What is the antibiotic of choice for a non-complicated urinary tract infection (UTI)?

Antibiotic of Choice for Uncomplicated UTI

For uncomplicated lower urinary tract infections in women, nitrofurantoin (100 mg twice daily for 5 days) is the preferred first-line antibiotic, with fosfomycin (3 g single dose) and trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 days) as equally appropriate alternatives. 1, 2

First-Line Treatment Options for Women

The most recent WHO Essential Medicines guidelines (2024) prioritize three Access-category antibiotics for uncomplicated lower UTI 1:

• Amoxicillin-clavulanic acid - Listed as first choice, though this represents a shift from earlier recommendations that excluded amoxicillin due to 75% median resistance rates in E. coli 1
• Nitrofurantoin - Maintains high susceptibility rates globally and demonstrates superior efficacy 1
• Trimethoprim-sulfamethoxazole - Effective when local resistance is acceptable 1

The European Urology guidelines (2025) provide more granular recommendations 2:

• Fosfomycin trometamol 3 g single dose 2
• Nitrofurantoin 100 mg twice daily for 5 days (multiple formulations acceptable) 2
• Pivmecillinam 400 mg three times daily for 3-5 days 2

Evidence Supporting Nitrofurantoin as Optimal Choice

Nitrofurantoin demonstrates superior microbiological cure rates compared to fosfomycin. A 2022 meta-analysis found that 5 days of nitrofurantoin showed significantly greater clinical and microbiologic resolution at 28 days compared to single-dose fosfomycin 1. This evidence led the WHO Expert Committee to exclude fosfomycin from their primary recommendations 1.

Placebo-controlled trials confirm nitrofurantoin's efficacy: bacteriological cure was achieved in 21/26 patients (81%) with nitrofurantoin versus 5/25 (20%) with placebo at 3 days (NNT = 1.6) 3. Clinical and symptomatic improvement occurred in 27/35 (77%) versus 19/35 (54%) respectively (NNT = 4.4) 3.

Alternative Options and When to Use Them

Cephalosporins (cefadroxil 500 mg twice daily for 3 days) should only be used if local E. coli resistance is <20% 2

Trimethoprim alone (200 mg twice daily for 5 days) is an alternative but contraindicated in first trimester pregnancy 2

Avoid fluoroquinolones for uncomplicated UTI due to their propensity for ecological damage and antimicrobial resistance - reserve them for serious infections like pyelonephritis 2, 4

Avoid amoxicillin/ampicillin empirically due to poor efficacy and high resistance rates (median 75% E. coli resistance globally) 1, 2

Treatment Duration and Special Populations

Women

• Standard duration: 3-5 days depending on agent 2, 5
• Nitrofurantoin: 5-7 days 5, 4
• Fosfomycin: single dose 2, 5
• Trimethoprim-sulfamethoxazole: 3 days 2, 5

Men with Uncomplicated UTI

Men require longer treatment courses (7 days) due to potential prostatic involvement 2, 5:

• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 7 days 2
• Trimethoprim for 7 days 5
• Nitrofurantoin for 7 days 5
• Always obtain urine culture and susceptibility testing in men 5
• Consider urethritis and prostatitis in the differential 5

Older Adults (≥65 years)

• Same first-line antibiotics and durations as younger adults 5
• Obtain urine culture with susceptibility testing to adjust therapy after empiric treatment 5
• Caution with long-term nitrofurantoin use in elderly due to potential pulmonary and hepatic toxicity 6

Women with Diabetes

• Treat similarly to women without diabetes if no voiding abnormalities present 4
• Use same first-line agents and durations 4

Critical Pitfalls to Avoid

Do not treat asymptomatic bacteriuria except in pregnant women and patients scheduled for invasive urinary procedures 2

Do not routinely obtain urine cultures in young healthy women with typical symptoms - clinical diagnosis is sufficient 5, 4

Reserve urine culture for: recurrent infection, treatment failure, history of resistant organisms, atypical presentation, all men, and older adults 5, 4

Do not use inadequate treatment duration in men - they require 7 days minimum versus 3-5 days in women 2

Avoid β-lactam agents (amoxicillin-clavulanate, cefpodoxime-proxetil) as empirical first-line therapy - they are less effective than other options 4

Treatment Failure Management

If symptoms persist or recur within 2 weeks 2:

• Obtain urine culture and antimicrobial susceptibility testing 2
• Use a different antibiotic for 7-day regimen 2
• Assume organism is not susceptible to original agent 2
• No routine post-treatment testing needed if asymptomatic 2