What is the recommended treatment for cellulitis?

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Last updated: July 18, 2025View editorial policy

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Treatment of Cellulitis

For typical cases of cellulitis without systemic signs of infection, a 5-day course of antibiotics active against streptococci is recommended as first-line therapy. 1

Classification and Initial Assessment

Severity Assessment

  • Mild cellulitis: No systemic signs of infection, localized erythema, warmth, tenderness
  • Moderate cellulitis: Systemic signs of infection present
  • Severe cellulitis: Associated with SIRS, immunocompromise, or hemodynamic instability

Diagnostic Approach

  • Cellulitis is primarily a clinical diagnosis based on expanding erythema, warmth, tenderness, and swelling 2
  • Cultures are not routinely recommended for typical cases 1
  • Blood cultures should be obtained in patients with:
    • Malignancy on chemotherapy
    • Neutropenia
    • Severe cell-mediated immunodeficiency
    • Immersion injuries
    • Animal bites
    • Systemic inflammatory response syndrome (SIRS)

Antibiotic Treatment Algorithm

First-Line Treatment (Mild Cellulitis)

  • Target organism: β-hemolytic streptococci
  • Recommended antibiotics:
    • Penicillin VK 250-500 mg every 6 hours
    • Amoxicillin 500 mg three times daily
    • Cephalexin 500 mg every 6 hours
    • Dicloxacillin 250 mg every 6 hours 3
  • Duration: 5 days 1, 4

Treatment for Moderate Cellulitis

  • Target organisms: Streptococci and consider MSSA coverage
  • Recommended antibiotics:
    • Dicloxacillin 500 mg every 6 hours
    • Cefazolin 1 g every 8 hours (IV)
    • Clindamycin 300-450 mg every 6-8 hours (for penicillin-allergic patients)
  • Duration: 5 days, extend if not improved 1

Treatment for Severe Cellulitis

  • Target organisms: Streptococci, MSSA, and consider MRSA in specific situations
  • MRSA coverage indicated if:
    • Penetrating trauma
    • Evidence of MRSA infection elsewhere
    • Nasal colonization with MRSA
    • Injection drug use
    • SIRS present
  • Recommended antibiotics for MRSA coverage:
    • Vancomycin 15 mg/kg every 12 hours (IV)
    • Linezolid 600 mg every 12 hours
    • Daptomycin 4 mg/kg daily
    • Clindamycin 600 mg every 8 hours (if susceptible)
  • For severely compromised patients: Vancomycin plus either piperacillin-tazobactam or imipenem/meropenem 1

Treatment Setting

  • Outpatient: For patients without SIRS, altered mental status, or hemodynamic instability
  • Inpatient: Consider for:
    • Concern for deeper or necrotizing infection
    • Poor adherence to therapy
    • Severely immunocompromised patients
    • Failing outpatient treatment

Adjunctive Measures

  • Elevate the affected area 1
  • Treat predisposing factors:
    • Edema
    • Underlying cutaneous disorders
    • Examine interdigital toe spaces for fissuring, scaling, or maceration in lower extremity cellulitis 1
  • Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults 1

Management of Recurrent Cellulitis

  • Identify and treat predisposing conditions:
    • Edema
    • Obesity
    • Eczema
    • Venous insufficiency
    • Toe web abnormalities 1
  • 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
    • Intramuscular benzathine penicillin every 2-4 weeks 1
  • Consider a 5-day decolonization regimen for recurrent S. aureus infections:
    • Intranasal mupirocin twice daily
    • Daily chlorhexidine washes
    • Daily decontamination of personal items (towels, sheets, clothes) 1

Common Pitfalls and Caveats

  1. Misdiagnosis: Many conditions mimic cellulitis including venous stasis dermatitis, contact dermatitis, and deep vein thrombosis 5
  2. Overtreatment for MRSA: MRSA coverage is not routinely needed for typical non-purulent cellulitis 5
  3. Inadequate follow-up: Extend treatment if infection has not improved after 5 days 1
  4. Failure to address underlying conditions: Treating predisposing factors is crucial to prevent recurrence 1
  5. Unnecessary cultures: Routine cultures are not recommended for typical cases and have poor yield 1

The evidence strongly supports a 5-day course of antibiotics targeting streptococci for uncomplicated cellulitis, with extension of therapy if the infection has not improved within this time period 1, 4.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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