Cephalexin Dosing for Outpatient Skin and Soft Tissue Infections
For uncomplicated skin and soft tissue infections in adults, cephalexin should be dosed at 500 mg orally every 6 hours (four times daily) for 5 days, extending only if clinical improvement has not occurred within this timeframe. 1, 2
Standard Adult Dosing
The FDA-approved dosing for skin and skin structure infections is 250 mg every 6 hours, but 500 mg every 12 hours (twice daily) is an acceptable alternative regimen. 1 However, the more traditional four-times-daily dosing at 500 mg provides more consistent drug levels and may be preferred for moderate infections. 1
- For mild infections: 250 mg orally every 6 hours 1
- For moderate infections or less susceptible organisms: 500 mg orally every 6 hours 1
- Alternative twice-daily dosing: 500 mg orally every 12 hours is FDA-approved specifically for skin infections 1
Treatment Duration
Treat for 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 2 This represents a significant departure from traditional 7-14 day courses, which are no longer necessary for uncomplicated cases. 3
Pediatric Dosing
For children with skin and soft tissue infections, the usual recommended dosage is 25-50 mg/kg/day divided into doses every 6 hours (four times daily). 1 For streptococcal pharyngitis and skin infections in patients over 1 year of age, the total daily dose may be divided and administered every 12 hours (twice daily). 1
When Cephalexin is Appropriate
Cephalexin is appropriate for typical nonpurulent cellulitis without systemic signs of infection, as beta-lactam monotherapy achieves 96% success rates even in settings with high MRSA prevalence. 3, 4 It provides excellent coverage against streptococci and methicillin-susceptible Staphylococcus aureus (MSSA), the predominant pathogens in uncomplicated cellulitis. 2, 3
When NOT to Use Cephalexin Alone
Do not use cephalexin monotherapy when MRSA risk factors are present, including: 2, 3
- Penetrating trauma or injection drug use
- Purulent drainage or exudate
- Evidence of MRSA infection elsewhere or nasal MRSA colonization
- Systemic inflammatory response syndrome (SIRS)
- Failure of initial beta-lactam therapy
In these scenarios, add MRSA-active therapy such as trimethoprim-sulfamethoxazole or doxycycline to the beta-lactam, or use clindamycin monotherapy instead. 3, 4
High-Dose Considerations
Emerging evidence suggests that high-dose cephalexin (1000 mg four times daily) may reduce treatment failure rates compared to standard dosing (500 mg four times daily), with treatment failure occurring in only 3.2% versus 12.9% of patients, though minor adverse effects are more common with higher doses. 5 This may be considered for patients at higher risk of treatment failure, though this is not yet standard practice.
Common Pitfalls to Avoid
- Do not reflexively add MRSA coverage simply because community-associated MRSA exists in your area—beta-lactam monotherapy remains highly effective for typical cellulitis. 3, 4
- Do not treat beyond 5 days if clinical improvement has occurred—longer courses provide no additional benefit. 2, 3
- Do not use twice-daily dosing for severe infections—reserve this for mild cases only and use four-times-daily dosing for moderate to severe infections. 1
- Reassess patients in 24-48 hours to verify clinical response, as treatment failure rates of up to 20% have been reported with oral regimens. 3, 5