What is the recommended dose of Keflex (cephalexin) for an adult patient with an uncomplicated urinary tract infection (UTI)?

Keflex Dosing for Uncomplicated UTI

For uncomplicated cystitis in adults, prescribe cephalexin 500 mg every 12 hours (twice daily) for 7-14 days, though cephalexin should be considered an alternative rather than first-line agent. 1, 2

Dosing Regimen

• Standard dose: 500 mg every 12 hours orally for uncomplicated cystitis in patients over 15 years of age 1
• Treatment duration: 7-14 days is recommended by the FDA label 1
• Twice daily dosing is as effective as four times daily: Recent high-quality evidence demonstrates no difference in treatment failure rates between 500 mg twice daily versus 500 mg four times daily (12.7% vs 17%, P = 0.343) 3, 4

Important Caveats About Cephalexin Use

Cephalexin is classified as an alternative, not first-line agent for uncomplicated UTI due to inferior efficacy and more adverse effects compared to preferred antimicrobials 2

• First-line agents include fosfomycin, nitrofurantoin, and pivmecillinam according to European Urology guidelines 2
• Only use cephalexin when: First-line agents cannot be used or local E. coli resistance to β-lactams is <20% 2
• Avoid in high-risk scenarios: Do not use if the patient has used fluoroquinolones in the last 6 months or is from a urology department with higher resistance rates 5

Clinical Considerations

When to Obtain Cultures

• Always obtain urine culture if symptoms persist or recur within 2-4 weeks after treatment 2
• Do not routinely culture asymptomatic patients post-treatment 2

Treatment Failure Management

• If symptoms persist or recur within 2 weeks: Obtain culture and susceptibility testing, assume the organism is not susceptible to cephalexin 2
• Retreatment strategy: Use a different antimicrobial class for 7 days 2

Complicated vs Uncomplicated UTI

• Do not confuse uncomplicated cystitis with pyelonephritis, which requires different treatment approaches 2
• Catheter-associated UTI requires 7-14 days of treatment and represents a complicated infection, not an uncomplicated UTI 2, 5
• Males with UTI: Consider 14-day treatment when prostatitis cannot be excluded 5

Pharmacologic Rationale for Twice Daily Dosing

• Excellent urinary penetration: Cephalexin achieves concentrations of 500-1000 mcg/mL in urine following 250-500 mg oral doses, far exceeding the minimum inhibitory concentration for typical uropathogens 6
• Complete absorption: 70-100% of the dose appears in urine within 6-8 hours 6
• Improved adherence: Twice daily dosing improves patient adherence without compromising effectiveness 3, 4

Renal Dosing Adjustment

• Reduce dosage proportionally in patients with creatinine clearance <30 mL/min 6
• Anephric patients: Single doses of 250-500 mg result in high, prolonged serum concentrations 7