What is the recommended use and dosage of linezolid (oxazolidinone antibiotic) for treating skin and skin structure infections, including those caused by Methicillin-resistant Staphylococcus aureus (MRSA)?

Linezolid for Skin and Skin Structure Infections Including MRSA

Linezolid is strongly recommended for both oral and intravenous treatment of skin and skin structure infections caused by MRSA, with a dosage of 600 mg twice daily for adults for 10-14 days. 1, 2

Recommended Dosage

Adults and Adolescents (≥12 years)

• Complicated skin and skin structure infections: 600 mg IV or oral every 12 hours for 10-14 days 2
• Uncomplicated skin and skin structure infections: 400 mg oral every 12 hours for adults; 600 mg oral every 12 hours for adolescents for 10-14 days 2

Pediatric Patients

• Children <5 years: 10 mg/kg oral every 8 hours 2
• Children 5-11 years: 10 mg/kg oral every 12 hours 2
• Children <12 years with complicated infections: 10 mg/kg IV or oral every 8 hours 2

Clinical Efficacy for MRSA Skin Infections

Linezolid demonstrates superior efficacy compared to vancomycin for MRSA skin infections:

• A Cochrane meta-analysis showed linezolid was significantly more effective than vancomycin for MRSA infections with better clinical cure rates (RR = 1.09; 95% CI, 1.03–1.17) and microbiological cure rates (RR = 1.17; 95% CI, 1.04–1.32) 1
• In a randomized trial comparing linezolid to vancomycin for complicated SSTIs due to MRSA, linezolid outcomes (88.6%) were superior to vancomycin outcomes (66.9%) 3
• Linezolid treatment is associated with significantly shorter hospital length of stay and decreased IV antibiotic treatment duration compared to vancomycin 4

Administration Advantages

• Linezolid has the advantage of early intravenous-to-oral switch capability 1
• The oral preparation has very high bioavailability and excellent tissue penetration 1
• IV to oral switch should occur when criteria of clinical stability have been reached 1
• No dose adjustment is necessary when switching from intravenous to oral administration 2

Treatment Algorithm for MRSA Skin Infections

1. For outpatient treatment of MRSA skin infections:

   • First-line: Oral linezolid 600 mg twice daily 1
   • Alternatives: TMP-SMX, tetracyclines (doxycycline or minocycline), or tedizolid 1

2. For hospitalized patients with complicated MRSA skin infections:

   • First-line: IV linezolid 600 mg every 12 hours, with switch to oral when clinically stable 1
   • Alternatives: IV vancomycin, daptomycin, ceftaroline, dalbavancin, or tedizolid 1

3. For coverage of both streptococci and MRSA:

   • Linezolid alone (provides coverage for both pathogens) 1
   • Alternative: Combination of TMP-SMX or tetracycline with a beta-lactam 1

Special Considerations

• Linezolid is effective for both methicillin-susceptible and methicillin-resistant S. aureus 5
• The daily cost of outpatient therapy is less with oral linezolid than with intravenous vancomycin 1
• Although inpatient treatment with linezolid costs more than vancomycin per day, the median length of hospital stay is 3 days shorter with linezolid 1
• In pediatric patients, linezolid is effective and well-tolerated for MRSA infections 6

Potential Adverse Effects and Precautions

• Monitor for potential adverse effects, which are generally similar to vancomycin's established safety profile 1
• Avoid using linezolid in series connections with other IV medications 2
• Physical incompatibilities exist when combined with amphotericin B, chlorpromazine HCl, diazepam, pentamidine isothionate, erythromycin lactobionate, phenytoin sodium, and trimethoprim-sulfamethoxazole 2
• Chemical incompatibility occurs when combined with ceftriaxone sodium 2

Linezolid represents an excellent choice for MRSA skin infections due to its proven efficacy, convenient oral formulation with excellent bioavailability, and potential to reduce hospital length of stay compared to traditional therapies.