What is the recommended treatment for cellulitis?

Treatment of Cellulitis

For typical uncomplicated cellulitis, beta-lactam monotherapy (such as cephalexin, dicloxacillin, or amoxicillin) for 5 days is the standard of care, as MRSA is an uncommon cause and adding MRSA coverage provides no additional benefit. 1

First-Line Antibiotic Selection

Uncomplicated Cellulitis (Non-Purulent)

• Beta-lactam monotherapy is successful in 96% of patients, confirming that MRSA coverage is usually unnecessary even in areas with high community MRSA prevalence 1, 2
• Recommended oral agents include:
  • Penicillin 1
  • Amoxicillin 1
  • Cephalexin 1
  • Dicloxacillin 1
  • Amoxicillin-clavulanate 1
  • Clindamycin (provides both streptococcal and MRSA coverage as monotherapy) 1

Treatment Duration

• 5 days of treatment is sufficient if clinical improvement has occurred 1, 2
• Extend treatment beyond 5 days only if symptoms have not improved within this timeframe 1, 2
• Traditional 7-14 day courses are no longer necessary for uncomplicated cases 1

When to Add MRSA Coverage

Specific Risk Factors Requiring MRSA Coverage

Add MRSA-active therapy when cellulitis is associated with: 1, 2

• Penetrating trauma 1
• Purulent drainage or exudate 1
• Concurrent evidence of MRSA infection elsewhere 2
• High-risk populations: athletes, prisoners, military recruits, long-term care residents, IV drug users, men who have sex with men 3

Combination Regimens for MRSA Coverage

When both streptococcal and MRSA coverage are needed: 1

• Trimethoprim-sulfamethoxazole (TMP-SMX) plus a beta-lactam (e.g., TMP-SMX + cephalexin) 1
• Doxycycline plus a beta-lactam 1
• Clindamycin monotherapy (covers both organisms, avoiding need for true combination) 1

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

Inpatient/IV Therapy

Indications for Hospitalization

Admit patients with: 2

• Signs of systemic toxicity (fever, hypotension, tachycardia, altered mental status) 1
• Rapid progression or suspected necrotizing fasciitis 1
• Failure of outpatient treatment 2
• Severe immunocompromise 2
• Poor adherence concerns 2

IV Antibiotic Selection

For complicated cellulitis requiring hospitalization: 1

• First-line: Vancomycin 15-20 mg/kg IV every 8-12 hours (A-I evidence) 1
• Alternatives with equivalent efficacy:
  • Linezolid 600 mg IV twice daily (A-I evidence) 1, 4
  • Daptomycin 4 mg/kg IV once daily (A-I evidence) 1
  • Clindamycin 600 mg IV three times daily (A-III evidence) 1

For severe infections with systemic toxicity or suspected necrotizing fasciitis: 1

• Mandatory broad-spectrum combination therapy: Vancomycin or linezolid PLUS piperacillin-tazobactam (3.375-4.5 g IV every 6 hours), a carbapenem, or ceftriaxone plus metronidazole 1
• Duration: 7-14 days depending on severity and clinical response 1

Important distinction: Even in hospitalized patients, if cellulitis is non-purulent and lacks MRSA risk factors, beta-lactam monotherapy (IV cefazolin or oxacillin) remains appropriate with a 96% success rate 1

Transition to Oral Therapy

• Switch to oral antibiotics (cephalexin, dicloxacillin, or clindamycin) once clinical improvement is demonstrated, typically after minimum 4 days of IV treatment 1
• For continued MRSA coverage orally, use clindamycin alone or TMP-SMX/doxycycline plus a beta-lactam 1

Adjunctive Measures

Non-Pharmacologic Interventions

• Elevation of the affected extremity hastens improvement by promoting gravity drainage of edema and inflammatory substances 1, 2
• Treat predisposing conditions: tinea pedis, toe web abnormalities, venous insufficiency, lymphedema, eczema, obesity 1, 2

Corticosteroids

• Systemic corticosteroids (e.g., prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited (weak recommendation, moderate evidence) 1, 2
• One small study showed NSAIDs (ibuprofen 400 mg every 6 hours for 5 days) significantly shortened time to resolution 5

Prevention of Recurrence

• Identify and treat predisposing conditions such as edema, obesity, eczema, venous insufficiency, and toe web abnormalities 1, 2
• For patients with 3-4 episodes per year despite treatment of predisposing factors, consider prophylactic antibiotics 2

Common Pitfalls to Avoid

• Do not reflexively add MRSA coverage simply because the patient is hospitalized - MRSA is uncommon in typical cellulitis even in high-prevalence settings 1
• Do not use combination therapy (TMP-SMX + cephalexin) for pure cellulitis without abscess, ulcer, or purulent drainage - it provides no additional benefit over cephalexin alone 1
• Do not treat for longer than 5 days if clinical improvement has occurred - traditional 7-14 day courses are outdated 1
• Do not use doxycycline or TMP-SMX as monotherapy - they lack reliable streptococcal coverage 1
• Beware of cellulitis mimickers - many non-infectious conditions (venous stasis dermatitis, contact dermatitis, eczema, lymphedema) can appear similar 6