What antibiotic is appropriate for a wound infected with MRSA that is resistant to erythromycin, other macrolides, and tetracyclines?

Treatment of MRSA Wound Infection with Multiple Resistance Patterns

For a wound infected with MRSA that is resistant to erythromycin, macrolides, and tetracyclines, use vancomycin 15-20 mg/kg IV every 8-12 hours, linezolid 600 mg IV or PO twice daily, or daptomycin 4 mg/kg IV once daily as first-line therapy. 1

Recommended Antibiotic Options

First-Line IV Agents (All A-I Evidence)

• Vancomycin 15-20 mg/kg IV every 8-12 hours remains the parenteral drug of choice for MRSA wound infections, targeting trough concentrations of 15-20 mg/L 1
• Linezolid 600 mg IV twice daily is equally effective and can be transitioned to oral therapy (600 mg PO twice daily) once clinically stable 1, 2
• Daptomycin 4 mg/kg IV once daily (use 10 mg/kg for severe infections) provides excellent bactericidal activity against MRSA 1

Alternative IV Options

• Ceftaroline 600 mg IV twice daily is the first beta-lactam with MRSA activity and represents a newer therapeutic option 1
• Telavancin 10 mg/kg IV once daily is a lipoglycopeptide alternative, though nephrotoxicity limits use in renal insufficiency 1, 3
• Dalbavancin (single-dose or two-dose regimen) offers long-acting glycopeptide coverage 1

Oral Options (When Appropriate for Step-Down Therapy)

• Linezolid 600 mg PO twice daily has excellent oral bioavailability and is the preferred oral agent for MRSA 1, 2
• Tedizolid 200 mg PO once daily is a newer oxazolidinone with similar efficacy 1

Why Certain Agents Are Excluded

• Clindamycin is NOT appropriate because 50% of MRSA strains have inducible or constitutive clindamycin resistance, and macrolide resistance (which this strain has) predicts clindamycin resistance 1
• Tetracyclines (doxycycline, minocycline) are contraindicated because the organism is already tetracycline-resistant 1
• Trimethoprim-sulfamethoxazole has reported treatment failure rates of 21% and should not be used as monotherapy for wound infections 1

Treatment Duration

• Treat for 7-14 days depending on infection severity and clinical response, with reassessment at 5 days 1
• For uncomplicated skin infections, 5 days may be sufficient if clinical improvement occurs (reduced warmth, tenderness, erythema) 1

Critical Decision Algorithm

1. Assess severity: Systemic toxicity (fever, hypotension, altered mental status) requires IV therapy 1
2. Choose initial agent:
   • Vancomycin for most hospitalized patients 1
   • Linezolid if concern for vancomycin-intermediate susceptibility or need for oral therapy 1, 2, 4
   • Daptomycin for bacteremia or endocarditis 1, 5
3. Monitor response: Reassess at 24-48 hours; lack of improvement warrants surgical consultation for debridement 1
4. Step-down therapy: Transition to oral linezolid once clinically stable (typically after 4-5 days IV therapy) 1

Special Considerations

• Linezolid may be superior to vancomycin for complicated skin and soft tissue infections based on network meta-analysis showing improved clinical cure rates (RR 1.71; 95%-CI 1.45-2.02) 4
• Vancomycin efficacy decreases with higher MICs within the susceptible range, making linezolid or daptomycin preferable in these cases 5, 6
• Surgical debridement is essential for wound infections; antibiotics alone are insufficient without adequate source control 1

Common Pitfalls to Avoid

• Do not use beta-lactams (cephalexin, dicloxacillin, amoxicillin) as they lack MRSA activity 1
• Do not delay surgical consultation if the wound shows signs of necrosis, severe pain out of proportion, or rapid progression 1
• Do not use tigecycline as first-line therapy due to controversy about reduced effectiveness in serious infections 5, 6
• Avoid quinupristin/dalfopristin as first-line due to insufficient data for severe MRSA infections 6