First-Line Treatment for Uncomplicated UTI
For women with uncomplicated cystitis, use fosfomycin trometamol 3 grams as a single dose, nitrofurantoin 100 mg twice daily for 5 days, or pivmecillinam 400 mg three times daily for 3-5 days as first-line therapy. 1
Recommended First-Line Antibiotics in Women
The 2024 European Association of Urology guidelines establish clear first-line options based on efficacy, minimal resistance development, and reduced collateral damage 1:
Fosfomycin trometamol: 3 grams single dose for 1 day—offers the convenience of one-time dosing and is FDA-approved specifically for uncomplicated bladder infections in women 1, 2
Nitrofurantoin: Multiple formulations available 1:
- Macrocrystals: 50-100 mg four times daily for 5 days
- Monohydrate or macrocrystals: 100 mg twice daily for 5 days
- Macrocrystals prolonged release: 100 mg twice daily for 5 days
- Preferred due to effectiveness while causing minimal resistance problems 3
Pivmecillinam: 400 mg three times daily for 3-5 days 1
Alternative Second-Line Options
Use these alternatives only when first-line agents are contraindicated or unavailable 1:
Trimethoprim-sulfamethoxazole: 160/800 mg twice daily for 3 days—only if local E. coli resistance rates are below 20% 1, 3, 4
Trimethoprim alone: 200 mg twice daily for 5 days 1
Cephalosporins (e.g., cefadroxil): 500 mg twice daily for 3 days—only if local E. coli resistance is <20% 1
Critical Caveat: Fluoroquinolones Are NOT First-Line
Fluoroquinolones should NOT be used as first-line therapy for uncomplicated cystitis despite their effectiveness, because they cause significant "collateral damage" by selecting for multi-resistant pathogens and are needed for life-threatening infections 5, 6. Reserve fluoroquinolones for complicated infections or pyelonephritis 1.
Treatment in Men
Men with uncomplicated UTI require different management 1:
- Trimethoprim-sulfamethoxazole: 160/800 mg twice daily for 7 days (note the longer duration compared to women) 1
- Fluoroquinolones can be prescribed according to local susceptibility testing 1
- Always obtain urine culture in men to guide therapy 4
- Consider urethritis and prostatitis as alternative diagnoses 4
When Antibiotics May Not Be Necessary
For women with mild to moderate symptoms, symptomatic therapy with ibuprofen may be considered as an alternative to antimicrobial treatment after discussing with the patient 1. This approach recognizes that complications are rare and helps reduce antibiotic resistance 4.
When to Obtain Urine Culture
Urine culture is NOT needed for typical uncomplicated cystitis in women 1. However, obtain culture before treatment in these situations 1:
- Suspected acute pyelonephritis
- Symptoms not resolving or recurring within 4 weeks after treatment completion
- Atypical symptoms
- Pregnancy
- Men with UTI symptoms 4
- History of resistant organisms 4
Treatment Failure Protocol
If symptoms persist after completing antibiotics 1:
- Obtain urine culture with antimicrobial susceptibility testing 1
- Assume the organism is resistant to the initially used agent 1
- Retreat with a 7-day regimen using a different antibiotic class 1
Red Flags Requiring Different Management
These symptoms indicate complicated infection requiring urgent evaluation and different treatment 3:
- Fever, chills, or feeling systemically ill
- Back pain or flank pain (suggests pyelonephritis)
- Nausea or vomiting
- Vaginal discharge (suggests alternative diagnosis)
Expected Timeline
Symptoms should improve within 2-3 days of starting appropriate antibiotic therapy 3. If no improvement occurs by this timeframe, reassess the diagnosis and consider treatment failure 1.