Monday, March 24, 2014

Urinary Tract Infection Prophylaxis without Antibiotics: What Really Works

Urinary tract infections (UTIs) are a significant burden on the health care system responsible for 8.1 million office visits, over 100,000 hospitalizations, and $1.6 billion in direct and indirect cost. [1] The vast majority of infections are caused by Escherichia coli (E. coli), which is a colonizer of our gastrointestinal tracts that can infect our normally sterile urinary tracts. Modifiable and nonmodifiable factors have been identified that predispose individuals to having a UTI (see below).

Risk factors for UTI: [2,3]


  • female sex (simply due to shorter urethral length)
  • being sexually active
  • poor hygiene
  • altered urinary anatomy
  • infected urinary stones
  • catheterization
  • advanced age
  • hormonal changes (such as menopause)
  • chronic illness
  • immune suppression

Many individuals will have recurrent UTIs, which is generally defined as having more than 2 urinary tract infections in a year. [4] Unfortunately, many of these individuals will require antibiotic prophylaxis to help prevent these infections putting them at risk for developing infections with antibiotic resistant organisms and altering their beneficial natural microbial flora. [5] Therefore, there is great interest in finding non-antibiotic treatments that can be used to prevent UTIs.

Here, we review the two most commonly encountered non-antimicrobial prophylaxis treatments and whether they really work. 


Cranberry Juice - an Age Old Remedy or Placebo?


For hundreds of years, cranberry juice has been used to treat and prevent urinary tract infections. [6] Rigorous research into its mechanism began in the early 20th century.[6]  Initial research suggested that the benzoic acid in cranberry juice, which is excreted as hippuric acid, makes urine more acidic and inhibits bacterial growth.[7]   Research towards the end of the 20th century suggested that fructose and proanthocyanidins found in cranberry juice help coat the bladder and prevent the bacterial attachment and growth.[8]  However their exact role and whether additional unidentified compounds are at play have not been definitively concluded. This uncertainty raises into question what is the true “active ingredient” in cranberry juice. This also makes it difficult to accurately compare the various concentrates and extracts available on the market.

The first small randomized placebo-control trial with post-menopausal women published 1994 demonstrated that chronic cranberry juice consumption decreased yearly UTIs sparking a flurry of additional studies to evaluate cranberry juice’s effectiveness in other populations.[9]  However, many of these additional studies, including 2 larger randomized placebo-controlled studies, did not show the same effect. These studies also examined juice concentrates and concentrated tablets which advertise their increased strength over off the shelf cocktail juice and found questionable to no benefit. Finally, in 2012 the Cochrane Collaboration, a well respected group that assimilates and analyzes previously performed studies in order to reach a consensus, reviewed 24 studies and concluded that “cranberry juice does not appear to have a significant benefit in preventing UTIs.”[10]


Probiotics - A New Hope? 


Probiotics, which are a preparation of live bacteria administered to restore beneficial bacteria, are a rapidly growing area of interest. Many of us are aware of probiotic laden yogurt to help improve bowel regularity - which has become a billion dollar industry. A different organism than those found in yogurt, lactobacillus, has been found to colonize the areas around the urethral orifice (where urine leaves the body) and that their levels may be disrupted in individuals suffering from recurrent UTIs . Two small studies demonstrated that lactobacillus vaginal suppositories decreased recurrent UTIs.[11] There are currently no FDA approved lactobacillus vaginal suppositories.  However there are over the counter products currently being sold in Europe (most are not available in the U.S., however there are trials underway).[12]

Given these promising results and looking for an easier application, a randomized double-blinded non-inferiority trial comparing lactobacillus tablets and the antibiotic sulfamethoxazole/trimethoprim (bactrim) was published in 2012.[5]  Although they found the lactobacillus tablets inferior in reducing the time to the first infection and had more bacterial proven UTIs within the year of treatment, the two treatments were equivocal in several other important parameters. Additionally, whereas 80+% of bacteria from individuals taking the antibiotic had developed antimicrobial resistance, the lactobacillus group did not. These findings have been seen overall as positive for lactobacillus prophylaxis and that although perhaps not as effective as antibiotics, lactobacillus can confer some UTI prevention without promoting antibiotic resistances. Lactobacillus tablets are as of now not readily available, however one hopes this research will promote its development.


Summary


  • UTIs affect many individuals and have a large impact on the health system.
  • Despite their age old use, cranberry juice has not been shown to be effective in preventing UTIs.
  • Lactobacillus, although not as effective as antibiotics, may provide some prevention in developing UTIs, however more research is needed. 


This blog was written by Nikolai Sopko, MD, PhD and 1st Year Urology Resident at the Brady Urological Institute and Department of Urology at Johns Hopkins.  








1. Foxman B, Barlow R, D’Arcy H, Gillespie B, Sobel JD. Urinary Tract Infection. Ann Epidemiol. 2000;10(8):509–515. doi:10.1016/S1047-2797(00)00072-7.
2. Remis RS, Gurwith MJ, Gurwith D, Hargrett-Bean NT, Layde PM. Risk factors for urinary tract infection. Am J Epidemiol. 1987;126(4):685–94. Available at: http://www.ncbi.nlm.nih.gov/pubmed/3631058. Accessed March 21, 2014.
3. Pabich WL, Fihn SD, Stamm WE, Scholes D, Boyko EJ, Gupta K. Prevalence and determinants of vaginal flora alterations in postmenopausal women. J Infect Dis. 2003;188(7):1054–8. doi:10.1086/378203.
4. Commentary SI. Lactobacilli vs Antibiotics to Prevent Urinary Tract Infections. 2014;172(9):704–712.
5. Beerepoot MAJ, ter Riet G, Nys S, et al. Lactobacilli vs antibiotics to prevent urinary tract infections: a randomized, double-blind, noninferiority trial in postmenopausal women. Arch Intern Med. 2012;172(9):704–12. doi:10.1001/archinternmed.2012.777.
6. Raz R, Chazan B, Dan M. Cranberry juice and urinary tract infection. Clin Infect Dis. 2004;38(10):1413–9. doi:10.1086/386328.
7. Sobota AE. Inhibition of bacterial adherence by cranberry juice: potential use for the treatment of urinary tract infections. J Urol. 1984;131(5):1013–6. Available at: http://www.ncbi.nlm.nih.gov/pubmed/6368872. Accessed March 21, 2014.
8. 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(15):1085–6. doi:10.1056/NEJM199810083391516.
9. Avorn J, Monane M, Gurwitz JH, Glynn RJ, Choodnovskiy I, Lipsitz L a. Reduction of bacteriuria and pyuria after ingestion of cranberry juice. JAMA. 1994;271(10):751–4. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8093138.
10. Rg J, Williams G, Jc C, Jepson RG, Williams G, Craig JC. Cranberries for preventing urinary tract infections ( Review ) Cranberries for preventing urinary tract infections. 2013;(10):2012–2014. doi:10.1002/14651858.CD001321.pub5.Copyright.
11. Reid G, Bruce AW, Taylor M. Influence of three-day antimicrobial therapy and lactobacillus vaginal suppositories on recurrence of urinary tract infections. Clin Ther. 14(1):11–6. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1576619. Accessed March 21, 2014.
12. 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. doi:10.1155/2007/35387. 

8 comments:

  1. Hello Philips, you have good insight about UTI. I have learned a lot from reading your articles. Thank you for sharing such information for free. I want to add some information about preventing and curing UTI. I hope you will find useful -

    1. Drink plenty of water to flush out bacteria from the bladder.
    2. Drinking Cranberry Concentrate Liquid may also help prevent UTIs.
    3. Take Vitamin C regularly.
    4. Don't hold your urine.
    5. When you feel like you need to urinate,make sure you urinate properly.
    6. Wipe from front to back after bowel movements.
    7. Avoid tight fitting pants.
    8. Take showers rather than baths.

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