What is the recommended treatment for cellulitis?

Treatment of Cellulitis

For typical uncomplicated cellulitis, beta-lactam monotherapy with agents like cephalexin, dicloxacin, or amoxicillin for 5 days is the standard of care, achieving 96% success rates without requiring MRSA coverage. 1, 2

First-Line Antibiotic Selection

For Nonpurulent Cellulitis (Most Cases)

• Beta-lactam monotherapy is sufficient because β-hemolytic streptococci and methicillin-sensitive S. aureus cause the majority of identifiable cases, not MRSA. 1, 3
• Recommended oral agents include:
  • Cephalexin 500 mg four times daily 1
  • Dicloxacillin 250-500 mg every 6 hours 1
  • Amoxicillin (standard dosing) 1, 2
  • Penicillin V 250-500 mg four times daily 2
• For hospitalized patients requiring IV therapy: Cefazolin 1-2 g IV every 8 hours is preferred. 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 1
  • Purulent drainage or exudate 1
  • Known MRSA colonization or prior MRSA infection 1
  • Systemic inflammatory response syndrome (SIRS) 1
  • Athletes, prisoners, military recruits, long-term care residents 3

• MRSA-active regimens when indicated:

  • Clindamycin 300-450 mg orally every 6 hours (covers both streptococci and MRSA, avoiding need for combination therapy, but only if local resistance <10%) 1, 2
  • Trimethoprim-sulfamethoxazole PLUS a beta-lactam (e.g., cephalexin) 1
  • Doxycycline 100 mg twice daily PLUS a beta-lactam 1

Critical pitfall: Never use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis—their activity against β-hemolytic streptococci is unreliable. 1, 2

Treatment Duration

• Treat for exactly 5 days if clinical improvement occurs. 1, 2
• Extend treatment only if symptoms have not improved within this 5-day timeframe. 1, 2
• Traditional 7-14 day courses are no longer necessary for uncomplicated cases. 1

Severe Cellulitis Requiring Hospitalization

Indications for Admission

• Systemic inflammatory response syndrome (fever, tachycardia, tachypnea) 1, 2
• Hypotension or hemodynamic instability 2
• Altered mental status or confusion 1, 2
• Severe immunocompromise or neutropenia 1, 2
• Concern for necrotizing fasciitis (severe pain out of proportion to exam, skin anesthesia, rapid progression, gas in tissue, bullous changes) 1

IV Antibiotic Regimens for Severe Disease

• For severe cellulitis with systemic toxicity or suspected necrotizing fasciitis: Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours. 1
• Alternative combinations: Vancomycin or linezolid PLUS a carbapenem, or ceftriaxone plus metronidazole. 1
• For documented group A streptococcal necrotizing fasciitis: Penicillin plus clindamycin specifically. 1
• Duration for severe infections: 7-14 days guided by clinical response, not the standard 5 days. 1

IV Monotherapy Options (When MRSA Coverage Needed Without Systemic Toxicity)

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

Essential Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravitational drainage of edema. 1, 2
• Examine and treat interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration—this eradicates colonization and reduces recurrence risk. 1, 2
• Address predisposing conditions: venous insufficiency, lymphedema, chronic edema, obesity, eczema. 1, 2
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited. 1

Prevention of Recurrent Cellulitis

• Annual recurrence rates are 8-20% in patients with previous cellulitis. 1
• For patients with 3-4 episodes per year despite treating predisposing factors: Consider prophylactic antibiotics such as penicillin V 250 mg orally twice daily or erythromycin 250 mg twice daily. 1, 2

Common Pitfalls to Avoid

• Do not reflexively add MRSA coverage for typical nonpurulent cellulitis—MRSA is uncommon even in high-prevalence settings, and beta-lactam monotherapy succeeds in 96% of cases. 1, 3
• Do not use combination therapy (e.g., trimethoprim-sulfamethoxazole plus cephalexin) for pure cellulitis without abscess, ulcer, or purulent drainage—it provides no additional benefit. 1
• Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates resistant organisms or a deeper/different infection. 1
• Do not delay surgical consultation if any signs of necrotizing infection are present—these progress rapidly and require debridement. 1
• Do not use doxycycline or trimethoprim-sulfamethoxazole alone for typical cellulitis—always combine with a beta-lactam for streptococcal coverage. 1

Special Populations

Penicillin/Cephalosporin Allergy

• Clindamycin 300-450 mg orally every 6 hours is the optimal choice, providing single-agent coverage for both streptococci and MRSA. 1
• Levofloxacin 500 mg daily can be used but should be reserved for beta-lactam allergies. 1

Bite-Associated Cellulitis

• Amoxicillin-clavulanate 875/125 mg twice daily as monotherapy provides coverage for polymicrobial oral flora. 1

Diabetic Foot Infections

• Consider broader coverage with amoxicillin-clavulanate, second or third-generation cephalosporins (cefuroxime, ceftriaxone), or fluoroquinolones. 1