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Nutrition 411: Urinary Tract Infection: Prevention Strategy to Improve Quality Measures

December 2013

  Urinary tract infections (UTIs) are the most prevalent infection in long-term care (LTC), accounting for at least 40% of all infections and more than 8% of total costs.1,2 UTIs are the leading driver of hospitalizations, with a 30% readmission rate from LTC within 30-days.3 They can cause urinary frequency, urgency, loss of bladder control, pain, burning upon urination, straining, flank or lower back pain, fever, a decrease in daily activity, and depression. Many times, alteration in mental status, confusion, lethargy, agitation, delirium, subtle changes in behavior, and falls can be the first indication of the presence of a UTI.4,5 UTIs can cause a decrease in appetite and an increase in metabolic rate, leading to unintended weight loss, negatively impacting nutritional status. These are all quality-of-care measures that can be improved by preventing UTIs.   UTIs are the most common condition (30% to 50%6,7) for which antibiotics are given in LTC. Including the treatment of asymptomatic UTIs,25% to 75% of antibiotic use in LTC is inappropriate.8,9 This can contribute to the 27,000 nursing home residents with antibiotic-resistant infections, a number that has significantly increased over the last decade.10 Other side effects of antibiotics include allergic reactions, nausea, interactions with foods or other drugs, and depletion of beneficial bacteria in the colon that can lead to diarrhea, stomach or intestinal upset, changes in mental status, yeast infections, and Clostridium difficile (C. diff) infection. Antibiotics also contribute to adverse drug reactions (ADRs) — 5% to 28% of resident admissions to the hospital are because of or involve an ADR.11 Up to 13% of residents on two medications and 82% on six or more medications develop an ADR.12 In LTC, a cost analysis found that for every $1 spent on medications, $1.33 was spent on treating ADRs.13

  The average cost to treat a UTI is approximately $691, not including costs associated with complications.14 Although antimicrobial therapy is generally effective at eradicating these infections, there is still a high rate of recurrence. By 4 to 6 weeks, 50% to 70% of individuals treated for a UTI will again have positive urine cultures.15,16 Based on these statistics, clinicians need to be proactive in preventing UTIs in order to stop this vicious cycle.

How Infections Occur

  In order for a UTI to develop, E. coli from a fecal or vaginal source must migrate upward, enter the urethra, attach, and begin to multiply. As the bacteria multiply, they can ascend further up the urethra into the bladder. E. coli have finger-like projections (fimbriae) on their cell surface that allow them to attach to receptors on epithelial cell walls using a Velcro-like effect that is resistant to the cleansing action of urine flow. Because E. coli are living, they continue to move after adherence, irritating and destroying the urethral or bladder wall and causing inflammation. The inflammation causes a painful burning sensation. In some cases, these pathogens will rupture underlying blood vessels, resulting in visible blood in the urine. Therefore, inhibiting E. coli from attaching to the urinary tract wall is key to preventing UTIs.

The Role of Proanthocyanidins

  Cranberries are the most promising nonpharmacological option for preventing UTIs that is also safe and well tolerated. Proanthocyanidins (PACs), the flavonoids in cranberries, are responsible for UTI prevention, inhibiting inhibit the adhesion of E. coli to the urinary tract wall. The PACs in cranberries contain a unique A-type linkage in their structure, while most other foods contain only the more common B-type PACs. The PACs are absorbed rapidly from the gastrointestinal tract and excreted in the urine. The unique molecular structure explains why cranberries are the only food associated with urinary tract health.

  PACs from cranberries target E. coli cells in three ways: 1) they alter E. coli cell membranes, 2) they compress fimbriae, greatly reducing E. coli’s ability to remain in place long enough to launch an infection, and 3) they change E. coli shape from rods to spheres, affecting their activity. All of these effects inhibit the bacteria’s ability to attach to cells lining the bladder wall, prevent the bacteria from making contact with cells, and disrupt bacterial communication. The E. coli then can be flushed out in the urine instead of causing an infection.

  A plethora of data support the efficacy of cranberry. More than 200 research and review articles have been published demonstrating their health benefits.17-24 A recent meta-analysis of 10 randomized controlled trials, including a total of 1,494 subjects that compared prevention of UTIs in users of cranberry-containing products versus placebo or non-placebo controls, concluded that cranberry-containing products are associated with protective effects against UTIs.25 Research shows 36 mg of PACs, the amount found in 10 fl oz of pure cranberry juice or 3,750 mg of cranberry powder, are needed to reduce the adhesion of E. coli to urinary tract walls. The beneficial effect on urinary tract health may start within 2 hours of consuming cranberry juice and can last up to 10 hours, demonstrating that cranberry products need to be taken daily to be effective and that their protective effect is gone once consumption is discontinued.26 The higher the concentration of PACs, the greater their impact on uropathogenic bacteria, suggesting that whole cranberry products, juice, and extracts that have not been highly diluted have the greatest health effects.

  Older adults are at increased risk for UTIs due to age-related changes. Decreased estrogen as part of menopause leads to thinning and weakening of the mucosa, reducing its ability to resist bacteria. A decrease in estrogen also leads to pH changes in the vagina, favoring E. coli colonization. An aging immune system decreases antibody response to pathogens. Changes in microbiota (microflora) include an increase in harmful bacteria and a decrease in beneficial bacteria. As we age, the ability to concentrate urine decreases, and it may be difficult to consume the large volumes of fluid needed to flush out the bacteria. Also, the prevalence of glucose intolerance and diabetes increases, causing increased glucose in the urine and fostering bacterial growth. To help counteract these changes, daily consumption of cranberry products is recommended.

Cranberry Products

  There are many different cranberry-containing products on the market, including cranberry juice cocktail, 100% cranberry juice, cranberry capsules, tablets, and liquid cranberry concentrates. Traditional cranberry juice is the formulation most studied and readily available. However, one of the problems that clinicians face regarding the amount of cranberry juice required for health benefits is the considerable variation in the amount of cranberry juice in beverages. Products containing <100% of the primary labeled ingredient must contain the words beverage, cocktail, or drink on the label. The determination of the content of cranberry in products represents a possible source of confusion. Also, the higher the percent cranberry, the higher the cost and many times facilities will purchase the cheaper product not realizing it contains little to no PACs. In addition, some studies with high dropout rates have indicated the prolonged consumption of cranberry juice is not feasible for many because of the volume required to consume, highly acidic taste, and caloric load.18,19,23,27 In this respect, concentrated cranberry products high in PACs may be a better alternative to cranberry juice in terms of patient compliance and tolerability.28

  Capsules and tablets typically contain 300–500 mg cranberry concentrate per tablet (~6–10 mg PACs), often given as two tablets, four times daily. Many elderly persons have challenges tolerating several additional tablets per day, and administering this form of cranberry can be cumbersome, especially if patients are receiving enteral feeding that requires the tablets to be crushed. This also contributes to polypharmacy.

  Subsequently, the discovery of PACs in cranberries has lead to the development of medical foods containing concentrated cranberry PACs. A medical food is a food that is formulated to be consumed or administered enterally under the supervision of a physician and is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.29 Most cranberry-containing medical foods contain a higher concentration of PACs than juice and tablets and appear to be much better tolerated due to the low volume serving size. UTI-Stat® (Nutricia NA, Rockville, MD) is an example of a cranberry-containing medical food clinically shown to help prevent recurrent UTIs (rUTI).30,31 UTI-Stat contains a proprietary blend of ingredients that work by helping to counteract the effects of E. coli: two anti-adhesion ingredients (cranberry concentrate and D-mannose), two anti-proliferation ingredients (vitamin C and fructooligosaccharides), and a natural anti-inflammatory agent (bromelain). No matter what product you recommend for your patients, it is critical that the product has been clinically shown to be effective at preventing UTIs.

  A clinical study was conducted in 23 pre- and postmenopausal female patients with history of UTIs to test the efficacy, tolerability, and safety of UTI-Stat.31 Quality of life (QoL) was measured using the American Urologic Association32 (AUA) Symptom Index and the Medical Outcomes Study Short-Form, 36-item Questionnaire33 (SF-36). Results showed 91% of study participants remained UTI-free over 3 months taking doses up to 60 mL/day; 9% reported a rUTI, results markedly better than historical data (36%). QoL and AUA scores were significantly improved (P = 0.0097 and P = 0.045, respectively). The product showed a good safety profile, tolerability, and demonstrated effectiveness in reducing rUTIs and increasing QoL in both pre- and post-menopausal women with history of rUTI. Another trial30 assessing the efficacy of UTI-Stat in the prevention of recurrent UTI symptoms in 88 LTC residents with a history of UTIs showed similar results. Participants in the study received 1 fl oz of UTI-Stat twice daily for 12 weeks. Results showed 92% remained symptom-free and did not require antibiotic therapy. These studies demonstrate how use of cranberry-containing medical foods can help prevent UTIs, which can affect 10 quality measures (see Table 1).

Practice Points

  When selecting a cranberry product, most importantly choose a product clinically shown to prevent a UTI. Also, the product should contain a high concentration of PACs. Look for ingredients with cranberry extract, concentrate, or pure cranberry juice and products in liquid form, requiring low volume to achieve adequate PACs, with an acceptable taste to help with ease of consumption and patient tolerability. Also look for a low sugar content. In addition to PACs, other ingredients for urinary tract health that may have a synergistic beneficial effect include vitamin C, D-Mannose, and prebiotics.   The next step is to identify patients at high risk for UTIs (see Table 2) and implement cranberry-containing medical foods as part of a collaborative care prevention program.34 Because the development of UTIs along with their complications affect 10 quality measures, preventing them can significantly impact resident QoL.

 Jennifer Sallit, PhD, RD, serves as Director of Medical and Scientific Affairs for Nutricia North America, Specialized Elderly Nutrition Division. She has been involved in nutrition research for the last 15 years, currently focusing on improving the nutritional status of older adults through specialized medical foods. Nancy Collins, PhD, RD, LD/N, FAPWCA, is founder and executive director of Nutrition411.com and Wounds411.com. For the past 20 years, she has served as a consultant to healthcare institutions and as a medico-legal expert to law firms involved in healthcare litigation. Correspondence may be sent to Dr. Collins at NCtheRD@aol.com.

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2. Richards CL. Urinary tract infections in the frail elderly: issues for diagnosis, treatment and prevention. Int Urol Nephrol. 2004;36(3):457–463.

3. Ouslander JG, Diaz S, Hain D, Tappen R, Frequency and diagnoses associated with 7-and 30-day readmission of skilled nursing facility patients to a nonteaching community hospital. J Am Med Dir Assoc. 2011;12(3):95-203.

4. Loeb M, Bentley DW, Bradley S, Crossley K, Garibaldi R, Gantz N, et al. Development of minimum criteria for the initiation of antibiotics in residents of long-term-care facilities: results of a consensus conference. Infect Control Hosp Epidemiol. 2001;22(2):120–24.

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10. Centers for Medicare and Medicaid Services. Long Term Care Minimum Data Set Resident profile table as of 05/02/2005. Available at: www.cdc.gov/getsmart/healthcare/learn-from-others/factsheets/nursing-homes.html. Accessed December 9, 2013.

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12. Field TS, Gurwitz JH, Harrold LR,Rothschild J, DeBellis KR, Seger AC, et al. Risk factors for adverse drug events among older adults in the ambulatory setting. J Am Geriatr Soc. 2004;52(8):1349–1354.

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18. Kontiokari T, Salo J, Eerola E, Uhari M. Cranberry juice and bacterial colonization in children—a placebo-controlled randomized trial. Clin Nutr. 2005;24(6):1065–1072.

19. Guay DR. Cranberry and urinary tract infections. Drugs. 2009;69(7):775–807.

20. Nowack R, Schmitt W. Cranberry juice for prophylaxis of urinary tract infections — conclusions from clinical experience and research. Phytomedicine. 2008;15(9):653–667.

21. Pérez-López FR, Haya J, Chedraui P. Vaccinium macrocarpon: an interesting option for women with recurrent urinary tract infections and other health benefits. J Obstet Gynaecol Res. 2009;35(4):630–639.

22. Bailey DT, Dalton C, Daugherty JF, Tempesta MS. Can a concentrated extract prevent recurrent urinary tract infections in women? A pilot study. Phytomedicine. 2007;14(4):237–241.

23. Kiel R, Nashelsky J, Robbins B, Bondi S. Clinical inquiries: does cranberry juice prevent or treat urinary tract infection? J Fam Pract. 2003;52(2):154–155.

24. Available at: www.cranberryinstitute.org. Accessed December 9, 2013.

25. Wang CH, Fang CC, Chen NC, Liu SS, Yu PH, Wu TY, et al. Cranberry-containing products for prevention of urinary tract infections in susceptible populations. Arch Intern Med. 2012;172(13):988–996.

26. Howell AB. Cranberry proanthocyanidins and the maintenance of urinary tract health. Crit Rev Food Sci Nutr. 2002;42(3 suppl):273–278.

27. Jepson RG, Williams G, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. 2008;(1):CD001321.

28. Stothers L. A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products against urinary tract infection in women. Can J Urol. 2002;9(3):1558–1562.

29. Food and Drug Administration. Compliance program guidance manual. Program 7321.002. Medical foods program — import and domestic. Revised September 2008. Available at: www.fda.gov/downloads/Food/GuidanceComplianceRegulatoryInformation/ComplianceEnforcement/ucm073339.pdf. Accessed April 8, 2011.

30. Posthauer ME. Can a cranberry concentrate complex liquid combined with increased hydration protect elderly residents from urinary tract infections? The Director. 2008;16:13–16.

31. Efros M, Bromberg W, Cossu L, Nakeleski E, Katz AE. Novel concentrated cranberry liquid blend, UTI-STAT with Proantinox, might help prevent recurrent urinary tract infections in women. Urology. 2010;76(4):841–845.

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33. Ware JE, Kosinski M. Interpreting SF-36 summary health measures: a response. Qual Life Res. 2001;10(5):405–413.

34. Buhr GT, Genao L, White HK. Urinary tract infections in long term care. Clin Geriatr Med. 2011;27(2):229–239.

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