Keflex (Cephalexin) for Non-Purulent Cellulitis
For non-purulent cellulitis, Keflex (cephalexin) is the preferred choice over Augmentin (amoxicillin-clavulanate), as beta-lactam monotherapy with cephalexin achieves 96% success rates and is specifically recommended as standard of care by the Infectious Diseases Society of America. 1
Why Cephalexin is Preferred
Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis, with cephalexin specifically listed among recommended oral agents including penicillin, amoxicillin, amoxicillin-clavulanate, dicloxacillin, or clindamycin. 1
MRSA is an uncommon cause of non-purulent cellulitis, making MRSA coverage unnecessary in typical cases, and adding MRSA coverage to beta-lactam therapy provides no additional benefit. 1
Cephalexin demonstrates 96% success rates in treating non-purulent cellulitis, confirming that broader spectrum coverage is usually unnecessary. 1
When Augmentin Has a Role
Augmentin is specifically appropriate for cellulitis associated with human or animal bites at 875/125 mg twice daily, where it provides single-agent coverage for both streptococci and common skin flora. 1
For typical non-purulent cellulitis without bite history, Augmentin offers no advantage over cephalexin and unnecessarily broadens coverage. 1
Dosing and Duration
Standard cephalexin dosing is 500 mg orally four times daily for non-purulent cellulitis. 1
Treatment duration is 5 days if clinical improvement occurs, with extension only if symptoms have not improved within this timeframe. 1
High-dose cephalexin (1000 mg four times daily) showed fewer treatment failures (3.2% vs 12.9%) in a 2023 pilot trial, though with more minor adverse effects. 2
Evidence Supporting Cephalexin Monotherapy
A 2017 JAMA trial demonstrated that adding trimethoprim-sulfamethoxazole to cephalexin provided no benefit for uncomplicated cellulitis, with clinical cure rates of 83.5% for combination therapy vs 85.5% for cephalexin alone (difference -2.0%, 95% CI -9.7% to 5.7%). 3
This confirms that combination therapy with MRSA coverage is no more efficacious than cephalexin alone in pure cellulitis without abscess, ulcer, or purulent drainage. 1
When NOT to Use Cephalexin Alone
Add MRSA-active antibiotics only when specific risk factors are present: 1
- Penetrating trauma or injection drug use
- Purulent drainage or exudate
- Known MRSA colonization or evidence of MRSA infection elsewhere
- Systemic inflammatory response syndrome (SIRS)
- Failure to respond to beta-lactam therapy after 48 hours
For these cases, use combination therapy with trimethoprim-sulfamethoxazole or doxycycline plus a beta-lactam, or clindamycin monotherapy. 1
Adjunctive Measures
Elevate the affected extremity to promote drainage and hasten improvement. 1
Treat predisposing conditions including tinea pedis, toe web abnormalities, venous insufficiency, edema, and lymphedema to reduce recurrence risk. 1
Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited. 1
Common Pitfalls
Do not reflexively add MRSA coverage simply because MRSA prevalence is high in your community—MRSA remains uncommon in typical non-purulent cellulitis. 1
Reassess at 24-48 hours to verify clinical response, as treatment failure rates up to 21% have been reported with some regimens. 1
Evaluate for abscess with ultrasound if there is any clinical uncertainty, as purulent collections require incision and drainage plus MRSA-active antibiotics. 1
Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates either resistant organisms or a deeper/different infection. 1