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

The daily ingestion of cranberry products—juice or capsules— has been promoted as a means to prevent recurrent urinary tract infection (UTI) since at least the first half of the last century.1 In that preantibiotic era, acidification of the urine was a recommended treatment for UTI. Initially, cranberry juice was explored as an approach to treating UTI following the observation that it could lower urine pH. This is attributed to formation of hippuric acid through metabolism of the quinic acid present in cranberry juice. Later studies reported that the concentration of hippuric acid in the urine was insufficient for an antibacterial effect unless very large volumes of cranberry juice were ingested. Subsequently, some lectins (proanthocyanidins) present in cranberries as well as blueberries were reported to inhibit binding of the type 1 P-fimbriae of Escherichia coli to uroepithelial cells, preventing bacterial adherence within the urinary tract. This proposed mechanism for a beneficial effect of cranberries has not yet been shown to have a role in human infection.2 Even though many clinical trials evaluating the use of cranberry products for prevention of UTI 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, double blind clinical trial enrolling 185 elderly women residing in nursing homes to evaluate the effect of cranberry capsules on clinical and microbiologic outcomes. During the 1-year study period, among the 92 women who received cranberry capsules (72 mg total, equivalent to 20 ounces of cranberry juice) compared with the 93 women who received placebo,therewasnosignificantdifferenceintheprimaryoutcome of presence of bacteriuria with pyuria (adjusted rates, 29.1% vs 29.0%; respectively, odds ratio, 1.01; 95% CI, 0.61-1.66; P=.98). Among the secondary outcomes, there were no 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 women without bacteriuria plus pyuria at enrollment, that there 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 the objective laboratory criteria of bacteriuria plus pyuria as the primary outcome, and of restrictive clinical criteria requiring localizing genitourinary findings for identification of symptomatic UTI,4 the most important secondary outcome. The clinical ascertainment of symptomatic UTI in elderly women residing in long-term care facilities can be problematic. The very high prevalence of bacteriuria in this population means that the urine culture, while necessary for diagnosis, has no specificity for identification of symptomatic infection. In addition, symptomatic infection is often inappropriately diagnosed through attribution of nonlocalizing nonspecific symptoms—such as increased confusion, fatigue, or falls—to UTI in patients in whom 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 episodes are identified based on nonspecific symptoms. The current restrictive definitions for identifying symptomatic infection in noncatheterized long-term care residents applied in the study by Juthani-Mehta et al increases the likelihood of ascertainment of true symptomatic UTI and gives confidence that the results are valid and the observations meaningful. Other clinical trials have evaluated the use of cranberry products in older women.5-8 Two of these, including one by the same authors, also reported no benefits of cranberry capsules5 or juice.6 One study, enrolling primarily older women (n =158) in the community,7 reported a decrease in bacteriuria with pyuria in individuals receiving cranberry juice, but this observation was likely confounded by a substantially higher frequency of symptomatic infection reported in the 6 months prior to enrollment for the placebo group. A recent study of the efficacy of cranberry capsules8 reported a benefit for older women (n = 401) and men (n = 115) residing in long-term care facilities who were judged to be at high risk of UTI, when a nonprecise definition for symptomatic infection was applied. However, when the more restrictive definition for symptomatic UTI was 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 cranberry products or have methodological issues that may compromise the reported outcomes. The current study, together with the observations in previous reports, is convincing in supporting a conclusion that cranberry products given to women residing in nursing homes without indwelling catheters do not improve outcomes of UTI for this population. Clinicaltrialsevaluatingtheuseofcranberryjuiceorcapsules in other patients at high risk of recurrent UTI have also reported conflicting results. Studies have enrolled young women with Related article Opinion