What is the recommended dose of cephalexin (Cephalexin) for uncomplicated cellulitis?

Recommended Dose of Cephalexin for Uncomplicated Cellulitis

For adults with uncomplicated cellulitis, cephalexin 500 mg orally four times daily (every 6 hours) for 5 days is the recommended regimen if clinical improvement occurs. 1, 2

Standard Adult Dosing

• The FDA-approved dosing for skin and skin structure infections is 500 mg every 12 hours, but the Infectious Diseases Society of America specifically recommends 500 mg four times daily (every 6 hours) for cellulitis. 1, 2
• Treatment duration should be exactly 5 days if clinical improvement has occurred, with extension only if symptoms have not improved within this timeframe. 3, 1
• A landmark randomized trial demonstrated that 5-day courses are as effective as 10-day courses for uncomplicated cellulitis, eliminating the need for traditional 7-14 day regimens. 3, 1

Evidence Supporting Cephalexin Monotherapy

• Beta-lactam monotherapy with cephalexin is successful in 96% of uncomplicated cellulitis cases, confirming that MRSA coverage is usually unnecessary. 3, 1
• A high-quality randomized controlled trial (JAMA, 2017) demonstrated that adding trimethoprim-sulfamethoxazole (for MRSA coverage) to cephalexin provided no additional benefit for uncomplicated cellulitis without purulent drainage. 4
• β-hemolytic streptococci, particularly group A streptococcus, are the predominant pathogens in typical cellulitis, and cephalexin provides excellent coverage for these organisms. 1

When Cephalexin is NOT Appropriate

Do not use cephalexin alone if any of the following MRSA risk factors are present: 3, 1

• Penetrating trauma or injection drug use
• Purulent drainage or exudate
• Known MRSA colonization or infection elsewhere
• Systemic inflammatory response syndrome (SIRS)
• Cellulitis associated with abscess (requires incision and drainage)

In these scenarios, use clindamycin 300-450 mg four times daily as monotherapy (covers both streptococci and MRSA), or combine cephalexin with trimethoprim-sulfamethoxazole or doxycycline. 3, 1

Pediatric Dosing

• For children with skin and skin structure infections, the FDA-approved dose is 25-50 mg/kg/day divided into doses every 6 hours (four times daily), or the total daily dose may be divided and administered every 12 hours. 2
• For more severe infections, the dosage may be doubled. 2

Alternative Dosing Considerations

• A 2023 pilot randomized controlled trial (CJEM) investigated high-dose cephalexin (1000 mg four times daily) versus standard-dose (500 mg four times daily), showing fewer treatment failures with high-dose (3.2% vs 12.9%), though with more minor adverse effects. 5
• However, this remains investigational, and the standard 500 mg four times daily remains the evidence-based recommendation until larger trials confirm benefit. 1, 5

Critical Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema and inflammatory substances. 3, 1
• Treat predisposing conditions including tinea pedis (toe web infections), venous insufficiency, eczema, and lymphedema to reduce recurrence risk. 3, 1
• Examine interdigital toe spaces for fissuring, scaling, or maceration, as treating these eradicates colonization. 3

Common Pitfalls to Avoid

• Do not reflexively add MRSA coverage for typical nonpurulent cellulitis simply because MRSA prevalence is high in your community—MRSA is an uncommon cause of typical cellulitis even in high-prevalence settings. 3, 1
• Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for cellulitis, as their activity against beta-hemolytic streptococci is unreliable. 3
• Do not continue cephalexin beyond 5 days if clinical improvement has occurred—traditional 7-14 day courses are no longer necessary and increase antibiotic resistance. 3, 1
• For patients with immediate hypersensitivity reactions to penicillin (anaphylaxis, urticaria), cephalexin should be avoided due to cross-reactivity risk. 1