Cephalexin Dosing for Simple Cellulitis
For simple cellulitis, cephalexin 500 mg twice daily (BID) is equally effective as four times daily (QID) dosing and should be the preferred regimen due to superior convenience and adherence. 1, 2
Evidence Supporting BID Dosing
The FDA label explicitly approves cephalexin 500 mg every 12 hours (BID) for skin and skin structure infections in adults, establishing this as a legitimate dosing option rather than an off-label modification 1. This approval is supported by clinical trial data demonstrating therapeutic equivalence between twice-daily and four-times-daily regimens.
A randomized controlled trial directly comparing cephalexin BID versus QID for staphylococcal skin infections found both regimens equally effective, with treatment failures uncommon in both groups (1 patient each). 2 Notably, twice-daily dosing actually showed a trend toward faster clearing of lesions compared to QID dosing in this study 2.
Additional evidence from a comparative trial of cefadroxil (once daily) versus cephalexin 250 mg QID for facial cellulitis demonstrated that less frequent dosing was therapeutically equivalent, with cure rates of 100% versus 98% respectively 3. This supports the principle that extended-interval dosing of beta-lactams maintains efficacy for skin infections.
Guideline-Recommended Treatment Approach
The Infectious Diseases Society of America (IDSA) guidelines establish beta-lactam monotherapy as the standard of care for typical uncomplicated cellulitis, with a 96% success rate 4, 5. MRSA coverage is unnecessary for simple cellulitis without specific risk factors (penetrating trauma, purulent drainage, injection drug use, known MRSA colonization, or systemic inflammatory response syndrome) 4, 5.
Recommended oral agents include cephalexin, dicloxacillin, penicillin, amoxicillin, or amoxicillin-clavulanate 4, 5. Among these options, cephalexin offers the advantage of flexible dosing.
Treatment Duration
Treat for 5 days if clinical improvement occurs; extend only if the infection has not improved within this timeframe. 4, 5 Traditional 7-14 day courses are no longer necessary for uncomplicated cases 5.
Practical Dosing Algorithm
- Standard dosing: Cephalexin 500 mg BID for 5 days 1, 2
- Alternative if BID dosing unavailable: Cephalexin 250 mg QID 1
- For more severe infections: Consider 500 mg QID or 1000 mg QID (though this represents higher-dose therapy requiring careful monitoring) 1, 6
Why BID is Preferred Over QID
Twice-daily dosing enhances medication adherence, which is critical for outpatient cellulitis management. 2 The convenience of BID dosing was specifically rated higher by patients in comparative studies, with mean usefulness scores significantly favoring less frequent administration 7. Poor adherence to QID regimens likely contributes to the approximately 20% treatment failure rate seen with cellulitis 6.
Critical Caveat About MRSA
A large randomized trial demonstrated that adding trimethoprim-sulfamethoxazole to cephalexin provided no additional benefit for uncomplicated cellulitis without purulent drainage 8. Clinical cure occurred in 83.5% with combination therapy versus 85.5% with cephalexin alone (difference -2.0%, 95% CI -9.7% to 5.7%) 8. This confirms that empiric MRSA coverage is unnecessary for typical cellulitis and cephalexin monotherapy remains appropriate. 8