What is the best antibiotic for treating uncomplicated cellulitis?

Best Antibiotic for Uncomplicated Cellulitis

For uncomplicated cellulitis, a cephalosporin (such as cephalexin), penicillin, or clindamycin is recommended as first-line therapy, with a 5-6 day course being as effective as longer treatment durations. 1

First-Line Antibiotic Selection

Standard Cases (No MRSA Risk Factors)

• Antibiotics active against streptococci should be used for typical cases of cellulitis 1
• Recommended oral options include:
  • Cephalexin 500 mg four times daily 1
  • Penicillin or amoxicillin 1
  • Dicloxacillin 1
  • Clindamycin 300-450 mg four times daily (especially for penicillin-allergic patients) 1, 2

Special Circumstances (MRSA Risk Factors)

• Consider MRSA coverage when cellulitis is associated with:
  • Penetrating trauma, especially from illicit drug use 1
  • Evidence of MRSA infection elsewhere 1
  • Nasal colonization with MRSA 1
  • Injection drug use 1
  • Systemic inflammatory response syndrome (SIRS) 1
• Options for MRSA coverage include:
  • Clindamycin (covers both streptococci and MRSA) 1
  • Trimethoprim-sulfamethoxazole (TMP-SMX) plus a β-lactam 1

Treatment Duration

• A 5-6 day course of antibiotics is as effective as a 10-day course for uncomplicated cellulitis 1
• The 2014 IDSA guideline recommends 5 days of therapy, with extension if the infection has not improved within this period 1
• The 2019 NICE guideline recommends a course of 5-7 days 1
• A randomized controlled trial showed no significant difference in clinical outcomes between 5 and 10 days of therapy with levofloxacin 3

Evidence Strength and Considerations

• MRSA is an unusual cause of typical cellulitis without purulent drainage 1
• A prospective study showed that β-lactam therapy was successful in 96% of patients with typical cellulitis, suggesting MRSA coverage is usually unnecessary 1
• A randomized trial comparing cephalexin plus TMP-SMX versus cephalexin alone found no significant difference in clinical cure rates in the per-protocol analysis (83.5% vs 85.5%) 4
• The activity of TMP-SMX against β-hemolytic streptococci is not well established, making it suboptimal as monotherapy 1

Adjunctive Measures

• Elevation of the affected area hastens improvement by promoting gravity drainage of edema 1
• Treat predisposing conditions such as tinea pedis, venous eczema, or trauma 1
• Examine interdigital toe spaces in lower-extremity cellulitis to identify and treat fissuring or maceration 1
• Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults with cellulitis 1

Monitoring and Follow-up

• Patients should be monitored for clinical improvement within 48-72 hours of starting antibiotics 1, 5
• Consider extending treatment if infection has not improved after 5 days 1
• Hospitalization should be considered for patients with:
  • Signs of systemic toxicity 1
  • Altered mental status 1
  • Hemodynamic instability 1
  • Concern for deeper or necrotizing infection 1
  • Poor adherence to therapy 1
  • Severe immunocompromise 1
  • Failure of outpatient treatment 1

Common Pitfalls

• Overuse of broad-spectrum antibiotics when narrow-spectrum options would be effective 1
• Unnecessary MRSA coverage for typical cellulitis without risk factors 1
• Prolonged antibiotic courses beyond 5-6 days when clinical improvement has occurred 1, 3
• Failure to address underlying predisposing conditions 1
• Not elevating the affected area to reduce edema and inflammation 1