CONTEXT: The prevention of urinary tract infection recurrence (UTI) in children has been a challenge yet to be solved. Current practice in children with recurrent UTI (RUTI) suggests that antibiotic prophylaxis may prevent further episodes of UTI and future complications. 

OBJECTIVE: To conduct a systematic review and meta-analysis of randomized controlled trials comparing prophylaxis options for the prevention of UTI and kidney scarring in children with a history of RUTI. 

DATA SOURCES: We conducted a systematic literature search through major electronic databases (PubMed/Medline, Scopus and Cochrane Library) up to November 26th, 2023. Mean difference and SD were used for continuous outcomes and odds ratio for dichotomous outcomes. 

STUDY SELECTION: Our meta-analysis included 3335 participants from 23 studies. 

DATA EXTRACTION: The primary outcome was the effect of the different prophylaxis options on the incidence of symptomatic UTI in children with RUTI during prophylactic treatment. 

RESULTS: Cranberry products and nitrofurantoin lead to lower odds of symptomatic UTI episodes during prophylaxis compared with the control group and control, trimethoprim-sulfamethoxazole, or trimethoprim groups accordingly. Nitrofurantoin may be the best option for UTI incidence reduction compared with all available documented interventions. 

LIMITATIONS: No prophylaxis option has been shown to reduce kidney scarring. 

CONCLUSIONS: Nitrofurantoin and cranberry products may decrease the incidence of symptomatic UTI episodes in pediatric patients with a history of RUTI. Future randomized control trials studying nonantibiotic prophylaxis options focusing on children with UTI recurrence and the risk for kidney scarring are needed to draw further conclusions. Copyright © 2024 by the American Academy of Pediatrics.

PURPOSE: The aim of this narrative literature review was to summarize evidence regarding bacteriuria and urinary tract infections (UTIs) in patients living with a urinary diversion and the use of cranberry products for the prevention of these infections. 

METHODS: We searched for articles in the English language and available in full text to address the role of cranberry products in the management of UTIs in those with urinary diversions. We searched the electronic databases of MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials between January 2003 and December 2023. Thirty-two elements were read in full and 9 elements that evaluated UTIs and/or the role of cranberries in preventing UTIs are included in this narrative review. 

RESULTS: Research indicates no significant difference in UTI rates, microbiology, or antibiotic sensitivity and resistance patterns between the different types of urinary diversions (orthoptic diversions, ileal conduit diversions, and continent cutaneous diversions). Similar to persons with an intact urinary tract, Escherichia coli (a prevalent coliform bacteria) was the most prevalent pathogen resulting in symptomatic UTIs. In addition, we found that E. coli strains persisted in urinary diversions involving reconstructed intestinal segments for prolonged periods of time despite antibiotic treatment. We found sparse evidence suggesting that cranberry products are effective for the prevention of UTIs after ileal conduit urinary diversion. 

CONCLUSIONS: There are inconsistencies in the definition of bacteriuria in the literature making it difficult to compare findings among the studies. Clinical guidance discussing the optimal method for obtaining a urine specimen from a urinary diversion and its management is limited. Research studies on the use of cranberry products to treat UTIs in persons living with a urinary diversion are urgently needed.

Cranberry supplements are commonly used to prevent urinary tract infections (UTIs). However, their usefulness is uncertain in pregnant women. We aimed to comprehensively summarize the current knowledge on cranberry supplements' efficacy and acceptability during pregnancy in addition to the outcome's measurement methods and studies' feasibility. To achieve it, we searched PubMed, PMC, and Europe PMC databases plus screened citations followed by critical appraisal of included eligible English written primary studies that (1) focused on pregnant women supplemented with any cranberry supplements; (2) provided data on cranberry supplements' efficacy, acceptability, outcomes measurement methods, and studies' feasibility; (3) included human subjects; and (4) published worldwide. Two randomized clinical trials (RCTs) and one nested cohort study, including 1156 pregnant women in total, contributed to our analysis. A tendency toward UTI reduction was demonstrated, although the results' validity was impacted by significant juice-induced gastrointestinal intolerance (23%; 44 of 188 subjects). Changing the form of supplementation from cranberry juice to capsules reduced the issue, causing side effects in one of 49 subjects (2%). Nevertheless, both RCTs still experienced significant recruitment and retention problems, which were at 33% and 59% on average, respectively. Newly acquired safety data on 919 more subjects suggests no increased risks of all malformations, vaginal bleeding, and neonatal complications. Investigating cranberry capsules' efficacy as a non-antibacterial option for UTI prevention in pregnant women has become a feasible and important direction with the current advancement in understanding cranberry supplements' actions, recommended doses plus regimens, and their safety in the population. We reviewed the challenges and discovered knowledge gaps and the implementation strategies for future studies.

Background: Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). The aim of this review is to assess the effectiveness of cranberries in treating such infections.

Objectives: To assess the effectiveness of cranberries for the treatment of UTIs.

Search methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 1 August 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 Registry Portal (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria: All randomised controlled trials (RCTs) or quasi-RCTs of cranberry juice or cranberry products for the treatment of UTIs. Studies of men, women or children were to be included.Data collection and analysisTitles and abstracts of studies that were potentially relevant to the review were screened and studies that were clearly ineligible were discarded. Further information was sought from the authors where papers contained insufficient information to make a decision about eligibility.Main resultsNo studies were found that fulfilled all of our inclusion criteria. Seven studies were excluded because they were the wrong study design, mixed interventions or did not report any relevant outcomes. One study is ongoing; however, its current status is unknown.

Authors' conclusions: After a thorough search, no RCTs which assessed the effectiveness of cranberry juice for the treatment of UTIs were found. Therefore, at the present time, there is no good quality evidence to suggest that it is effective for the treatment of UTIs. Well-designed parallel-group, double-blind studies comparing cranberry juice and other cranberry products versus placebo to assess the effectiveness of cranberry juice in treating UTIs are needed. Outcomes should include a reduction in symptoms, sterilisation of the urine, side effects and adherence to therapy. The dosage (amount and concentration) and duration of therapy should also be assessed. Consumers and clinicians will welcome the evidence from these studies.

PLAIN LANGUAGE SUMMARY: Still waiting for evidence about whether cranberries are useful for treating urinary tract infectionsCranberries contain a substance that can prevent bacteria from sticking to the walls of the bladder. This may help reduce bladder and other urinary tract infections (UTIs). Cranberries (usually as cranberry juice) have been used to try and treat UTIs, particularly in high-risk groups such as older people. Cranberries have few adverse effects. This review found no studies reporting the effects of cranberry juice or other cranberry products on the treatment of UTIs.

BACKGROUND AND OBJECTIVE: With over 50% of women suffering from at least one episode of urinary tract infection (UTI) each year and an increasing prevalence of antimicrobial resistance, efforts need to be made to clearly identify the evidence supporting potential non-drug interventions. This study aims to compare the effects of cranberry juice, cranberry tablets, and increased liquids for the management of UTIs.

METHODS: PubMed, Embase, and Cochrane CENTRAL were searched for randomised controlled trials. The primary outcome was the number of UTIs, and the secondary outcomes were UTI symptoms and antimicrobial consumption. A risk of bias assessment was performed using the Cochrane risk of bias tool, and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation.

KEY FINDINGS AND LIMITATIONS: A total of 20 trials (3091 participants) were included, with 18 studies highlighting a 54% lower rate of UTIs with cranberry juice consumption than no treatment and a 27% lower rate than placebo liquid. Cranberry juice also resulted in a 49% lower rate of antibiotic use than placebo liquid and a 59% lower rate than no treatment, based on a network meta-analysis of six studies. The use of cranberry compounds also reduced the prevalence of symptoms associated with UTIs.

CONCLUSIONS AND CLINICAL IMPLICATIONS: With moderate to low certainty, the evidence supports the use of cranberry juice for the prevention of UTIs. While increased liquids reduce the rate of UTIs compared with no treatment, cranberry in liquid form provides even better clinical outcomes in terms of reduction in UTIs and antibiotic use and should be considered for the management of UTIs.

PATIENT SUMMARY: With the increasing prevalence of antimicrobial-resistant UTIs, alternate non-drug treatment options for its management are required. Available evidence supports the use of cranberry compounds and increases in fluid intake for managing UTIs.

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.

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.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.

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.