Treatment of Cellulitis with Keflex (Cephalexin)
Yes, cephalexin (Keflex) is an appropriate and FDA-approved first-line antibiotic for treating cellulitis, with cure rates of 90% or higher for typical streptococcal and staphylococcal skin infections. 1, 2
FDA-Approved Indication
- Cephalexin is specifically FDA-approved for skin and skin structure infections caused by Staphylococcus aureus and/or Streptococcus pyogenes, which are the primary pathogens in cellulitis 1
Guideline-Based Recommendations
For typical, non-purulent cellulitis, cephalexin is explicitly recommended by the Infectious Diseases Society of America (IDSA) as a first-line oral antibiotic option. 3, 4
- The IDSA guidelines specify that therapy should include an antibiotic active against streptococci, as these organisms (particularly groups A, B, C, and G streptococci) are the most common causative pathogens in cellulitis 3
- Other acceptable first-line oral options include dicloxacillin, clindamycin, or erythromycin (unless resistance is common in your community) 3
Dosing and Duration
- Standard dosing: Cephalexin 500 mg orally four times daily 5
- High-dose option: Cephalexin 1000 mg orally four times daily may reduce treatment failure rates (12.9% vs 3.2%) but causes more minor adverse effects 5
- Treatment duration: 5 days of antibiotic therapy is as effective as 10 days for uncomplicated cellulitis if clinical improvement occurs 3, 4
When Cephalexin Alone May Be Insufficient
Do NOT add MRSA coverage (such as trimethoprim-sulfamethoxazole) to cephalexin for typical cellulitis, as this combination provides no additional benefit. 6
However, consider alternatives to cephalexin in these specific scenarios:
- Purulent cellulitis with drainage or associated abscess 3
- Penetrating trauma or injection drug use history 4
- Concurrent evidence of MRSA infection elsewhere 4
- Geographic areas with high CA-MRSA prevalence where empiric MRSA coverage may be warranted 7
In these situations, switch to antibiotics with MRSA activity such as trimethoprim-sulfamethoxazole or clindamycin rather than adding them to cephalexin 7
Parenteral Therapy Indications
For severely ill patients or those unable to tolerate oral medications, use parenteral cefazolin (a first-generation cephalosporin equivalent to cephalexin) 3
Critical Adjunctive Measures
- Elevate the affected extremity to promote drainage of edema and inflammatory substances 8
- Identify and treat predisposing factors including tinea pedis (toe web infections), venous insufficiency, lymphedema, or trauma 3, 8
- Streptococci causing lower extremity cellulitis frequently originate from macerated interdigital toe spaces, making treatment of tinea pedis essential 3
Common Pitfall to Avoid
The most common error is unnecessarily adding MRSA coverage to cephalexin for typical cellulitis. MRSA is an unusual cause of typical cellulitis according to IDSA guidelines 4, and the addition of trimethoprim-sulfamethoxazole to cephalexin showed no benefit in a randomized controlled trial (85% cure rate with combination vs 82% with cephalexin alone, p=0.66) 6