First-Line Treatment for Cellulitis
For typical uncomplicated cellulitis, beta-lactam monotherapy with oral agents such as cephalexin, dicloxacillin, penicillin, or amoxicillin is the standard of care, as MRSA is an uncommon cause and beta-lactam treatment succeeds in 96% of cases. 1, 2
Recommended First-Line Oral Antibiotics
The Infectious Diseases Society of America establishes the following as appropriate first-line options for most patients with cellulitis:
- Cephalexin (500 mg four times daily) 1, 3
- Dicloxacillin 1, 2
- Penicillin 1, 2
- Amoxicillin 1, 2
- Clindamycin (provides both streptococcal and MRSA coverage if needed) 1, 2
These agents target β-hemolytic streptococci and methicillin-sensitive Staphylococcus aureus, which account for the majority of identified cellulitis cases. 4, 5
Treatment Duration
Treat for 5 days if clinical improvement has occurred; extend only if symptoms have not improved within this timeframe. 1, 2, 3 This represents a significant departure from traditional 7-14 day courses and is supported by high-quality evidence showing equivalent efficacy. 1, 2
When to Add MRSA Coverage
MRSA coverage is not routinely necessary for typical cellulitis, even in hospitals with high MRSA prevalence. 1, 2 However, consider adding MRSA-active therapy in these specific circumstances:
- Penetrating trauma (especially injection drug use) 1, 2
- Purulent drainage or exudate 1, 2, 3
- Concurrent MRSA infection elsewhere 1, 2
- Failure to respond to beta-lactam therapy 2
When MRSA coverage is needed, appropriate oral options include:
- Clindamycin monotherapy (covers both streptococci and MRSA) 1, 2
- Doxycycline 100 mg twice daily PLUS a beta-lactam (doxycycline alone lacks reliable streptococcal activity) 2, 3
- Trimethoprim-sulfamethoxazole PLUS a beta-lactam 2
Critical Pitfalls to Avoid
Do not reflexively add MRSA coverage simply because the patient is hospitalized or because community MRSA rates are high. 1, 2 Beta-lactam monotherapy remains appropriate for non-purulent cellulitis without specific risk factors, with a 96% success rate. 1, 2
Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable. 2, 3 These agents must be combined with a beta-lactam when treating non-purulent cellulitis. 2
Do not extend treatment beyond 5 days if clinical improvement has occurred. 2, 3 This unnecessarily increases antibiotic exposure, costs, and adverse effects without additional benefit. 1, 2
Adjunctive Measures
- Elevate the affected extremity to promote drainage and hasten improvement 1, 2, 3
- Treat predisposing conditions such as tinea pedis, toe web abnormalities, venous insufficiency, lymphedema, and obesity 2, 6
- Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 2, 3
When to Hospitalize
Most patients can be treated as outpatients. 3 Consider hospitalization for:
- Systemic toxicity (fever, hypotension, tachycardia, confusion) 1, 2, 3
- Rapidly progressive infection or suspected necrotizing fasciitis 2
- Severe immunocompromise 3
- Hemodynamic instability 3
For hospitalized patients requiring IV therapy, cefazolin or oxacillin remains appropriate for typical cellulitis, with vancomycin reserved for purulent cases or MRSA risk factors. 1, 2