What are the best antibiotics for an uncomplicated urinary tract infection (UTI) in an adult patient?

Best Antibiotics for Uncomplicated UTI

For uncomplicated lower urinary tract infections (acute cystitis) in adult women, the three recommended first-line antibiotics are nitrofurantoin (100 mg twice daily for 5 days), fosfomycin tromethamine (3 g single dose), or trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 days), with nitrofurantoin preferred when local resistance patterns allow. 1, 2, 3

First-Line Treatment Options for Women

The following antibiotics represent the optimal empiric choices based on efficacy, resistance patterns, and minimal collateral damage:

Nitrofurantoin (Preferred in Most Settings)

• Dosing: 100 mg orally twice daily for 5 days 1, 3
• Demonstrates superior clinical and microbiological cure rates compared to fosfomycin at 28 days post-treatment 1
• Proven significantly more effective than placebo for both symptomatic relief and bacteriological cure within 3 days (NNT = 1.6) 4
• Minimal propensity for collateral damage to intestinal flora, reducing risk of C. difficile infection 2, 5
• Important caveat: Not appropriate for pyelonephritis or upper UTIs due to insufficient tissue penetration 2

Fosfomycin Tromethamine (Single-Dose Convenience)

• Dosing: 3 g oral single dose, mixed with water before ingesting 2, 6
• Provides therapeutic urinary concentrations for 24-48 hours after single administration 2
• Comparable clinical efficacy to other first-line agents despite somewhat lower bacteriological efficacy 2, 7
• Excellent choice for multidrug-resistant organisms including ESBL-producing E. coli, VRE, and MRSA 2, 5
• Single-dose regimen improves adherence compared to multi-day courses 2
• Cost consideration: More expensive than nitrofurantoin, which influenced WHO's decision to prioritize nitrofurantoin 1

Trimethoprim-Sulfamethoxazole (When Resistance <20%)

• Dosing: 160/800 mg (one double-strength tablet) orally twice daily for 3 days 8, 3, 7
• Critical resistance threshold: Should only be used when local E. coli resistance is documented below 20% 2, 7
• Approximately 30% of gram-negative bacteria in some populations are now resistant 2
• When appropriate, highly effective with established efficacy data 3, 7

Second-Line Options

When first-line agents are contraindicated or unavailable:

Amoxicillin-Clavulanate

• Listed by WHO as first-choice for lower UTI alongside trimethoprim-sulfamethoxazole 1
• Important limitation: Generally inferior efficacy compared to first-line agents; amoxicillin or ampicillin alone should never be used empirically due to high resistance rates 9, 5

Fluoroquinolones (Reserve for Severe Infections)

• Critical warning: Should be reserved for more serious infections (pyelonephritis, prostatitis) due to FDA safety concerns affecting tendons, muscles, joints, nerves, and central nervous system 1
• High propensity for collateral damage and resistance development 2, 9
• Ciprofloxacin recommended by WHO only for mild-to-moderate pyelonephritis/prostatitis, not simple cystitis 1

Oral Cephalosporins

• Cefadroxil 500 mg twice daily for 3 days may be used when local E. coli resistance is <20% 9
• Generally less effective than first-line agents with more adverse effects 9, 5

Treatment in Men

Men with uncomplicated UTI require 7 days of treatment (not 3-5 days like women) and should always have urine culture performed to guide therapy: 3

• First-line: Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 7 days 1, 3
• Alternatives: Trimethoprim alone or nitrofurantoin for 7 days 3
• Important consideration: Always evaluate for possible urethritis or prostatitis in men presenting with UTI symptoms 3

Special Populations

Pregnant Women

• Fosfomycin 3 g single dose is safe and recommended for asymptomatic bacteriuria 2, 9
• Trimethoprim should be avoided in first trimester; trimethoprim-sulfamethoxazole avoided in third trimester 9

Patients with Renal Insufficiency

• Caution with fosfomycin: Elimination half-life increases from 5.7 hours to 40-50 hours in anuric patients 2
• Also use caution in patients with hypernatremia or cardiac insufficiency 2

Key Clinical Pitfalls to Avoid

1. Do not use fluoroquinolones for simple cystitis - Reserve for pyelonephritis or complicated infections 1, 9

2. Do not use fosfomycin for pyelonephritis or in men - Insufficient efficacy data for these populations 2, 9

3. Do not use amoxicillin/ampicillin alone empirically - High resistance rates make these inappropriate for empiric therapy 9, 5

4. Do not routinely culture urine in women with typical symptoms - Clinical diagnosis is sufficient for uncomplicated cystitis 9, 3

5. Culture IS required for: Treatment failure, recurrent infection within 4 weeks, atypical symptoms, men, pregnant women, or suspected pyelonephritis 9, 3

When to Consider Resistance Patterns

• If trimethoprim-sulfamethoxazole resistance exceeds 20% locally: Switch to nitrofurantoin or fosfomycin as first-line 2, 7
• If quinolone resistance exceeds 10% locally: Avoid fluoroquinolones for empiric therapy 5
• For patients recently exposed to antibiotics: Choose an agent from a different class 5
• For ESBL-producing organisms: Fosfomycin, nitrofurantoin, or pivmecillinam remain effective oral options 2, 5

Treatment Duration Summary

• Women with uncomplicated cystitis: 3-5 days (fosfomycin: single dose) 1, 3
• Men with uncomplicated UTI: 7 days 3
• Pyelonephritis (mild-moderate): Typically 7-14 days with fluoroquinolones or cephalosporins 1