Urology
Uncomplicated Urinary Tract Infections
The Role of Long-term Antibiotic Prophylaxis in Recurrent Uncomplicated Urinary Tract Infections
Long-term antibiotic prophylaxis for recurrent uncomplicated urinary tract infections (UTIs) remains a last-line strategy due to the risks of antibiotic resistance, adverse effects, and the lack of clarity about when to stop treatment. Clinicians should confirm the presence of infection, address modifiable risk factors, and exhaust nonantibiotic measures before considering low-dose antibiotics for carefully selected patients.
Long-term antibiotics have inherent risks that include gastrointestinal upset, blood dyscrasias, thrush, vaginitis, and liver strain. There is also the potential for the development of antibiotic resistance in subsequent infections. So, we do not want to put everyone on long-term antibiotics for the prevention of recurrent uncomplicated UTIs, nor do most patients want to be on them long-term. I consider long-term prophylactic antibiotics to be at the far end of my treatment paradigm. I would rather address all modifiable risk factors first before entertaining the idea of prescribing daily oral prophylaxis.
I start by making sure that the patient is having true recurrent UTIs, with documented urine cultures proving the infections, because other conditions can mimic UTIs. For example, conditions such as vaginitis, overactive bladder, interstitial cystitis, a low estrogen state, or genitourinary syndrome of menopause can also cause dysuria and burning in the vagina, so you do not want to just blame these symptoms on a UTI.
If someone really has recurrent UTIs, which is 3 UTIs in 1 year or 2 UTIs in a 6-month period, I start with education on healthy bladder habits, including urinating often enough and hydrating well enough. Then we may start the patient on the lowest toxicity form of UTI prevention. Based on the recent guideline from the American Urological Association (AUA), the Canadian Urological Association (CUA), and the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU), I often start with cranberry supplementation—a good-quality cranberry supplement with proanthocyanidins, the binding molecule responsible for preventing UTIs. If that is ineffective, my next step is methenamine hippurate. Finally, using vaginal estrogen in women can provide a double benefit, restoring the vaginal microbiome and improving genitourinary syndrome of menopause.
If a person tries these more conservative strategies but still gets UTIs, I usually start a workup, including a kidney ultrasound and a cystoscopy, to ensure that they do not have a nidus of infection. If the results are normal, this is when I will consider daily oral prophylactic antibiotics in patients with recurrent uncomplicated UTIs. The AUA/CUA/SUFU guideline lists recommended antibiotics and doses for oral prophylaxis. These include daily nitrofurantoin, trimethoprim, cephalosporins, and, less commonly, daily penicillins (because of gastrointestinal upset). These daily regimens are taken at a low dose at bedtime to provide longer contact with the urine. There is also oral fosfomycin, which is taken once a week. We stay away from daily fluoroquinolones because of their side-effect profiles.
However, the guideline does not definitively advise when to stop antibiotics. I tend to start patients with a 3-month antibiotic course, and, at every visit, I address the possibility of stopping the antibiotic, using shared decision making to develop a plan with the patient that considers the impact of recurrent UTIs on their own life.
Abolanle P, Akintelure D, Eylert M, et al. Exploring the efficacy of methenamine hippurate across different patient groups with recurrent urinary tract infections: experience from a university teaching hospital in South Wales, United Kingdom. Cureus. 2025;17(12):e98511. doi:10.7759/cureus.98511
Ackerman AL, Bradley M, D’Anci KE, Hickling D, Kim SK, Kirkby E. Updates to recurrent uncomplicated urinary tract infections in women: AUA/CUA/SUFU guideline (2025). J Urol. 2026;215(1):3-12. doi:10.1097/JU.0000000000004723
Chatterjee A, Ali I, Wong F, et al. Methenamine hippurate for the management and prophylaxis of recurrent urinary tract infections: a scoping review protocol. BMJ Open. 2025;15(4):e100458. doi:10.1136/bmjopen-2025-100458
Liu J, Xu K, Hu J, Wang L, Liu Z. Recurrent uncomplicated lower urinary tract infections in women. Curr Urol. 2025;19(2):90-94. doi:10.1097/CU9.0000000000000273
Muiños Fernández N, Martínez Salamanca JI, Pardo González de Quevedo JI, et al. Efficacy and safety of an ultra-low-dose 0.005% estriol vaginal gel in the prevention of urinary tract infections in postmenopausal women with genitourinary syndrome of menopause: a randomized double-blind placebo-controlled trial. Maturitas. 2024;190:108128. doi:10.1016/j.maturitas.2024.108128
Neugent ML, Kumar A, Hulyalkar NV, et al. Recurrent urinary tract infection and estrogen shape the taxonomic ecology and function of the postmenopausal urogenital microbiome. Cell Rep Med. 2022;3(10):100753. doi:10.1016/j.xcrm.2022.100753
Sanyaolu L, Best V, Cannings-John R, et al. Recurrent urinary tract infections and prophylactic antibiotic use in women: a cross-sectional study in primary care. Br J Gen Pract. 2024;74(746):e619-e627. doi:10.3399/BJGP.2024.0015
Xiong Z, Gao Y, Yuan C, Jian Z, Wei X. Preventive effect of cranberries with high dose of proanthocyanidins on urinary tract infections: a meta-analysis and systematic review. Front Nutr. 2024;11:1422121. doi:10.3389/fnut.2024.1422121
