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

First-Line Antibiotic Selection

Uncomplicated Nonpurulent Cellulitis

Beta-lactam antibiotics achieve a 96% success rate in typical cellulitis, confirming that MRSA coverage is unnecessary in most cases. 1 The causative organisms are predominantly β-hemolytic streptococci and methicillin-sensitive Staphylococcus aureus when identified (which occurs in only 15% of cases). 2, 3

Recommended oral agents include: 1

• Cephalexin (first-generation cephalosporin)
• Dicloxacillin 250-500 mg every 6 hours
• Amoxicillin
• Penicillin
• Amoxicillin-clavulanate (Augmentin)
• Clindamycin 300-450 mg every 6 hours (covers both streptococci and MRSA if local resistance <10%)

When to Add MRSA Coverage

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 prior MRSA infection
• Systemic inflammatory response syndrome (SIRS)
• Failure to respond to beta-lactam therapy after 48 hours

For cellulitis requiring MRSA coverage, use: 1

• Clindamycin monotherapy 300-450 mg orally every 6 hours (provides coverage for both streptococci and MRSA, avoiding need for combination therapy)
• Trimethoprim-sulfamethoxazole (TMP-SMX) PLUS a beta-lactam (never use TMP-SMX alone due to unreliable streptococcal coverage)
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam (never use doxycycline alone due to inadequate streptococcal activity)

Treatment Duration

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

Inpatient/IV Antibiotic Therapy

Indications for Hospitalization

Hospitalize patients with: 1

• SIRS (fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm)
• Hypotension or altered mental status
• Severe immunocompromise or neutropenia
• Rapid progression or suspected necrotizing fasciitis

IV Antibiotic Selection for Complicated Cellulitis

First-line IV therapy: 1

• Vancomycin 15-20 mg/kg IV every 8-12 hours (A-I evidence)
• Linezolid 600 mg IV twice daily (A-I evidence, equally effective alternative)
• Daptomycin 4 mg/kg IV once daily (A-I evidence)
• Cefazolin 1-2 g IV every 8 hours (for uncomplicated cellulitis without MRSA risk factors)

Severe Cellulitis with Systemic Toxicity

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

• Vancomycin or linezolid PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours
• Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours)
• Vancomycin PLUS ceftriaxone 2 g IV daily and metronidazole 500 mg IV every 8 hours

Duration for severe infections: 7-14 days guided by clinical response, with reassessment at 5 days. 1

Pediatric Dosing

For children with cellulitis: 1

• Oral therapy: 10 mg/kg every 8 hours for children <5 years; 10 mg/kg every 12 hours for children 5-11 years
• IV vancomycin: 15 mg/kg every 6 hours for hospitalized children
• IV clindamycin: 10-13 mg/kg/dose every 6-8 hours (only if local resistance <10%)
• Linezolid: 10 mg/kg/dose every 8 hours for children <12 years; 600 mg twice daily for children ≥12 years 4

Never use doxycycline in children under 8 years of age due to tooth discoloration and bone growth effects. 1

Adjunctive Measures

Elevation of the affected extremity hastens improvement by promoting drainage. 1 This simple intervention accelerates resolution and should be implemented in all cases. 1

Treat predisposing conditions: 1, 5

• Tinea pedis and toe web abnormalities
• Venous insufficiency and chronic edema
• Lymphedema
• Eczema and venous stasis dermatitis

Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited. 1

Critical Pitfalls to Avoid

Do not routinely add MRSA coverage for typical nonpurulent cellulitis without specific risk factors—this represents overtreatment and increases antibiotic resistance. 1 Even in hospitals with high MRSA prevalence, MRSA is an uncommon cause of typical cellulitis. 1

Do not use doxycycline or TMP-SMX as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable. 1 These agents must always be combined with a beta-lactam when treating nonpurulent cellulitis. 1

Reassess patients in 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some regimens. 1 If cellulitis is spreading despite appropriate antibiotics, immediately evaluate for necrotizing fasciitis (severe pain out of proportion to exam, skin anesthesia, rapid progression, gas in tissue, bullous changes) and obtain emergent surgical consultation. 1

Distinguish cellulitis from purulent collections (abscesses, furuncles)—purulent collections require incision and drainage as primary treatment, with antibiotics playing a subsidiary role. 1 Use ultrasound if clinical uncertainty exists. 1

Transition to Oral Therapy

Patients can transition to oral antibiotics once clinical improvement is demonstrated, typically after a minimum of 4 days of IV treatment. 1 Appropriate oral options include cephalexin, dicloxacillin, or clindamycin (for continued MRSA coverage). 1