Introduction and Hypothesis: Urinary tract infections (UTIs) are a common medical problem and prophylaxis of recurrent UTIs is an ongoing clinical challenge. In the present study we examined whether acupuncture is able to prevent recurrent UTIs in women. 

Methods: This multicentre randomised controlled trial, based at a University clinic and private acupuncture clinics, recruited women suffering from recurrent uncomplicated UTIs. Participants were randomised to the acupuncture group or control group. Acupuncture therapy consisted of 12 treatments over a period of 18 weeks, using a set of predefined body and ear acupuncture points. Cranberry products were recommended to all participants as standard of care.

Results: A total of 137 women were randomised (68 acupuncture, 69 control group) and occurrence of UTIs at 6 and 12 months could be assessed in 123 and 120 women respectively. Acupuncture combined with cranberry slightly increased the proportion of UTI-free women compared with cranberry alone at 6 months (59% vs 46%, p = 0.2). Between 6 and 12 months the proportion of UTI-free women was significantly higher in the acupuncture group (66 vs 45%, p = 0.03). The number of UTIs decreased from baseline to 12 months in both study groups. The number of UTIs at 12 months was significantly lower in the acupuncture group (median difference 1, p = 0.01).

Conclusions: Segmental acupuncture may be an effective treatment option for women with recurrent UTIs over a longer follow-up period and may limit antibiotics use. Further studies are needed.

Urinary tract infections (UTIs) are the most common bacterial infections in postmenopausal women, and women with diabetes are possibly at a higher risk. The aim of this study is to evaluate the potential benefit on the prevention of UTI episodes, assessed by urinalysis and urine culture (primary outcome) after two, four and six months, of daily oral dietary supplement (120 mg highly standardized cranberry extract phytosome), compared to placebo, in diabetic postmenopausal women taking SGLT-2 inhibitors. Forty-six subjects (mean age 72.45 +/- 1.76) completed the study (23 placebo/23 supplement). Considering UTI episodes, during the six-month supplementation period, an increase of 1.321 (95% CI: -0.322; 2.9650) was observed in the placebo group, while it remained at a steady value of 0.393 (95% CI: -4.230; 5.016) in the supplemented group. Regarding UTI episodes, in both groups, interaction between times for supplementation was statistically significant (p = 0.001). In particular, at follow-up 4, 9% of the placebo group showed infection versus only 3% with cranberry supplementation. Glycaemia and glycated hemoglobin values (secondary outcomes) were not modified at the end of six months with respect to the basal values in both groups, as expected. While in terms of quality of life per the SF-12 health questionnaire, there were no differences between the two groups, an improvement in SF-12 quality of life was observed in both groups (six months vs. basal). In conclusion, highly standardized cranberry extract phytosome supplementation reduced UTI recurrence.

Background: Urinary tract infection has a one-year prevalence of 11% in women and ranges among the most common reasons for consulting a primary care physician and for receiving a prescription for antibiotics. In the case of recurrent urinary tract infection (rUTI), there are questions about the further work-up, treatment, and preventive measures. 

Methods: The systematic literature search performed for the update of the German clinical practice guideline on uncomplicated urinary tract infection (043-044) (up to February 2022) was supplemented with a selective search for clinical trials (up to August 2023). 

Results: Urine culture and ultrasonography are reasonable steps in the diagnostic evaluation of rUTI. Further invasive testing is suggested for men but is not routinely indicated for women. Antibiotics are among the most effective preventive measures (risk ratio [RR] 0.15, 95% confidence interval [0.1; 0.3]) but carry a high risk of side effects. Non-antibiotic preparations such as cranberry juice (RR 0.74 [0.5; 0.99]), mannose (RR 0.23 [0.14; 0.37]), and vaginal estrogen (RR, 0.42 [0.30; 0.59]) can also reduce the infection rate, with a low risk of side effects. Increased daily fluid intake has been shown to lower infection rates in the short term (odds ratio [OR] 0.13 [0.07; 0.25]); the use of hygienically advisable wiping techniques after passing stool or urine has been little studied but can be implemented with no risk. 

Conclusion: rUTI poses a challenge for the treating physician. The measures to be taken must be considered on an individual basis. Vulnerable groups, such as older patients, need special attention.

The treatment of infectious diseases typically includes the administration of anti-infectives; however, the increasing rates of antimicrobial resistance (AMR) have led to attempts to develop other modalities, such as antimicrobial peptides, nanotechnology, bacteriophages, and natural products. Natural products offer a viable alternative due to their potential affordability, ease of access, and diverse biological activities. Flavonoids, a class of natural polyphenols, demonstrate broad anti-infective properties against viruses, bacteria, fungi, and parasites. Their mechanisms of action include disruption of microbial membranes, inhibition of nucleic acid synthesis, and interference with bacterial enzymes. This review explores the potential of natural compounds, such as flavonoids, as an alternative therapeutic approach to combat infectious diseases. Moreover, it discusses some commonly used natural products, such as cranberry and D-mannose, to manage urinary tract infections (UTIs). Cranberry products and D-mannose both, yet differently, inhibit the adhesion of uropathogenic bacteria to the urothelium, thus reducing the likelihood of UTI occurrence. Some studies, with methodological limitations and small patient samples, provide some encouraging results suggesting the use of these substances in the prevention of recurrent UTIs. While further research is needed to determine optimal dosages, bioavailability, and potential side effects, natural compounds hold promise as a complementary or alternative therapeutic strategy in the fight against infectious diseases.

Importance Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence. 

Objective To create a clinical guideline for the diagnosis and management of urinary tract infections that addresses the gap between the evidence and recommendation strength. 

Evidence Review This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In May 2023, new and existing members were solicited for questions on urinary tract infection prevention, diagnosis, and management. For each topic, literature searches were conducted up until early 2024 in any language. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were developed discussing the available literature and associated risks and benefits of various approaches. 

Findings A total of 54 members representing 12 countries reviewed 914 articles and submitted information relevant to 5 sections: prophylaxis and prevention (7 questions), diagnosis and diagnostic stewardship (7 questions), empirical treatment (3 questions), definitive treatment and antimicrobial stewardship (10 questions), and special populations and genitourinary syndromes (10 questions). Of 37 unique questions, a clear recommendation could be provided for 6 questions. In 3 of the remaining questions, a clear recommendation could only be provided for certain aspects of the question. Clinical reviews were generated for the remaining questions and aspects of questions not meeting criteria for a clear recommendation. 

Conclusions and Relevance In this consensus statement that applied the WikiGuidelines method for clinical guideline development, the majority of topics relating to prevention, diagnosis, and treatment of urinary tract infections lack high-quality prospective data and clear recommendations could not be made. Randomized clinical trials are underway to address some of these gaps; however further research is of utmost importance to inform true evidence-based, rather than eminence-based practice.

Introduction: One of the most prevalent bacterial diseases in both the general population and hospitals are urinary tract infections (UTIs). There is still conflicting scientific data about the usefulness of cranberry products in preventing UTIs. Our meta-analysis investigated whether the content of the main component, proanthocyanidins (PACs), in cranberries affects their ability to prevent UTIs. 

Methods: The average daily intake of PACs has already been reported in previous randomized controlled trials (RCTs) that intended to investigate the effectiveness of cranberry in preventing UTIs, which were collected in our meta-analysis. The results were reported as the number of participants with UTIs. Random effect or fixed effect models were chosen for statistical analysis based on the heterogeneity. 

Results: Ten RCTs that matched the requirements were included. The results showed that when the daily intake of PACs was at least 36mg, the risk of UTIs was reduced by 18% (RR = 0.82, 95% CI = 0.69–0.98, p = 0.03). But when the daily intake of PACs was less than 36 mg, there was no statistical significance risk decrease (p = 0.39). The results of the sub-group analysis showed that cranberries only significantly reduced the risk of UTIs when the duration of cranberry product use falls between 12 and 24 weeks (RR = 0.75, 95% CI = 0.61–0.91, p = 0.004). Additionally, cranberries also significantly reduced the risk of UTIs only in subgroups that just included females (RR = 0.84, 95% CI = 0.71–0.98, p = 0.02). 

Discussion: These findings showed a strong correlation between the daily use of the active ingredient PACs found in cranberry products and the prevention of UTIs. Our meta-analysis is the first to show that there are minimum daily PAC consumption intake levels in cranberry products and length of use considerations that are needed to achieve clinically relevant UTI prevention benefits.

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. 

An acute uncomplicated urinary tract infection (UTI) is a bacterial infection of the lower urinary tract with no sign of systemic illness or pyelonephritis in a noncatheterized, nonpregnant adult with no urologic abnormalities or immunocompromise. In women, a self-diagnosis of a UTI with the presence of typical symptoms (e.g., frequency, urgency, dysuria/burning sensation, nocturia, suprapubic pain), without vaginal discharge, is accurate enough to diagnose an uncomplicated UTI without further testing. Urine culture and susceptibility testing should be reserved for women with recurrent infection, treatment failure, history of resistant isolates, or atypical presentation to make a definitive diagnosis and guide antibiotic selection. First-line antibiotics include nitrofurantoin for five days, fosfomycin in a single dose, trimethoprim for three days, or trimethoprim/sulfamethoxazole for three days. Symptomatic treatment with nonsteroidal anti-inflammatory drugs and delayed antibiotics may be considered because the risk of complications is low. Increased fluids, intake of cranberry products, and methenamine hippurate can prevent recurrent infections. Antibiotic prophylaxis is also effective in preventing recurrence but has a risk of adverse effects and antimicrobial resistance. Men with lower UTI symptoms should always receive antibiotics, with urine culture and susceptibility results guiding the antibiotic choice. Clinicians should also consider the possibility of urethritis and prostatitis in men with UTI symptoms. First-line antibiotics for men with uncomplicated UTI include trimethoprim, trimethoprim/sulfamethoxazole, and nitrofurantoin for seven days. Uncomplicated UTIs in nonfrail women and men 65 years and older with no relevant comorbidities also necessitate a urine culture with susceptibility testing to adjust the antibiotic choice after initial empiric treatment; first-line antibiotics and treatment durations do not differ from those recommended for younger adults.

This work seeks to generate new knowledge about the mechanisms underlying the protective effects of cranberry against urinary tract infections (UTI). Using Caco-2 cells grown in Transwell inserts as an intestinal barrier model, we found that a cranberry-derived digestive fluid (containing 135 ± 5 mg of phenolic compounds/L) increased transepithelial electrical resistance with respect to control (ΔTEER = 54.5 Ω cm²) and decreased FITC-dextran paracellular transport by about 30%, which was related to the upregulation of the gene expression of tight junction (TJ) proteins (i.e., occludin, zonula occludens-1 [ZO-1], and claudin-2) (∼3–4-fold change with respect to control for claudin-2 and ∼2–3-fold for occludin and ZO-1). Similar protective effects, albeit to a lesser extent, were observed when Caco-2 cells were previously infected with uropathogenic Escherichia coli (UPEC). In a urinary barrier model comprising T24 cells grown in Transwell inserts and either noninfected or UPEC-infected, treatments with the cranberry-derived phenolic metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and phenylacetic acid (PAA) (250 μM) also promoted favorable changes in barrier integrity and permeability. In this line, incubation of noninfected T24 cells with these metabolites induced positive regulatory effects on claudin-2 and ZO-1 expression (∼3.5- and ∼2-fold change with respect to control for DOPAC and ∼1.5- and >2-fold change with respect to control for PAA, respectively). Overall, these results suggest that the protective action of cranberry polyphenols against UTI might involve molecular mechanisms related to the integrity and functionality of the urothelium and intestinal epithelium.

Background: Urinary tract infection (UTI) prevention benefits of cranberry intake are clinically validated, especially for women and children. To ensure the benefits of cranberry dietary supplement products, the anti-adhesion activity (AAA) against uropathogenic bacteria is routinely used in in vitro bioassays to determine the activity in whole product formulations, isolated compounds, and ex vivo bioassays to assess urinary activity following intake. D-mannose is another dietary supplement taken for UTI prevention, based on the anti-adhesion mechanism.

Objective: Compare the relative AAA of cranberry and D-mannose dietary supplements against the most important bacterial types contributing to the pathogenesis of UTI and consider how certain components potentially induce in vivo activity.

Methods: The current study used a crossover design to determine ex vivo AAA against both P- and Type 1-fimbriated uropathogenic Escherichia coli of either D-mannose or a cranberry fruit juice dry extract product containing 36 mg of soluble proanthocyanidins (PACs), using bioassays that measure urinary activity following consumption. AAA of extracted cranberry compound fractions and D-mannose were compared in vitro and potential induction mechanisms of urinary AAA explored.

Results: The cranberry dietary supplement exhibited both P-type and Type 1 in vitro and ex vivo AAA, while D-mannose only prevented Type 1 adhesion. Cranberry also demonstrated more robust and consistent ex vivo urinary AAA than D-mannose over each 1-week study period at different urine collection time points. The means by which the compounds with in vitro activity in each supplement product could potentially induce the AAA in urines was discussed relative to the data.

Conclusions: Results of the current study provide consumers and healthcare professionals with additional details on the compounds and mechanisms involved in the positive, broad-spectrum AAA of cranberry against both E. coli bacterial types most important in UTIs and uncovers limitations on AAA and effectiveness of D-mannose compared to cranberry.