What is the recommended dosing for Keflex (Cephalexin) in severe skin infections?

Keflex Dosing for Severe Skin Infections

For severe skin infections in adults, administer cephalexin 500 mg orally every 6 hours (four times daily) for 7-10 days, with the critical caveat that cephalexin should only be used if methicillin-resistant Staphylococcus aureus (MRSA) is not suspected. 1, 2, 3

Adult Dosing Regimen

• Standard dose: 500 mg orally four times daily (every 6 hours) for severe skin and soft tissue infections 1, 2, 3
• Duration: 7-10 days depending on clinical response, with the IDSA recommending at least 5 days but extending therapy if infection has not improved 4, 1, 2
• Maximum daily dose: 4 grams per day 2, 3
• For severe infections or less susceptible organisms, larger doses may be needed, but if daily doses exceed 4 grams, parenteral cephalosporins should be considered 3

Critical Clinical Considerations Before Prescribing

You must first determine if MRSA is suspected, as cephalexin is completely ineffective against MRSA and should not be used in these scenarios 1, 2:

Use Cephalexin When:

• Non-purulent cellulitis without systemic signs of infection 2
• Confirmed methicillin-susceptible Staphylococcus aureus (MSSA) or streptococcal infections 1, 2
• No risk factors for MRSA 2

Do NOT Use Cephalexin When (Use MRSA-Active Agents Instead):

• Purulent drainage present 2
• Systemic signs of infection (SIRS) 4, 2
• History of MRSA colonization or previous MRSA infection 2
• Injection drug use 4, 2
• Failed initial antibiotic therapy 2
• Penetrating trauma 4

For these MRSA-risk scenarios, the IDSA recommends vancomycin or other MRSA-active agents (trimethoprim-sulfamethoxazole, doxycycline, or clindamycin) instead 4, 2

Pediatric Dosing

• Standard dose: 25-50 mg/kg/day divided into 4 doses 1, 3
• For severe infections: dosage may be doubled 3
• Duration is 7-10 days depending on clinical response 1

Monitoring and Response

• Clinical response should be evident within 48-72 hours of initiating therapy 1
• If no improvement within 72 hours, consider alternative diagnoses, resistant organisms (particularly MRSA), or deeper/necrotizing infection 1
• The IDSA recommends extending treatment beyond 5 days if infection has not improved 4
• Complete the full course even if symptoms improve before completion 1

Important Caveats and Pitfalls

Common pitfall: Using cephalexin for purulent infections without considering MRSA. The presence of purulent drainage is a red flag that should prompt consideration of MRSA-active antibiotics instead 2

Necrotizing infections require immediate broad-spectrum IV antibiotics and urgent surgical intervention—cephalexin is completely inappropriate for these cases 2. The IDSA recommends vancomycin plus either piperacillin-tazobactam or imipenem/meropenem for severe infections requiring hospitalization 4

For severely compromised patients (malignancy on chemotherapy, neutropenia, severe immunodeficiency, immersion injuries, animal bites), broad-spectrum coverage is needed rather than cephalexin alone 4

Special Populations

• Penicillin-allergic patients (except those with immediate hypersensitivity reactions): cephalexin is a suitable alternative 1, 2
• Pregnant patients: cephalexin is FDA pregnancy category B and generally considered safe 1
• Renal impairment: patients with creatinine clearance less than 30 mL/min require dose reduction proportional to reduced renal function 5

Adjunctive Measures

• Elevation of the affected area 4
• Treatment of predisposing factors such as edema, obesity, eczema, venous insufficiency 4
• Careful examination of interdigital toe spaces in lower-extremity cellulitis, as treating toe web abnormalities may reduce recurrence 4