Exploring the evidence behind antibiotic alternatives for recurrent UTIs

7 min read

About the Author

Dr. Carrie Aisen is a San Diego-based urologist focused on evidence-based medicine. Dr. Aisen received her MD from Columbia University.

More about this author

About the author

Dr. Carrie Aisen is a San Diego-based urologist focused on evidence-based medicine. Dr. Aisen received her MD from Columbia University.

More about this author

The goal in recurrent urinary tract infections is to decrease the number and lengthen the time between them, so a UTI recurrence should not be seen as a complete failure of the treatment.

There are many people who suffer from urinary tract infections and we need good strategies and treatments to offer these patients. Many patients are already searching for non-antibiotic alternatives when they present to the doctor or become interested in learning more about other options once they learn about some of the risks of antibiotic use. For more on the impact on antibiotic use, .

There are many possible treatments, but high quality research is limited on the topic. The AUA/SUFU/CUA guidelines include three recommendations for recurrent UTI prevention. The two highest recommendations are “moderate recommendations” based on level B evidence and are for antibiotic prophylaxis and vaginal estrogen (for peri/post-menopausal women). They also include a “conditional recommendation” for cranberry based on level C evidence (1). Below I review research discussed in the guidelines regarding some of the more commonly used non antibiotic treatments for recurrent urinary tract infections.

Upon review my takeaways include: there is some data, although of variable quality, supporting non antibiotic treatments for prevention of recurrent urinary tract infections; we need more ongoing research so that we can guide our patients with high quality evidence based medicine; and the goal in recurrent urinary tract infections is to decrease the number and lengthen the time between them, so a UTI recurrence should not be seen as a complete failure of the treatment.

The guidelines recommend that vaginal estrogen should be recommended to all peri and post-menopausal women(1). Raz et al found that topical estrogen was associated with significant decrease in the incidence of UTIs (16). A 2008 Cochrane review concluded that vaginal estrogen reduced the number of recurrent UTIs in post-menopausal women and that this reduction is not seen from oral estrogen (15).

Cranberry is included in the AUA/SUFU/CUA guidelines as a “conditional recommendation” based on level C evidence. Multiple small studies comparing cranberry to placebo have found a decrease risk in UTI recurrence with cranberry in formularies including juice, tablets, and powder. Kontiokari et al published that in a group of 150 women with e coli UTIs cranberry-lingonberry juice led to a decrease in the number of women who had a UTI in the next six months when compared to women taking a placebo or a lactobacillus drinks (2). Maki et al reported that drinking a cranberry beverage led to a decrease in the number of clinically diagnosed UTIs compared to placebo (3). Stothers et al found a decrease in the number of women reporting a UTI within one year in the cranberry tablet and juice groups when compared to placebo (4). Takahashi et al found a decreased recurrence rate of UTIs in the cranberry juice group compared to placebo (5). Vostalova et al reported that cranberry fruit powder with a quantified proanthocyanidin (PAC) content of 0.56% led to fewer UTIs and a longer time to first UTI compared to placebo (6). However, the Cochrane review from 2012 including 24 studies with over 4000 participants reported that cranberry products were not associated with a decrease in recurrent UTIs (7). One difficulty with cranberry as a treatment is the amount of PACs in each supplement or juice/juice cocktail is not often included. The low risk of cranberry and ease of access can be highly appealing to patients, however the Cochrane review highlighted the high drop out rate seen, particularly in the cranberry juice groups, suggesting that many patients do not find cranberry juice a sustainable regimen (7).

There is interest in lactobacillus probiotics as a preventive method for UTIs. Two double blinded, placebo controlled, randomized trials suggest a reduction in UTIs with probiotic use. Stapleton et al found a reduction in the number of recurrent UTIs in premenopausal women given a lactobacillus intravaginal probiotic compared to placebo in a small study over 10 weeks (9). Beerepoot et al compared bactrim prophylaxis to oral lactobacillus probiotics in post menopausal women in a non-inferiority trial. They showed a reduction in mean number of UTIs over 12 months with lactobacillus probiotics from 6.8 baseline to 3.3 with probiotics. However, they report that when compared to the bactrim group the probiotic did not meet their non-inferiority criteria (8).

Hooten et al reported that increased hydration lead to a decrease in the number of recurrent UTIs, increase in time between UTIs, and decrease risk of having 3 UTIs in a 12 month period (10). This study looked at women who drank less than 1.5 L of fluid daily and randomized them to an increased 1.5L of fluid daily or no additional fluids. This treatment option is especially interesting because there is minimal risk of adverse events or additional cost in encouraging patients to improve their hydration.

Alternative methods for preventing and managing chronic UTIs are emerging.

Emerging Non-antibiotic Prevention Options

D-mannose is another promising preventive strategy that has been investigated. Two studies compared D-mannose to antibiotics commonly used for recurrent UTI prophylaxis. Kranjcec et al compared D-mannose, nitrofurantoin, or no prophylaxis. They found a significant decrease in the risk of recurrent UTIs in the D-mannose and nitrofurantoin groups compared to the placebo group. While both nitrofurantoin and D-mannose were well tolerated, patients in the D-mannose group had a significantly lower risk of side effects than patients in the nitrofurantoin group (11). Porru et al compared D-mannose to bactrim and found a longer mean time to recurrence in the D-mannose group (200 days) than in the bactrim group (52.7 days) (12).

Another non antibiotic preventive medication that has been studied is methenamine. A study from 1981 by Brumfitt et al comparing methenamine and nitrofurantoin found a decrease in incidence of recurrent UTIs in both treatments, however the nitrofurantoin group had a greater reduction (13). In 1983 Brumfitt et al studied methenamine vs bactrim and also found a reduction in incidence of recurrent UTIs in both treatment groups (14).

Most of the available data is based on small studies of varying quality, making it difficult for these treatments to be included in guidelines. However, there is some data supporting the efficacy of many of these non-antibiotic methods to prevent recurrent UTIs. When I discuss the options with my patients I highlight the limited data because I want to make sure that they are making an informed decision. Hopefully, doctor and patient interest will help drive more of this research so that we can provide our patients with the best evidence based medicine possible. The studies that looked at adverse events found that most of these non-antibiotic treatments were well tolerated and come with low risk of adverse events. Finally, most of the studies look at end points of the number of UTIs in 12 months or time until the next recurrent UTI. This highlights that recurrent UTIs can be a lifelong struggle. I discuss with my patients that the goal is to decrease the number of UTIs, increase the time between them, and try to decrease the number of antibiotic courses that they need. With this understanding and approach, it does not make getting any UTIs a failure for the patient and their regimen and helps the patients find what works best for them.

References

  1. Anger J, Lee U, Ackerman AL, Chou R, Chughtai B, Clemens JQ, Hickling D, Kapoor A, Kenton KS, Kaufman MR, Rondanina MA, Stapleton A, Stothers L, Chai TC (2019) Recurrent uncomplicated urinary tract infections in women: AUA/CUA/SUFU guideline. J Urol 202(2):282–289.
  2. Kontiokari T, Sundqvist K, Nuutinen M et al: Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. BMJ 2001; 322:1571.
  3. Maki KC, Kaspar KL, Khoo C et al: Consumption of a cranberry juice beverage lowered the number of clinical urinary tract infection episodes in women with a recent history of urinary tract infection. Am J Clin Nutr 2016; 103:1434.
  4. 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.
  5. Takahashi S, Hamasuna R, Yasuda M et al: A randomized clinical trial to evaluate the preventive effect of cranberry juice (UR65) for patients with recurrent urinary tract infection. J Infect Chemother 2013;19:112.
  6. Vostalova J, Vidlar A, Simanek V et al: Are high proanthocyanidins key to cranberry efficacy in the prevention of recurrent urinary tract infection? Phytother Res 2015;29:1559.
  7. Jepson RG, Williams G, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database of Systematic Reviews 2012, Issue 10. Art. No.: CD001321. DOI: 10.1002/14651858.CD001321.pub5
  8. Beerepoot MA, 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; 172:704.
  9. Stapleton AE, Au-Yeung M, Hooton TM et al: 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.
  10. Hooton TM, Vecchio M, Iroz A et al. Effect of increased daily water intake in premenopausal women with recurrent urinary tract infections. JAMA Intern Med 2018; 178: 1509.
  11. Kranjcec B, Papes D, Altarac S: D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial. World J Urol 2014;32:79.
  12. Porru D, Parmigiani A, Tinelli C et al: Oral D-mannose in recurrent urinary tract infections in women: A pilot study. J Clin Urol 2014;7:208.
  13. Brumfitt W, Cooper J, Hamilton-Miller JM: Prevention of recurrent urinary infections in women: a comparative trial between nitrofurantoin and methenamine hippurate. J Urol 1981; 126:71.
  14. Brumfitt W, Hamilton-Miller JM, Gargan RA et al: Long-term prophylaxis of urinary infections in women: comparative trial of trimethoprim, methenamine hippurate and topical povidone-iodine. J Urol 1983;130:1110.
  15. Perotta C, Aznar M, Mejia R et al: Oestrogens for preventing recurrent urinary tract infection in postmenopausal women. Cochrane Database Syst Rev 2008; CD005131.
  16. 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.

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