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To the Editor: Urinary tract infections (UTIs) account for more than 11 million physician visits annually in the United States and have become increasingly resistant to first-line antibiotic therapy.¹ Recent evidence suggests that consumption of cranberry juice beverages is effective at preventing UTIs,^2-3 although further studies are needed to validate potential treatment effects. While early research focused on a mechanism of urinary acidification, the largest clinical trial to date found no evidence to support this.² Recent studies suggest that cranberry proanthocyanidins (condensed tannins) may inhibit P-fimbriated Escherichia coli from adhering to uroepithelial cells,⁴ the initial step in development of UTI. The effectiveness of cranberry proanthocyanidins and cranberry beverages against antibiotic-resistant E coli, however, has not been previously tested. We assessed whether consumption of cranberry juice cocktail prevents adhesion of antibiotic-resistant uropathogenic P-fimbriated E coli to the uroepithelium.

Methods
Thirty-nine uropathogenic P-fimbriated E coli isolates were obtained from women aged 18 to 39 years with clinically diagnosed, culture-confirmed UTIs. Isolates were incubated for 20 minutes in urine collected over a 12-hour period from healthy women before and after consumption of 240 mL of commercial cranberry juice cocktail, and in cranberry proanthocyanidin extract (pH 6.5) (2-fold dilution series). Isolates tested were a subset of those previously screened for resistance; 24 (62%) of those selected were resistant to trimethoprim-sulfamethoxazole.⁵ These bacteria were then harvested and screened for ability to adhere to isolated uroepithelial cells, agglutinate human red blood cells (A¹, Rh⁺), and resin beads coated with isolated P-receptor oligosaccharides.

Results
Urine after cranberry juice cocktail consumption (average pH 6.2) prevented adhesion of 31 (80%) of the 39 isolates and 19 (79%) of the 24 antibiotic-resistant isolates in all bioassays, while preconsumption urine (average pH 6.2) failed to prevent adhesion in any of the samples. Antiadhesion activity was evident in the urine within 2 hours and persisted for up to 10 hours following cranberry juice cocktail ingestion. The extracted proanthocyanidins inhibited adhesion of all isolates at concentrations ranging from 6 to 375 µg/mL, demonstrating potent in vitro antiadhesion activity against these antibiotic-resistant strains.

Conclusions
These data suggest that consumption of cranberry juice cocktail may offer protection against both sensitive and resistant strains of P-fimbriated E coli by a mechanism that is not likely to increase selective pressures associated with antibiotic resistance. In light of the evidence that antibiotic usage is a contributing factor in development of trimethoprim-sulfamethoxazole–resistant uropathogenic E coli,⁵ further trials are warranted to explore the use of cranberry juice as an alternative strategy to prevent UTIs and potentially reduce the rate of antibiotic resistance.

AUTHOR INFORMATION
Funding/Support: Isolate collection was supported by National Institutes of Health grant R01 DK35368, and bacterial antiadhesion work was supported by Ocean Spray Cranberries, Inc. Ocean Spray provided monetary support only and did not participate in the design, analysis, or interpretation of the data.

Amy B. Howell, PhD
Marucci Center for Blueberry and Cranberry Research
Rutgers University
Chatsworth, NJ

Betsy Foxman, PhD
Department of Epidemiology
University of Michigan School of Public Health
Ann Arbor

1. Manges AR, Johnson JR, Foxman B, O'Bryan TT, Fullerton KE, Riley LW. Widespread distribution of urinary tract infections caused by a multidrug-resistant Escherichia coli clonal group. N Engl J Med. 2001;345:1007-1013. FREE FULL TEXT 2. Avorn J, Monane M, Gurwitz JH, Glynn RJ, Choodnovskiy I, Lipsitz LA. Reduction of bacteriuria and pyruria after ingestion of cranberry juice. JAMA. 1994;271:751-754. FREE FULL TEXT 3. Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, Koskela M, Uhari M. Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. BMJ. 2001;322:1571-1573. FREE FULL TEXT 4. Howell AB, Vorsa N, Der Marderosian A, Foo LY. Inhibition of adherence of P-fimbriated Escherichia coli to uroepithelial-cell surfaces by proanthocyanidin extracts from cranberries. N Engl J Med. 1998;339:1085-1086. FREE FULL TEXT 5. Brown PD, Freeman A, Foxman B. Prevalence and predictors of trimethoprim-sulfamethoxazole resistance among uropathogenic Escherichia coli in Michigan. Clin Infect Dis. 2002;34:1061-1066. FULL TEXT | ISI | PUBMED

Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.

JAMA. 2002;287:3082-3083.

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