What is the recommended dose of Keflex (Cephalexin) for treating cellulitis?

Cephalexin Dosing for Cellulitis

For typical non-purulent cellulitis, prescribe cephalexin 500 mg orally four times daily (every 6 hours) for 5 days, extending treatment only if symptoms have not improved within this timeframe. 1, 2

Standard Adult Dosing

• Cephalexin 500 mg orally every 6 hours (four times daily) is the recommended dose for uncomplicated cellulitis in adults. 1, 2
• The FDA-approved dosing range for adults is 1-4 grams daily in divided doses, with 250 mg every 6 hours as the usual adult dose, though 500 mg every 6 hours is standard for skin and soft tissue infections. 2
• Treatment duration should be 5 days if clinical improvement occurs—extending to 7-10 days only if the infection has not improved within this initial period. 3, 1

When Cephalexin Monotherapy is Appropriate

• Beta-lactam monotherapy with cephalexin is successful in 96% of typical non-purulent cellulitis cases, as MRSA is an uncommon cause even in high-prevalence settings. 3, 1
• Use cephalexin alone for cellulitis without purulent drainage, abscess, penetrating trauma, injection drug use, or known MRSA colonization. 3, 1
• Do not reflexively add MRSA coverage (such as trimethoprim-sulfamethoxazole) to cephalexin—combination therapy provides no additional benefit in pure cellulitis without these risk factors. 3, 4

When to Add MRSA Coverage Instead

Do not use cephalexin monotherapy if any of these risk factors are present: 3, 1

• Purulent drainage or exudate
• Penetrating trauma or injection drug use
• Known MRSA colonization or infection elsewhere
• Systemic inflammatory response syndrome (SIRS)
• Failure to respond to initial beta-lactam therapy after 48-72 hours

In these cases, switch to clindamycin 300-450 mg orally every 6 hours (covers both streptococci and MRSA), or use combination therapy with trimethoprim-sulfamethoxazole plus a beta-lactam. 3, 1

Pediatric Dosing

• The usual pediatric dose is 25-50 mg/kg/day divided into four doses (every 6 hours). 2
• For skin and soft tissue infections in children over 1 year, the total daily dose may be divided and given every 12 hours instead. 2
• In severe infections, the pediatric dosage may be doubled. 2

High-Dose Cephalexin Consideration

• Emerging evidence suggests cephalexin 1000 mg four times daily may reduce treatment failure rates (3.2% vs 12.9% with standard dosing), though this comes with a higher proportion of minor gastrointestinal adverse effects. 5
• This high-dose regimen is not yet standard practice but may be considered for patients at higher risk of treatment failure. 5

Critical Adjunctive Measures

• Elevate the affected extremity to promote gravitational drainage and hasten improvement. 3, 1
• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration—treating these predisposing factors reduces recurrence risk. 3, 1
• Address underlying conditions such as venous insufficiency, lymphedema, and chronic edema. 3, 1

Common Pitfalls to Avoid

• Do not extend treatment beyond 5 days if clinical improvement has occurred—longer courses (7-14 days) are unnecessary for uncomplicated cellulitis. 3, 1
• Do not add MRSA coverage reflexively without specific risk factors—this represents overtreatment and increases antibiotic resistance. 3, 4
• Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable. 3

When to Hospitalize or Escalate Therapy

Consider hospitalization and IV antibiotics (cefazolin 1-2 g IV every 8 hours or vancomycin 15-20 mg/kg IV every 8-12 hours) if: 3, 1

• Systemic toxicity (fever, hypotension, tachycardia, altered mental status)
• Severe immunocompromise or neutropenia
• Concern for necrotizing fasciitis (severe pain out of proportion, rapid progression, skin anesthesia, bullous changes)
• Failure of outpatient oral therapy after 48-72 hours

Special Populations

• Morbidly obese patients (BMI ≥40): Standard cephalexin dosing appears adequate, with failure rates similar to non-obese patients (20% vs 14.5%, not statistically significant). 6
• Penicillin-allergic patients (except immediate hypersensitivity): Cephalexin remains an option due to low cross-reactivity. 1