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#322 A dose a day keeps the UTI away?


CLINICAL QUESTION
What is the efficacy of antibiotic prophylaxis for recurrent urinary tract infections (UTI) in non-pregnant women?

BOTTOM LINE
Antibiotic prophylaxis decreases the risk of recurrent UTIs from 66% with placebo to 12% with prophylaxis over 6-12 months. More women will experience an adverse event with antibiotics (15% versus 8% with placebo). Long-term bacterial resistance and its individual clinical impact has not been well studied.


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EVIDENCE
  • Antibiotic prophylaxis for 6-12 months compared to placebo:
    • Meta-analysis, 10 Randomized Controlled Trials (RCTs), 430 women, 5 different antibiotics, varying regimens.1
      • ³1 microbiological recurrence, 8 RCTs, 372 women: 12% versus 66% placebo; number needed to treat (NNT)=2.
      • ³1 clinical UTI (example dysuria), 8 RCTs, 257 women: 7% versus 51% placebo; NNT=3.
      • Adverse events (most commonly skin rash, nausea): 15% versus 8% placebo, number needed to harm=14.
      • No difference in serious adverse events.
      • Limitations: Small studies, many >25 years old.
    • RCT not in above meta-analysis, 302 women, fosfomycin 3g every 10 days versus placebo for 6 months.2
      • ³1 microbiological recurrence: 7% versus 75% placebo; NNT=2.
    • Antibiotic prophylaxis for 6-12 months compared to non-antibiotic prophylaxis:
      • Meta-analysis, 3 RCTs, 482 women, antibiotics (nitrofurantoin 50mg or 100mg, TMP-SMX 400-80mg daily) versus non-antibiotics (oral lactobacillus, vaginal estrogen, or D-mannose powder):3
        • ³1 microbiological recurrence: 43% antibiotics versus 54% non-antibiotics; NNT=9.
        • No difference in adverse events.
        • Limitations: Large variation between comparators.
      • A small RCT not included in above meta-analysis showed no benefit.4
Context
  • Recurrent UTIs defined as: 3 episodes in 12 months, or 2 episodes in 6 months.5,6
  • No significant difference between nitrofurantoin and other antibiotics for UTI reduction;7 however, nitrofurantoin increased adverse events (example gastrointestinal) (~1.8x).
  • Rare cases of pulmonary toxicity with nitrofurantoin [1/5000 (acute) and 1/750-7500 (chronic)].8
  • One RCT, TMP-SMX versus lactobacillus: TMP-SMX resistance increased to 80-95% during treatment but returned to baseline (20-40%) after treatment.9
    • No difference in UTI recurrence 3 months after prophylaxis was stopped.
  • One cohort reported bacterial resistance to be 16% in controls and 21% in those receiving prophylactic antibiotics at 30 days to 1-year, clinical impact unclear.10

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Author(s):

  • Caitlin Finley MSc MD
  • Christina Korownyk MD CCFP
  • Jamie Falk BSc(Pharm) PharmD

1. Albert X, Huertas I, Pereiro I, et al. Cochrane Database Syst Rev. 2004; 3:CD001209.

2. Rudenko N, Dorofeyev A. Drug Res. 2005; 55:420−7.

3. Ahmed H, Davies F, Francis N, et al. BMJ Open. 2017; 7:e015233.

4. McMurdo MET, Argo I, Phillips G, et al. J Antimicrob Chemother. 2009; 63:389-95.

5. Bugs and Drugs. Treatment recommendations: recurrent cystitis. Alberta Health Services. Available at: https://www.bugsanddrugs.org/6B8724C9-6CDC-480F-8263-FCF94DA89FD9. Accessed March 14, 2022.

6. DynaMed. Recurrent Cystitis in Women. EBSCO Information Services. Available at: https://www.dynamed.com/condition/recurrent-cystitis-in-women. Accessed March 14, 2022.

7. Price JR, Guran LA, Gregory WT, et al. Am J Obstet Gynecol. 2016; 548-60.

8. LeBras M, Gauthier A. RxFiles Q&A Summary. March 2017. Available from: https://www.rxfiles.ca/RxFiles/uploads/documents/Nitrofurantoin-Pulmonary-Toxicity.pdf Accessed August 29, 2022.

9. Beerepoot MA, ter Riet G, Nys S, et al. Arch Intern Med. 2012; 172:704-12.

10. Langford BJ, Brown KA, Diong C, et al. Clin Infect Dis. 2021; 73(3):e782-e791.

Authors do not have any conflicts of interest to declare.