Recommended Oral Cephalosporin for Cellulitis
Cephalexin is the recommended oral cephalosporin for treating uncomplicated cellulitis, as it provides excellent coverage against beta-hemolytic streptococci, which are the primary causative organisms in most cases. 1
First-Line Oral Cephalosporin Selection
Cephalexin (a first-generation cephalosporin) is the standard oral agent for cellulitis because beta-hemolytic streptococci cause the majority of typical cellulitis cases, and cephalexin demonstrates cure rates of 86-100% in clinical studies 1
The typical dosing is cephalexin 500 mg orally four times daily for 5-7 days, though emerging evidence suggests high-dose cephalexin (1000 mg four times daily) may reduce treatment failure rates from 12.9% to 3.2%, albeit with more minor adverse effects 2
When Cephalexin May Not Be Sufficient
Consider adding MRSA coverage (not using cephalexin alone) in specific scenarios: purulent drainage or exudate, penetrating trauma or bug bites, evidence of MRSA infection elsewhere or known nasal colonization, systemic inflammatory response syndrome, or failure to respond to beta-lactam therapy 3
In areas with high community-associated MRSA prevalence, cephalexin alone had a 26% treatment failure rate compared to MRSA-active agents, making it less effective when MRSA is likely 4
However, adding trimethoprim-sulfamethoxazole to cephalexin did not significantly improve clinical cure rates in the per-protocol analysis (83.5% vs 85.5%), though the modified intention-to-treat analysis showed a trend favoring combination therapy that did not reach statistical significance 5
Treatment Duration and Adjunctive Measures
Treat for 5-7 days if clinical improvement occurs, as this is as effective as 10-day courses for uncomplicated cellulitis 3, 1
Elevate the affected extremity to promote drainage of edema and inflammatory substances 3, 1
Treat predisposing conditions such as tinea pedis, venous eczema, or trauma 3, 1
Critical Pitfalls to Avoid
Do not use cephalexin as monotherapy in patients with risk factors for MRSA (see scenarios above), as therapy with an antibiotic not active against community-associated MRSA increases treatment failure risk significantly (adjusted odds ratio 4.22) 4
In sulfa-allergic patients who cannot receive cephalexin due to cross-reactivity concerns, use clindamycin 300-450 mg orally three times daily as first-line therapy instead 3