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

For typical nonpurulent cellulitis, use beta-lactam monotherapy—this approach is successful in 96% of patients, confirming that MRSA coverage is usually unnecessary. 1

Recommended Oral Agents:

• Cephalexin (preferred for most cases) 1
• Dicloxacillin 250-500 mg every 6 hours 1
• Amoxicillin 1, 2
• Amoxicillin-clavulanate (Augmentin) 1
• Penicillin 1, 2

Treatment duration is 5 days if clinical improvement has occurred, with extension only if symptoms have not improved. 1, 2 This represents a significant departure from traditional 7-14 day courses and is supported by high-quality evidence. 1

When to Add MRSA Coverage

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

• Penetrating trauma or injection drug use 1
• Purulent drainage or exudate 1
• Evidence of MRSA infection elsewhere or documented MRSA colonization 1
• Systemic inflammatory response syndrome (SIRS) 1
• Failure to respond to beta-lactam therapy 1

MRSA-Active Regimens:

• Clindamycin monotherapy 300-450 mg orally every 6 hours (covers both streptococci and MRSA, avoiding need for combination therapy) 1
• Trimethoprim-sulfamethoxazole (SMX-TMP) PLUS a beta-lactam (e.g., cephalexin) 1
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam 1

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

Inpatient/IV Antibiotic Selection

For Hospitalized Patients Requiring IV Therapy:

First-line for uncomplicated cellulitis requiring hospitalization (without MRSA risk factors):

• Cefazolin 1-2 g IV every 8 hours 1
• Oxacillin 2 g IV every 6 hours (alternative) 1

For complicated cellulitis or when MRSA coverage is needed:

• Vancomycin 15-20 mg/kg IV every 8-12 hours (A-I evidence) 1
• Linezolid 600 mg IV twice daily (A-I evidence) 1, 3
• Daptomycin 4 mg/kg IV once daily (A-I evidence) 1
• Clindamycin 600 mg IV every 8 hours (only if local MRSA resistance <10%) 1

For Severe Cellulitis with Systemic Toxicity:

Mandatory broad-spectrum combination therapy is required for patients with signs of systemic toxicity, rapid progression, or suspected necrotizing fasciitis: 1

• Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 1
• Alternative: Linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam 1
• Alternative: Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours) 1
• Alternative: Vancomycin PLUS ceftriaxone 2 g IV daily and metronidazole 500 mg IV every 8 hours 1

Treatment duration for severe infections: 7-14 days, guided by clinical response. 1

Indications for Hospitalization

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

• Systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm 1
• Hypotension or hemodynamic instability 1, 2
• Altered mental status or confusion 1, 2
• Severe immunocompromise or neutropenia 1, 2
• Concern for deeper or necrotizing infection 1, 2
• Failure of outpatient treatment 2

Adjunctive Measures

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

Treat predisposing conditions to reduce recurrence risk: 1, 2

• Tinea pedis and toe web abnormalities 1, 2
• Venous insufficiency and chronic edema 1, 2
• Eczema and venous stasis dermatitis 1
• Obesity 1

Systemic corticosteroids (e.g., prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited. 1, 2

Special Situations

Bite-Associated Cellulitis:

Augmentin 875/125 mg twice daily as monotherapy (provides single-agent coverage for polymicrobial oral flora) 1

Penicillin/Cephalosporin Allergy:

• Clindamycin 300-450 mg orally every 6 hours (if local resistance <10%) 1
• Levofloxacin 500 mg daily (reserve for beta-lactam allergies) 1

Pediatric Dosing:

• Vancomycin 15 mg/kg IV every 6 hours (hospitalized children) 1
• Clindamycin 10-13 mg/kg/dose IV every 6-8 hours (if stable, no bacteremia, local resistance <10%) 1
• Doxycycline 2 mg/kg/dose orally every 12 hours (children >8 years and <45 kg) 1

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

Common Pitfalls to Avoid

Do not routinely add MRSA coverage for typical cellulitis without specific risk factors—this represents overtreatment and increases antibiotic resistance. 1

Do not use combination therapy (SMX-TMP plus cephalexin) for pure cellulitis without abscess, ulcer, or purulent drainage—it provides no additional benefit over cephalexin alone. 1

Assess for abscess with ultrasound if there is any clinical uncertainty, as purulent collections require incision and drainage plus MRSA-active antibiotics, not antibiotics alone. 1

Reassess patients in 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some oral regimens. 1

Evaluate for warning signs of necrotizing fasciitis if cellulitis spreads despite appropriate antibiotics: severe pain out of proportion to examination, skin anesthesia, rapid progression, gas in tissue, systemic toxicity, or bullous changes—these require emergent surgical consultation. 1