What is the treatment for cellulitis of the legs?

Treatment of Leg Cellulitis

For typical uncomplicated leg cellulitis, treat with beta-lactam monotherapy (such as cephalexin 500mg orally twice daily, dicloxacillin 250mg every 6 hours, or amoxicillin) for 5 days, combined with leg elevation—MRSA coverage is unnecessary in 96% of cases and should only be added for specific risk factors like purulent drainage, penetrating trauma, or injection drug use. 1

First-Line Antibiotic Selection

Beta-lactam monotherapy is the standard of care because typical cellulitis is caused by beta-hemolytic streptococci and methicillin-sensitive Staphylococcus aureus, not MRSA, even in hospitals with high MRSA prevalence. 1, 2

Recommended Oral Agents:

• Cephalexin 500mg orally twice daily 1
• Dicloxacillin 250mg every 6 hours 1
• Amoxicillin (standard dosing) 1
• Amoxicillin-clavulanate 875/125mg twice daily 1
• Clindamycin 300-450mg three times daily (provides both streptococcal and MRSA coverage if needed) 1

Beta-lactam treatment succeeds in 96% of patients, confirming that reflexive MRSA coverage is unnecessary and represents overtreatment. 1

Treatment Duration

Treat for exactly 5 days if clinical improvement occurs—extend only if symptoms have not improved within this timeframe. 1, 3 Traditional 7-14 day courses are outdated and no longer necessary for uncomplicated cases. 1

Essential Adjunctive Measures

Elevation of the affected leg is mandatory, not optional—it hastens improvement by promoting gravitational drainage of edema and inflammatory substances. 1, 3 This should be emphasized to patients as equally important as antibiotics.

Address Predisposing Factors:

• Examine toe web spaces for tinea pedis and treat aggressively 1, 3
• Treat venous eczema as skin breakdown provides bacterial entry 3
• Manage venous insufficiency and lymphedema to reduce recurrence risk (8-20% annual recurrence rate) 3, 4
• Control edema through compression when appropriate 1, 3

When to Add MRSA Coverage

Do NOT add MRSA coverage reflexively—it is only indicated when specific risk factors are present: 1

MRSA Risk Factors Requiring Combination Therapy:

• Purulent drainage or exudate 1
• Penetrating trauma or injection drug use 1, 2
• Known MRSA colonization or prior MRSA infection 1
• Systemic inflammatory response syndrome (SIRS) 1

When MRSA Coverage is Needed:

• Trimethoprim-sulfamethoxazole PLUS a beta-lactam (e.g., cephalexin) 1
• Doxycycline 100mg twice daily PLUS a beta-lactam 1
• Clindamycin monotherapy (covers both streptococci and MRSA, avoiding true combination therapy) 1

Critical caveat: Never use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis—they lack reliable activity against beta-hemolytic streptococci. 1

Inpatient Management

For patients requiring hospitalization due to systemic toxicity, altered mental status, or hemodynamic instability: 1

IV Antibiotic Options:

• Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line for complicated cellulitis) 1
• Cefazolin or oxacillin (appropriate for non-purulent cellulitis without MRSA risk factors) 1
• Linezolid 600mg IV twice daily (alternative to vancomycin) 1
• Daptomycin 4mg/kg IV once daily (alternative to vancomycin) 1

For severe infections with systemic toxicity or suspected necrotizing fasciitis, use broad-spectrum combination therapy: vancomycin or linezolid PLUS piperacillin-tazobactam 3.375-4.5 grams IV every 6 hours. 1 Obtain emergent surgical consultation if necrotizing infection is suspected (severe pain out of proportion to exam, skin anesthesia, rapid progression, bullous changes). 1

Transition to Oral Therapy:

Switch to oral antibiotics after minimum 4 days of IV treatment once clinical improvement is demonstrated. 1

Adjunctive Corticosteroids

Consider prednisone 40mg daily for 7 days in non-diabetic adults to reduce inflammation, though evidence is limited (weak recommendation, moderate evidence). 1, 3 Do not use in diabetic patients.

Reassessment and Treatment Failure

Mandatory reassessment in 24-48 hours to verify clinical response. 1 If cellulitis spreads despite appropriate antibiotics:

1. Evaluate for necrotizing fasciitis (pain out of proportion, anesthesia, gas in tissue, bullous changes) 1
2. Reassess for MRSA risk factors and switch to vancomycin or linezolid if present 1
3. Consider misdiagnosis—venous insufficiency, eczema, deep vein thrombosis, and gout are frequently mistaken for cellulitis 5
4. Do not continue ineffective antibiotics beyond 48 hours 1

Prevention of Recurrence

For patients with 3-4 episodes per year despite controlling predisposing factors, consider prophylactic penicillin or erythromycin twice daily for 4-52 weeks. 3