What is the dosing regimen for Cephalexin (Keflex) in the treatment of cellulitis, especially in patients with impaired renal function?

Cephalexin (Keflex) Dosing for Cellulitis

For non-purulent cellulitis in adults with normal renal function, cephalexin should be dosed at 500 mg orally four times daily (2 grams total daily dose) for 5-7 days. 1, 2

Standard Dosing Regimen

Adults with Normal Renal Function

• First-line dosing: 500 mg orally four times daily (every 6 hours) 1
• Duration: 5 days if clinical improvement occurs; otherwise continue for up to 7-10 days 1
• Alternative dosing: 1000 mg twice daily may be considered for improved adherence, though this is not FDA-approved 3

Pediatric Dosing

• Standard dose: 25-50 mg/kg/day divided into four doses 2
• Maximum: 500 mg per dose, four times daily

Renal Dosing Adjustments

Cephalexin requires dose adjustment in patients with impaired renal function:

Creatinine Clearance	Dosing Recommendation
>50 mL/min	500 mg every 6 hours (normal dose)
10-50 mL/min	500 mg every 8-12 hours
<10 mL/min	250-500 mg every 12-24 hours

Clinical Considerations

When to Use Cephalexin for Cellulitis

• Cephalexin is recommended for non-purulent cellulitis, which is typically caused by beta-hemolytic streptococci 1
• It is effective as monotherapy for uncomplicated cellulitis without abscess or purulent drainage 1

When to Consider Alternative Therapy

• For purulent cellulitis or when MRSA is suspected (e.g., with abscess, penetrating trauma, or injection drug use), alternative therapy should be considered 1
• In patients with severe penicillin allergy, clindamycin (300-450 mg TID) is an alternative 1

Monitoring and Duration

• Assess for clinical improvement within 48-72 hours
• Complete resolution typically occurs within 5-7 days
• If no improvement after 48-72 hours, consider:
  1. Possible MRSA infection requiring alternative antibiotics
  2. Deeper infection requiring surgical evaluation
  3. Non-infectious etiology

Evidence Quality and Considerations

Recent evidence suggests that 5 days of therapy is as effective as 10 days for uncomplicated cellulitis if clinical improvement occurs 1. A 2023 pilot study suggested that high-dose cephalexin (1000 mg QID) may have fewer treatment failures than standard dosing (500 mg QID), but with more minor adverse effects 3.

The 2014 IDSA guidelines provide the most current recommendations for cellulitis treatment, emphasizing that MRSA is an unusual cause of typical non-purulent cellulitis, and beta-lactam monotherapy (like cephalexin) is appropriate in most cases 1.

Common Pitfalls to Avoid

• Unnecessarily adding MRSA coverage for non-purulent cellulitis (a recent study showed no benefit of adding TMP-SMX to cephalexin for uncomplicated cellulitis) 4
• Using first-generation cephalosporins for suspected Lyme disease (they are ineffective) 1
• Failing to adjust dosing in patients with renal impairment
• Inadequate duration of therapy (less than 5 days)
• Missing deeper infections that may require surgical intervention

Remember to elevate the affected area to promote drainage of edema and inflammatory substances, which can hasten improvement 1.