What are the first-line treatments for Methicillin-resistant Staphylococcus aureus (MRSA)?

From the Guidelines

First-line treatment for MRSA infections typically involves vancomycin, administered intravenously at 15-20 mg/kg every 8-12 hours for serious infections, with dosing adjusted based on therapeutic drug monitoring to maintain trough levels of 15-20 μg/mL, as recommended by the Infectious Diseases Society of America 1. For less severe MRSA infections, oral options include trimethoprim-sulfamethoxazole (TMP-SMX) at 1-2 double-strength tablets twice daily, doxycycline 100 mg twice daily, or linezolid 600 mg twice daily.

Key Considerations

• Treatment duration typically ranges from 7-14 days, depending on infection severity and clinical response.
• For skin and soft tissue infections, incision and drainage remains a crucial component of therapy when applicable.
• Patients should complete the full course of antibiotics even if symptoms improve quickly to prevent recurrence and resistance development.
• MRSA's resistance to beta-lactam antibiotics (including methicillin, oxacillin, and cephalosporins) necessitates these alternative agents that target different bacterial mechanisms.
• Treatment should be tailored based on culture and sensitivity results, infection site, severity, and patient factors such as kidney function and medication allergies.

Empirical Coverage

For empirical coverage of CA-MRSA in outpatients with SSTI, oral antibiotic options include:

• Clindamycin (A-II)
• Trimethoprim-sulfamethoxazole (TMP-SMX) (A-II)
• A tetracycline (doxycycline or minocycline) (A-II)
• Linezolid (A-II) As noted in the guidelines by the Infectious Diseases Society of America 1.

From the FDA Drug Label

The cure rates by pathogen for microbiologically evaluable patients are presented in Table 18. Table 18 Cure Rates at the Test-of-Cure Visit for Microbiologically Evaluable Adult Patients with Complicated Skin and Skin Structure Infections Pathogen Cured ZYVOX n/N (%) Oxacillin/Dicloxacillin n/N (%) Methicillin-resistant S aureus 2/3 (67) 0/0 (-)

The cure rates in microbiologically evaluable patients with MRSA skin and skin structure infection were 26/33 (79%) for linezolid-treated patients and 24/33 (73%) for vancomycin-treated patients

Table 16: Clinical Success Rates by Infecting Pathogen in the cSSSI Trials in Adult Patients (Population: Microbiologically Evaluable) Pathogen Success Rate n/N (%) Daptomycin for Injection Comparator* Methicillin-resistant Staphylococcus aureus (MRSA) 21/28 (75%) 25/36 (69%)

First-Line Treatments for MRSA include:

• Linezolid (PO) with a cure rate of 79% in microbiologically evaluable patients with MRSA skin and skin structure infection 2
• Vancomycin with a cure rate of 73% in microbiologically evaluable patients with MRSA skin and skin structure infection 2
• Daptomycin (IV) with a success rate of 75% in microbiologically evaluable patients with MRSA complicated skin and skin structure infections 3

From the Research

First-Line Treatments for MRSA

• Vancomycin has been the cornerstone of treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections 4, 5, 6, 7, 8
• New MRSA-active antibiotics have recently been introduced, including ceftaroline, ceftobiprole, tedizolid, telavancin, dalbavancin, and oritavancin 4, 6
• Daptomycin is currently the only antibiotic to have shown noninferiority to vancomycin in the treatment of MRSA bacteremia 5, 7, 8
• Linezolid is probably the drug of choice for the treatment of complicated MRSA skin and soft tissue infections (SSTIs) and may be a potential first-line drug against MRSA bacteremia 6, 7
• Combination therapy of β-lactams with vancomycin or daptomycin is increasing 4, 8

Treatment Options

• Vancomycin remains an acceptable treatment option, with moves toward individualized dosing to a pharmacokinetic/pharmacodynamic (PK/PD) target 5
• Lipoglycopeptides, such as telavancin, have excellent in vitro potency but may have limitations in critically ill patients 5
• Anti-MRSA cephalosporins, such as ceftaroline, provide great promise in the treatment of MRSA but should be reserved for patients with MRSA infections to minimize resistance 4, 5, 6
• Quinupristin/dalfopristin and tigecycline are options in patients with no other alternatives but have insufficient data to recommend as first-line treatments 5, 6

Emerging Resistance and Future Directions

• Resistance has emerged against many new anti-MRSA antimicrobials, including ceftaroline 4
• Further studies are required for more invasive infections, such as bacteremia and endocarditis 4, 8
• Several new MRSA-active agents are now approved for use, and many promising agents are in the pipeline 4, 6