What is the proper dosing for Keflex (Cephalexin) for cellulitis?

Cephalexin Dosing for Cellulitis

For typical uncomplicated cellulitis, the proper dose of cephalexin (Keflex) is 500 mg orally four times daily (every 6 hours) for 5 days, extending only if clinical improvement has not occurred within this timeframe. 1, 2, 3, 4

Standard Adult Dosing Regimen

• Cephalexin 500 mg orally every 6 hours (four times daily) is the recommended dose for cellulitis in adults. 1, 2, 3
• The FDA-approved dosage 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. 4
• For uncomplicated cellulitis, 500 mg may alternatively be administered every 12 hours (twice daily), though four times daily dosing is more commonly recommended by the IDSA. 4

Treatment Duration

• Treat for exactly 5 days if clinical improvement has occurred—this is as effective as 10-14 day courses for uncomplicated cellulitis. 1, 2, 3
• Extend treatment beyond 5 days ONLY if the infection has not improved within this initial timeframe. 1, 2, 3
• Traditional 7-14 day courses are no longer necessary for uncomplicated cases. 1

When Cephalexin Monotherapy is Appropriate

• Cephalexin alone is appropriate for typical nonpurulent cellulitis without systemic signs of infection (no fever, hypotension, altered mental status, or rapid progression). 1, 2, 3
• Beta-lactam monotherapy like cephalexin is successful in 96% of typical cellulitis cases, confirming that MRSA coverage is usually unnecessary. 1
• Use cephalexin for patients without MRSA risk factors: no penetrating trauma, no injection drug use, no purulent drainage, no known MRSA colonization, and no systemic inflammatory response syndrome (SIRS). 1, 2, 3

Critical Situations Where Cephalexin Should NOT Be Used Alone

• Do NOT use cephalexin monotherapy if any of the following are present: 1, 2, 3

  • Penetrating trauma or injection drug use
  • Purulent drainage or exudate
  • Evidence of MRSA infection elsewhere or nasal MRSA colonization
  • Systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90 bpm, tachypnea >24 breaths/min
  • Signs of systemic toxicity, hypotension, or altered mental status
  • Suspected necrotizing fasciitis (severe pain out of proportion, skin anesthesia, rapid progression, bullous changes)

• In these scenarios, add MRSA coverage with trimethoprim-sulfamethoxazole, doxycycline (plus cephalexin), or use clindamycin monotherapy instead. 1

Pediatric Dosing

• For children with mild to moderate cellulitis: 25-50 mg/kg/day divided into 4 doses. 2, 4
• For more severe infections or MSSA: 75-100 mg/kg/day divided into 3-4 doses. 2, 4
• The FDA label specifies that for streptococcal pharyngitis and skin infections in children over 1 year, the total daily dose may be divided and given every 12 hours. 4

High-Dose Cephalexin Consideration

• A 2023 pilot trial found that high-dose cephalexin (1000 mg four times daily) had fewer treatment failures (3.2%) compared to standard-dose 500 mg (12.9% failure rate), though with more minor adverse effects. 5
• High-dose cephalexin (2000/125 mg twice daily for amoxicillin-clavulanate) can be considered for patients failing standard therapy or in regions with high antibiotic resistance. 1
• However, standard 500 mg four times daily remains the guideline-recommended dose. 1, 2, 3

Essential Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily—this promotes gravity drainage of edema and hastens improvement. 1, 2, 3
• Examine and treat interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration in lower extremity cellulitis—this reduces recurrence risk. 1, 2, 3
• Address predisposing conditions: venous insufficiency, lymphedema, chronic edema, eczema, and obesity. 1, 2, 3
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited. 1, 3

Common Pitfalls to Avoid

• Do NOT automatically add MRSA coverage for typical nonpurulent cellulitis—this represents overtreatment and increases antibiotic resistance. 1, 2, 3
• Do NOT extend treatment to 10-14 days if clinical improvement occurs by day 5—5 days is equally effective. 1, 2, 3
• Do NOT use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable. 1
• Do NOT overlook underlying conditions like tinea pedis or venous insufficiency that predispose to recurrent cellulitis. 2, 3

When to Hospitalize

• Hospitalize if systemic inflammatory response syndrome (SIRS), hypotension, altered mental status, severe immunocompromise, neutropenia, or concern for necrotizing infection is present. 1
• For hospitalized patients requiring IV therapy, use cefazolin 1-2 g IV every 8 hours as the preferred beta-lactam. 1