What antibiotics are recommended for treating uncomplicated cellulitis?

Antibiotic Treatment for Uncomplicated Cellulitis

For uncomplicated cellulitis, first-line treatment should include a 5-6 day course of antibiotics active against streptococci, with options including cephalexin, penicillins, or clindamycin for non-purulent cellulitis, while MRSA coverage should be added for purulent cellulitis or in patients with specific risk factors. 1, 2

First-Line Treatment Options

Non-Purulent Cellulitis (Most Common)

• Beta-lactams (target streptococci):
  • Cephalexin 500 mg PO four times daily
  • Amoxicillin PO
  • Penicillin PO
  • Clindamycin 300-450 mg PO three times daily (alternative for penicillin-allergic patients)

Purulent Cellulitis or MRSA Risk Factors

• MRSA coverage required when:

  • Purulent drainage present
  • Evidence of MRSA infection elsewhere
  • Nasal MRSA colonization
  • Injection drug use
  • Systemic inflammatory response syndrome
  • Prior treatment failure with beta-lactams
  • High local MRSA prevalence

• MRSA-active options:

  • TMP-SMX 1-2 DS tablets PO twice daily
  • Clindamycin 300-450 mg PO three times daily
  • Doxycycline/minocycline 100 mg PO twice daily
  • Linezolid 600 mg PO twice daily (reserve for severe cases) 2

Treatment Duration

The most recent evidence supports shorter antibiotic courses:

• 5-6 days is sufficient for most uncomplicated cellulitis 1
• Consider extending treatment only if:
  • Infection has not improved after 5 days
  • Severe initial infection
  • Immunocompromised patient
  • Presence of complicating factors 1, 2

Combination Therapy Considerations

• For patients requiring both streptococcal and MRSA coverage, options include:

  • Clindamycin alone (covers both)
  • TMP-SMX or tetracycline plus amoxicillin
  • Linezolid alone (covers both) 2

• Recent evidence does not support routine combination therapy:

  • A randomized trial found no significant benefit of adding TMP-SMX to cephalexin for uncomplicated cellulitis 3, 4

Special Populations

Children

• Avoid tetracyclines in children under 8 years
• For hospitalized children:
  • Vancomycin IV or clindamycin 10-13 mg/kg/dose IV every 6-8 hours
  • Linezolid dosing for children under 12 years: 10 mg/kg/dose PO/IV every 8 hours 2

Monitoring and Follow-up

• Daily follow-up until definite improvement is noted
• Monitor for:
  • Decreased erythema, swelling, and pain
  • Resolution of systemic symptoms (fever, chills)
  • No new lesions appearing in preceding 48 hours 2
• Consider hospitalization if:
  • No improvement within 24-48 hours of outpatient therapy
  • Progressive infection
  • Development of systemic toxicity 2

Common Pitfalls to Avoid

1. Overtreatment with MRSA coverage when not indicated for non-purulent cellulitis
2. Inadequate duration of therapy (less than 5 days)
3. Failure to obtain cultures from abscesses or purulent drainage before starting antibiotics
4. Missing warning signs of deeper infection, including pain disproportionate to physical findings
5. Not recognizing when incision and drainage is needed for abscessed cellulitis 2

Prevention of Recurrence

• Maintain good personal hygiene
• Keep draining wounds covered with clean, dry bandages
• Address underlying conditions: edema, obesity, eczema, venous insufficiency
• Consider prophylactic antibiotics for patients with 3-4 episodes per year 2