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

Keflex (Cephalexin) Dosing for Skin Infections

Standard Adult Dosing

For skin and soft tissue infections in adults, cephalexin should be dosed at 500 mg orally four times daily (every 6 hours) for 7-10 days, with treatment duration adjusted based on clinical response. 1, 2, 3

• The FDA-approved dosing range is 1-4 grams daily in divided doses, with 250 mg every 6 hours as the usual adult dose, though 500 mg every 12 hours may be used for uncomplicated skin infections 3
• The IDSA guidelines specifically recommend 500 mg four times daily for optimal coverage of skin infections 1, 2
• Maximum daily dose should not exceed 4 grams per day 1, 2

Pediatric Dosing

• The recommended pediatric dosage is 25-50 mg/kg/day divided into four doses 3
• For streptococcal pharyngitis and skin infections, the IDSA recommends 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days in penicillin-allergic patients 4
• Treatment duration is typically 7-10 days depending on clinical response 5

Critical Pre-Treatment Assessment: MRSA Risk Stratification

Before prescribing cephalexin, you must rule out MRSA risk, as cephalexin is completely ineffective against MRSA despite appearing to work in some clinical scenarios. 1, 2

When Cephalexin is APPROPRIATE:

• Non-purulent cellulitis without systemic signs of infection 1, 2
• Confirmed methicillin-susceptible Staphylococcus aureus (MSSA) or streptococcal infections 1, 2
• No MRSA risk factors present 1, 2
• Penicillin-allergic patients (except those with immediate hypersensitivity reactions) 4, 1, 5, 2

When Cephalexin is CONTRAINDICATED - Use MRSA-Active Agents Instead:

• Purulent drainage present 1, 2
• Systemic signs of infection (SIRS criteria) 1, 2
• History of MRSA colonization or previous MRSA infection 1, 2
• Injection drug use 1, 2
• Failed initial antibiotic therapy 1, 2
• Penetrating trauma 1

For these scenarios, use trimethoprim-sulfamethoxazole, doxycycline, clindamycin, or vancomycin instead 1, 2

Common Pitfall: The MRSA Paradox

A critical caveat: Some studies show cephalexin appearing to work for MRSA infections (92% cure rate in one trial), but this is misleading. 6

• The apparent efficacy is due to incision and drainage, spontaneous drainage, or needle aspiration—not the antibiotic itself 6
• Cephalosporins have no accepted, clinically relevant in vitro activity against MRSA, and relying on cephalexin for MRSA infections is a dangerous clinical error 6
• Always assume purulent infections may harbor MRSA and choose MRSA-active antibiotics 1, 2

Monitoring and Treatment Response

• Clinical improvement should be evident within 48-72 hours of initiating therapy 1, 5
• If no improvement occurs within 72 hours, consider: 1, 5
  • Alternative diagnoses
  • Resistant organisms (particularly MRSA)
  • Deeper or necrotizing infection requiring surgical intervention
• The IDSA recommends extending treatment beyond 5 days if infection has not improved 1
• Complete the full course even if symptoms resolve early 5

Special Clinical Scenarios

Necrotizing Infections - DO NOT USE CEPHALEXIN

• Necrotizing fasciitis requires immediate broad-spectrum IV antibiotics (ampicillin-sulbactam plus clindamycin plus ciprofloxacin, or carbapenems) and urgent surgical debridement 4, 1, 2
• Group A streptococcal necrotizing infections require clindamycin plus penicillin 4

Severely Immunocompromised Patients

• Patients with malignancy on chemotherapy, neutropenia, severe immunodeficiency, immersion injuries, or animal bites require broad-spectrum coverage rather than cephalexin alone 1

Pregnancy

• Cephalexin is FDA pregnancy category B and generally considered safe for pregnant patients 1, 5

Adjunctive Measures to Reduce Recurrence

• Elevate the affected extremity 1
• Address predisposing factors: edema, obesity, eczema, venous insufficiency 1
• Examine interdigital toe spaces in lower-extremity cellulitis for tinea pedis or maceration 1

Comparative Efficacy Data

• Cephalexin demonstrates equivalent clinical cure rates (87-96%) compared to other oral cephalosporins and fluoroquinolones for susceptible organisms 6, 7, 8, 9
• Twice-daily dosing (500 mg BID) shows equivalent efficacy to four-times-daily dosing (250 mg QID) for uncomplicated infections, though the IDSA prefers QID dosing for severe infections 3, 8, 10
• Adverse events occur in 11-26% of patients, primarily diarrhea (4-10%), nausea (3-6%), and vaginal mycosis (3-6% of females) 6, 9