What are the treatment approaches for mild, moderate, and severe cellulitis?

Treatment of Cellulitis by Severity

For mild to moderate cellulitis, use beta-lactam monotherapy (cephalexin 500 mg every 6 hours or dicloxacillin 250-500 mg every 6 hours) for 5 days, reserving MRSA coverage only for specific risk factors like purulent drainage, penetrating trauma, or injection drug use; for severe cellulitis with systemic toxicity, initiate broad-spectrum IV combination therapy with vancomycin 15-20 mg/kg every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g every 6 hours. 1

Mild Cellulitis (Outpatient Management)

First-Line Antibiotic Selection

• Beta-lactam monotherapy is the standard of care with 96% success rates, as MRSA is an uncommon cause of typical uncomplicated cellulitis even in high-prevalence settings. 1
• Recommended oral agents include:
  • Cephalexin 500 mg every 6 hours (four times daily) 1
  • Dicloxacillin 250-500 mg every 6 hours 1
  • Amoxicillin (standard dosing) 1
  • Penicillin V 250-500 mg four times daily 1

Treatment Duration

• Treat for exactly 5 days if clinical improvement occurs (warmth and tenderness resolved, erythema improving, patient afebrile). 1
• Extend treatment only if symptoms have not improved within this 5-day timeframe—do not reflexively extend to 7-14 days based on residual erythema alone. 1

When NOT to Use Beta-Lactam Monotherapy

• Do not use beta-lactam alone if any of these MRSA risk factors are present: 1
  • Penetrating trauma or injection drug use
  • Purulent drainage or exudate visible
  • Known MRSA colonization or prior MRSA infection
  • Systemic inflammatory response syndrome (SIRS)

Essential Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage. 1
• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration and treat aggressively to eradicate colonization. 1
• Address venous insufficiency, lymphedema, and chronic edema as these predispose to recurrence. 1

Moderate Cellulitis (May Require Hospitalization)

Indications for Hospitalization

• Hospitalize if any of the following are present: 1
  • SIRS (fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm)
  • Hypotension or hemodynamic instability
  • Altered mental status or confusion
  • Severe immunocompromise or neutropenia
  • Concern for deeper or necrotizing infection

IV Antibiotic Selection for Hospitalized Patients

• For uncomplicated cellulitis requiring hospitalization WITHOUT MRSA risk factors: 1

  • Cefazolin 1-2 g IV every 8 hours (preferred) 1, 2
  • Oxacillin 2 g IV every 6 hours (alternative) 1
  • Nafcilina 1-2 g IV every 4-6 horas (alternativa) 2

• For cellulitis WITH MRSA risk factors or purulent features: 1

  • Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line, A-I evidence) 1, 2
  • Linezolid 600 mg IV twice daily (equally effective alternative, A-I evidence) 1
  • Daptomycin 4 mg/kg IV once daily (alternative, A-I evidence) 1
  • Clindamycin 600 mg IV every 8 hours (only if local MRSA resistance <10%, A-III evidence) 1
  • Ceftarolina 600 mg cada 12 horas (opción para casos severos con factores de riesgo para MRSA) 2

Combination Therapy for Moderate Cellulitis with MRSA Risk

• When both streptococcal and MRSA coverage are needed (penetrating trauma, purulent drainage, MRSA risk factors): 1
  • Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS a beta-lactam (cephalexin or amoxicillin) 1
  • Doxycycline 100 mg twice daily PLUS a beta-lactam 1
  • OR clindamycin 300-450 mg four times daily as monotherapy (covers both streptococci and MRSA, avoiding need for true combination) 1

Transition to Oral Therapy

• Transition to oral antibiotics once clinical improvement is demonstrated, typically after minimum 4 days of IV treatment. 1
• Oral options include cephalexin, dicloxacillin, or clindamycin (if continued MRSA coverage needed). 1

Treatment Duration

• La duración recomendada es de 5-7 días inicialmente, con extensión si la infección no ha mejorado en este período. 2

Severe Cellulitis (Systemic Toxicity or Suspected Necrotizing Infection)

Immediate Assessment

• Evaluate urgently for necrotizing fasciitis warning signs: 1, 3
  • Severe pain out of proportion to examination
  • Skin anesthesia or "wooden-hard" subcutaneous tissues
  • Rapid progression or bullous changes
  • Gas in tissue on imaging
  • Skin sloughing 3
• Obtain blood cultures in patients with malignancy, severe systemic features, neutropenia, or severe immunodeficiency. 1, 3

Mandatory Broad-Spectrum Combination Therapy

• For severe cellulitis with systemic toxicity, rapid progression, or suspected necrotizing fasciitis, use: 1, 3
  • Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 1, 2, 3
  • OR Linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam 1
  • OR Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours) 1
  • OR Vancomycin PLUS ceftriaxone 2 g IV daily and metronidazole 500 mg IV every 8 hours 1

Special Consideration: Documented Group A Streptococcal Necrotizing Fasciitis

• Specific regimen: Penicillin PLUS clindamycin (clindamycin inhibits toxin production). 1

Treatment Duration for Severe Infections

• Plan for 7-14 days minimum for severe infections with systemic toxicity or skin sloughing, guided by clinical response and source control. 1, 3
• Reassess at 5 days but expect longer courses than uncomplicated cellulitis. 1

Surgical Consultation

• Obtain emergent surgical consultation if any signs of necrotizing infection are present, as these require diagnostic and therapeutic debridement. 1, 3
• Do not delay surgical consultation—necrotizing infections progress rapidly. 1

Adjunctive Measures for Severe Cases

• Elevation of affected area to promote gravity drainage. 1, 3
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited. 1, 3
• Daily assessment of vital signs and laboratory markers of inflammation. 3

Critical Pitfalls to Avoid

• Do not add MRSA coverage reflexively simply because the patient is hospitalized—beta-lactam monotherapy remains appropriate for typical nonpurulent cellulitis even in the inpatient setting. 1
• Never use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable. 1
• Do not extend treatment to 10-14 days based on tradition rather than evidence—this increases antibiotic resistance without improving outcomes in uncomplicated cases. 1
• Using both piperacillin-tazobactam AND daptomycin simultaneously for simple cellulitis represents significant overtreatment—reserve this combination only for life-threatening infections or documented resistant organisms. 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: 1, 3
  • Penicillin V 250 mg orally twice daily 1
  • Erythromycin 250 mg orally twice daily 1
  • Penicilina benzatínica (para prevención de recurrencias) 2