What is the best antibiotic for an otherwise healthy adult with an uncomplicated urinary tract infection caused by Escherichia coli (E. coli)?

Best Antibiotic for E. coli Urinary Tract Infection

For an otherwise healthy adult with uncomplicated E. coli cystitis, nitrofurantoin (5-day course), fosfomycin trometamol (single 3-g dose), or pivmecillinam (5-day course) are the recommended first-line treatments. 1

First-Line Treatment Options for Uncomplicated Cystitis

The 2024 European Association of Urology guidelines prioritize the following empiric regimens for uncomplicated cystitis caused by E. coli 1:

• Nitrofurantoin: 5-day course 1, 2
• Fosfomycin trometamol: Single 3-g dose 1, 2
• Pivmecillinam: 5-day course 1, 2

These agents are preferred because they maintain high efficacy against E. coli while minimizing collateral damage to normal flora and reducing selection pressure for resistance 2.

Second-Line Options

When first-line agents are contraindicated or unavailable 1:

• Trimethoprim-sulfamethoxazole: Only if local resistance rates are <20% and the patient has not recently been exposed to this agent 1, 3, 2
• Fluoroquinolones (ciprofloxacin, levofloxacin): Reserved for situations where resistance is <10% locally 1, 2
• Oral cephalosporins (cephalexin, cefixime): Alternative options 2
• Amoxicillin-clavulanate: Can be considered as second-line 2

Critical Resistance Considerations

A major pitfall is empirically using trimethoprim-sulfamethoxazole or fluoroquinolones without knowing local resistance patterns. 2, 4 High community resistance rates to these agents have been documented globally, particularly in patients with:

• Recent antibiotic exposure 2
• Risk factors for ESBL-producing organisms 2
• Healthcare-associated infections 1

The increasing prevalence of multidrug-resistant E. coli clones (such as ST131) has made knowledge of local susceptibility patterns essential 4.

Treatment Duration

For uncomplicated cystitis 1:

• 3-5 days for most first-line agents
• Single dose for fosfomycin trometamol
• 7 days for nitrofurantoin in some protocols

Shorter courses (3-day regimens) are more effective than single-dose therapy for most antimicrobials except fosfomycin 5, 6.

When to Avoid Certain Antibiotics

Do not use for uncomplicated cystitis 1:

• Nitrofurantoin, fosfomycin, or pivmecillinam for pyelonephritis (insufficient data on efficacy) 1
• Broad-spectrum agents (carbapenems, novel β-lactam combinations) unless culture confirms multidrug-resistant organisms 1

Monitoring and Follow-Up

• No routine post-treatment cultures are needed if symptoms resolve 1
• Obtain urine culture if symptoms persist beyond treatment completion or recur within 2 weeks 1
• If treatment fails, assume resistance to the initial agent and use a different class for 7 days 1