What is the best antibiotic for treating uncomplicated cellulitis?

Best Antibiotic for Uncomplicated Cellulitis

For uncomplicated cellulitis, cephalexin (500 mg four times daily) is the recommended first-line antibiotic treatment, with a 5-6 day course being as effective as longer treatment durations. 1

First-Line Antibiotic Selection

• Cephalexin, penicillin, or amoxicillin are recommended as first-line therapy for uncomplicated cellulitis by the American College of Physicians and the Infectious Diseases Society of America, as these antibiotics provide appropriate coverage against streptococci, which are the predominant pathogens in typical cellulitis 1, 2
• For penicillin-allergic patients, clindamycin 300-450 mg four times daily is the recommended alternative 1, 3
• The standard dosing for cephalexin is 500 mg four times daily for 5-6 days 1

Treatment Duration

• A 5-6 day course of antibiotics is as effective as a 10-day course for uncomplicated cellulitis 1, 4
• In a randomized controlled trial, 5 days of antibiotic therapy had a 98% success rate, equal to 10 days of therapy 4
• Treatment should be extended if the infection has not improved after the initial 5-day course 1

MRSA Considerations

• MRSA coverage is generally not necessary for typical non-purulent cellulitis 1, 5

• Consider MRSA coverage only in specific circumstances:

  • Cellulitis associated with penetrating trauma 1
  • Evidence of MRSA infection elsewhere 1
  • Nasal colonization with MRSA 1
  • Injection drug use 1
  • Systemic inflammatory response syndrome (SIRS) 1
  • High community prevalence of MRSA 6

• When MRSA coverage is indicated, options include:

  • Clindamycin (covers both streptococci and MRSA) 1, 3
  • Trimethoprim-sulfamethoxazole (TMP-SMX) plus a β-lactam 1

Monitoring and Follow-up

• Patients should be monitored for clinical improvement within 48-72 hours of starting antibiotics 1
• Signs of improvement include decreased erythema, swelling, and tenderness 1, 2
• Failure to improve within 48-72 hours should prompt reassessment for:
  • Resistant organisms 2
  • Conditions mimicking cellulitis 2, 5
  • Underlying complicating conditions 2

Adjunctive Measures

• Elevation of the affected area helps reduce edema and speeds recovery 1
• Treat predisposing conditions such as tinea pedis or venous eczema 1
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults with cellulitis 1

Common Pitfalls to Avoid

• Overuse of broad-spectrum antibiotics when narrow-spectrum options would be effective 1
• Unnecessary MRSA coverage for typical cellulitis without risk factors 1, 5
• Prolonged antibiotic courses beyond 5-6 days when clinical improvement has occurred 1, 4
• Failure to address underlying predisposing conditions that may lead to recurrence 1
• Using TMP-SMX as monotherapy, as its activity against β-hemolytic streptococci is not well established 1

Special Considerations

• 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