Can cephalexin be dosed at 500mg every 8 hours (q8h) for uncomplicated skin and soft tissue infections?

Cephalexin 500mg Every 8 Hours for Uncomplicated Skin and Soft Tissue Infections

No, you should not use cephalexin 500mg every 8 hours (q8h) for uncomplicated skin and soft tissue infections—the correct dosing is 500mg every 6 hours (four times daily) according to both FDA labeling and IDSA guidelines. 1, 2, 3

Standard Dosing Regimen

The FDA-approved dosing for cephalexin in skin and soft tissue infections is 500mg orally four times daily (every 6 hours), not every 8 hours. 1 The IDSA guidelines consistently recommend cephalexin 500mg four times daily (qid) for methicillin-susceptible staphylococcal and streptococcal skin infections. 2

• The maximum daily dose is 4 grams per day, which the standard 500mg qid regimen achieves. 1
• Treatment duration should be 5-10 days depending on clinical response, with the IDSA specifically recommending at least 5 days but extending therapy if infection has not improved. 2, 3
• An every-8-hour dosing schedule (500mg tid) would only provide 1.5 grams daily, which is subtherapeutic for most skin infections requiring 500mg dosing. 1

Critical Prescribing Considerations

Before prescribing cephalexin at any interval, you must exclude MRSA risk factors, as cephalexin is completely ineffective against MRSA. 3, 2

Appropriate Use (When Cephalexin is Suitable):

• Non-purulent cellulitis without systemic signs of infection 2, 3
• Confirmed methicillin-susceptible Staphylococcus aureus (MSSA) or streptococcal infections 2
• No risk factors for MRSA colonization or infection 3

Contraindications to Cephalexin (Require MRSA-Active Agents):

• Purulent drainage present 3, 2
• Systemic signs of infection (SIRS criteria: temperature >38.5°C, heart rate >110 bpm, WBC >12,000) 2, 3
• History of MRSA colonization or previous MRSA infection 3
• Injection drug use 2, 3
• Penetrating trauma 2, 3
• Failed initial antibiotic therapy 3

For MRSA-risk scenarios, the IDSA strongly recommends vancomycin, trimethoprim-sulfamethoxazole, doxycycline, or clindamycin instead. 2, 3

Alternative Dosing Option

The FDA label does specify that for uncomplicated skin and skin structure infections, 500mg every 12 hours may be administered as an alternative regimen, but this is distinct from the every-8-hour schedule you asked about. 1 However, the every-6-hour (qid) regimen remains the standard recommendation in IDSA guidelines for more reliable coverage. 2

Monitoring and Expected Response

• Clinical response should be evident within 48-72 hours of initiating therapy. 3
• If no improvement occurs within 72 hours, consider alternative diagnoses, resistant organisms (particularly MRSA), or deeper/necrotizing infection. 3
• Complete the full course even if symptoms improve before completion. 3

Common Pitfalls to Avoid

The most critical error is using cephalexin for purulent infections without considering MRSA—in these cases, MRSA-active antibiotics should be used instead. 3 Additionally, necrotizing infections require immediate broad-spectrum IV antibiotics and urgent surgical intervention; cephalexin is completely inappropriate for these cases. 2, 3