What is the typical dosing regimen for cephalexin (Keflex) in the treatment of skin infections?

Keflex Dosing for Skin Infections

For adults with skin infections, cephalexin (Keflex) should be dosed at 500 mg orally four times daily (every 6 hours) for 7-10 days, but only if methicillin-resistant Staphylococcus aureus (MRSA) is not suspected. 1, 2, 3

Adult Dosing Regimen

• Standard dose: 500 mg orally every 6 hours (four times daily) for most skin and soft tissue infections 1, 2, 3, 4
• Alternative dosing: 500 mg every 12 hours may be used for uncomplicated skin infections, though four-times-daily dosing is preferred for more reliable coverage 4
• Duration: 7-10 days depending on clinical response, with the Infectious Diseases Society of America (IDSA) recommending at least 5 days but extending therapy if infection has not improved 1, 2, 3
• Maximum daily dose: 4 grams per day 2, 4

Pediatric Dosing

• Standard dose: 25-50 mg/kg/day divided into four doses (every 6 hours) 1, 4
• Alternative dosing: Total daily dose may be divided every 12 hours for streptococcal pharyngitis and skin infections in children over 1 year of age 4
• Duration: 7-10 days depending on clinical response 1
• For severe infections: Dosage may be doubled 4

Critical Decision Points: When to Use vs. Avoid Cephalexin

Appropriate Use (When Cephalexin IS Indicated):

• Non-purulent cellulitis without systemic signs of infection 2, 3
• Confirmed methicillin-susceptible Staphylococcus aureus (MSSA) or streptococcal infections 1, 3
• Impetigo caused by Staphylococcus and Streptococcus species 3
• Penicillin-allergic patients (except those with immediate/anaphylactic hypersensitivity reactions) 5, 2, 3

Avoid Cephalexin (Use MRSA-Active Agents Instead):

• Purulent drainage present (abscesses, furuncles, carbuncles) 2, 3
• Systemic signs of infection (fever, tachycardia, hypotension, SIRS criteria) 2
• History of MRSA colonization or previous MRSA infection 2, 3
• Injection drug use 2, 3
• Failed initial antibiotic therapy 2, 3
• Penetrating trauma 2

For these MRSA-risk scenarios, the IDSA recommends empiric MRSA coverage with trimethoprim-sulfamethoxazole, doxycycline, or clindamycin instead of cephalexin. 2, 3

Monitoring and Expected Response

• Clinical improvement should be evident within 48-72 hours of initiating therapy 1, 2
• If no improvement within 72 hours, consider alternative diagnoses, resistant organisms (particularly MRSA), or deeper/necrotizing infection 1, 2
• Complete the full course even if symptoms improve before completion 1

Special Populations

• Pregnancy: FDA category B, generally considered safe 1, 2
• Penicillin allergy: Cephalexin is suitable for those without immediate hypersensitivity reactions, offering advantages over dicloxacillin due to suspension formulation availability and less frequent dosing 3

Common Pitfalls to Avoid

• Using cephalexin for purulent infections without considering MRSA is the most common error; MRSA-active antibiotics should be used instead 2
• Necrotizing infections require immediate broad-spectrum IV antibiotics and urgent surgical intervention; cephalexin is completely inappropriate for these cases 5, 2, 3
• Severely immunocompromised patients (malignancy on chemotherapy, neutropenia, severe immunodeficiency, immersion injuries, animal bites) require broad-spectrum coverage rather than cephalexin alone 2
• Cephalexin is completely ineffective against MRSA despite some older studies showing clinical response (likely due to spontaneous drainage or incision and drainage procedures rather than antibiotic effect) 2, 6

Adjunctive Measures

• Elevation of the affected area 2
• Treatment of predisposing factors: edema, obesity, eczema, venous insufficiency 2
• Examination of interdigital toe spaces in lower-extremity cellulitis to identify and treat tinea pedis 2