What are the recommended antibiotics for treating uncomplicated cellulitis?

Recommended Antibiotics for Uncomplicated Cellulitis

For uncomplicated non-purulent cellulitis, a 5-6 day course of antibiotics active against streptococci is recommended as first-line treatment. 1

Causative Organisms

• Streptococci (particularly group A streptococci) are the most common cause of typical cellulitis 2
• Staphylococcus aureus (including MRSA) typically causes cellulitis only when associated with abscess formation or penetrating trauma 2

First-Line Treatment Options

For typical non-purulent cellulitis (without abscess):

• β-lactam antibiotics (active against streptococci):
  • Penicillin
  • Amoxicillin
  • Cephalexin (first-generation cephalosporin)

These antibiotics effectively target streptococci, which are the predominant pathogens in uncomplicated cellulitis 2.

When to Consider MRSA Coverage

Add coverage for methicillin-resistant Staphylococcus aureus (MRSA) only if:

• Purulent drainage or abscess is present
• Patient has prior MRSA infection or colonization
• Penetrating trauma is involved
• Injection drug use history
• Systemic inflammatory response syndrome is present
• Initial treatment failure with β-lactam antibiotics 1, 2

MRSA Coverage Options

If MRSA coverage is indicated, consider:

• Clindamycin (300-450 mg orally four times daily) 2
• Trimethoprim-sulfamethoxazole (TMP-SMX) 2, 3
• Doxycycline (100 mg orally twice daily) 2
• Linezolid (600 mg orally twice daily) for severe cases 2, 4

Research shows that in areas with high MRSA prevalence, TMP-SMX had significantly higher success rates (91%) compared to cephalexin (74%) for empiric treatment of cellulitis 3.

Treatment Duration

• 5-6 days is sufficient for uncomplicated cellulitis 1, 2, 5
• Longer courses have not demonstrated superior outcomes for uncomplicated cases 2
• Extended therapy increases risk of adverse effects and antimicrobial resistance 2

A randomized controlled trial comparing 5 days versus 10 days of levofloxacin for uncomplicated cellulitis found equal efficacy (98% success in both groups) 5.

Route of Administration

• Oral antibiotics are appropriate for most uncomplicated cases 6
• Intravenous antibiotics should be considered for:
  • Severe or extensive disease
  • Rapid progression
  • Systemic illness signs
  • Immunosuppression
  • Significant comorbidities
  • Extremes of age
  • Difficult-to-drain locations
  • Associated septic phlebitis
  • Lack of response to oral therapy 2

A randomized trial demonstrated that oral antibiotics were non-inferior to parenteral antibiotics for uncomplicated cellulitis 6.

Monitoring Response

• Assess for clinical improvement within 48-72 hours
• Consider extending treatment or changing antibiotics if:
  • Infection has not improved after 5 days 1
  • Signs of deeper infection develop
  • Pain disproportionate to physical findings occurs
  • Systemic symptoms worsen 2

Warning Signs Requiring Urgent Attention

• Orbital involvement (proptosis, pain with eye movements, vision changes)
• Pain disproportionate to physical findings (may indicate necrotizing infection)
• Rapid progression
• Systemic toxicity
• Extensive facial involvement
• Airway compromise concerns 2

Key Takeaways

1. First-line treatment for uncomplicated non-purulent cellulitis is a 5-6 day course of antibiotics active against streptococci
2. MRSA coverage should be added only when specific risk factors are present
3. Oral antibiotics are appropriate for most uncomplicated cases
4. Monitor for clinical improvement within 48-72 hours and adjust therapy if needed