What is the recommended treatment for cellulitis?

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Last updated: October 9, 2025View editorial policy

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Treatment of Cellulitis

For uncomplicated cellulitis, a 5-day course of antibiotics active against streptococci is the recommended first-line treatment, with extension if the infection has not improved within this timeframe. 1

Antibiotic Selection

First-line therapy:

  • For typical cases of cellulitis, use antibiotics active against streptococci, as they are the most common causative pathogens 1
  • Recommended oral options include:
    • Penicillin
    • Amoxicillin
    • Amoxicillin-clavulanate
    • Dicloxacillin
    • Cephalexin
    • Clindamycin 1, 2

Parenteral therapy (for severely ill patients):

  • Indicated for patients with severe illness or those unable to tolerate oral medications 1
  • Options include:
    • Nafcillin (penicillinase-resistant penicillin)
    • Cefazolin (first-generation cephalosporin)
    • Clindamycin or vancomycin (for patients with life-threatening penicillin allergies) 1

MRSA Considerations

  • MRSA is an unusual cause of typical cellulitis without purulent drainage 1
  • Coverage for MRSA should be considered in specific situations:
    • Cellulitis associated with penetrating trauma
    • History of illicit drug use
    • Presence of purulent drainage
    • Concurrent evidence of MRSA infection elsewhere 1
  • When MRSA coverage is needed, options include:
    • Intravenous: vancomycin, daptomycin, linezolid, or telavancin
    • Oral: doxycycline, clindamycin, or trimethoprim-sulfamethoxazole (SMX-TMP) 1

Important note: A randomized controlled trial showed that adding trimethoprim-sulfamethoxazole to cephalexin did not significantly improve outcomes in uncomplicated cellulitis compared to cephalexin alone in the per-protocol analysis 3, supporting the guideline recommendation that β-lactam monotherapy is appropriate for non-purulent cellulitis 1.

Duration of Therapy

  • A 5-day course of antimicrobial therapy is as effective as a 10-day course for uncomplicated cellulitis, provided clinical improvement has occurred by day 5 1
  • The 2019 National Institute for Health and Care Excellence (NICE) guideline recommends a course of 5 to 7 days 1
  • Treatment should be extended if the infection has not improved after 5 days 1, 2

Adjunctive Measures

  • Elevation of the affected area is an important and often neglected aspect of treatment 1
    • Promotes gravity drainage of edema and inflammatory substances
    • Hastens improvement of symptoms 1
  • Treat any predisposing conditions that may have contributed to the infection:
    • Tinea pedis
    • Venous eczema ("stasis dermatitis")
    • Trauma 1

Anti-inflammatory Therapy

  • Systemic corticosteroids (e.g., prednisone 40 mg daily for 7 days) could be considered in non-diabetic adult patients with cellulitis 1, 2
  • A randomized, double-blind, placebo-controlled trial showed that systemic corticosteroids attenuated inflammatory reactions and hastened resolution 1
  • Some evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) may also help hasten resolution of cellulitis-related inflammation when added to antibiotic therapy 4

Prevention of Recurrence

  • Patients with previous attacks of cellulitis have annual recurrence rates of about 8%-20%, usually in the same area 1
  • Risk factors for recurrence include:
    • Edema (especially lymphedema)
    • Venous insufficiency
    • Prior trauma to the area
    • Tinea pedis or other toe web abnormalities 1
  • Address underlying risk factors to reduce recurrence risk 1

Common Pitfalls and Caveats

  • Avoid unnecessary MRSA coverage for typical non-purulent cellulitis 1, 5
  • Don't forget to elevate the affected area, which is crucial for treatment success 1
  • Be aware that inflammation may worsen after initiating therapy due to pathogen destruction releasing enzymes that increase local inflammation 1
  • Consider extending treatment beyond 5 days if clinical improvement is not observed 1
  • Cultures of blood, tissue aspirates, or skin biopsies are unnecessary for typical cases of cellulitis but should be obtained for patients with:
    • Malignancy
    • Severe systemic features (high fever, hypotension)
    • Unusual predisposing factors (immersion injury, animal bites, neutropenia, severe cell-mediated immunodeficiency) 1

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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