Feasibility of Cranberry Capsule Administration and Clean‐catch Urine Collection in Long‐term Care Residents

To the Editor: Urinary tract infection (UTI) is a common bacterial infection in nursing home residents, and there is no accepted prevention strategy. Cranberry products are a nonantimicrobial method for UTI prevention, and cranberry juice has been shown to reduce bacteriuria in older adults,1–3 but daily ingestion of large volumes of cranberry juice is challenging for long-term care residents, making cranberry capsules an appealing alternative. The goal of this pilot study was to determine the feasibility of administering cranberry capsules and noninvasively collecting urine samples. Four dementia units participated in this study. Exclusion criteria were chronic indwelling catheter, residence less than 4 weeks, prednisone therapy, active UTI symptoms, terminal, end-stage renal disease, younger than 60, chronic suppressive antibiotic therapy, history of kidney stones, unable to provide baseline urine, and warfarin therapy.4 Surrogates of residents were approached for verbal consent. Chart review and clean-catch urine specimens were performed at baseline and monthly for 6 months. Participants were assigned to one of three arms using a random number generator: no capsules, one capsule daily, and one capsule twice daily. Each capsule contained 16.25 mg of proanthocyanidins. The Yale Human Investigation Committee approved the study. The ClinicalTrials.gov identifier is NCT00596635. The primary outcomes were the rate of successful cranberry capsule administration and the collection of uncontaminated urine specimens. Additional outcomes included the incidence of possible adverse outcomes and preliminary effectiveness. Analyses were conducted with the t-test, Fisher exact test, and log-rank test using SAS 9.1 (SAS Institute, Inc., Cary, NC). Of 123 eligible residents, 56 enrolled (45.5% participation rate) and were followed from September 2007 to June 2008. The mean age of participants was 87, 82.1% were female, and all were Caucasian. Twenty-eight (50%) had had a UTI in the previous year. Thirty-one (55%) were able to provide clean-catch urine samples monthly for 5 months, with 24 (42%) being able to provide urine for all 6 months. Overall, 207 (86%) of 240 scheduled monthly urine collections were successfully completed. Of the 263 urine cultures obtained, 39 (15%) were negative (no growth), 85 (32%) were contaminated (≥3 organisms), and 139 (53%) were positive (103, 1 organism; 36, 2 organisms). Forty participants had at least one contaminated sample (71%). Escherichia coli was present at least once from 28 of the participants (50%). Thirteen participants were treated for a UTI during the study, resulting in study termination. Only seven of a total of 237 scheduled doses (3%) were missed or refused. Six participants (10.5%) had an adverse event possibly attributable to cranberry capsules (nausea, vomiting, or diarrhea). Seventeen participants were randomized to the control arm, 20 to the one capsule daily arm, and 19 to the one capsule twice daily arm. E. coli bacteriuria before randomization was similar in the control (29%) and treatment arms (28%) and remained similar during the intervention period (47% and 51%, respectively). Time to first E. coli–positive culture or to first urine culture greater than 100,000 colony forming units/mL was no different between the three groups, and history of UTI did not change this association (Table 1). The incidence of treated UTI was 4.66 per 100 person-months and was not significantly different between the control and treatment arms. This study demonstrates that a cranberry UTI prevention study is feasible to conduct in long-term care. Although the incidence of contaminated urine specimens was high, negative or positive clean-catch samples were obtained in 68% of attempts. Because maintaining oral hydration is challenging,5 and many residents dislike the acrid flavor and volume of cranberry juice necessary,3,6 it is not an optimal UTI preventive strategy. Cranberry tablets reduce UTI in patients with spinal cord injury with neurogenic bladder.7 In this small sample, efficacy of cranberry capsules was not demonstrated in long-term care residents, but the primary goal of this study was to determine feasibility. The results of this pilot study have implications for designing a definitive trial. The inability to follow all participants for the full 6 months reflects the vulnerability of the population. Future studies will require unique recruitment strategies because loss to follow-up is common in this population.8 In addition, because there was no trend toward efficacy of cranberry capsules, it is possible that the cranberry capsules were underdosed. Escalating doses of proanthocyanidins (up to 108 mg) were increasingly effective at inhibiting E. coli adherence to uroepithelium.9,10 Additional clinical studies of higher doses of proanthocyanidins are warranted to identify the optimal dose of cranberry capsules for prevention of bacteriuria and UTI in long-term care residents. Such a preventive strategy could be well tolerated with few side effects and have a major effect on long-term care. Conflict of Interest: The cranberry capsules used in the study were donated by Theralogix Inc. The company did not play a role in the study design, conduct, or interpretation or reporting of study results. No authors have any personal relationships with owners or employees of Theralogix Inc. Funding was provided by Patrick and Catherine Weldon Donaghue Medical Research Foundation Grant DF06-005 (KG, MJM). MJM is supported by National Institutes of Health, National Institute on Aging Grant K23 AG028691; Claude D. Pepper Older Americans Independence Center Grant P30 AG21342; Atlantic Philanthropies; the Infectious Diseases Society of America/Foundation for Infectious Diseases; the John A. Hartford Foundation: the Association of Specialty Professors, and Clinical and Translational Science Awards Grant UL1 RR024139 from the National Center for Research Resources. Author Contributions: MJM and KG: study concept and design, analysis and interpretation of data, and preparation of manuscript. LP: acquisition of subjects and data and preparation of manuscript. JD and SC: analysis and interpretation of data and preparation of manuscript. Sponsor's Role: The Donaghue Foundation had no role in the design, methods, subject recruitment, data collection, analysis, or preparation of the manuscript.