What is the antibiotic of choice for uncomplicated urinary tract infections (UTIs)?

Antibiotic of Choice for Uncomplicated UTI

Nitrofurantoin 100 mg twice daily for 5 days is the preferred first-line antibiotic for uncomplicated urinary tract infections in women, based on the most recent WHO and major society guidelines. 1, 2

First-Line Treatment Options

The choice among first-line agents depends primarily on local resistance patterns and patient-specific factors:

Preferred First-Line Agents

• Nitrofurantoin 100 mg twice daily for 5 days is recommended as the primary first-line option by IDSA, AUA, and WHO guidelines 1, 2

  • Has demonstrated lower treatment failure rates compared to trimethoprim-sulfamethoxazole 2
  • Causes minimal "collateral damage" (selection of resistant organisms) 1, 3
  • Remains effective against multidrug-resistant organisms 2

• Fosfomycin trometamol 3 g single dose is an alternative first-line option 1, 2, 4

  • Convenient single-dose regimen improves adherence
  • May have slightly inferior efficacy compared to 5-day nitrofurantoin regimens 2
  • WHO excluded it from their essential medicines list due to inferior outcomes versus nitrofurantoin 1

• Trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg twice daily for 3 days should only be used if local E. coli resistance rates are below 20% 1, 2, 3

  • Rising resistance rates globally have necessitated downgrading this from universal first-line status 1, 2
  • Should be avoided in patients recently exposed to this antibiotic 5

Second-Line Agents (Reserve for Specific Situations)

Fluoroquinolones should be avoided as first-line therapy despite high efficacy, due to serious safety concerns and antimicrobial stewardship principles:

• Ciprofloxacin and levofloxacin are highly effective in 3-day regimens but cause significant collateral damage 1, 3
• FDA has issued warnings about serious adverse effects affecting tendons, muscles, joints, nerves, and central nervous system 1
• Should be reserved for complicated infections where benefits outweigh risks 1
• Resistance rates are rising, particularly in patients previously exposed to fluoroquinolones 5, 3

Beta-lactam agents (amoxicillin-clavulanate, cefdinir, cefaclor, cefpodoxime-proxetil) in 3-7 day regimens:

• Should only be used when first-line agents cannot be used 1
• Have inferior efficacy and more adverse effects compared to first-line options 1
• Amoxicillin or ampicillin alone should never be used empirically due to high resistance rates and poor efficacy 1

Treatment Duration

• Nitrofurantoin: 5 days 1, 2, 4
• Fosfomycin: Single 3 g dose 1, 4
• TMP-SMX: 3 days 1, 4
• General principle: Use the shortest effective duration, generally no longer than 7 days 1

Critical Contraindications and Limitations

Nitrofurantoin should NOT be used for:

• Upper urinary tract infections or pyelonephritis (inadequate tissue concentrations) 2
• Infants under 4 months of age (risk of hemolytic anemia) 2
• Patients with significant renal impairment 2

Diagnostic Considerations

For initial uncomplicated UTI in women:

• Self-diagnosis with typical symptoms (frequency, urgency, dysuria, suprapubic pain) without vaginal discharge is sufficiently accurate 4
• Urine culture is NOT necessary before starting empiric therapy 2, 4

Urine culture with susceptibility testing IS required for:

• Recurrent UTIs (≥3 episodes per year or 2 within 6 months) 1, 6
• Treatment failure 1, 4
• History of resistant organisms 1, 4
• Atypical presentation 4
• All men with UTI symptoms 4
• Adults ≥65 years old 4

Special Populations

Men with uncomplicated UTI:

• Always obtain urine culture before treatment 4
• First-line: TMP-SMX, trimethoprim, or nitrofurantoin for 7 days (longer than women) 4
• Consider urethritis and prostatitis as alternative diagnoses 7, 4

Pregnant women:

• Cephalosporins (e.g., cefuroxime) or nitrofurantoin are preferred 6
• Avoid nitrofurantoin in late pregnancy near delivery 2

Key Antimicrobial Stewardship Principles

• Avoid surveillance testing in asymptomatic patients - do not treat asymptomatic bacteriuria except in pregnancy or before urologic procedures 1, 2
• Reserve fluoroquinolones and third-generation cephalosporins for serious infections to prevent selection of multidrug-resistant organisms 1, 3
• Consider local antibiograms when selecting empiric therapy, as resistance patterns vary significantly by region 2, 5
• Patient-initiated treatment may be appropriate for select patients with recurrent UTIs while awaiting culture results 1