What is the antibiotic of choice for a patient with an uncomplicated urinary tract infection (UTI) due to Escherichia coli (E. coli)?

Antibiotic of Choice for Uncomplicated E. coli UTI

For uncomplicated urinary tract infections caused by E. coli, nitrofurantoin 100 mg orally every 6 hours for 7 days is the preferred first-line agent, with trimethoprim-sulfamethoxazole as an alternative only if local resistance rates remain below 20%. 1

First-Line Treatment Options

• Nitrofurantoin 100 mg orally every 6 hours for 7 days demonstrates 99% susceptibility rates against E. coli and should be the primary choice for uncomplicated lower UTI 2
• Trimethoprim-sulfamethoxazole (TMP/SMX) can be used as first-line therapy only when local E. coli resistance rates are below 19-21%, as treatment failure increases significantly above this threshold 1
• Fosfomycin 3 g orally as a single dose is FDA-approved for uncomplicated UTI caused by E. coli and represents a convenient alternative 3, 4

Fluoroquinolones: Use With Caution

• Ciprofloxacin and levofloxacin should be reserved for complicated UTI or pyelonephritis, not uncomplicated cystitis, due to resistance concerns and the need to preserve these agents for more serious infections 5, 4
• Levofloxacin 750 mg orally daily for 5 days is FDA-approved for complicated UTI and acute pyelonephritis caused by E. coli 4
• Local resistance patterns must guide empiric fluoroquinolone use—avoid if community resistance exceeds 10% 5

Treatment Duration

• 7 days is the standard duration for uncomplicated UTI in women using nitrofurantoin or TMP/SMX 6
• 5-7 days is appropriate for complicated UTI without bacteremia or severe sepsis 5
• Extend to 10-14 days only when concurrent bloodstream infection is documented or source control is inadequate 5

Critical Clinical Considerations

When to Suspect Resistance

• Healthcare-associated UTI, recent antibiotic exposure, skilled nursing facility residence, and age ≥65 years increase risk of multidrug-resistant E. coli 2
• ESBL-producing E. coli requires carbapenem therapy (imipenem, meropenem, or ertapenem) for severe infections, but fosfomycin or aminoglycosides may suffice for uncomplicated UTI if susceptible 3

Common Pitfalls to Avoid

• Never use cephalexin empirically—bug-drug mismatches occur in 41% of treatment failures versus 15% in successful cases 2
• Obtain urine culture before initiating therapy in patients with risk factors for resistance (healthcare exposure, recent antibiotics, recurrent UTI) 7
• Ensure culture follow-up occurs, as lack of follow-up correlates with higher return visit rates (75% vs 100%) 2

Algorithm for Antibiotic Selection

For uncomplicated cystitis in otherwise healthy women:

1. Start nitrofurantoin 100 mg PO q6h × 7 days 2
2. If contraindicated (CrCl <60 mL/min), use fosfomycin 3g single dose 3, 4
3. If TMP/SMX local resistance <20%, use TMP/SMX DS twice daily × 7 days 1

For complicated UTI or pyelonephritis:

1. Obtain blood and urine cultures before antibiotics 5
2. Start ciprofloxacin 500-750 mg PO twice daily or levofloxacin 750 mg PO daily 5, 4
3. If ESBL suspected (healthcare exposure, prior ESBL), use IV carbapenem then transition to oral agent based on susceptibilities 3
4. Treat for 5-7 days total unless bacteremia present (then 10-14 days) 5

For suspected ESBL-producing E. coli:

• Severe infection: meropenem or imipenem IV, then step down to oral agent per susceptibilities 3
• Non-severe UTI: fosfomycin 3g single dose or IV fosfomycin if available 3
• Aminoglycosides (gentamicin 5-7 mg/kg IV daily) for 5-7 days are effective for UTI specifically, even with carbapenem resistance 5