What is the Keflex (cephalexin) regimen for uncomplicated urinary tract infections (UTIs) in the outpatient setting following an emergency department visit?

Cephalexin Regimen for UTI in Emergency Department Outpatient Treatment

For uncomplicated urinary tract infections (UTIs), cephalexin should be administered at 500 mg every 12 hours (twice daily) for 7-14 days, with 7 days being sufficient for most uncomplicated cases. 1, 2

Dosing Recommendations

• Dosage: 500 mg twice daily (BID)
• Duration: 7-14 days (7 days typically sufficient for uncomplicated UTIs)
• Total daily dose: Should fall within 1-4 grams per day as per FDA labeling 1

Recent research strongly supports the twice-daily dosing regimen, which is as effective as the traditional four-times-daily dosing while improving patient adherence:

• A 2023 multicenter cohort study showed no significant difference in treatment failure between twice-daily (12.7%) versus four-times-daily (17%) dosing (p=0.343) 3
• A 2025 study specifically examining ED patients found treatment failure rates of 18.7% for twice-daily versus 15.0% for four-times-daily dosing (p=0.465), confirming non-inferiority 4

Clinical Efficacy

Cephalexin has demonstrated good clinical outcomes for UTI treatment:

• 81.1% clinical success rate in patients discharged from the ED with uncomplicated UTIs 5
• High urinary concentrations make it effective against common UTI pathogens 6

Patient Selection Considerations

Cephalexin is most appropriate for:

• Patients with uncomplicated UTIs
• Cases where local antibiogram data supports cephalexin use
• Patients who would benefit from a simpler twice-daily regimen

Important Caveats

1. Culture and Susceptibility: While empiric therapy can begin immediately, urine culture with susceptibility testing is essential to confirm appropriate treatment 2

2. Alternative Agents: According to IDSA guidelines, oral β-lactams (including cephalexin) are generally considered less effective than other available agents for pyelonephritis 7. For pyelonephritis:

   • Fluoroquinolones for 5-7 days or TMP-SMX for 14 days are preferred if susceptible 2
   • If using cephalexin for pyelonephritis, consider an initial IV dose of ceftriaxone 1g 7

3. Treatment Failure: Monitor for clinical improvement within 48-72 hours. Consider alternative antibiotics if symptoms persist 2

4. Complicated UTIs: May require longer treatment duration (full 14 days) and closer monitoring 2

By following these guidelines, emergency department physicians can effectively treat uncomplicated UTIs with cephalexin in the outpatient setting while maximizing adherence through the simplified twice-daily dosing regimen.