Cranberry Extract for Preventing Recurrent Urinary Tract Infections: An Outcome-Specific Meta-Analysis of Prospective Trials
Author(s): Jana Havranova, Steven Cardio, Matthew Krinock, Max Widawski, Rachel Sluder, Ashish Kumar, John Hippen, Harsh Goel
Background: Urinary tract infection (UTI) is one of the most common bacterial infections, representing enormous healthcare-cost and morbidity burdens. Though cranberries have long been used to prevent recurrent UTI (r-UTI), extant evidence is inconsistent. Potentials reasons for inconsistency include using different cranberry preparations (juice versus tablet/capsule), heterogenous populations, and outcome definition. Importantly, juice hardly a feasible long-term therapeutic option and there are no meta-analyses specifically examining tablet/capsule form of cranberry. We conducted an updated meta-analysis to address these inconsistencies.
Methods: MEDLINE was systematically searched for, i) placebo-controlled clinical trials, ii) restricted to adults, iii) exclusively investigating cranberry extract in tablet/capsule form to prevent r-UTI, and iv) clearly reporting incidence of any of the three outcomes (detailed subsequently) in treatment and placebo groups. Three outcome measures, i.e culture-confirmed UTI, asymptomatic pyuria/bacteriuria, and symptomatic UTI were meta-analyzed separately.
Results: 15 RCTs met inclusion criteria. Ten trials reported culture-confirmed UTI, seven reported asymptomatic pyuria/bacteriuria, and 5 trials reported symptomatic but not culture-confirmed UTI as primary outcome, yielding twelve (n=2391 subjects), ten (n=2565 urine cultures), and seven (n=1325 subjects) independent cohorts, respectively. Meta-analysis revealed a 30% reduced risk of culture-confirmed UTI (pooled RR 0.70, 95% CI 0.54, 0.91; I2=59%), 23% reduction in asymptomatic bacteriuria/pyuria (pooled RR 0.77, 95% CI 0.69, 0.86, I2=75%), and 14% reduction in symptomatic UTI (RR 0.86, 95% CI 0.75, 0.98; I2=48%). Excluding low-risk patients and those with neurogenic bladder having indwelling/intermittent catheterization reduced heterogeneity among culture-confirmed UTI trials revealing baseline risk profile of patients is a significant factor contributing to heterogeneity in extant literature. Funnel plot analysis did not reveal significant publication bias.
Discussion: Cranberry extract in capsule/tablet form reduces risk of r-UTI in those with a history of r-UTI, but not in those without such history, or those using indwelling or intermittent catheterization. Major limitation of available data was significant heterogeneity, though without evidence of publication bias.