What is the recommended management for cellulitis?

Management of Cellulitis

For typical uncomplicated cellulitis, treat with beta-lactam monotherapy (cephalexin, dicloxacillin, or amoxicillin) for 5 days, extending only if symptoms have not improved—MRSA coverage is unnecessary in 96% of cases. 1

Initial Assessment and Risk Stratification

Determine if this is purulent vs. nonpurulent cellulitis:

• Nonpurulent cellulitis (no abscess, no purulent drainage, no penetrating trauma): Beta-lactam monotherapy is appropriate 1, 2
• Purulent cellulitis (abscess present, purulent drainage, or exudate): Add MRSA coverage 1
• Look for MRSA risk factors: penetrating trauma, injection drug use, known MRSA colonization, or concurrent MRSA infection elsewhere 1, 2

Assess severity to determine treatment setting:

• Outpatient management is appropriate for patients without systemic inflammatory response syndrome (SIRS), altered mental status, hemodynamic instability, or concern for deeper infection 2
• Hospitalization is indicated for systemic toxicity (fever, hypotension, tachycardia, confusion), suspected necrotizing fasciitis, severe immunocompromise, or failed outpatient therapy 1, 2

Antibiotic Selection Algorithm

Outpatient Nonpurulent Cellulitis (First-Line)

Beta-lactam monotherapy is the standard of care with 96% success rate: 1

• Cephalexin 500 mg PO twice daily 1
• Dicloxacillin 500 mg PO four times daily 1
• Amoxicillin 500 mg PO three times daily 1
• Amoxicillin-clavulanate 875/125 mg PO twice daily (particularly for bite-related cellulitis) 1
• Clindamycin 300-450 mg PO three times daily (covers both streptococci and MRSA, useful for penicillin allergy) 1, 2

Duration: 5 days if clinical improvement occurs, extend only if no improvement 1, 2

Outpatient Purulent Cellulitis or MRSA Risk Factors

When MRSA coverage is needed, use combination therapy or clindamycin monotherapy:

• Trimethoprim-sulfamethoxazole PLUS a beta-lactam (e.g., cephalexin) 1
• Doxycycline 100 mg PO twice daily PLUS a beta-lactam 1
  • Critical caveat: Never use doxycycline or TMP-SMX as monotherapy for typical cellulitis—they lack reliable streptococcal coverage 1
• Clindamycin monotherapy 300-450 mg PO three times daily (covers both pathogens, avoiding need for true combination) 1

Inpatient Complicated Cellulitis (IV Therapy)

For hospitalized patients requiring IV antibiotics:

• Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line, A-I evidence) 1
• Linezolid 600 mg IV twice daily (alternative with A-I evidence) 1, 3
• Daptomycin 4 mg/kg IV once daily (alternative with A-I evidence) 1
• Clindamycin 600 mg IV three times daily (if local resistance rates are low, A-III evidence) 1
• Cefazolin or oxacillin IV (appropriate for nonpurulent cellulitis without MRSA risk factors, even in hospitalized patients) 1

Duration: 7-14 days for complicated infections, guided by clinical response 1

Severe Cellulitis with Systemic Toxicity or Suspected Necrotizing Fasciitis

Broad-spectrum combination therapy is mandatory:

• Vancomycin or linezolid PLUS piperacillin-tazobactam 3.375-4.5 grams IV every 6 hours 1
• Vancomycin or linezolid PLUS a carbapenem 1
• Vancomycin or linezolid PLUS ceftriaxone and metronidazole 1
• For documented Group A streptococcal necrotizing fasciitis: Penicillin plus clindamycin 1
• Obtain emergent surgical consultation for diagnostic and therapeutic debridement 1

Duration: 7-14 days minimum, often longer depending on surgical findings and clinical response 1

Transition to Oral Therapy

Switch from IV to oral antibiotics once clinical improvement is demonstrated:

• Typically after minimum 4 days of IV treatment 1
• Use cephalexin, dicloxacillin, or clindamycin for continued coverage 1
• For continued MRSA coverage: clindamycin alone or TMP-SMX/doxycycline plus a beta-lactam 1

Adjunctive Measures

These interventions hasten improvement and reduce recurrence:

• Elevate the affected extremity to promote gravity drainage of edema 1, 2
• Treat predisposing conditions: tinea pedis, toe web abnormalities, venous insufficiency, lymphedema, eczema, obesity 1, 2
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 1

Monitoring and Treatment Failure

Reassess in 24-48 hours to verify clinical response: 1

• If spreading despite appropriate antibiotics (e.g., cloxacillin), evaluate for:
  • Necrotizing fasciitis warning signs: severe pain out of proportion to exam, skin anesthesia, rapid progression, gas in tissue, bullous changes 1
  • MRSA involvement: Switch to vancomycin or linezolid 1
  • Misdiagnosis: Consider pseudocellulitis (venous stasis dermatitis, DVT, gout, eczema) 4, 5
• Do not continue ineffective antibiotics beyond 48 hours 1
• Obtain blood cultures in patients with malignancy, severe systemic features, neutropenia, or severe immunodeficiency 1, 2

Prevention of Recurrence

For patients with 3-4 episodes per year despite addressing predisposing factors:

• Consider prophylactic antibiotics (oral penicillin or erythromycin twice daily for 4-52 weeks) 6, 2
• Aggressively treat underlying conditions: tinea pedis, venous insufficiency, lymphedema 1, 7

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 hospitals 1
• Do not use doxycycline or TMP-SMX as monotherapy for nonpurulent cellulitis—streptococcal coverage is inadequate 1
• Do not fail to elevate the extremity—this simple measure significantly hastens improvement 1, 6
• Do not delay surgical consultation if any signs of necrotizing infection are present 1
• Do not use combination therapy (e.g., vancomycin plus piperacillin-tazobactam plus daptomycin) for simple cellulitis—this represents significant overtreatment reserved only for life-threatening infections 1