Antibiotics Effective Against MRSA
For MRSA skin and soft tissue infections, vancomycin remains the standard intravenous option for severe infections, while linezolid, trimethoprim-sulfamethoxazole (TMP-SMX), and doxycycline are preferred oral agents for less severe cases. 1
Intravenous Antibiotics for MRSA
First-line IV options include:
- Vancomycin - The traditional standard for severe MRSA infections including bacteremia, endocarditis, and complicated skin/soft tissue infections 1
- Daptomycin (10 mg/kg/dose IV once daily) - Non-inferior to vancomycin for MRSA bacteremia, right-sided endocarditis, and complicated skin/soft tissue infections 1, 2
- Linezolid (600 mg IV twice daily for adults) - Superior to vancomycin for skin/soft tissue infections with better clinical cure rates (OR 1.41) 1
- Ceftaroline - Broad-spectrum cephalosporin with MRSA activity, non-inferior to vancomycin for skin/soft tissue infections 1
- Dalbavancin - Long-acting lipoglycopeptide option 1
- Tigecycline - Alternative for complicated infections 1
- Tedizolid - Newer oxazolidinone option 1
Key consideration: Linezolid demonstrates better treatment success than vancomycin specifically in skin and soft tissue infections (OR 1.40,95% CI 1.01-1.95), though no difference exists for bacteremia or pneumonia 1
Oral Antibiotics for MRSA
Recommended oral agents for community-acquired MRSA skin/soft tissue infections:
- Linezolid (600 mg PO twice daily for adults; 10 mg/kg/dose every 8 hours for children <12 years) - Highest quality evidence with excellent bioavailability 1, 3
- Trimethoprim-sulfamethoxazole (TMP-SMX) - Effective for uncomplicated infections, supported by observational studies and randomized trials 1
- Doxycycline or minocycline - Tetracyclines with proven efficacy; minocycline may be more reliable when doxycycline or TMP-SMX fails 1, 4
- Tedizolid - Newer oxazolidinone with strong recommendation 1
- Clindamycin (300-450 mg PO three times daily for adults; 10-20 mg/kg/day in 3 divided doses for children) - Effective when local resistance is low (<10%), but resistance is increasingly common 1, 3
Critical caveat for clindamycin: Approximately 50% of MRSA strains may have inducible or constitutive clindamycin resistance, and it carries higher risk of Clostridioides difficile infection compared to other oral agents 3
Treatment Duration
- Uncomplicated skin/soft tissue infections: 5-10 days 3
- Complicated skin/soft tissue infections: 7-14 days based on clinical response 1, 3
- Bacteremia/endocarditis: Up to 42 days depending on infection site and complexity 2
Special Populations and Situations
For hospitalized children with complicated MRSA skin/soft tissue infections:
- Vancomycin is recommended first-line 1
- Clindamycin (10-13 mg/kg/dose IV every 6-8 hours) is an option if clindamycin resistance rate is low and patient is stable without ongoing bacteremia 1
- Linezolid (10 mg/kg/dose every 8 hours for children <12 years) is an alternative 1
For diabetic foot infections with suspected/confirmed MRSA:
For necrotizing fasciitis with MRSA:
- Vancomycin or linezolid PLUS piperacillin-tazobactam or a carbapenem 1
- Alternative: Ceftriaxone plus metronidazole (with or without vancomycin) 1
Important Clinical Pitfalls
Vancomycin limitations: Rising MICs within the susceptible range reduce vancomycin effectiveness, and clinical failures occur with isolates at higher MICs even when technically susceptible 5, 6
TMP-SMX and tetracyclines: While effective against MRSA, their activity against beta-hemolytic streptococci is not well-defined 1. When dual coverage is needed, combine TMP-SMX or doxycycline with a beta-lactam (penicillin, cephalexin, or amoxicillin), or use clindamycin alone if local resistance is low 1
Avoid rifampin monotherapy: Resistance develops rapidly; rifampin should only be used in combination with another active agent 1