What is the recommended treatment for a typical community‑acquired MRSA skin infection (cellulitis, erythema, or abscess)?

Treatment for MRSA Skin Infection

For simple abscesses or boils caused by community-acquired MRSA, incision and drainage alone is the primary treatment, and antibiotics are not routinely necessary. 1

Treatment Algorithm Based on Infection Type

Simple Abscesses Without Surrounding Cellulitis

• Incision and drainage is the definitive treatment for simple abscesses or boils, and antibiotics should not be used routinely 1
• Drainage alone achieves a 90.5% cure rate even when MRSA is the causative organism 2
• However, add antibiotics after drainage when any of the following conditions are present:
  • Multiple sites of infection 1
  • Systemic inflammatory response (fever >38°C, tachycardia, hypotension) 1
  • Associated comorbidities or immunosuppression (diabetes, HIV/AIDS, malignancy) 1
  • Extremes of age 1
  • Abscess in difficult-to-drain locations (face, hand, genitalia) 1
  • Lack of response to drainage alone 1
  • Rapidly progressive or extensive disease involving multiple sites 1

Purulent Cellulitis (Cellulitis with Drainage or Exudate)

Empiric MRSA coverage is recommended for purulent cellulitis. 1

Oral antibiotic options (choose one):

• Clindamycin 300-450 mg orally every 6-8 hours for 5 days (provides single-agent coverage for both streptococci and MRSA) 1, 3

  • Use only if local MRSA clindamycin resistance is <10% 1, 3
  • More frequent Clostridioides difficile-associated disease compared to other oral agents 1

• Trimethoprim-sulfamethoxazole (TMP-SMX) 1-2 double-strength tablets twice daily for 5 days 1, 3

  • Pregnancy category C/D; not recommended in third trimester or children <2 months 1
  • Must be combined with a beta-lactam (cephalexin or amoxicillin) if treating non-purulent cellulitis, as TMP-SMX lacks reliable streptococcal coverage 1, 3

• Doxycycline 100 mg orally twice daily for 5 days 1, 3

  • Not recommended for children <8 years (tooth discoloration, bone growth effects) 1, 3
  • Pregnancy category D 1
  • Must be combined with a beta-lactam for non-purulent cellulitis 1, 3

• Linezolid 600 mg orally twice daily for 5 days 1, 3

  • More expensive compared to alternatives 1

Non-Purulent Cellulitis (No Drainage or Abscess)

Beta-lactam monotherapy is the standard of care for typical non-purulent cellulitis, achieving 96% success. 3

First-line treatment:

• Cephalexin 500 mg orally every 6 hours for 5 days 1, 3
• Dicloxacillin 500 mg orally every 6 hours for 5 days 1, 3

Add empiric MRSA coverage only when specific risk factors are present:

• Penetrating trauma or injection drug use 1
• Purulent drainage or exudate 1
• Known MRSA colonization or prior MRSA infection 1, 3
• Failure to respond to beta-lactam therapy after 48-72 hours 1, 3
• Systemic inflammatory response syndrome 1, 3

Complicated SSTI Requiring Hospitalization

Intravenous antibiotic options (choose one):

• Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line, A-I evidence) 1, 3

  • Target trough concentrations 15-20 mg/L 1

• Linezolid 600 mg IV twice daily (A-I evidence) 1, 3

• Daptomycin 4 mg/kg IV once daily (A-I evidence) 1, 3

• Clindamycin 600 mg IV every 8 hours (A-III evidence) 1, 3

  • Only if local MRSA clindamycin resistance <10% 1, 3

For severe infections with systemic toxicity or suspected necrotizing fasciitis:

• Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 3
• Alternative: Linezolid PLUS piperacillin-tazobactam 3
• Treatment duration: 7-14 days guided by clinical response 1, 3

Pediatric Dosing

Oral regimens:

• Clindamycin 10-13 mg/kg/dose every 6-8 hours (max 40 mg/kg/day) 1
• TMP-SMX: trimethoprim 4-6 mg/kg/dose every 12 hours 1
• Doxycycline (≥8 years, <45 kg): 2 mg/kg/dose every 12 hours 1

IV regimens:

• Vancomycin 15 mg/kg IV every 6 hours (first-line) 1, 3
• Clindamycin 10-13 mg/kg/dose IV every 6-8 hours 1, 3
• Linezolid 10 mg/kg/dose every 8 hours (max 600 mg/dose) 1, 3

Treatment Duration

Treat for exactly 5 days if clinical improvement occurs (resolution of warmth/tenderness, improving erythema, no fever); extend only if symptoms have not improved. 3

For complicated infections requiring hospitalization, treat for 7-14 days guided by clinical response 1, 3

Critical Evidence Supporting Drainage Over Antibiotics

A randomized placebo-controlled trial demonstrated that antibiotics provide additional benefit beyond drainage alone for abscesses ≤5 cm, with cure rates of 83.1% for clindamycin, 81.7% for TMP-SMX, versus 68.9% for placebo (P<0.001) 4. However, another trial showed drainage alone achieved 90.5% cure rate, suggesting antibiotics may be unnecessary for truly uncomplicated abscesses 2.

The benefit of antibiotics was restricted to participants with confirmed S. aureus infection 4. Clindamycin reduced new infections at 1 month (6.8%) compared to TMP-SMX (13.5%, P=0.03) or placebo (12.4%, P=0.06) 4.

Common Pitfalls to Avoid

• Do not use beta-lactams (cephalexin, dicloxacillin, amoxicillin) for purulent cellulitis or abscesses, as they lack MRSA activity 1, 5
• Do not use TMP-SMX or doxycycline as monotherapy for typical non-purulent cellulitis, as they lack reliable streptococcal coverage 1, 3
• Do not routinely add MRSA coverage to all cellulitis cases; MRSA is uncommon in typical non-purulent cellulitis even in high-prevalence settings 3
• Do not prescribe antibiotics for simple abscesses that can be adequately drained without the risk factors listed above 1, 2
• Do not extend treatment beyond 5 days based on residual erythema alone; some inflammation persists after bacterial eradication 3

Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote drainage 3
• Examine and treat interdigital toe spaces for tinea pedis, fissuring, or maceration to reduce recurrence 3
• Address predisposing conditions including venous insufficiency, lymphedema, chronic edema, obesity, and eczema 1, 3