What are the best empiric antibiotics for treating uncomplicated cellulitis?

Best Empiric Antibiotics for Uncomplicated Cellulitis

For uncomplicated cellulitis, first-line empiric antibiotic therapy should include a cephalosporin (such as cephalexin), penicillin, or clindamycin that targets streptococci and methicillin-sensitive Staphylococcus aureus (MSSA) for a 5-6 day course. 1

Pathogen Considerations

Common Causative Organisms

• β-hemolytic streptococci (most common, especially group A)
• Staphylococcus aureus (less common unless associated with abscess or penetrating trauma)
• Source of streptococci often includes:
  • Macerated interdigital toe spaces
  • Fissured toe webs
  • Occasionally anal canal or vagina 1

MRSA Coverage

• Not routinely needed for typical uncomplicated cellulitis
• Consider MRSA coverage only in specific situations:
  • Penetrating trauma
  • Evidence of MRSA infection elsewhere
  • Nasal colonization with MRSA
  • Injection drug use
  • Systemic inflammatory response syndrome
  • Other high-risk groups: athletes, children, men who have sex with men, prisoners, military recruits, residents of long-term care facilities 1, 2

Recommended Antibiotic Regimens

First-Line Oral Options (for uncomplicated cases)

• Cephalexin: 500 mg four times daily
• Dicloxacillin: 500 mg four times daily
• Clindamycin: 300-450 mg three times daily (also covers MRSA)
• Erythromycin: 250-500 mg four times daily (note: increasing macrolide resistance in some regions) 1

When MRSA Coverage is Indicated

• Trimethoprim-sulfamethoxazole (TMP-SMX): 1-2 DS tablets twice daily
• Clindamycin: 300-450 mg three times daily
• Doxycycline: 100 mg twice daily (for patients ≥8 years old) 2

Parenteral Options (for severe cases)

• Nafcillin or oxacillin: 1-2 g every 4-6 hours
• Cefazolin: 1-2 g every 8 hours
• Clindamycin: 600-900 mg every 8 hours (for penicillin-allergic patients)
• Vancomycin: 15-20 mg/kg every 8-12 hours (for penicillin-allergic patients or when MRSA is suspected) 1

Duration of Therapy

• 5-6 days is sufficient for uncomplicated cellulitis 1
• Consider extending treatment if infection has not improved after 5 days 1
• The DANCE trial compared a 6-day course of flucloxacillin with the standard 12-day course and found similar cure rates 1
• A randomized controlled trial showed 5 days of levofloxacin was as effective as 10 days for uncomplicated cellulitis (98% success in both groups) 3

Important Clinical Considerations

Combination Therapy

• Adding TMP-SMX to cephalexin did not improve outcomes in uncomplicated cellulitis without abscess, suggesting routine MRSA coverage is unnecessary 4, 5

Adjunctive Measures

• Elevation of the affected area is important to promote drainage of edema and inflammatory substances
• Address underlying conditions that predispose to infection (tinea pedis, venous eczema, etc.)
• Consider systemic corticosteroids in selected adult patients to hasten resolution (contraindicated in diabetics, pregnant women, and those <18 years) 1

Treatment Failure Considerations

• If no improvement after 5 days, consider:
  • Resistant organisms
  • Deeper infection
  • Underlying conditions (diabetes, venous insufficiency, lymphedema)
  • Misdiagnosis (mimicking conditions) 6

Pitfalls to Avoid

1. Don't routinely cover for MRSA in typical uncomplicated cellulitis without risk factors
2. Don't forget to elevate the affected area, a simple but often neglected aspect of treatment
3. Don't overlook and treat underlying predisposing conditions like tinea pedis
4. Don't automatically prescribe longer courses (>5-6 days) for uncomplicated cases
5. Don't miss purulent collections that may require drainage in addition to antibiotics

Remember that cellulitis is primarily caused by streptococci, and S. aureus is less common unless there is an abscess or penetrating trauma. Five to six days of appropriate antibiotic therapy targeting these organisms is sufficient for most uncomplicated cases.