Infect Chemother.  2012 Oct;44(5):343-356. 10.3947/ic.2012.44.5.343.

Prevention of Recurrent Urinary Tract Infections in Women

• Kim BN

• KMID: 2170378
• DOI: http://doi.org/10.3947/ic.2012.44.5.343

Abstract

Urinary tract infection (UTI) is one of the most common bacterial infections affecting women. One in four of these women will develop a recurrence. Recurrent UTIs are common among otherwise healthy women with anatomically and physiologically normal urinary tracts. These conditions have a significant effect on their quality of life and have a considerable economic impact due to health care costs. This article will review risk factors predisposing pre- and postmenopausal women to recurrent UTIs, and discuss antimicrobial prophylaxis and other non-antimicrobial preventive measures, including modification of behavioral factors, estrogen, and cranberry products.

Keyword

Urinary tract infections; Cystitis; Pyelonephritis; Prevention and control; Anti-bacterial agents; Antibiotic prophylaxis; Recurrence

MeSH Terms

Anti-Bacterial Agents
Antibiotic Prophylaxis
Bacterial Infections
Cystitis
Estrogens
Female
Health Care Costs
Humans
Pyelonephritis
Quality of Life
Recurrence
Risk Factors
Urinary Tract
Urinary Tract Infections
Vaccinium macrocarpon
Anti-Bacterial Agents
Estrogens

Reference

1. Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med. 2002. 113:Suppl 1A. 5S–13S.

2. Hooton TM. Recurrent urinary tract infection in women. Int J Antimicrob Agents. 2001. 17:259–268.

3. Foxman B, Brown P. Epidemiology of urinary tract infections: transmission and risk factors, incidence, and costs. Infect Dis Clin North Am. 2003. 17:227–241.

4. Ikaheimo R, Siitonen A, Heiskanen T, Karkkainen U, Kuosmanen P, Lipponen P, Makela PH. Recurrence of urinary tract infection in a primary care setting: analysis of a 1-year follow-up of 179 women. Clin Infect Dis. 1996. 22:91–99.

5. Foxman B. Recurring urinary tract infection: incidence and risk factors. Am J Public Health. 1990. 80:331–333.

6. O'Reilly M. Stanton SL, Dwyer PL, editors. Recurrent urinary tract infection. Urinary tract infection in the female. 2000. London: Martin Dunitz;227–240.

7. Brumfitt W, Gargan RA, Hamilton-Miller JM. Periurethral enterobacterial carriage preceding urinary infection. Lancet. 1987. 1:824–826.

8. Gupta K, Stapleton AE, Hooton TM, Roberts PL, Fennell CL, Stamm WE. Inverse association of H2O2-producing lactobacilli and vaginal Escherichia coli colonization in women with recurrent urinary tract infections. J Infect Dis. 1998. 178:446–450.

9. Fihn SD. Clinical practice. Acute uncomplicated urinary tract infection in women. N Engl J Med. 2003. 349:259–266.

10. Schilling JD, Mulvey MA, Hultgren SJ. Structure and function of Escherichia coli type 1 pili: new insight into the pathogenesis of urinary tract infections. J Infect Dis. 2001. 183:Suppl 1. S36–S40.

11. Lane MC, Mobley HL. Role of P-fimbrial-mediated adherence in pyelonephritis and persistence of uropathogenic Escherichia coli (UPEC) in the mammalian kidney. Kidney international. 2007. 72:19–25.

12. Kallenius G, Mollby R, Svenson SB, Helin I, Hultberg H, Cedergren B, Winberg J. Occurrence of P-fimbriated Escherichia coli in urinary tract infections. Lancet. 1981. 2:1369–1372.

13. Rosen DA, Hooton TM, Stamm WE, Humphrey PA, Hultgren SJ. Detection of intracellular bacterial communities in human urinary tract infection. PLoS medicine. 2007. 4:e329.

14. Stamm WE, Raz R. Factors contributing to susceptibility of postmenopausal women to recurrent urinary tract infections. Clin Infect Dis. 1999. 28:723–725.

15. Hooton TM, Scholes D, Hughes JP, Winter C, Roberts PL, Stapleton AE, Stergachis A, Stamm WE. A prospective study of risk factors for symptomatic urinary tract infection in young women. N Engl J Med. 1996. 335:468–474.

16. Hooton TM. Pathogenesis of urinary tract infections: an update. J Antimicrob Chemother. 2000. 46:Suppl 1. 1–7. discussion 63-5.

17. Scholes D, Hooton TM, Roberts PL, Stapleton AE, Gupta K, Stamm WE. Risk factors for recurrent urinary tract infection in young women. J Infect Dis. 2000. 182:1177–1182.

18. Hooton TM, Hillier S, Johnson C, Roberts PL, Stamm WE. Escherichia coli bacteriuria and contraceptive method. JAMA. 1991. 265:64–69.

19. Remis RS, Gurwith MJ, Gurwith D, Hargrett-Bean NT, Layde PM. Risk factors for urinary tract infection. Am J Epidemiol. 1987. 126:685–694.

20. Nicolle LE, Harding GK, Preiksaitis J, Ronald AR. The association of urinary tract infection with sexual intercourse. J Infect Dis. 1982. 146:579–583.

21. Foxman B, Frerichs RR. Epidemiology of urinary tract infection: I. Diaphragm use and sexual intercourse. Am J Public Health. 1985. 75:1308–1313.

22. Bran JL, Levison ME, Kaye D. Entrance of bacteria into the female urinary bladder. N Engl J Med. 1972. 286:626–629.

23. Buckley RM Jr, McGuckin M, MacGregor RR. Urine bacterial counts after sexual intercourse. N Engl J Med. 1978. 298:321–324.

24. Czaja CA, Stamm WE, Stapleton AE, Roberts PL, Hawn TR, Scholes D, Samadpour M, Hultgren SJ, Hooton TM. Prospective cohort study of microbial and inflammatory events immediately preceding Escherichia coli recurrent urinary tract infection in women. J Infect Dis. 2009. 200:528–536.

25. Foxman B, Frerichs RR. Epidemiology of urinary tract infection: II. Diet, clothing, and urination habits. Am J Public Health. 1985. 75:1314–1317.

26. Fihn SD, Boyko EJ, Normand EH, Chen CL, Grafton JR, Hunt M, Yarbro P, Scholes D, Stergachis A. Association between use of spermicide-coated condoms and Escherichia coli urinary tract infection in young women. Am J Epidemiol. 1996. 144:512–520.

27. Fihn SD, Boyko EJ, Chen CL, Normand EH, Yarbro P, Scholes D. Use of spermicide-coated condoms and other risk factors for urinary tract infection caused by Staphylococcus saprophyticus. Arch Intern Med. 1998. 158:281–287.

28. McGroarty JA, Tomeczek L, Pond DG, Reid G, Bruce AW. Hydrogen peroxide production by Lactobacillus species: correlation with susceptibility to the spermicidal compound nonoxynol-9. J Infect Dis. 1992. 165:1142–1144.

29. Klebanoff SJ. Effects of the spermicidal agent nonoxynol-9 on vaginal microbial flora. J Infect Dis. 1992. 165:19–25.

30. Stamey TA, Sexton CC. The role of vaginal colonization with enterobacteriaceae in recurrent urinary infections. J Urol. 1975. 113:214–217.

31. Gupta K, Stamm WE. Pathogenesis and management of recurrent urinary tract infections in women. World J Urol. 1999. 17:415–420.

32. Herthelius BM, Hedstrom KG, Mollby R, Nord CE, Pettersson L, Winberg J. Pathogenesis of urinary tract infections--amoxicillin induces genital Escherichia coli colonization. Infection. 1988. 16:263–266.

33. Winberg J, Herthelius-Elman M, Mollby R, Nord CE. Pathogenesis of urinary tract infection--experimental studies of vaginal resistance to colonization. Pediatric nephrology. 1993. 7:509–514.

34. Reid G, Bruce AW, Cook RL, Llano M. Effect on urogenital flora of antibiotic therapy for urinary tract infection. Scand J Infect Dis. 1990. 22:43–47.

35. Hooton TM, Winter C, Tiu F, Stamm WE. Randomized comparative trial and cost analysis of 3-day antimicrobial regimens for treatment of acute cystitis in women. JAMA. 1995. 273:41–45.

36. Hooton TM, Johnson C, Winter C, Kuwamura L, Rogers ME, Roberts PL, Stamm WE. Single-dose and three-day regimens of ofloxacin versus trimethoprim-sulfamethoxazole for acute cystitis in women. Antimicrob Agents Chemother. 1991. 35:1479–1483.

37. Engel JD, Schaeffer AJ. Evaluation of and antimicrobial therapy for recurrent urinary tract infections in women. Urol Clin North Am. 1998. 25:685–701. x

38. Foxman B, Barlow R, D'Arcy H, Gillespie B, Sobel JD. Urinary tract infection: self-reported incidence and associated costs. Ann Epidemiol. 2000. 10:509–515.

39. Smith HS, Hughes JP, Hooton TM, Roberts P, Scholes D, Stergachis A, Stapleton A, Stamm WE. Antecedent antimicrobial use increases the risk of uncomplicated cystitis in young women. Clin Infect Dis. 1997. 25:63–68.

40. Hopkins WJ, Uehling DT, Wargowski DS. Evaluation of a familial predisposition to recurrent urinary tract infections in women. Am J Med Genet. 1999. 83:422–424.

41. Scholes D, Hawn TR, Roberts PL, Li SS, Stapleton AE, Zhao LP, Stamm WE, Hooton TM. Family history and risk of recurrent cystitis and pyelonephritis in women. J Urol. 2010. 184:564–569.

42. Stapleton A, Hooton TM, Fennell C, Roberts PL, Stamm WE. Effect of secretor status on vaginal and rectal colonization with fimbriated Escherichia coli in women with and without recurrent urinary tract infection. J Infect Dis. 1995. 171:717–720.

43. Sheinfeld J, Schaeffer AJ, Cordon-Cardo C, Rogatko A, Fair WR. Association of the Lewis blood-group phenotype with recurrent urinary tract infections in women. N Engl J Med. 1989. 320:773–777.

44. Kinane DF, Blackwell CC, Brettle RP, Weir DM, Winstanley FP, Elton RA. ABO blood group, secretor state, and susceptibility to recurrent urinary tract infection in women. Br Med J (Clin Res Ed). 1982. 285:7–9.

45. Lomberg H, Cedergren B, Leffler H, Nilsson B, Carlstrom AS, Svanborg-Eden C. Influence of blood group on the availability of receptors for attachment of uropathogenic Escherichia coli. Infect Immun. 1986. 51:919–926.

46. Raz R, Gennesin Y, Wasser J, Stoler Z, Rosenfeld S, Rottensterich E, Stamm WE. Recurrent urinary tract infections in postmenopausal women. Clin Infect Dis. 2000. 30:152–156.

47. Frendeus B, Godaly G, Hang L, Karpman D, Svanborg C. Interleukin-8 receptor deficiency confers susceptibility to acute pyelonephritis. J Infect Dis. 2001. 183:Suppl 1. S56–S60.

48. Frendeus B, Godaly G, Hang L, Karpman D, Lundstedt AC, Svanborg C. Interleukin 8 receptor deficiency confers susceptibility to acute experimental pyelonephritis and may have a human counterpart. J Exp Med. 2000. 192:881–890.

49. Hooton TM, Stapleton AE, Roberts PL, Winter C, Scholes D, Bavendam T, Stamm WE. Perineal anatomy and urine-voiding characteristics of young women with and without recurrent urinary tract infections. Clin Infect Dis. 1999. 29:1600–1601.

50. Reid G. Potential preventive strategies and therapies in urinary tract infection. World J Urol. 1999. 17:359–363.

51. Eriksen B. A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infections in postmenopausal women. Am J Obstet Gynecol. 1999. 180:1072–1079.

52. Hu KK, Boyko EJ, Scholes D, Normand E, Chen CL, Grafton J, Fihn SD. Risk factors for urinary tract infections in postmenopausal women. Arch Intern Med. 2004. 164:989–993.

53. Jackson SL, Boyko EJ, Scholes D, Abraham L, Gupta K, Fihn SD. Predictors of urinary tract infection after menopause: a prospective study. Am J Med. 2004. 117:903–911.

54. Foxman B, Somsel P, Tallman P, Gillespie B, Raz R, Colodner R, Kandula D, Sobel JD. Urinary tract infection among women aged 40 to 65: behavioral and sexual risk factors. J Clin Epidemiol. 2001. 54:710–718.

55. Stern JA, Hsieh YC, Schaeffer AJ. Residual urine in an elderly female population: novel implications for oral estrogen replacement and impact on recurrent urinary tract infection. J Urol. 2004. 171:768–770.

56. Moore EE, Hawes SE, Scholes D, Boyko EJ, Hughes JP, Fihn SD. Sexual intercourse and risk of symptomatic urinary tract infection in post-menopausal women. J Gen Intern Med. 2008. 23:595–599.

57. Hooton TM. Clinical practice. Uncomplicated urinary tract infection. N Engl J Med. 2012. 366:1028–1037.

58. Grabe M, Bjerklund-Johansen TE, Botto H, Wullt B, Çek M, Naber KG, Pickard RS, Tenke P, Wagenlehner F. Guidelines on urological infections. Accessed Date Oct 01 2012. Available at: www.uroweb.org/gls/pdf/15_Urological_Infections.pdf.

59. Lichtenberger P, Hooton TM. Antimicrobial prophylaxis in women with recurrent urinary tract infections. Int J Antimicrob Agents. 2011. 38:Suppl. 36–41.

60. Stapleton A, Stamm WE. Prevention of urinary tract infection. Infect Dis Clin North Am. 1997. 11:719–733.

61. Sen A. Recurrent cystitis in non-pregnant women. Clin Evid (Online). 2008. 2008:pii: 0801.

62. Epp A, Larochelle A, Lovatsis D, Walter JE, Easton W, Farrell SA, Girouard L, Gupta C, Harvey MA, Robert M, Ross S, Schachter J, Schulz JA, Wilkie D, Ehman W, Domb S, Gagnon A, Hughes O, Konkin J, Lynch J, Marshall C. Society of O, Gynaecologists of C. Recurrent urinary tract infection. J Obstet Gynaecol Can. 2010. 32:1082–1101.

63. Albert X, Huertas I, Pereiro II, Sanfelix J, Gosalbes V, Perrota C. Antibiotics for preventing recurrent urinary tract infection in non-pregnant women. Cochrane Database Syst Rev. 2004. CD001209.

64. Salvatore S, Cattoni E, Siesto G, Serati M, Sorice P, Torella M. Urinary tract infections in women. Eur J Obstet Gynecol Reprod Biol. 2011. 156:131–136.

65. Stapleton A, Latham RH, Johnson C, Stamm WE. Postcoital antimicrobial prophylaxis for recurrent urinary tract infection. A randomized, double-blind, placebo-controlled trial. JAMA. 1990. 264:703–706.

66. Cetti RJ, Venn S, Woodhouse CR. The risks of long-term nitrofurantoin prophylaxis in patients with recurrent urinary tract infection: a recent medico-legal case. BJU Int. 2009. 103:567–569.

67. Nicolle LE, Harding GK, Thomson M, Kennedy J, Urias B, Ronald AR. Efficacy of five years of continuous, low-dose trimethoprim-sulfamethoxazole prophylaxis for urinary tract infection. J Infect Dis. 1988. 157:1239–1242.

68. Nicolle LE. Prophylaxis: recurrent urinary tract infection in women. Infection. 1992. 20:Suppl 3. S203–S205. discussion S206-10.

69. Melekos MD, Asbach HW, Gerharz E, Zarakovitis IE, Weingaertner K, Naber KG. Post-intercourse versus daily ciprofloxacin prophylaxis for recurrent urinary tract infections in premenopausal women. J Urol. 1997. 157:935–939.

70. Dason S, Dason JT, Kapoor A. Guidelines for the diagnosis and management of recurrent urinary tract infection in women. Can Urol Assoc J. 2011. 5:316–322.

71. Schaeffer AJ, Stuppy BA. Efficacy and safety of self-start therapy in women with recurrent urinary tract infections. J Urol. 1999. 161:207–211.

72. Gupta K, Hooton TM, Roberts PL, Stamm WE. Patient-initiated treatment of uncomplicated recurrent urinary tract infections in young women. Ann Intern Med. 2001. 135:9–16.

73. Wong ES, McKevitt M, Running K, Counts GW, Turck M, Stamm WE. Management of recurrent urinary tract infections with patient-administered single-dose therapy. Ann Intern Med. 1985. 102:302–307.

74. . ACOG Practice Bulletin No. 91: Treatment of urinary tract infections in nonpregnant women. Obstet Gynecol. 2008. 111:785–794.

75. Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med. 1993. 329:753–756.

76. Perrotta C, Aznar M, Mejia R, Albert X, Ng CW. Oestrogens for preventing recurrent urinary tract infection in postmenopausal women. Cochrane Database Syst Rev. 2008. CD005131.

77. Cardozo L, Lose G, McClish D, Versi E, de Koning Gans H. A systematic review of estrogens for recurrent urinary tract infections: third report of the hormones and urogenital therapy (HUT) committee. Int Urogynecol J Pelvic Floor Dysfunct. 2001. 12:15–20.

78. Brown JS, Vittinghoff E, Kanaya AM, Agarwal SK, Hulley S, Foxman B. Urinary tract infections in postmenopausal women: effect of hormone therapy and risk factors. Obstet Gynecol. 2001. 98:1045–1052.

79. . SOGC clinical practice guidelines. The detection and management of vaginal atrophy. Number 145, May 2004. Int J Gynaecol Obstet. 2005. 88:222–228.

80. Schmidt DR, Sobota AE. An examination of the anti-adherence activity of cranberry juice on urinary and nonurinary bacterial isolates. Microbios. 1988. 55:173–181.

81. Zafriri D, Ofek I, Adar R, Pocino M, Sharon N. Inhibitory activity of cranberry juice on adherence of type 1 and type P fimbriated Escherichia coli to eucaryotic cells. Antimicrob Agents Chemother. 1989. 33:92–98.

82. Howell AB, Vorsa N, Der Marderosian A, Foo LY. Inhibition of the adherence of P-fimbriated Escherichia coli to uroepithelial-cell surfaces by proanthocyanidin extracts from cranberries. N Engl J Med. 1998. 339:1085–1086.

83. Ofek I, Goldhar J, Zafriri D, Lis H, Adar R, Sharon N. Anti-Escherichia coli adhesin activity of cranberry and blueberry juices. N Engl J Med. 1991. 324:1599.

84. Avorn J, Monane M, Gurwitz JH, Glynn RJ, Choodnovskiy I, Lipsitz LA. Reduction of bacteriuria and pyuria after ingestion of cranberry juice. JAMA. 1994. 271:751–754.

85. Howell AB, Foxman B. Cranberry juice and adhesion of antibiotic-resistant uropathogens. JAMA. 2002. 287:3082–3083.

86. Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. 2008. CD001321.

87. 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.

88. Stothers L. A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women. Can J Urol. 2002. 9:1558–1562.

89. Barbosa-Cesnik C, Brown MB, Buxton M, Zhang L, DeBusscher J, Foxman B. Cranberry juice fails to prevent recurrent urinary tract infection: results from a randomized placebo-controlled trial. Clin Infect Dis. 2011. 52:23–30.

90. Wang CH, Fang CC, Chen NC, Liu SS, Yu PH, Wu TY, Chen WT, Lee CC, Chen SC. Cranberry-containing products for prevention of urinary tract infections in susceptible populations: A systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2012. 172:988–996.

91. Stapleton AE, Dziura J, Hooton TM, Cox ME, Yarova-Yarovaya Y, Chen S, Gupta K. Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily: a randomized controlled trial. Mayo Clin Proc. 2012. 87:143–150.

92. McMurdo ME, Argo I, Phillips G, Daly F, Davey P. Cranberry or trimethoprim for the prevention of recurrent urinary tract infections? A randomized controlled trial in older women. J Antimicrob Chemother. 2009. 63:389–395.

93. Beerepoot MA, ter Riet G, Nys S, van der Wal WM, de Borgie CA, de Reijke TM, Prins JM, Koeijers J, Verbon A, Stobberingh E, Geerlings SE. Cranberries vs antibiotics to prevent urinary tract infections: a randomized double-blind noninferiority trial in premenopausal women. Arch Intern Med. 2011. 171:1270–1278.

94. Raz R, Chazan B, Dan M. Cranberry juice and urinary tract infection. Clin Infect Dis. 2004. 38:1413–1419.

95. Wing DA, Rumney PJ, Preslicka CW, Chung JH. Daily cranberry juice for the prevention of asymptomatic bacteriuria in pregnancy: a randomized, controlled pilot study. J Urol. 2008. 180:1367–1372.

96. Sen A. Recurrent cystitis in non-pregnant women. Clin Evid. 2006. 2558–2564.

97. Guay DR. Cranberry and urinary tract infections. Drugs. 2009. 69:775–807.

98. Sheffield JS, Cunningham FG. Urinary tract infection in women. Obstet Gynecol. 2005. 106:1085–1092.

99. Howell AB, Botto H, Combescure C, Blanc-Potard AB, Gausa L, Matsumoto T, Tenke P, Sotto A, Lavigne JP. Dosage effect on uropathogenic Escherichia coli anti-adhesion activity in urine following consumption of cranberry powder standardized for proanthocyanidin content: a multicentric randomized double blind study. BMC Infect Dis. 2010. 10:94.

100. Hisano M, Bruschini H, Nicodemo AC, Srougi M. Cranberries and lower urinary tract infection prevention. Clinics. 2012. 67:661–668.

101. Torpy JM, Schwartz LA, Golub RM. JAMA patient page. Urinary tract infection. JAMA. 2012. 307:1877.

102. Kontiokari T, Laitinen J, Jarvi L, Pokka T, Sundqvist K, Uhari M. Dietary factors protecting women from urinary tract infection. Am J Clin Nutr. 2003. 77:600–604.

103. Head KA. Natural approaches to prevention and treatment of infections of the lower urinary tract. Altern Med Rev. 2008. 13:227–244.

104. Handley MA, Reingold AL, Shiboski S, Padian NS. Incidence of acute urinary tract infection in young women and use of male condoms with and without nonoxynol-9 spermicides. Epidemiology. 2002. 13:431–436.

105. Franco AV. Recurrent urinary tract infections. Best Pract Res Clin Obstet Gynaecol. 2005. 19:861–873.

106. Hooton TM, Stamm WE. Diagnosis and treatment of uncomplicated urinary tract infection. Infect Dis Clin North Am. 1997. 11:551–581.

107. Strom BL, Collins M, West SL, Kreisberg J, Weller S. Sexual activity, contraceptive use, and other risk factors for symptomatic and asymptomatic bacteriuria. A case-control study. Ann Intern Med. 1987. 107:816–823.

108. Reid G. Probiotic agents to protect the urogenital tract against infection. Am J Clin Nutr. 2001. 73:2 Suppl. 437S–443S.

109. Reid G. The scientific basis for probiotic strains of Lactobacillus. Appl Environ Microbiol. 1999. 65:3763–3766.

110. Falagas ME, Betsi GI, Tokas T, Athanasiou S. Probiotics for prevention of recurrent urinary tract infections in women: a review of the evidence from microbiological and clinical studies. Drugs. 2006. 66:1253–1261.

111. Baerheim A, Larsen E, Digranes A. Vaginal application of lactobacilli in the prophylaxis of recurrent lower urinary tract infection in women. Scand J Prim Health Care. 1994. 12:239–243.

112. Uehara S, Monden K, Nomoto K, Seno Y, Kariyama R, Kumon H. A pilot study evaluating the safety and effectiveness of Lactobacillus vaginal suppositories in patients with recurrent urinary tract infection. Int J Antimicrob Agents. 2006. 28:Suppl 1. S30–S34.

113. Stapleton AE, Au-Yeung M, Hooton TM, Fredricks DN, Roberts PL, Czaja CA, Yarova-Yarovaya Y, Fiedler T, Cox M, Stamm WE. Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. Clin Infect Dis. 2011. 52:1212–1217.

114. Czaja CA, Stapleton AE, Yarova-Yarovaya Y, Stamm WE. Phase I trial of a Lactobacillus crispatus vaginal suppository for prevention of recurrent urinary tract infection in women. Infect Dis Obstet Gynecol. 2007. 2007:35387.

115. Reid G, Bruce AW, Fraser N, Heinemann C, Owen J, Henning B. Oral probiotics can resolve urogenital infections. FEMS Immunol Med Microbiol. 2001. 30:49–52.

116. Beerepoot MA, Ter Riet G, Nys S, van der Wal WM, de Borgie CA, de Reijke TM, Prins JM, Koeijers J, Verbon A, Stobberingh E, Geerlings SE. Lactobacilli vs antibiotics to prevent urinary tract infections: A randomized, double-blind, noninferiority trial in postmenopausal women. Arch Intern Med. 2012. 172:704–712.

117. Barrons R, Tassone D. Use of Lactobacillus probiotics for bacterial genitourinary infections in women: a review. Clin Ther. 2008. 30:453–468.

118. Abad CL, Safdar N. The role of lactobacillus probiotics in the treatment or prevention of urogenital infections--a systematic review. J Chemother. 2009. 21:243–252.

119. Naber KG, Cho YH, Matsumoto T, Schaeffer AJ. Immunoactive prophylaxis of recurrent urinary tract infections: a meta-analysis. Int J Antimicrob Agents. 2009. 33:111–119.

120. Bauer HW, Rahlfs VW, Lauener PA, Blessmann GS. Prevention of recurrent urinary tract infections with immuno-active E. coli fractions: a meta-analysis of five placebo-controlled double-blind studies. Int J Antimicrob Agents. 2002. 19:451–456.

121. Bauer HW, Alloussi S, Egger G, Blumlein HM, Cozma G, Schulman CC. A long-term, multicenter, double-blind study of an Escherichia coli extract (OM-89) in female patients with recurrent urinary tract infections. Eur Urol. 2005. 47:542–548. discussion 8.

122. Kim KS, Kim JY, Jeong IG, Paick JS, Son H, Lim DJ, Shim HB, Park WH, Jung HC, Choo MS. A prospective multi-center trial of Escherichia coli extract for the prophylactic treatment of patients with chronically recurrent cystitis. J Korean Med Sci. 2010. 25:435–439.

123. Ha US, Cho YH. Immunostimulation with Escherichia coli extract: prevention of recurrent urinary tract infections. Int J Antimicrob Agents. 2008. 31:Suppl 1. S63–S67.

124. Grabe M, Bishop MC, Bjerklund-Johansen TE, Botto H, Çek M, Lobel B, Naber KG, Palou J, Tenke P, Wagenlehner F. Guidelines on urological infections. Accessed 1 October 2012. Available at: http://www.uroweb.org/professional-resources/guidelines/online/.

125. Hopkins WJ, Elkahwaji J, Beierle LM, Leverson GE, Uehling DT. Vaginal mucosal vaccine for recurrent urinary tract infections in women: results of a phase 2 clinical trial. J Urol. 2007. 177:1349–1353. quiz 591.

126. Sivick KE, Mobley HL. Waging war against uropathogenic Escherichia coli: winning back the urinary tract. Infect Immun. 2010. 78:568–585.

127. Aune A, Alraek T, LiHua H, Baerheim A. Acupuncture in the prophylaxis of recurrent lower urinary tract infection in adult women. Scand J Prim Health Care. 1998. 16:37–39.

128. Alraek T, Soedal LI, Fagerheim SU, Digranes A, Baerheim A. Acupuncture treatment in the prevention of uncomplicated recurrent lower urinary tract infections in adult women. Am J Public Health. 2002. 92:1609–1611.

129. Cohen-Mansfield J, Biddison JR. The potential of wash-and-dry toilets to improve the toileting experience for nursing home residents. Gerontologist. 2005. 45:694–699.

130. Ogino M, Iino K, Minoura S. Habitual use of warm-water cleaning toilets is related to the aggravation of vaginal microflora. J Obstet Gynaecol Res. 2010. 36:1071–1074.

131. Nicolle LE. Uncomplicated urinary tract infection in adults including uncomplicated pyelonephritis. Urol Clin North Am. 2008. 35:1–12. v

132. Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, Moran GJ, Nicolle LE, Raz R, Schaeffer AJ, Soper DE. Infectious Diseases Society of America. European Society for Microbiology and Infectious Diseases. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011. 52:e103–e120.

133. Mayo Clinic. Prevention of urinary tract infection. Accessed 1 October 2012. Available at: http://www.mayoclinic.com/health/urinary-tract-infection/ds00286/dsection=prevention.

134. National Kidney and Urologic Diseases Information Clearinghouse. What I need to know about urinary tract infections. Accessed 1 October 2012. Available at: http://kidney.niddk.nih.gov/KUDiseases/pubs/uti_ez/index.aspx.

135. American Academy of Family Physicians. Tips on preventing urinary tract infections. Accessed 1 October 2012. Available at: http://familydoctor.org/familydoctor/en/diseases-conditions/urinary-tract-infections/prevention.html.