What is the recommended antibiotic regimen for Methicillin-resistant Staphylococcus aureus (MRSA) cellulitis?

Antibiotic Regimen for MRSA Cellulitis

For outpatient MRSA cellulitis, use trimethoprim-sulfamethoxazole (TMP-SMX) 1-2 double-strength tablets orally twice daily or doxycycline 100 mg orally twice daily for 5-10 days; for hospitalized patients with complicated MRSA cellulitis, use vancomycin 15-20 mg/kg/dose IV every 8-12 hours for 7-14 days. 1

Classification Determines Treatment Approach

The Infectious Diseases Society of America recommends first classifying cellulitis as either purulent (with abscess or drainage) or nonpurulent (diffuse erythema without purulent drainage) to guide therapy 1:

• Purulent cellulitis: Empirical MRSA coverage is recommended immediately, pending culture results 1
• Nonpurulent cellulitis: Start with β-lactam therapy targeting streptococci; add MRSA coverage only if no response to initial therapy or if systemic toxicity develops 1

Critical pitfall: Obtain cultures from purulent drainage before starting antibiotics to confirm MRSA and guide definitive therapy 1, 2. For purulent lesions, incision and drainage is the mainstay of therapy and should be performed whenever feasible 2.

Outpatient Oral Regimens for Uncomplicated MRSA Cellulitis

First-Line Options:

• TMP-SMX: 1-2 double-strength tablets (160/800 mg) orally twice daily 1

  • High success rates in MRSA-prevalent settings 1
  • Limitation: Poor activity against β-hemolytic streptococci 1
  • Consider adding a β-lactam if streptococcal coverage is needed 2

• Doxycycline: 100 mg orally twice daily 1, 2

  • Alternative: Minocycline 200 mg loading dose, then 100 mg orally twice daily 1
  • Contraindication: Do not use in children <8 years of age 1

• Clindamycin: 300-450 mg orally three times daily 1

  • Critical restriction: Use only if local MRSA resistance rates are <10% 1, 2
  • Advantage: Covers both MRSA and streptococci 2

Treatment Duration:

• 5-10 days for uncomplicated infections, individualized based on clinical response 1, 2

Inpatient IV Regimens for Complicated MRSA Cellulitis

First-Line IV Therapy:

• Vancomycin: 15-20 mg/kg/dose IV every 8-12 hours 1
  • Target trough concentrations of 15-20 mg/L for serious infections 3
  • Duration: 7-14 days, individualized based on clinical response 1, 2
  • Dosing pitfall: Standard 1 g every 12 hours is inadequate for critically ill patients; doses of at least 1 g every 8 hours are needed to achieve therapeutic troughs 3

Alternative IV Options:

• Daptomycin: 4-6 mg/kg IV once daily 2

  • FDA-approved for complicated skin and soft tissue infections 4
  • Clinical success rate of 79% for MRSA skin infections 5
  • Higher doses (≥7 mg/kg) may improve survival in severe MRSA infections 6
  • Advantage: Only antibiotic showing noninferiority to vancomycin for MRSA bacteremia 7

• Linezolid: 600 mg IV or PO twice daily 1, 2

  • Clinical success rate of 90% in complicated skin infections 5
  • MRSA-specific success rate of 67% (though small sample size) 5
  • Limitation: More expensive than other options 1
  • Advantage: Excellent oral bioavailability allows early IV-to-oral transition 2

Transitioning to Oral Therapy:

After clinical improvement and ability to tolerate oral medications, transition to oral TMP-SMX, doxycycline, or linezolid 2

Pediatric Considerations

• Hospitalized children: Vancomycin is the preferred IV agent 1, 2
• Alternative: Clindamycin 10-13 mg/kg/dose IV every 6-8 hours, but only if patient is stable and local resistance <10% 1, 2
• Outpatient pediatric dosing: Clindamycin 300-450 mg orally three times daily (weight-adjusted) for 5-10 days 1
• Avoid tetracyclines (doxycycline, minocycline) in children <8 years of age 1

Critical Warnings and Pitfalls

• Never use rifampin as monotherapy or adjunctive therapy for MRSA skin infections due to rapid resistance development 1, 2
• β-lactam antibiotics alone are inadequate for MRSA coverage 2
• Failure to drain abscesses leads to treatment failure regardless of antibiotic choice 2
• For recurrent infections, consider decolonization with mupirocin (nasal) and chlorhexidine (body) 2

Prevention of Recurrence

• Keep draining wounds covered with clean, dry bandages 2
• Regular handwashing with soap and water or alcohol-based gel 2
• Avoid sharing personal items 2
• Evaluate and potentially treat household contacts if recurrent infections persist 2