Cephalexin Dosing for Adult Soft Tissue Infections
For typical adult soft tissue infections, the recommended dose of cephalexin is 500 mg orally four times daily (every 6 hours), not 1000 mg three times daily. 1, 2, 3
Standard Dosing Regimen
- The FDA-approved and guideline-recommended dose is 500 mg every 6 hours (four times daily) for skin and soft tissue infections in adults 3, 1
- The total daily dose ranges from 1-4 grams per day in divided doses 3
- Duration of therapy is typically 7 days, though this may be extended if clinical improvement is inadequate 2, 3
Alternative Dosing for Specific Infections
- For mild, uncomplicated infections only: 500 mg every 12 hours (twice daily) may be considered for streptococcal pharyngitis, skin and skin structure infections, and uncomplicated cystitis 3
- However, the standard four-times-daily regimen remains preferred for most soft tissue infections to maintain adequate tissue concentrations 1, 2
Critical Coverage Limitations
Cephalexin provides good coverage against methicillin-susceptible Staphylococcus aureus (MSSA) and streptococci but has NO activity against MRSA 1, 2
- If MRSA is suspected (purulent infections, failed initial therapy, known MRSA colonization), switch to MRSA-active agents such as trimethoprim-sulfamethoxazole, doxycycline, clindamycin, or vancomycin 1, 2
- Cephalexin misses Pasteurella multocida and anaerobes, making it inappropriate for animal/human bite wounds 1, 2
Important Clinical Caveats
- For penicillin-allergic patients with immediate hypersensitivity reactions (anaphylaxis, urticaria), avoid cephalexin due to cross-reactivity risk 1, 2
- For non-immediate penicillin allergies, cephalexin or cefazolin are acceptable alternatives to nafcillin/oxacillin 1, 2
- If doses greater than 4 grams daily are required, switch to parenteral cephalosporins (e.g., cefazolin 1 g every 8 hours IV) 3, 1
Why Not 1000 mg Three Times Daily?
The proposed regimen of 1000 mg TID (3 grams total daily) falls within the acceptable 1-4 gram daily range 3, but this dosing schedule is not supported by guidelines or the FDA label 1, 2, 3. The pharmacokinetics of cephalexin favor more frequent dosing (every 6-8 hours) to maintain therapeutic tissue levels, as the drug is rapidly cleared by the kidneys with 70-100% excreted in urine within 6-8 hours 4.