Recurrent urinary tract infections are a common, bothersome problem, particularly in female patients. As a result, providers will often try to stave off future infections by prescribing prophylactic antibiotics. Patients can often end up taking these antibiotics for months or even years, either for continued UTI prophylaxis or because their pharmacist or physician does not re-evaluate the therapy. While there may be clinical reasons for antibiotic prophylaxis to continue for 6-12 months or longer, it does not come without risks.

Studies show that long-term antibiotics do produce a statistically significant reduction in the recurrence of UTI. Often that the rate of UTI occurrence will return to baseline once those antibiotics are stopped. The typical duration of treatment is 6-12 months and guidelines state that there is no evidence supporting a duration longer than 12 months. However, many patients do continue UTI prophylaxis longer than that without any adverse events.

Some of the most common, evidence-supported options for prophylaxis include:

• Nitrofurantoin 50-100mg daily
• Trimethoprim/Sulfamethoxazole 40/200mg once daily or three times weekly
• Trimethoprim 100mg once daily
• Cephalexin 125-250mg once daily*
• Fosfomycin 3g every 10 days

*European guidelines recommend cephalexin only be used for treatment of susceptible strains

All antibiotics have risks that should be discussed with the patient prior to beginning prophylaxis and while making the decision to continue it. General adverse effects include allergy, rash, GI upset and oral or vaginal candidiasis.

Nitrofurantoin has the potential to cause pulmonary and hepatotoxicity, the risk of which increases with long-term exposure. Trimethoprim/sulfamethoxazole treatment can result in neurological effects, methemoglobinemia, blood dyscrasias, and Stevens-Johnson syndrome. Fluoroquinolones have been studied as UTI prophylaxis, but are not recommended due to the risk for tendon rupture, QT prolongation, and C. difficile infection.

Drug interactions with sulfamethoxazole/trimethoprim and fluoroquinolones are also important to consider. With sulfamethoxazole, I worry about 2C9 and potassium interactions. Quinolones are well known to exacerbate QT prolongation. I discuss the interaction profiles of these drugs at great length in my Drug Interactions book which you can get for free on Audible if its your first book.

Some clinicians are inclined to rotate antibiotics in an effort to mitigate side effects or resistance, but there is little evidence to support this practice.

The increasing concerns of antibiotic resistance are another reason to consider the implications of long-term antibiotic therapy, especially with broader spectrum agents like TMP/SMX. Additionally, data for most agents as UTI prophylaxis is older, which may overestimate efficacy and underestimate resistance. However, there is very little long-term data on resistance, which contributes to this being a clinical gray area.

One thing that providers should keep in mind is the guideline recommendation for non-antibiotic prophylaxis and lifestyle measures to help prevent recurrent UTIs. Some options include cranberry juice/supplements, adequate fluid intake, behavior modifications, and estrogen therapy when indicated.

This article was written by Meredith Grunig in collaboration with Eric Christianson, PharmD, BCPS, BCGP

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References:

AUA/CUA/SUFU. Recurrent Uncomplicated Urinary Tract Infections in Women Guideline, 2019. https://www.auanet.org/guidelines/recurrent-uti#x14424.

National Institute for Health and Care Excellence. Urinary tract infection (recurrent) guideline, 2018. https://www.nice.org.uk/guidance/ng112/chapter/Recommendations.

Ahmed H, Davies F, Francis N, et al. Long-term antibiotics for prevention of recurrent urinary tract infection in older adults: systematic review and meta-analysis of randomised trials. BMJ Open 2017;7.

Cetti R, Venn S, Woodhouse RJ. The risks of long-term nitrofurantoin prophylaxis in patients with recurrent urinary tract infection: A recent medico-legal case. British Journal of Urology International, 103, 2009.

Eells SJ, Bharadwa K, McKinnell JA, and Miller LG. Recurrent urinary tract infections among women: Comparative effectiveness of 5 prevention and management strategies using a Markov Chain Monte Carlo model. Clinical Infectious Diseases 58, 2, 2014.

Lichtenberger P, Horton TM. Antimicrobial prophylaxis in women with recurrent urinary tract infections. International Journal of Antimicrobial Agents, 38. 2011.

Muller AE, Verhaegh EM, Harbarth S, Mouton JW, Huttner A. Nitrofurantoin’s efficacy and safety as prophylaxis for urinary tract infections: A systematic review of the literature and meta-analysis of controlled trials. Clinical Microbiology and Infection, 23 2017.