Treatment of Uncomplicated UTI Caused by E. coli
For uncomplicated urinary tract infections caused by E. coli, use fosfomycin trometamol 3g single dose, nitrofurantoin 100mg twice daily for 5 days, or pivmecillinam 400mg three times daily for 3-5 days as first-line therapy. 1, 2
First-Line Antibiotic Options
The 2024 European Association of Urology guidelines establish three preferred first-line agents for uncomplicated cystitis in women:
- Fosfomycin trometamol: 3g single dose for 1 day 1, 2
- Nitrofurantoin: 100mg twice daily for 5 days (macrocrystals, monohydrate, or prolonged-release formulations) 1, 2
- Pivmecillinam: 400mg three times daily for 3-5 days 1, 2
These agents maintain excellent activity against E. coli despite widespread resistance to other antibiotics. Nitrofurantoin demonstrates particularly favorable resistance patterns, with only 2.6% baseline resistance and declining resistance rates over time (20.2% at 3 months, 5.7% at 9 months). 1, 2
Second-Line Options (When First-Line Unavailable)
Use these alternatives only if local E. coli resistance rates are documented below 20%:
- Trimethoprim-sulfamethoxazole: 160/800mg twice daily for 3 days 1, 2, 3
- Cephalosporins (e.g., cefadroxil): 500mg twice daily for 3 days 1, 2
- Trimethoprim alone: 200mg twice daily for 5 days 1
The FDA label confirms trimethoprim-sulfamethoxazole is indicated for UTIs caused by susceptible E. coli, but resistance rates exceeding 20% in many regions limit its empiric use. 1, 3
Antibiotics to Avoid as First-Line
Do not use fluoroquinolones (ciprofloxacin, levofloxacin) as first-line therapy for uncomplicated UTIs. 1, 2 The FDA issued an advisory in 2016 warning against fluoroquinolone use for uncomplicated UTIs due to disabling and serious adverse effects that create an unfavorable risk-benefit ratio. 1 These agents cause significant collateral damage to fecal microbiota, promote C. difficile infection, and accelerate antimicrobial resistance. 1, 2
Similarly, avoid beta-lactam antibiotics as first-line therapy because they promote more rapid UTI recurrence through disruption of protective periurethral and vaginal microbiota. 1
Diagnostic Approach
For women presenting with typical lower urinary tract symptoms (dysuria, frequency, urgency) without vaginal discharge, clinical diagnosis alone is sufficient—do not routinely order urine culture or urinalysis for uncomplicated cases. 1, 2
Order urine culture only in these specific situations:
- Suspected acute pyelonephritis 1
- Symptoms persisting or recurring within 4 weeks after treatment completion 1, 2
- Atypical symptom presentation 1
- Pregnancy 1
Treatment Failure Management
If symptoms do not resolve by treatment completion or recur within 2 weeks, obtain urine culture with susceptibility testing. 1 Assume the organism is not susceptible to the initially used agent and retreat with a 7-day course of a different antibiotic. 1
Special Population Considerations
Men with UTI: Use trimethoprim-sulfamethoxazole 160/800mg twice daily for 7 days (longer duration than women). 1, 2 Always obtain urine culture in men to guide therapy. 4
Pregnant women: Use nitrofurantoin (avoid in first trimester), fosfomycin trometamol single dose, or short-course standard therapy. 1 Avoid trimethoprim in the first trimester and trimethoprim-sulfamethoxazole in the last trimester. 1, 2
Elderly patients (≥65 years): Use the same first-line agents and durations as younger adults, but obtain urine culture with susceptibility testing to adjust therapy after initial empiric treatment. 4
Common Pitfalls to Avoid
Do not treat asymptomatic bacteriuria in non-pregnant women, patients with diabetes, postmenopausal women, elderly institutionalized patients, or those with recurrent UTIs—treatment increases risk of symptomatic infection and promotes resistance. 1
Do not perform routine post-treatment urinalysis or cultures in asymptomatic patients after successful treatment. 1
Do not prescribe antibiotics based solely on per-dose cost. While fosfomycin and nitrofurantoin cost more per dose than trimethoprim-sulfamethoxazole, total treatment costs are lower when accounting for treatment failures from resistant organisms. 5
Alternative: Symptomatic Treatment
For women with mild to moderate symptoms, consider symptomatic therapy with ibuprofen as an alternative to immediate antimicrobial treatment after shared decision-making discussion. 1 This approach carries low risk of complications but may prolong symptom duration. 4