First-Line Antibiotics for Uncomplicated UTI
For women with uncomplicated cystitis, use nitrofurantoin (100 mg twice daily for 5 days), fosfomycin trometamol (3 g single dose), or pivmecillinam (400 mg three times daily for 3-5 days) as first-line therapy; for men, use trimethoprim-sulfamethoxazole (160/800 mg twice daily for 7 days) as first-line treatment. 1
Treatment for Women
First-Line Options
The 2024 European Association of Urology guidelines establish clear first-line agents for women with uncomplicated cystitis:
- Fosfomycin trometamol: 3 g single dose (1 day) 1, 2
- Nitrofurantoin: Multiple formulations available 1, 3
- Macrocrystals: 50-100 mg four times daily for 5 days
- Monohydrate or macrocrystals: 100 mg twice daily for 5 days
- Prolonged release: 100 mg twice daily for 5 days
- Pivmecillinam: 400 mg three times daily for 3-5 days (where available) 1, 3
These agents are preferred because they demonstrate equivalent efficacy to broader-spectrum antibiotics while minimizing collateral damage to normal flora and reducing resistance development. 4, 5
Alternative Options (When First-Line Agents Cannot Be Used)
- Trimethoprim-sulfamethoxazole: 160/800 mg twice daily for 3 days—only if local E. coli resistance is <20% 1, 3
- Trimethoprim alone: 200 mg twice daily for 5 days (avoid in first trimester of pregnancy) 1
- Cephalosporins (e.g., cefadroxil): 500 mg twice daily for 3 days—only if local E. coli resistance is <20% 1, 3
Critical caveat: Fluoroquinolones should be reserved for more invasive infections due to their propensity for ecological adverse effects and resistance development, despite high efficacy. 6 Amoxicillin and ampicillin should not be used empirically due to high resistance rates. 3
Treatment for Men
Men with uncomplicated UTI require longer treatment duration (7 days) compared to women. 1
First-Line Option
- Trimethoprim-sulfamethoxazole: 160/800 mg twice daily for 7 days 1
- Fluoroquinolones can be prescribed according to local susceptibility testing 1
Alternative Options
Important consideration: Always obtain urine culture in men before initiating treatment, as UTIs in men warrant investigation for underlying urologic abnormalities or prostatitis. 7 The longer treatment duration (7 days vs. 3-5 days in women) accounts for potential prostatic involvement even in apparently uncomplicated cases. 7
Key Clinical Decision Points
When to Obtain Urine Culture Before Treatment
Urine culture is recommended in these specific situations: 1, 3
- Suspected acute pyelonephritis
- Symptoms that do not resolve or recur within 4 weeks after treatment completion
- Women presenting with atypical symptoms
- Pregnant women
- All men with UTI symptoms 7
Pregnancy Considerations
- Avoid trimethoprim in the first trimester 1, 3
- Avoid trimethoprim-sulfamethoxazole in the last trimester 1, 3
- Preferred agents include cephalosporins (e.g., cefuroxime) or nitrofurantoin 8
Treatment Failure Management
If symptoms do not resolve by the end of treatment or recur within 2 weeks: 1, 3
- Obtain urine culture and antimicrobial susceptibility testing
- Assume the infecting organism is not susceptible to the original agent
- Retreat with a 7-day regimen using a different antibiotic class
Non-Antimicrobial Option
For women with mild to moderate symptoms only, symptomatic therapy with ibuprofen may be considered as an alternative to immediate antimicrobial treatment after shared decision-making with the patient. 1, 3 However, this approach carries a low risk of progression and should be reserved for highly selected patients who understand the trade-offs. 7
Resistance Pattern Considerations
The choice of empirical therapy must account for local resistance patterns: 1, 3
- Local resistance rates should be <10% for pyelonephritis and <20% for lower UTI treatment 1
- Trimethoprim-sulfamethoxazole and fluoroquinolones have high resistance rates in many communities, precluding their routine empiric use 4, 6
- Nitrofurantoin, fosfomycin, and pivmecillinam maintain favorable resistance profiles globally 4, 5
Common Pitfalls to Avoid
- Do not use routine post-treatment urinalysis or urine cultures in asymptomatic patients 1
- Do not prescribe fluoroquinolones as first-line therapy for uncomplicated cystitis—reserve them for complicated infections or pyelonephritis 3, 6
- Do not use beta-lactams (amoxicillin-clavulanate, cefpodoxime-proxetil) as first-line empirical therapy—they are less effective than other options 6
- Do not treat men with the same short-course regimens used in women—men require 7 days minimum 1, 7