth >/=10(5 )colony forming units/ml in a clean voided midstream urine specimen.
The cumulative rate of first recurrence of urinary tract infection during the 12 month follow up differed significantly between the groups (P=0.048). At six months, eight (16%) women in the cranberry group, 19 (39%) in the lactobacillus group, and 18 (36%) in the control group had had at least one recurrence. This is a 20% reduction in absolute risk in the cranberry group compared with the control group (95% confidence interval 3% to 36%, P=0.023, number needed to treat=5, 95% confidence interval 3 to 34).
Regular drinking of cranberry juice but not lactobacillus seems to reduce the recurrence of urinary tract infection.
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.
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.
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%) (p<0.05). 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.
Cranberry tablets provided the most cost-effective prevention for UTI.
To determine whether antibacterial effects of cranberry extract will reduce or eliminate bacteriuria and pyuria in persons with spinal cord injury (SCI).
Randomized, double-blind, placebo-controlled study.
Participants were people with SCI residing in the community who were 1 year or longer postinjury with neurogenic bladder managed by intermittent catheterization or external collection device and a baseline urine culture demonstrating at least 10(5) colonies per milliliter of bacteria.
Each participant ingested 2 g of concentrated cranberry juice or placebo in capsule form daily for 6 months. Baseline urinalysis and cultures were performed at the time of the initial clinic visit and monthly for 6 months. Microbiologic data were evaluated using analysis of variance with repeated measures.
Twenty-six persons received cranberry extract and 22 persons received placebo. There were no differences or trends detected between participants and controls with respect to number of urine specimens with bacterial counts of at least 10(4) colonies per milliliter, types and numbers of different bacterial species, numbers of urinary leukocytes, urinary pH, or episodes of symptomatic urinary tract infection.
Cranberry extract taken in capsule form did not reduce bacteriuria and pyuria in persons with SCI and cannot be recommended as a means to treat these conditions.
cranberry juice is often given to older people in hospital to prevent urinary tract infection (UTI), although there is little evidence to support its use.
to assess whether cranberry juice ingestion is effective in reducing UTIs in older people in hospital.
randomised, placebo-controlled, double-blind trial.
Medicine for the Elderly assessment and rehabilitation hospital wards.
376 older patients in hospital.
participants were randomised to daily ingestion of 300 ml of cranberry juice or matching placebo beverage. The primary outcome was time to onset of first UTI. Secondary outcomes were adherence to beverage drinking, courses of antibiotics prescribed, and organisms responsible for UTIs.
a total of 21/376 (5.6%) participants developed a symptomatic UTI: 14/189 in the placebo group and 7/187 in the cranberry juice group. These between-group differences were not significant, relative risk (RR) 0.51 [95% CI 0.21-1.22, P = 0.122). Although there were significantly fewer infections with Escherichia coli in the cranberry group (13 versus 4) RR 0.31 [95% CI 0.10-0.94, P = 0.027], this should be interpreted with caution as it was a secondary outcome.
despite having the largest sample size of any clinical trial yet to have examined the effect of cranberry juice ingestion, the actual infection rate observed was lower than anticipated, making the study underpowered. This study has confirmed the acceptability of cranberry juice to older people. Larger trials are now required to determine whether it is effective in reducing UTIs in older hospital patients.
To determine whether Methenamine Hippurate (MH) or cranberry tablets prevent urinary tract infections (UTI) in people with neuropathic bladder following spinal cord injury (SCI).
Double-blind factorial-design randomized controlled trial (RCT) with 2 year recruitment period from November 2000 and 6 month follow-up.
In total, 543 eligible predominantly community dwelling patients were invited to participate in the study, of whom 305 (56%) agreed.
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.
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).
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.
Urinary tract infections are one of the most common bacterial infectious diseases. Depending on the localization and the symptoms of the illness, various clinical pictures (lower urinary tract infection, pyelonephritis, asymptomatic bacteriuria) can be differentiated. The manifestation and the course of the infection are determined by pathogenic properties and by different virulence factors of the microorganisms as well as the defense mechanisms of the host. The process of bacterial attachment to the uroepithelial cells in the urinary tract, the internalization of the microorganism within these cells and invasiveness of the bacteria are decisive for the acute and chronic disease. The diagnosis is made by microbiological analysis of the urine. Additional laboratory as well as ultrasound findings are helpful for treatment decision. There are different treatment strategies for acute complicated and uncomplicated infections as well as for chronic disease and asymptomatic bacteriuria. Further investigations on the host-pathogen interactions are neccessary to develop evidence based recommandation for high risk patients with kidney transplantation, diabetes mellitus, during pregnancy and in the elderly.
The risk of urinary tract infection (UTI) among women undergoing elective gynecologic surgery where a catheter is placed is high: 10 to 64% following catheter removal. We conducted the first randomized, double-blind, placebo-controlled trial of the therapeutic efficacy of cranberry juice capsules in preventing UTI post surgery.
We recruited patients from a single hospital between August 2011 and January 2013. Eligible participants were undergoing elective gynecologic surgery that did not involve a fistula repair or vaginal mesh removal. 160 patients were randomized and received two cranberry juice capsules two times a day, equivalent to two 8-ounce servings of cranberry juice, for 6 weeks after surgery, or matching placebo. The primary endpoint was time from randomization to clinically-diagnosed and treated UTI with or without positive urine culture. Kaplan-Meier plots and logrank tests compared the two treatment groups.
The occurrence of UTI was significantly lower in the cranberry treatment group compared to the placebo group (15/80 (19%) versus 30/80 (38%); OR=0.38; 95% CI: 0.19, 0.79; p=0.008). After adjustment for known confounders, including frequency of intermittent self-catheterization in the post- operative period, the protective effects of cranberry remained (OR=0.42; 95% CI: 0.18, 0.94). There were no treatment differences in the incidence of adverse events; including gastrointestinal upset (56% vs. 61% for cranberry vs. placebo).
Among women undergoing elective benign gynecologic surgery involving urinary catheterization, use of cranberry extract tablets during the postoperative period reduced the rate of UTI by half.
Copyright © 2015 Elsevier Inc. All rights reserved.
Increasing antimicrobial resistance has stimulated interest in non-antibiotic prophylaxis of recurrent urinary tract infections (UTIs). We assessed effectiveness, tolerability and safety of non-antibiotic prophylaxis in adults with recurrent UTIs.
MEDLINE, EMBASE, the Cochrane Library and reference lists of relevant reviews were searched to April 2013 for relevant English language citations. Two reviewers selected randomized controlled trials that met the predefined criteria for population, interventions and outcomes. The difference in the proportions of patients with at least one UTI was calculated for individual studies and pooled risk ratios (RR) were calculated using random and fixed effects models. Adverse event rates were also extracted. The Jadad-score was used to assess risk of bias (0-2 "high risk"; 3-5 "low risk").
We identified 4,834 records and included 17 studies with data for 2,165 patients. The oral immunostimulant OM-89 reduced UTI recurrence (4 trials; n= 891; median Jadad-score 3; RR=0.61, 95%CI 0.48-0.78) and had a good safety profile. The vaginal vaccine Urovac slightly reduced UTI recurrence (3 trials; n=220; Jadad-score 3; RR 0.81, 95%CI 0.68-0.96), and primary immunization followed by booster immunization increased time to re-infection. Vaginal estrogens showed a trend toward preventing UTI recurrences (2 trials; n=201; Jadad-score 2.5; RR=0.42, 95%CI 0.16-1.10), but vaginal irritation occurred in 6 to 20% of women. Cranberries decreased UTI recurrence (2 trials; n=250, Jadad-score 4; RR 0.53, 95%CI 0.33-0.83). Acupuncture reduced recurrences (2 open-label trials; n=165; Jadad-score 2; RR 0.48, 95%CI 0.29-0.79). Oral estrogens and lactobacilli prophylaxis did not decrease UTI recurrence.
The evidence for the effectiveness of the oral immunostimulant, OM-89, is promising. Pooled findings for the other interventions, although sometimes statistically significant, should be considered tentative until corroborated by more research. Large head-to-head trials should be performed to optimally inform clinical decision-making.
Recurrent urinary tract infections (UTIs) increase mortality and reduce graft survival after renal transplantation. Strategies to prevent recurrent UTIs include L-methionine, cranberry juice, and antibiotics. Data on the efficacy of cranberry and L-methionine, however, are controversial in the general population; there are few data in renal transplant recipients.
We performed a retrospective analysis of 82 transplant recipients with recurrent UTIs, who underwent prophylaxis with cranberry juice (2 × 50 mL/d, n = 39, 47.6%), or L-methionine (3 × 500 mg/d, n = 25, 30.5%), or both modalities (n = 18, 21.9%). Thirty patients without prophylaxis served as controls. We analyzed symptoms, pyuria/nitrituria, and incidence of UTI events during 1 year before versus after initiation of prophylaxis.
Prophylaxis highly significantly decreased the annual UTI incidence by 58.3% (P < .001) in the study population with no change in the control group (P = .85); in addition, 53.7% of symptomatic patients reported relief of symptoms and pyuria/nitrituria disappeared in 42.4% of the dipstick-positive patients (P < .001 each). Cranberry reduced the annual number of UTI episodes by 63.9% from 3.6 ± 1.4 to 1.3 ± 1.3/year (P < .001) and L-methionine by 48.7% from 3.9 ± 1.8 to 2.0 ± 1.3/year (P < .001).
Cranberry juice and L-methionine successfully reduced the incidence of UTI after renal transplantation.
: Cranberry cocktail has been reported to reduce bacteriuria and pyuria in elderly women and self-reported urinary tract infection (UTI) in young female undergraduates, but commercially prepared cranberry concentrate supplements have never been evaluated in multiple sclerosis (MS) patients with neurogenic bladder. The purpose of this study was to determine whether one 8,000-mg cranberry concentrate supplement daily could prevent UTI in MS participants with bladder symptoms. We conducted a double-blind, randomized, placebo-controlled longitudinal trial of cranberry supplement versus placebo with participants who have MS. After informed consent had been obtained from the participants, baseline data were collected and participants were randomized to receive either one cranberry supplement or placebo daily for 6 months. The sample consisted of 135 participants. In the cranberry group 34.6% of participants failed (i.e., developed a UTI) versus 32.4% in the control group (p = .849). Not all cranberry supplements have been found to contain proanthocyanidins, the active ingredient of cranberries. Because there is no way for the consumer to distinguish supplements that contain proanthocyanidins from those that do not, taking juice or whole cranberries may be preferable.
(C) 2002 American Association of Neuroscience Nurses
We examined the rate of relapse, as a variable index, in patients with urinary tract infection (UTI) who suffered from multiple relapses when using cranberry juice (UR65). A randomized, placebo-controlled, double-blind study was conducted from October 2007 to September 2009 in Japan. The subjects were outpatients aged 20 to 79 years who were randomly divided into two groups. One group received cranberry juice (group A) and the other a placebo beverage (group P). To keep the conditions blind, the color and taste of the beverages were adjusted. The subjects drank 1 bottle (125 mL) of cranberry juice or the placebo beverage once daily, before going to sleep, for 24 weeks. The primary endpoint was relapse of UTI. In the group of females aged 50 years or more, there was a significant difference in the rate of relapse of UTI between groups A and P (log-rank test; p = 0.0425). In this subgroup analysis, relapse of UTI was observed in 16 of 55 (29.1 %) patients in group A and 31 of 63 (49.2 %) in group P. In this study, cranberry juice prevented the recurrence of UTI in a limited female population with 24-week intake of the beverage.
Proanthocyanidins found in cranberry have been reported to have in vitro and in vivo antibacterial activity. We determined the effectiveness of cranberry juice for the prevention of urinary tract infections in children.
A total of 40 children were randomized to receive daily cranberry juice with high concentrations of proanthocyanidin vs cranberry juice with no proanthocyanidin for a 1-year period. The study was powered to detect a 30% decrease in the rate of symptomatic urinary tract infection with type I and II errors of 0.05 and 0.2, respectively. Toilet trained children up to age 18 years were eligible if they had at least 2 culture documented nonfebrile urinary tract infections in the calendar year before enrollment. Patients with anatomical abnormalities (except for primary vesicoureteral reflux) were excluded from study. Subjects were followed for 12 months. The participants, clinicians, outcome assessor and statistician were all blinded to treatment allocation.
Of the children 39 girls and 1 boy were recruited. Mean and median patient age was 9.5 and 7 years, respectively (range 5 to 18). There were 20 patients with comparable baseline characteristics randomized to each group. After 12 months of followup the average incidence of urinary tract infection in the treatment group was 0.4 per patient per year and 1.15 in the placebo group (p = 0.045), representing a 65% reduction in the risk of urinary tract infection.
Cranberry juice with high concentrations of proanthocyanidin appears to be effective in the prevention of pediatric nonfebrile urinary tract infections. Further studies are required to determine the cost-effectiveness of this approach.
Radical pelvic radiotherapy is one of the main treatment modalities for cancers of the bladder and cervix. The side-effects of pelvic radiotherapy include urinary symptoms, such as urinary frequency and cystitis. The therapeutic effects of cranberry juice in the prevention and treatment of urinary tract infections in general are well documented. The purpose of this study was to evaluate the effectiveness of cranberry juice on the incidence of urinary tract infections and urinary symptoms in patients undergoing pelvic radiotherapy for cancer of the bladder or cervix.
The study was a placebo-controlled, double-blind design. Participants were randomised to receive cranberry juice, twice a day (morning and night) for the duration of their radiotherapy treatment and for 2 weeks after treatment (6 weeks in total) or a placebo beverage, for the same duration.
The incidence of increased urinary symptoms or urinary tract infections was 82.5% on cranberry and 89.3% on placebo (P=0.240, adjusted odds ratio [cranberry/placebo] 0.48, 95% confidence interval 0.14-1.63).
The power of the study to detect differences was limited by the below target sample size and poor compliance. Further research is recommended, taking cognisance of the factors contributing to the limitations of this study.
A number of observational studies and a few small or open randomized clinical trials suggest that the American cranberry may decrease incidence of recurring urinary tract infection (UTI).
We conducted a double-blind, placebo-controlled trial of the effects of cranberry on risk of recurring UTI among 319 college women presenting with an acute UTI. Participants were followed up until a second UTI or for 6 months, whichever came first. A UTI was defined on the basis of the combination of symptoms and a urine culture positive for a known uropathogen. The study was designed to detect a 2-fold difference between treated and placebo groups, as was detected in unblinded trials. We assumed 30% of participants would experience a UTI during the follow-up period.
Overall, the recurrence rate was 16.9% (95% confidence interval, 12.8%-21.0%), and the distribution of the recurrences was similar between study groups, with the active cranberry group presenting a slightly higher recurrence rate (20.0% vs 14.0%). The presence of urinary symptoms at 3 days, 1-2 weeks, and at ≥ 1 month was similar between study groups, with overall no marked differences. CONCLUSIONS.: Among otherwise healthy college women with an acute UTI, those drinking 8 oz of 27% cranberry juice twice daily did not experience a decrease in the 6-month incidence of a second UTI, compared with those drinking a placebo.
We compared the effects of daily cranberry juice cocktail to those of placebo during pregnancy on asymptomatic bacteriuria and symptomatic urinary tract infections.
A total of 188 women were randomized to cranberry or placebo in 3 treatment arms of A-cranberry 3 times daily (58), B-cranberry at breakfast then placebo at lunch and dinner (67), and C-placebo 3 times daily (63). After 27.7% (52 of 188) of the subjects were enrolled in the study the dosing regimens were changed to twice daily dosing to improve compliance.
There were 27 urinary tract infections in 18 subjects in this cohort, with 6 in 4 group A subjects, 10 in 7 group B subjects and 11 in 7 group C subjects (p = 0.71). There was a 57% and 41% reduction in the frequency of asymptomatic bacteriuria and all urinary tract infections, respectively, in the multiple daily dosing group. However, this study was not sufficiently powered at the alpha 0.05 level (CI 0.14-1.39 and 0.22-1.60, respectively, incidence rate ratios). Of 188 subjects 73 (38.8%) withdrew, most for gastrointestinal upset.
These data suggest there may be a protective effect of cranberry ingestion against asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy. Further studies are planned to evaluate this effect.
To determine the effect of cranberry prophylaxis on rates of bacteriuria and symptomatic urinary tract infection in children with neurogenic bladder receiving clean intermittent catheterization.
Double-blind, placebo-controlled, crossover study of 15 children receiving cranberry concentrate or placebo concentrate for 6 months (3 months receiving one concentrate, followed by 3 months of the other). Weekly home visits were made. During each visit, a sample of bladder urine was obtained by intermittent catheterization. Signs and symptoms of urinary tract infection and all medications were recorded, and juice containers were counted.
During consumption of cranberry concentrate, the frequency of bacteriuria remained high. Cultures of 75% (114 of 151) of the 151 samples obtained during consumption of placebo were positive for a pathogen (>/=10(4) colony-forming units/mL) compared with 75% (120 of 160) of the 160 samples obtained during consumption of cranberry concentrate. Escherichia coli remained the most common pathogen during placebo and cranberry periods. Three symptomatic infections each occurred during the placebo and cranberry periods. No significant difference was observed in the acidification of urine in the placebo group versus the cranberry group (median, 5.5 and 6.0, respectively).
The frequency of bacteriuria in patients with neurogenic bladder receiving intermittent catheterization is 70%; cranberry concentrate had no effect on bacteriuria in this population.
Randomized, double blind, placebo-controlled trial with a crossover design.
To evaluate cranberry tablets for the prevention of urinary tract infection (UTI) in spinal cord injured (SCI) patients.
Spinal Cord Injury Unit of a Veterans Administration Hospital, MA, USA.
Subjects with spinal cord injury and documentation of neurogenic bladder were randomized to receive 6 months of cranberry extract tablet or placebo, followed by the alternate preparation for an additional 6 months. The primary outcome was the incidence of UTI.
Forty-seven subjects completed the trial. We found a reduction in the likelihood of UTI and symptoms for any month while receiving the cranberry tablet (P<0.05 for all). During the cranberry period, 6 subjects had 7 UTI, compared with 16 subjects and 21 UTI in the placebo period (P<0.05 for both number of subjects and incidence). The frequency of UTI was reduced to 0.3 UTI per year vs 1.0 UTI per year while receiving placebo. Subjects with a glomerular filtration rate (GFR) greater than 75 ml min(-1) received the most benefit.
Cranberry extract tablets should be considered for the prevention of UTI in SCI patients with neurogenic bladder. Patients with a high GFR may receive the most benefit.
Spinal Cord Research Foundation, sponsored by the Paralyzed Veterans of America.
Cranberry supplementation in the prevention of non-severe lower urinary tract infections: a pilot study
- Ledda
Ledda A, Bottari A, Luzzi R et al: Cranberry
supplementation in the prevention of non-severe
lower urinary tract infections: a pilot study. Eur
Rev Med Pharmacol Sci 2015; 19: 77.
Spinal-injured neuropathic bladder antisepsis (SINBA) trial
- Lee