What is the first-line antibiotic for an uncomplicated urinary tract infection (UTI)?

First-Line Antibiotic for Uncomplicated UTI

Nitrofurantoin 100 mg twice daily for 5 days is the preferred first-line antibiotic for uncomplicated lower urinary tract infections in otherwise healthy, non-pregnant women. 1

Primary First-Line Options

The most recent WHO and IDSA/AUA guidelines establish a clear hierarchy for empiric treatment:

• Nitrofurantoin 100 mg twice daily for 5 days is the preferred first-line agent 2, 1

  • Demonstrates superior efficacy with lower treatment failure rates compared to trimethoprim-sulfamethoxazole 3
  • Maintains excellent activity against common uropathogens including E. coli despite decades of use 4
  • Has the lowest risk of pyelonephritis (0.3%) and prescription switch (12.7%) among first-line agents 3

• Trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg twice daily for 3 days is an alternative first-line option only if local E. coli resistance rates are below 20% 2, 1, 5

  • Real-world data shows TMP-SMX has 0.2% higher absolute risk of pyelonephritis and 1.6% higher risk of prescription switch compared to nitrofurantoin 3
  • Rising resistance rates have diminished its reliability in many communities 6, 3

• Fosfomycin trometamol 3 g single dose is listed as first-line but may have slightly inferior efficacy compared to nitrofurantoin 1

  • WHO guidelines excluded fosfomycin from top-tier recommendations based on RCT data showing nitrofurantoin achieved significantly greater clinical and microbiologic resolution at 28 days 2

Second-Line Options

When first-line agents cannot be used:

• Amoxicillin-clavulanate is recommended by WHO as a first-choice agent for lower UTI 2
• Oral cephalosporins (cephalexin, cefixime) for 3-7 days 6
• Fluoroquinolones (ciprofloxacin, levofloxacin) should be reserved as alternatives due to FDA safety warnings regarding tendons, muscles, joints, nerves, and central nervous system effects 2, 1

Critical Contraindications and Limitations

Do not use nitrofurantoin for:

• Upper UTIs or pyelonephritis (inadequate tissue concentrations) 1
• Infants under 4 months (risk of hemolytic anemia) 1
• Any degree of renal impairment 7
• Last trimester of pregnancy 7

Do not use for empiric therapy:

• Amoxicillin or ampicillin alone (poor efficacy, high resistance) 1
• TMP-SMX if patient recently exposed or in areas with >20% resistance 1, 5

Treatment Duration

• Nitrofurantoin: 5 days (balances efficacy with adverse effect minimization) 1
• TMP-SMX: 3 days 1, 5
• β-lactams: 3-7 days when other agents cannot be used 1
• Maximum duration should not exceed 7 days for acute cystitis 1

Diagnostic Approach

• Urine culture is not necessary before starting empiric therapy for uncomplicated UTI 1
• Obtain culture only if: symptoms persist or recur within 2-4 weeks after treatment 1
• Do not treat asymptomatic bacteriuria (except specific circumstances like pregnancy) 1

Common Pitfalls to Avoid

• Overuse of fluoroquinolones: Despite high efficacy, their use as first-line therapy contributes to collateral damage and resistance development 1, 6
• Ignoring local resistance patterns: TMP-SMX may be inappropriate in many communities due to resistance exceeding 20% 1, 3
• Using nitrofurantoin for pyelonephritis: This is ineffective and delays appropriate therapy 1
• Excessive treatment duration: Longer courses increase adverse effects without improving outcomes 1