What is the recommended treatment for uncomplicated urinary‑tract infection (cystitis) in a healthy adult, including alternatives for pregnancy, men, and complicated infections?

Treatment of Uncomplicated Urinary Tract Infection

For uncomplicated cystitis in healthy adult women, prescribe nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days as first-line therapy, or alternatively fosfomycin trometamol 3 g as a single dose, or trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days only if local E. coli resistance is <20%. 1

First-Line Treatment Options for Women

The 2024 European Association of Urology guidelines establish a clear hierarchy of first-line agents for uncomplicated cystitis in women:

Preferred First-Line Agents

• Fosfomycin trometamol 3 g single dose – recommended specifically for women with uncomplicated cystitis, offering the convenience of single-dose therapy 1, 2

• Nitrofurantoin (multiple formulations acceptable):

  • Macrocrystals 50–100 mg four times daily for 5 days 1
  • Monohydrate or macrocrystals 100 mg twice daily for 5 days 1
  • Macrocrystals prolonged release 100 mg twice daily for 5 days 1
  • Achieves clinical cure rates of 88–93% and bacterial cure rates of 81–92% 3

• Pivmecillinam 400 mg three times daily for 3–5 days (available primarily in Europe, not North America) 1

Alternative First-Line Agents

• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days – use ONLY when local E. coli resistance is documented to be <20% 1, 4

  • Clinical cure rates of 90–100% when organisms are susceptible 4
  • Efficacy plummets to 41–54% when organisms are resistant 4
  • Critical pitfall: Do not use empirically if the patient has taken trimethoprim-sulfamethoxazole in the preceding 3–6 months or has traveled outside the United States in the preceding 3–6 months 4

• Trimethoprim alone 200 mg twice daily for 5 days – contraindicated in the first trimester of pregnancy 1

• Cephalosporins (e.g., cefadroxil) 500 mg twice daily for 3 days – use only if local E. coli resistance is <20% 1

Treatment for Men

Men with uncomplicated cystitis require longer treatment duration than women:

• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 7 days (not 3 days as in women) 1, 4
• Fluoroquinolones may also be prescribed according to local susceptibility testing 1
• Critical distinction: The 3-day regimens effective in women are inadequate for men and should never be used 4

Treatment in Pregnancy

Pregnant women require special consideration:

• Screen for and treat asymptomatic bacteriuria with standard short-course treatment or single-dose fosfomycin trometamol 1
• Avoid trimethoprim-sulfamethoxazole in the last trimester of pregnancy 1, 4
• Avoid trimethoprim alone in the first trimester of pregnancy 1
• Nitrofurantoin and fosfomycin remain appropriate throughout pregnancy 3
• Urine culture is mandatory in pregnant women presenting with UTI symptoms 1

Symptomatic (Non-Antibiotic) Treatment Option

For women with mild to moderate symptoms, symptomatic therapy with ibuprofen may be considered as an alternative to antimicrobial treatment after consultation with the patient 1

Reserve (Second-Line) Agents

These should be used only when first-line agents cannot be used:

Fluoroquinolones (Reserve for Complicated Infections)

• Ciprofloxacin 250 mg twice daily for 3 days achieves 93–97% bacteriologic eradication rates 4, 3
• Levofloxacin is FDA-approved for uncomplicated UTI 5
• Critical caveat: Fluoroquinolones should be reserved for pyelonephritis or complicated infections, not simple cystitis, despite their high efficacy, to preserve their utility for serious infections and minimize collateral damage to normal flora 4, 3

β-Lactam Agents (Inferior Efficacy)

• Amoxicillin-clavulanate, cefdinir, cefaclor, cefpodoxime-proxetil for 3–7 days 3
• These agents have inferior efficacy and more adverse effects compared to first-line options 3
• Use only when no first-line agents are available 3

Agents to Avoid

Never use amoxicillin or ampicillin empirically for uncomplicated cystitis due to poor efficacy and worldwide resistance rates exceeding 30% among uropathogens 3, 6

Diagnostic Approach

When Urine Culture IS Recommended

• Suspected acute pyelonephritis 1
• Symptoms that do not resolve or recur within 4 weeks after completing treatment 1
• Women who present with atypical symptoms 1
• All pregnant women 1

When Urine Culture IS NOT Needed

• Routine post-treatment urinalysis or urine cultures are not indicated for asymptomatic patients 1
• In patients presenting with typical symptoms of uncomplicated cystitis (dysuria, frequency, urgency, absence of vaginal discharge), urine analysis leads to only minimal increase in diagnostic accuracy 1

Treatment Failure Management

If symptoms do not resolve by the end of treatment or recur within 2 weeks:

• Perform urine culture and antimicrobial susceptibility testing 1
• Assume the infecting organism is not susceptible to the agent originally used 1
• Retreat with a 7-day regimen using a different agent 1

Recurrent UTI (≥3 UTIs/year or 2 UTIs in 6 months)

Preventive Strategies

• Increase fluid intake in premenopausal women (weak recommendation) 1
• Vaginal estrogen replacement in postmenopausal women (strong recommendation) 1
• Immunoactive prophylaxis to reduce recurrent UTI in all age groups (strong recommendation) 1
• Consider probiotics containing strains of proven efficacy for vaginal flora regeneration (weak recommendation) 1
• Cranberry products may reduce recurrent UTI episodes, but evidence quality is low with contradictory findings (weak recommendation) 1

Diagnostic Workup for Recurrent UTI

• Diagnose recurrent UTI via urine culture (strong recommendation) 1
• Do not perform extensive routine workup (e.g., cystoscopy, full abdominal ultrasound) in women younger than 40 years with recurrent UTI and no risk factors (weak recommendation) 1

Key Resistance Thresholds and Decision Points

• The 20% resistance threshold for trimethoprim-sulfamethoxazole is critical: above this level, treatment failures outweigh benefits 4
• Hospital antibiograms often overestimate community resistance rates; local outpatient surveillance data is more accurate for guiding empiric therapy 4
• Recent antibiotic exposure (within 3–6 months) independently predicts resistance and should guide agent selection 4

Special Populations: Renal Impairment

• If eGFR >30 mL/min: nitrofurantoin 100 mg twice daily for 5 days is appropriate 3
• If eGFR <30 mL/min: consider fosfomycin 3 g single dose as an alternative 3