First-Line Treatment for Uncomplicated UTI
For women with uncomplicated UTI, use nitrofurantoin (100 mg twice daily for 5 days), fosfomycin (3g single dose), or trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 days) as first-line therapy, with the choice guided by local resistance patterns. 1, 2
Treatment Selection Algorithm
For Women with Uncomplicated Cystitis
Primary first-line options include: 1, 2
- Nitrofurantoin: 100 mg twice daily for 5 days (preferred due to extremely low resistance rates of 2.6-5.7%) 2
- Fosfomycin trometamol: 3g single dose for 1 day 1
- Trimethoprim-sulfamethoxazole: 160/800 mg twice daily for 3 days (only if local E. coli resistance is <20%) 1, 3
Alternative second-line options when first-line agents are contraindicated: 1
- Cephalosporins (e.g., cefadroxil 500 mg twice daily for 3 days) if local E. coli resistance <20% 1
- Trimethoprim alone: 200 mg twice daily for 5 days 1
For Men with Uncomplicated UTI
Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 7 days is the recommended first-line treatment, with fluoroquinolones reserved for culture-directed therapy based on susceptibility testing. 1, 4
Men require a longer 7-day treatment duration compared to the 3-5 day courses used in women. 4
Critical Resistance Considerations
Avoid fluoroquinolones as first-line therapy due to the FDA's 2016 warning about serious and potentially disabling side effects, plus their high collateral damage including C. difficile infection and disruption of protective microbiota. 2 Ciprofloxacin resistance rates can reach 24-83.8% in some communities. 5, 6
Avoid beta-lactams (including amoxicillin alone) as first-line therapy because they promote rapid UTI recurrence and damage protective periurethral and vaginal microbiota. 2 The WHO removed amoxicillin alone from first-line recommendations in 2021 due to high resistance rates. 2
Trimethoprim-sulfamethoxazole should only be used when local E. coli resistance is documented to be <20%, as resistance rates can reach 60-78% in many communities. 1, 5, 6
Diagnostic Approach Before Treatment
For women with typical symptoms (frequency, urgency, dysuria, nocturia, suprapubic pain) without vaginal discharge, self-diagnosis is sufficiently accurate to initiate empiric treatment without urine culture. 4
Obtain urine culture and sensitivity testing before treatment in these situations: 1, 4
- Recurrent UTIs (≥3 UTIs/year or 2 UTIs in 6 months) 1
- Suspected pyelonephritis 1
- Treatment failure or symptom recurrence within 4 weeks 1
- Atypical symptoms 1
- Men with UTI symptoms 4
- Adults ≥65 years old 4
- History of resistant organisms 4
Treatment Duration
Use the shortest reasonable antibiotic duration, generally no longer than 7 days. 1, 2 Specific durations vary by agent: nitrofurantoin and pivmecillinam for 5 days, trimethoprim-sulfamethoxazole for 3 days, fosfomycin as a single dose. 1
Common Pitfalls to Avoid
Never treat asymptomatic bacteriuria (except in pregnant women or before invasive urologic procedures), as treatment increases the risk of symptomatic infection, promotes bacterial resistance, and adds unnecessary costs. 1, 2
Do not perform routine post-treatment urine cultures in asymptomatic patients. 1 Only reculture if symptoms persist at the end of treatment or recur within 2 weeks. 1
Do not use fluoroquinolones empirically given their serious adverse effect profile and the availability of safer, equally effective alternatives. 2