Prevention of Recurrent UTIs in Women

For the most current information on this topic, please see Urinary Tract Infections.

Full update July 2017

About 25% of women with a history of urinary tract infection (UTI) have recurrent uncomplicated UTIs.1,2 Evaluation for recurrent UTIs is beyond the scope of this document, but includes physical exam, post-void residual, diabetes screening in at-risk patients, and cystoscopy and/or imaging in patients with risk factors for a complicated etiology (e.g., unusual organisms, repeated pyelonephritis, pelvic floor dysfunction).1,2 Patients with hematuria and negative cultures require further workup to rule out more serious conditions (e.g., bladder cancer).2 The charts below review risk factors and therapeutic options to prevent recurrent UTIs.

Definitions and Risk Factors

Recurrent UTIs are more common than having a relapse.1 Hydration and postcoital voiding have not been proven to help, but cause no harm.8 Avoiding tight clothing is not expected to help, because wearing tight clothing is not a risk factor.1 The chart below differentiates between recurrent UTIs and relapses and identifies risk factors associated with recurrent UTIs.

Clinical Question

Suggested Approach Pertinent Information

How do you differentiate between recurrent infections and relapse?

Recurrent uncomplicated UTI:1,2

  • Two or more uncomplicated UTIs within six months.

OR

  • Three or more within 12 months.

Relapse (persistence):1,2

  • Infection with same isolate within two weeks after adequate treatment of an UTI.

What are the risk factors associated with recurrent UTIs?

Risk factors for recurrent UTIs:1,8

  • Diabetes
  • Elevated post-void residual
  • History of UTI before age 15
  • Incontinence
  • Increased frequency of intercourse
  • Maternal history of UTI
  • New sexual partners
  • Pelvic floor prolapse
  • Use of spermicides, diaphragms, or catheters

Therapeutic Options to Prevent Recurrent UTIs

Patients with frequent or particularly bothersome symptoms associated with recurrent UTIs may wish to try some form of prophylaxis.4 Over a six- to 12-month period, the number needed to treat (NNT) to prevent one symptomatic recurrence is about two patients [Evidence level B; nonquantitative systematic review].5 Prophylactic antibiotics may reduce the frequency of UTIs to less than one per year.5 Before starting prophylactic therapy, get a culture one to two weeks after an infection to rule out relapse.1 Recommend continuing prophylaxis for six to 12 months, or up to five years in difficult cases.1,8 Recurrences may happen shortly stopping prophylaxis.1 Vaginal estrogen can be offered to postmenopausal women based on small studies.1 Advise patients that it can take up to 12 weeks for vaginal estrogen to work.1 Probiotics (including lactobacillus), methenamine, vitamin C, and d-mannose cannot be recommended as proven preventive therapy based on current evidence.1,3,5,8,11 Avoid delaying treatment or relying on symptom management alone without antibiotics (e.g., ibuprofen, phenazopyridine). This may lead to negative outcomes (e.g., longer duration of symptoms, pyelonephritis).15 The chart below reviews therapeutic options to prevent recurrent UTIs in women.

Prophylactic Strategy

Options for Nonpregnant Womena,b,1,2

Comments

Continuous Antibiotic Prophylaxis

Cefaclor 250 mg

Cephalexin 125-250 mg

Ciprofloxacin 125 mgd

Fosfomycin 3 g every 10 days

Nitrofurantoin 50-100 mgc

Norfloxacin 200 mgd

Trimethoprim 100 mg

Trimethoprim/sulfamethoxazole 40/200 mg (1/2 single-strength tablet)

Take once daily at bedtime, unless otherwise noted at left.1

  • Alternatively, trimethoprim/sulfamethoxazole can be taken three nights a week.1
  • Best regimen unknown.1,2

Can reduce recurrent UTIs by 95%.4

Uropathogen resistance can occur.4

Incidence of adverse effects related to antibiotic prophylaxis is unknown.4,5

  • Adverse effects may include yeast infection, gastrointestinal upset, dermatologic reactions, and even C. difficile diarrhea.4,5

Postcoital Antibiotic Prophylaxis

Cephalexin 125-250 mg

Ciprofloxacin 125 mgd

Nitrofurantoin 50-100 mgc

Norfloxacin 200 mgd

Ofloxacin 100 mgd

Trimethoprim/sulfamethoxazole 40/200 mg or 80/400 mg (1/2 to 1 single-strength tablet)

For women who get UTIs 24 to 48 hours after intercourse.1

Take a single dose within two hours of intercourse.2

Fewer doses means fewer side effects compared to continuous prophylaxis.1

Acute Antibiotic
Self-treatment

Ciprofloxacin 250 mg twice dailyd

Norfloxacin 200 mg twice dailyd

Trimethoprim/sulfamethoxazole 160/800 mg (1 double-strength tablet) twice daily

Treat for three days.1

Reserve for reliable patient with well-documented, recurrent infections and good rapport with prescriber.1

When symptoms (e.g., dysuria, frequency, suprapubic pain) occur, patient initiates treatment.1

Instruct patients to call prescriber if symptoms last longer than 48 hours.1,8

Not an appropriate option for pregnant women.1

Cranberry

Multiple dosage forms available (e.g., juice, capsules, tablets).

Juice: limited evidence with ~120 to 300 mL daily.9

Capsules or tablets:

  • Limited evidence with products using at least
    36 mg of proanthocyanidins (PACs) daily (e.g., Ellura, CranTec Ultra [U.S.]).9,16
  • Limited evidence with products not documenting PACs (e.g., Cran-Max, Natural Cranberry Extract [Solgar Vitamin and Herb Co], both only available in the U.S.).9
  • Due to very limited evidence and issues with doses studied, avoid recommending Azo-Cranberry (U.S.).9

Optimal duration not clearly established, but most studies support a trial of up to about six months to see potential benefits.10

Capsules or tablets avoid additional sugar and calories associated with drinking juice.10

  • Juice adds sugar and up to 300 calories per day.10
  • Adverse effect with juice may include nausea, rash, and reflux.14

Though unproven, proposed mechanism may involve inhibiting E. coli adherence to urogenital mucosa.10

May be tried as a “natural” way to avoid or delay use of antibiotics.

  • Possible small benefit if any.
  • Some studies show no benefit, but unlikely to harm.9,10
  • Women may need to consume cranberry juice daily for three years to prevent one UTI.17
  1. Choose antibiotic based on tolerability, previous efficacy, local resistance patterns, and cost.1,2
  2. For pregnant women, indications for prophylaxis include recurrent UTIs prepregnancy, persistent bacteriuria despite two antibiotic courses, or one UTI plus conditions that increase risk of complications (e.g., diabetes, sickle cell trait). Use continuous or postcoital prophylaxis with nitrofurantoin 50 mg or cephalexin 250 mg until the last four weeks of pregnancy.1
  3. Long-term nitrofurantoin use, especially in the elderly, can lead to peripheral neuropathy and lung and liver toxicity.6,7,13 Avoid nitrofurantoin in patients with creatinine clearance <30 mL/min.12 Counsel patients to report possible symptoms of lung toxicity (e.g., cough, shortness of breath) and liver toxicity (e.g., headache, malaise, flu-like symptoms), and neuropathy (e.g., numbness, tingling).6
  4. Consider reserving quinolones for patients unable to take other alternatives (e.g., drug allergies, sensitivity results), as the benefits may not outweigh the risks (e.g., tendon, joint, muscle problems).18

Levels of Evidence

In accordance with the trend towards Evidence-Based Medicine, we are citing the LEVEL OF EVIDENCE for the statements we publish.

Level

Definition

A

High-quality randomized controlled trial (RCT)

High-quality meta-analysis (quantitative systematic review)

B

Nonrandomized clinical trial

Nonquantitative systematic review

Lower quality RCT

Clinical cohort study

Case-control study

Historical control

Epidemiologic study

C

Consensus

Expert opinion

D

Anecdotal evidence

In vitro or animal study

Adapted from Siwek J, et al. How to write an evidence-based clinical review article. Am Fam Physician 2002;65:251-8.

Project Leader in preparation of this clinical resource (330707): Beth Bryant, Pharm.D., BCPS, Assistant Editor

References

  1. Epp A, Larochelle A, Lovatsis D, et al. Recurrent urinary tract infection. J Obstet Gynaecol Can 2010;32:1082-101.
  2. Dason S, Dason JT, Kapoor A. Guidelines for the diagnosis and management of recurrent urinary tract infection in women. Can Urol Assoc J 2011;5:316-22.
  3. 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.
  4. Lichtenberger P, Hooton TM. Antimicrobial prophylaxis in women with recurrent urinary tract infections. Int J Antimicrob Agents 2011;(Suppl 38):36-41.
  5. Albert X, Huertas I, Pereiró II, et al. Antibiotics for preventing recurrent urinary tract infection in non-pregnant women. Cochrane Database Syst Rev 2004;(4):CD001209.
  6. 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;103:567-9.
  7. ADEs in elderly on long-term nitrofurantoin. ISMP Medication Safety Alert! Community/ambulatory care edition. October 2011.
  8. American College of Obstetricians and Gynecologists. ACOG practice bulletin No. 91: treatment of urinary tract infections in nonpregnant women. Obstet Gynecol 2008;111:785-94.
  9. Jellin JM, Gregory PJ, et al. Natural Medicines Comprehensive Database. http://naturaldatabase.com. (Accessed June 5, 2017).
  10. Allan GM, Nicolle L. Cranberry for preventing urinary tract infection. Can Fam Physician 2013;59:367.
  11. Beerepoot M, Geerlings S. Non-antibiotic prophylaxis for urinary tract infections. Pathogens 2016;5(2). doi: 10.3390/pathogens5020036.
  12. 2015 AGS Beers Criteria and Evidence Tables. http://geriatricscareonline.org/toc/american-geriatrics-society-updated-beers-criteria-for-potentially-inappropriate-medication-use-in-older-adults/CL001/. (Accessed June 5, 2017).
  13. Muller AE, Verhaegh EM, Harbarth S, et al. Nitrofurantoin’s efficacy and safety as prophylaxis for urinary tract infections: a systemic review of the literature and meta-analysis of controlled trials. Clin Microbiol Infect 2017;23:355-62.
  14. Hisano M, Bruschini H, Nicodemo AC, Srougi M. Cranberries and lower urinary tract infection prevention. Clinics (Sao Paulo) 2012;67:661-8.
  15. Grigoryan L, Trautner BW, Gupta K. Diagnosis and management of urinary tract infections in the outpatient setting: a review. JAMA 2014;312:1677-84.
  16. Jepson RG, Williams G, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev 2012;(10):CD001321.
  17. 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;103:1434-42.
  18. FDA. FDA drug safety communication: FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to disabling side effects. July 26, 2016. https://www.fda.gov/Drugs/DrugSafety/ucm511530.htm. (Accessed June 12, 2017).

Cite this document as follows: Clinical Resource, Prevention of Recurrent UTIs in Women. Pharmacist’s Letter/Prescriber’s Letter. July 2017.


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