What is the recommended treatment for cellulitis?

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Cellulitis Treatment

First-Line Antibiotic Therapy

For uncomplicated cellulitis, treat with a 5-day course of oral antibiotics targeting streptococci, such as penicillin, amoxicillin, cephalexin (500 mg four times daily), dicloxacillin, or clindamycin, extending treatment only if clinical improvement has not occurred by day 5. 1, 2

Antibiotic Selection Algorithm

  • Uncomplicated cases without systemic signs: Use antibiotics active against streptococci alone 1, 3

    • Options: penicillin, amoxicillin, amoxicillin-clavulanate, dicloxacillin, cephalexin, or clindamycin 1, 2
    • The majority of non-purulent cellulitis is caused by β-hemolytic streptococci or methicillin-sensitive S. aureus 4, 3
  • Moderate infections with systemic signs (fever, tachycardia, elevated WBC): Add coverage for methicillin-susceptible S. aureus (MSSA) 1

    • Options: cefazolin or nafcillin for intravenous therapy 5

Duration of Treatment

  • 5 days is sufficient if clinical improvement occurs by day 5 1, 2
  • This is as effective as 10-day courses and avoids unnecessary antibiotic exposure 1
  • Extend treatment only if infection has not improved within the initial 5-day period 2

MRSA Coverage: When and When Not

MRSA coverage is NOT routinely needed for typical non-purulent cellulitis 1, 3

Specific Indications for MRSA Coverage

Add MRSA-targeted therapy ONLY when these risk factors are present: 1, 2

  • Penetrating trauma 1, 2
  • Purulent drainage 1, 2
  • Concurrent evidence of MRSA infection elsewhere 1, 2
  • History of injection drug use 2
  • Athletes, prisoners, military recruits, long-term care facility residents, or prior MRSA exposure 4

MRSA Treatment Options

  • Clindamycin alone 2
  • Combination of trimethoprim-sulfamethoxazole (SMX-TMP) or doxycycline with a β-lactam 2
  • Linezolid 600 mg every 12 hours for complicated cases 6

Essential Adjunctive Measures

Elevation of the affected extremity is critical to promote gravity drainage of edema and inflammatory substances 1, 2

Identify and Treat Predisposing Conditions

  • Tinea pedis and toe web abnormalities: Examine interdigital spaces in all lower-extremity cellulitis cases 1, 2
  • Venous insufficiency and lymphedema: Particularly important in older adults 2
  • Trauma, eczema, or venous stasis dermatitis: Address at initial presentation 1

Consider Systemic Corticosteroids

  • Prednisone 40 mg daily for 7 days may hasten resolution in non-diabetic adults 1, 2
  • This reduces inflammation and can shorten time to complete resolution 2, 7
  • Do NOT use in diabetic patients 1, 2

Hospitalization Criteria

Admit patients with any of the following: 1, 2

  • Systemic inflammatory response syndrome (SIRS) 1, 2
  • Altered mental status 1, 2
  • Hemodynamic instability 1, 2
  • Concern for deeper or necrotizing infection 1, 2
  • Severe immunocompromise 1, 2
  • Poor adherence to outpatient therapy 1, 2
  • Failure of outpatient treatment 1, 2

Prevention of Recurrent Cellulitis

For patients with 3-4 episodes per year despite treating predisposing factors, initiate prophylactic antibiotics 1

Prophylaxis Options

  • Oral penicillin 5, 2
  • Oral erythromycin 5, 2
  • Intramuscular benzathine penicillin 5, 2

Address Underlying Risk Factors

  • Treat tinea pedis aggressively 1, 2
  • Manage venous insufficiency and lymphedema 2
  • Address obesity and chronic edema 1

Common Pitfalls to Avoid

  • Don't extend treatment beyond 5 days if clinical improvement has occurred 2
  • Don't automatically add MRSA coverage for typical non-purulent cellulitis without specific risk factors 2, 3
  • Don't forget to examine interdigital toe spaces, as treating fissuring or maceration reduces recurrence 2
  • Don't overlook elevation of the affected area, especially in patients with venous insufficiency 2
  • Don't obtain blood cultures routinely—reserve for patients with malignancy, severe systemic features, or unusual predisposing factors 1

Special Diagnostic Considerations

  • Cellulitis is a clinical diagnosis based on acute onset of erythema, warmth, swelling, tenderness, and pain 3
  • Microbiological diagnosis is often unobtainable due to poor culture sensitivity 3
  • Consider clinical mimickers: venous stasis dermatitis, contact dermatitis, eczema, lymphedema, and erythema migrans 3
  • Failure to improve with appropriate first-line antibiotics should prompt consideration for resistant organisms or alternative diagnoses 4

References

Guideline

Cellulitis Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Management of Cellulitis in Older Adults

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Cellulitis: A Review.

JAMA, 2016

Guideline

Treatment of Preseptal Cellulitis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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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