What medications are used for long-term treatment of urinary tract infections (UTIs) without antibiotics?

Non-Antibiotic Medications for Long-Term Treatment of Urinary Tract Infections

For long-term treatment of urinary tract infections without antibiotics, methenamine hippurate (1g twice daily) is the most effective non-antibiotic medication, followed by vaginal estrogen in postmenopausal women and cranberry products containing 36mg of proanthocyanidin. 1

First-Line Non-Antibiotic Options

Methenamine Hippurate

• FDA-approved for prophylactic or suppressive treatment of frequently recurring UTIs when long-term therapy is considered necessary 2
• Recommended dosage: 1g twice daily 1
• Works by releasing formaldehyde in acidic urine, creating a bactericidal effect 1
• Most effective in patients without incontinence and with fully functional bladders 1
• Should only be used after eradication of the initial infection with appropriate antimicrobial agents 2
• Has low risk of adverse events and doesn't contribute to antibiotic resistance 1
• Long-term studies show it reduces UTI recurrence by approximately two-thirds compared to pre-treatment periods 3

Vaginal Estrogen (for postmenopausal women)

• Clear recommendation with strong evidence from 30 RCTs and 1 large retrospective observational study 1
• Available as vaginal rings, inserts, or creams 1
• Helps restore vaginal microbiome, reduces vaginal atrophy, and decreases UTI frequency 1
• Minimal systemic absorption with no concerning safety signals regarding stroke, venous thromboembolism, breast cancer, colorectal cancer, or endometrial cancer 1
• Women with history of estrogen-related malignancies should discuss risks/benefits with their healthcare team 1
• Oral estrogen is NOT effective for UTI prevention 1

Cranberry Products

• Clear recommendation for products containing proanthocyanidin levels of 36mg 1
• Effective in reducing recurrent UTIs in women, children, and individuals susceptible to UTIs 1
• Evidence shows cranberry products reduce UTI risk by approximately 26% 1
• Insufficient data for older people, those with bladder emptying problems, or pregnant women 1

Second-Line Non-Antibiotic Options

Increased Water Intake

• Additional 1.5L of water daily may decrease UTI frequency 1
• Shown to decrease UTIs in one RCT among healthy women 1
• Low-risk intervention that can be reasonably offered to healthy women with recurrent UTIs 1

Probiotics

• Evidence is mixed and inconclusive 1
• Studies are heterogeneous regarding patient populations, specific probiotic strains, routes of administration, and study design 1
• Some evidence suggests certain Lactobacillus strains may be beneficial, particularly vaginal suppositories containing L. crispatus CTV-05 or combination of L. rhamnosus GR-1 + L. fermentum B-54 1
• Currently no formal recommendation due to inconsistent evidence 1

Monitoring and Follow-Up

• Patients should seek immediate medical attention if symptoms don't resolve within 4 weeks after treatment completion, recur within 2 weeks, or if they develop signs of pyelonephritis 4
• For patients whose symptoms don't resolve by the end of treatment or recur within 2 weeks, a urine culture with antimicrobial susceptibility testing should be performed 4
• Routine post-treatment urinalysis or urine cultures are NOT indicated for asymptomatic patients 4

Special Considerations

• Methenamine hippurate is most effective as prophylaxis after achieving abacteriuria, rather than for treating established infections 3
• For established infections, appropriate antibiotics should be used first, followed by methenamine hippurate for prophylaxis 3
• No evidence of urinary calculus formation, deterioration of renal function, or hematological changes with long-term methenamine hippurate use 3
• The growing problem of antibiotic resistance makes non-antibiotic approaches increasingly important 5, 6, 7
• Patients with risk factors for complicated UTI require closer monitoring and potentially different management approaches 4