What is the recommended treatment for cellulitis?

Treatment of Cellulitis

Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis, with a 5-day treatment duration if clinical improvement occurs. 1, 2

First-Line Antibiotic Selection

For typical nonpurulent cellulitis, use beta-lactam monotherapy without MRSA coverage, as this approach succeeds in 96% of patients and MRSA is an uncommon cause even in high-prevalence settings. 1, 2

Recommended oral agents include: 1, 2

• Cephalexin (first-generation cephalosporin)
• Dicloxacillin 250 mg every 6 hours for moderate infections
• Amoxicillin or amoxicillin-clavulanate
• Penicillin
• Clindamycin (provides both streptococcal and MRSA coverage as monotherapy)

The rationale is straightforward: when organisms are identified in cellulitis (which occurs in <20% of cases), most are β-hemolytic streptococci or methicillin-sensitive S. aureus. 1, 3, 4

Treatment Duration

Treat for 5 days if clinical improvement has occurred; extend only if symptoms have not improved within this timeframe. 1, 2 This represents a major shift from traditional 7-14 day courses, which are no longer necessary for uncomplicated cases. 1

When to Add MRSA Coverage

Add MRSA-active antibiotics ONLY when specific risk factors are present: 1, 2

• Penetrating trauma or injection drug use
• Purulent drainage or exudate
• Known MRSA colonization or evidence of MRSA infection elsewhere
• Systemic inflammatory response syndrome (SIRS)

For cellulitis requiring MRSA coverage, use combination therapy: 1

• Trimethoprim-sulfamethoxazole (TMP-SMX) PLUS a beta-lactam (e.g., cephalexin), OR
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam, OR
• Clindamycin monotherapy (covers both streptococci and MRSA, avoiding need for true combination)

Critical pitfall: Never use doxycycline or TMP-SMX as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable. 1

Inpatient/IV Antibiotic Therapy

For hospitalized patients with complicated cellulitis requiring IV therapy, vancomycin 15-20 mg/kg IV every 8-12 hours is first-line (A-I level evidence). 1

Alternative IV agents with equivalent efficacy include: 1

• Linezolid 600 mg IV twice daily (A-I evidence)
• Daptomycin 4 mg/kg IV once daily (A-I evidence)
• Clindamycin 600 mg IV three times daily (only if local MRSA resistance <10%)

For severe infections with systemic toxicity, rapid progression, or suspected necrotizing fasciitis, use mandatory broad-spectrum combination therapy: 1

• Vancomycin or linezolid PLUS piperacillin-tazobactam (3.375-4.5 grams IV every 6 hours), OR
• Vancomycin or linezolid PLUS a carbapenem, OR
• Vancomycin or linezolid PLUS ceftriaxone and metronidazole

Duration for severe infections is 7-14 days, guided by clinical response. 1

Indications for Hospitalization

Hospitalize if any of the following are present: 1, 2

• SIRS, fever, hypotension, or altered mental status
• Severe immunocompromise or neutropenia
• Concern for necrotizing infection (severe pain out of proportion to exam, skin anesthesia, rapid progression, gas in tissue, bullous changes)
• Failure of outpatient treatment

Adjunctive Measures

Elevation of the affected extremity hastens improvement by promoting gravity drainage of edema and inflammatory substances. 1, 2

Treat predisposing conditions to reduce recurrence risk: 1, 2

• Tinea pedis and toe web abnormalities
• Venous insufficiency and lymphedema
• Eczema and chronic edema
• Obesity

Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited. 1, 2 Some data suggest anti-inflammatory therapy may hasten resolution, with one study showing 82.8% of patients achieving regression of inflammation within 1-2 days when NSAIDs were added to antibiotics. 5

Common Pitfalls to Avoid

Do not reflexively add MRSA coverage simply because the patient is hospitalized - even in hospitals with high MRSA prevalence, MRSA remains an uncommon cause of typical cellulitis. 1

Reassess in 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some regimens. 1 If spreading despite appropriate antibiotics, evaluate for necrotizing fasciitis, MRSA, or misdiagnosis (venous stasis dermatitis, contact dermatitis, DVT). 1, 4

Obtain emergent surgical consultation if any signs of necrotizing infection are present, as these progress rapidly and require debridement. 1

For purulent collections (abscesses, furuncles), incision and drainage is primary treatment - antibiotics play a subsidiary role. 1