What is the drug of choice for an uncomplicated urinary tract infection caused by Escherichia coli in a patient with normal renal function (estimated glomerular filtration rate ≥ 60 mL/min)?

Drug of Choice for E. coli UTI

Nitrofurantoin 100 mg orally twice daily for 5 days is the preferred first-line treatment for uncomplicated E. coli urinary tract infections in adults with normal renal function. 1

Primary Recommendation: Nitrofurantoin

Nitrofurantoin should be your default choice for uncomplicated cystitis caused by E. coli in patients with eGFR ≥60 mL/min. 1 This recommendation is based on:

• Exceptional susceptibility rates: 95.6% of E. coli isolates remain susceptible to nitrofurantoin despite over 60 years of clinical use 1, 2
• Minimal resistance development: Only 2.3% resistance rate, compared to 24% for fluoroquinolones and 29% for trimethoprim-sulfamethoxazole 2
• High cure rates: Achieves 88-93% clinical cure and 81-92% bacteriological eradication 3
• Antimicrobial stewardship: Classified as WHO "Access" antibiotic, preserving broader-spectrum agents 3

Alternative First-Line Option: Fosfomycin

Fosfomycin trometamol 3 g as a single oral dose is an equally acceptable alternative, particularly convenient for women. 1, 4 The FDA label specifically indicates fosfomycin for uncomplicated UTI caused by susceptible E. coli strains. 4

When Trimethoprim-Sulfamethoxazole May Be Used

Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days can only be considered if: 1

• Local E. coli resistance rates are documented to be <20% 1
• The patient has not used it in the previous 3 months 3

Critical caveat: Community resistance rates now approach 29%, which directly correlates with clinical treatment failure. 1 The 2011 IDSA/ESMID guidelines downgraded this agent from first-line status due to these resistance concerns. 1

Agents to Avoid for Empiric E. coli UTI

• Amoxicillin/ampicillin alone: Very high worldwide resistance rates in E. coli make these unsuitable for empiric therapy 1
• Fluoroquinolones (ciprofloxacin, levofloxacin): Should be reserved for pyelonephritis or complicated infections, not simple cystitis, due to 24% resistance rates and stewardship concerns 3, 2

Critical Contraindications to Nitrofurantoin

Do not use nitrofurantoin if: 1, 3

• eGFR <60 mL/min: Insufficient urinary drug concentrations and increased risk of peripheral neuropathy
• Suspected pyelonephritis: Poor renal tissue penetration makes it ineffective for upper tract infections
• Last trimester of pregnancy: Contraindicated in final 3 months

Clinical Decision Algorithm

For lower tract symptoms only (dysuria, frequency, urgency without fever or flank pain):

• → Prescribe nitrofurantoin 100 mg twice daily for 5 days 1, 3
• → Alternative: fosfomycin 3 g single dose 1

For upper tract suspicion (fever, flank pain, costovertebral angle tenderness):

• → Do NOT use nitrofurantoin 3
• → Use fluoroquinolone (ciprofloxacin 500-750 mg twice daily for 7 days OR levofloxacin 750 mg daily for 5 days) if local resistance permits 5
• → Alternative: oral cephalosporin (cefpodoxime 200 mg twice daily for 10 days) 5

Follow-Up Recommendations

• Routine post-treatment cultures are NOT indicated in asymptomatic patients 1, 3
• If symptoms persist or recur within 2 weeks: 1
  • Obtain urine culture with susceptibility testing
  • Assume possible resistance to initial agent
  • Re-treat with different appropriate agent for full 7-day course

Common Pitfalls to Avoid

• Using nitrofurantoin for "borderline" upper tract infections (mild flank pain or low-grade fever) is ineffective because it does not reach therapeutic concentrations in renal tissue 3
• Empiric ciprofloxacin for simple cystitis contributes to rising resistance and should be avoided unless resistance data specifically support its use 3
• Prescribing TMP-SMX without knowing local resistance rates leads to unacceptably high treatment failure when resistance exceeds 20% 1, 3