Cranberry for Prevention of Urinary Tract Infection?: Time to Move On.

Abstract

The daily ingestion of cranberry products—juice or capsules— hasbeenpromotedasameanstopreventrecurrenturinarytract infection (UTI) since at least the first half of the last century.1 In thatpreantibioticera,acidificationof theurinewasa recommendedtreatmentforUTI. Initially, cranberry juice was explored as an approach to treatingUTI following the observation that it could lower urine pH. This is attributed to formation of hippuric acid through metabolismofthequinicacidpresent incranberry juice.Laterstudies reported that theconcentrationofhippuric acid in theurine was insufficient for anantibacterial effectunlessvery largevolumesofcranberry juicewere ingested.Subsequently, some lectins (proanthocyanidins)present in cranberries aswell asblueberrieswere reported to inhibit bindingof the type 1P-fimbriae ofEscherichiacoli touroepithelial cells,preventingbacterial adherencewithin theurinary tract.Thisproposedmechanismfor abeneficial effectof cranberrieshasnotyetbeenshowntohave a role in human infection.2 Even though many clinical trials evaluating the use of cranberry products for prevention ofUTI have been reported, results have been inconsistent and the efficacy, if any, remains unknown after almost 100 years. In this issue of JAMA, the report by Juthani-Mehta and colleagues3 adds another study to the extensive list of clinical trials that have evaluated the potential benefit of cranberry products for prevention of UTI. The authors conducted a randomized,doubleblindclinical trialenrolling185elderlywomen residing in nursing homes to evaluate the effect of cranberry capsules on clinical and microbiologic outcomes. During the 1-year study period, among the 92womenwho received cranberry capsules (72 mg total, equivalent to 20 ounces of cranberry juice) compared with the 93 women who received placebo,therewasnosignificantdifferenceintheprimaryoutcome ofpresenceof bacteriuriawithpyuria (adjusted rates, 29.1%vs 29.0%; respectively, odds ratio, 1.01; 95%CI, 0.61-1.66;P=.98). Among the secondaryoutcomes, therewereno significant differences in symptomatic UTI (10 vs 12 episodes), mortality (17 vs16deaths),hospitalizations(33vs50episodes),orofanyother clinically meaningful outcomes for this population. As expected for elderly women residing in long-term care facilities, 31% of the study participants already had bacteriuria and pyuriapresentatenrollment.Sensitivityanalysissuggested,among womenwithoutbacteriuriapluspyuriaatenrollment,thatthere were no between-group differences in the presence of bacteriuria plus pyuria over one year. Some important strengths of this study include the use of theobjective laboratorycriteriaofbacteriuriapluspyuriaas the primaryoutcome,andof restrictiveclinical criteria requiring localizing genitourinary findings for identification of symptomaticUTI,4 themost important secondaryoutcome.The clinicalascertainmentofsymptomaticUTI inelderlywomenresiding in long-term care facilities can be problematic. The very high prevalenceofbacteriuria inthispopulationmeansthat theurine culture,whilenecessaryfordiagnosis,hasnospecificityfor identification of symptomatic infection. In addition, symptomatic infection is often inappropriately diagnosed through attribution of nonlocalizing nonspecific symptoms—such as increasedconfusion, fatigue, or falls—toUTI inpatients inwhom a high prevalence of bacteriuria always exists. Previous studies in this population have often been compromised by inadequate description of clinical criteria for diagnosis of symptomatic infection or when a high proportion of symptomatic episodesare identifiedbasedonnonspecificsymptoms.Thecurrent restrictive definitions for identifying symptomatic infection innoncatheterized long-termcare residents applied in the study by Juthani-Mehta et al increases the likelihood of ascertainmentof truesymptomaticUTIandgivesconfidencethat the results are valid and the observationsmeaningful. Other clinical trials have evaluated the use of cranberry products inolderwomen.5-8Twoof these, includingoneby the sameauthors, also reportednobenefits of cranberry capsules5 or juice.6 One study, enrolling primarily older women (n =158) in the community,7 reported a decrease in bacteriuriawith pyuria in individuals receiving cranberry juice, but this observation was likely confounded by a substantially higher frequencyofsymptomatic infectionreported inthe6monthsprior to enrollment for the placebo group. A recent study of the efficacyof cranberry capsules8 reportedabenefit forolderwomen (n = 401) andmen (n = 115) residing in long-termcare facilities who were judged to be at high risk of UTI, when a nonprecise definition for symptomatic infection was applied. However, when themore restrictive definition for symptomatic UTIwas applied, there were no differences between participants randomized to receive cranberry capsules or placebo. Thus, prior studies in this population have also reported no benefits with cranberryproductsorhavemethodological issuesthatmaycompromise the reported outcomes. The current study, together with theobservations inprevious reports, is convincing in supporting a conclusion that cranberry products given to women residing innursinghomeswithout indwelling catheters donot improve outcomes of UTI for this population. Clinicaltrialsevaluatingtheuseofcranberryjuiceorcapsules inotherpatientsathigh riskof recurrentUTIhavealso reported conflicting results. Studies have enrolled young women with Related article Opinion

DOI: 10.1001/jama.2016.16140

Cite this paper

@article{Nicolle2016CranberryFP, title={Cranberry for Prevention of Urinary Tract Infection?: Time to Move On.}, author={Lindsay E . Nicolle}, journal={JAMA}, year={2016}, volume={316 18}, pages={1873-1874} }