What is the best antibiotic for a possible Methicillin-resistant Staphylococcus aureus (MRSA) skin infection?

Best Antibiotic for Possible MRSA Skin Infection

For outpatient treatment of possible MRSA skin infections, trimethoprim-sulfamethoxazole (TMP-SMX) 1-2 double-strength tablets twice daily is the preferred first-line oral antibiotic, with treatment duration of 5-10 days. 1

Outpatient Oral Antibiotic Options

First-Line Agent

• TMP-SMX is recommended as the preferred first-line choice due to its high clinical effectiveness in MRSA-prevalent settings, with demonstrated high cure rates in observational studies and clinical trials 1
• Dosing: 1-2 double-strength tablets (160-800 mg) twice daily for 5-10 days 2, 1
• Critical limitation: TMP-SMX has limited activity against β-hemolytic streptococci, so it should NOT be used as monotherapy for nonpurulent cellulitis where streptococcal coverage is needed 1

Alternative Oral Agents When TMP-SMX is Not Appropriate

For dual coverage of both MRSA and streptococci (purulent or nonpurulent cellulitis):

• Clindamycin 300-450 mg orally three times daily provides coverage for both MRSA and β-hemolytic streptococci 2, 1
• Avoid clindamycin if local resistance rates are high (>10%) or if inducible resistance (D-test positive) is present 1
• Clindamycin carries higher risk of Clostridioides difficile infection compared to other oral agents 1

Alternative monotherapy options:

• Doxycycline 100 mg orally twice daily (contraindicated in children <8 years) 2, 1
• Minocycline 200 mg initially, then 100 mg twice daily (contraindicated in children <8 years) 1
• Linezolid 600 mg orally twice daily 2

If streptococcal coverage is also needed but clindamycin is not suitable:

• Combine TMP-SMX or a tetracycline with a β-lactam (e.g., amoxicillin) 2
• Use linezolid alone (covers both MRSA and streptococci) 2

Inpatient Parenteral Options for Complicated Infections

For hospitalized patients with complicated skin and soft tissue infections requiring IV therapy:

• Vancomycin IV is the standard empirical choice 2, 3
• Alternatives include: linezolid 600 mg IV twice daily, daptomycin 4 mg/kg IV once daily, or telavancin 10 mg/kg IV once daily 2
• Treatment duration: 7-14 days based on clinical response 2

Essential Management Principles

Incision and drainage is the cornerstone of treatment for abscesses - antibiotics alone are insufficient 1

Always obtain cultures from purulent drainage before starting antibiotics to confirm MRSA and guide therapy 1

When to use parenteral therapy instead of oral:

• Severe or extensive disease involving multiple sites 4
• Rapid progression with associated cellulitis 4
• Signs of systemic illness (fever, hypotension, altered mental status) 4
• Associated comorbidities or immunosuppression 4
• Associated septic phlebitis 4

Critical Pitfalls to Avoid

Never use rifampin as monotherapy or adjunctive therapy for MRSA skin infections due to rapid resistance development 2, 1

Beta-lactam antibiotics (penicillins, cephalosporins) are completely ineffective against MRSA and should never be used 1

For nonpurulent cellulitis without purulent drainage, consider that β-hemolytic streptococci may be the primary pathogen - a β-lactam antibiotic (e.g., cefazolin) may be appropriate with modification to MRSA-active therapy only if there is no clinical response 2