Can Keflex (Cephalexin) Be Ordered for Cellulitis?
Yes, cephalexin (Keflex) is an appropriate and guideline-recommended first-line antibiotic for the treatment of typical, non-purulent cellulitis.
Primary Indication and FDA Approval
- Cephalexin is FDA-approved for skin and skin structure infections caused by Staphylococcus aureus and Streptococcus pyogenes, which are the primary pathogens in cellulitis 1
- The Infectious Diseases Society of America (IDSA) explicitly lists cephalexin as a suitable oral agent for typical cellulitis cases 2
When to Use Cephalexin for Cellulitis
For non-purulent cellulitis (the typical presentation):
- Cephalexin should be prescribed as monotherapy for patients presenting with diffuse erythema, warmth, swelling, and tenderness without purulent drainage 2, 3
- The majority of non-purulent cellulitis cases are caused by β-hemolytic streptococci or methicillin-sensitive S. aureus, making cephalexin an appropriate choice 3
- A 5-day course is as effective as a 10-day course if clinical improvement occurs by day 5 2
MRSA coverage is NOT routinely needed:
- Multiple high-quality randomized controlled trials demonstrate that adding trimethoprim-sulfamethoxazole to cephalexin provides no additional benefit for non-purulent cellulitis 4, 5
- A 2017 JAMA trial of 496 patients showed clinical cure in 85.5% with cephalexin alone versus 83.5% with cephalexin plus trimethoprim-sulfamethoxazole (no significant difference) 4
- MRSA is an unusual cause of typical cellulitis, with β-lactams like cephalexin successful in 96% of cases even in high-MRSA prevalence areas 2
When to Consider Alternative or Additional Coverage
Add MRSA-active antibiotics only when:
- Purulent drainage is present 2
- Penetrating trauma occurred, especially from injection drug use 2
- Evidence of MRSA infection exists elsewhere or documented nasal MRSA colonization 2
- Systemic inflammatory response syndrome (fever, hypotension, delirium) is present 2
For these high-risk scenarios, combine cephalexin with:
- Trimethoprim-sulfamethoxazole, OR
- Doxycycline, OR
- Use clindamycin monotherapy (covers both streptococci and MRSA) 2
Dosing and Duration
- Standard dose: Cephalexin 500 mg orally four times daily 1
- Duration: 5-6 days for uncomplicated cellulitis with clinical improvement 2
- Extend treatment only if infection has not improved after 5 days 2
Essential Adjunctive Measures
- Elevate the affected extremity to promote drainage of edema and inflammatory substances 2, 6
- Treat predisposing conditions including tinea pedis, venous insufficiency, or toe web abnormalities 2
- Consider prednisone 40 mg daily for 7 days in non-diabetic adults to hasten resolution (weak recommendation) 2
Critical Pitfalls to Avoid
Do not routinely add MRSA coverage: The evidence is clear that empiric MRSA coverage for non-purulent cellulitis provides no benefit and contributes to unnecessary broad-spectrum antibiotic use 4, 5
Do not treat for 10-14 days by default: Shorter 5-6 day courses are equally effective and reduce antibiotic exposure 2
Do not prescribe antibiotics without addressing predisposing factors: Failure to treat underlying conditions like tinea pedis increases recurrence risk 2
Recognize cellulitis mimics: Venous stasis dermatitis, contact dermatitis, and lymphedema are frequently misdiagnosed as cellulitis and do not require antibiotics 3