What is the best antibiotic for a wound culture positive for Vancomycin-Resistant Enterococcus (VRE) that is sensitive to penicillin, between Zosyn (piperacillin/tazobactam) and Zyvox (linezolid)?

Best Antibiotic for Vancomycin-Resistant Enterococcus (VRE) in Wound Culture

Linezolid (Zyvox) 600 mg IV or PO every 12 hours is the recommended treatment for wound infections caused by VRE, even when the organism shows penicillin sensitivity. 1

Rationale for Choosing Linezolid over Zosyn

When comparing Zyvox (linezolid) and Zosyn (piperacillin/tazobactam) for VRE wound infections:

1. Strong Guideline Support: Linezolid has a strong recommendation (1C) specifically for enterococcal infections including VRE 1
2. FDA Approval: Linezolid is FDA-approved for VRE infections with documented clinical efficacy 2
3. Penicillin Sensitivity Considerations:
   • Despite the culture showing penicillin sensitivity (level 4), linezolid remains preferred for VRE infections
   • Penicillins (including Zosyn) are not reliably bactericidal against enterococci, even when showing in vitro sensitivity 1

Dosing and Administration

• Linezolid: 600 mg IV or PO every 12 hours 1
• Duration: Treatment duration should be based on the site of infection and clinical response 1
• Bioavailability: Oral linezolid has nearly 100% bioavailability, allowing for easy IV-to-oral transition 3

Clinical Evidence Supporting Linezolid for VRE

• Clinical trials demonstrate 67% cure rate with high-dose linezolid (600 mg q12h) for VRE infections 2
• Compassionate-use program showed 86.4% microbiological and 81.4% clinical cure rates for VRE infections 1
• Linezolid showed 62.4% survival rate in solid organ transplant recipients with VRE infections, including those with bacteremia 4

Alternative Options if Linezolid Cannot Be Used

If linezolid is contraindicated or unavailable, consider:

1. High-dose ampicillin (18-30g IV daily in divided doses) if the isolate is truly penicillin-susceptible 1
2. Daptomycin at high doses (8-12 mg/kg/day) - though primarily recommended for bacteremia 1
3. Tigecycline (100 mg IV loading dose, then 50 mg IV q12h) - primarily recommended for intra-abdominal infections but can be considered for wound infections 1

Important Clinical Considerations

• Differentiate colonization from true infection: Ensure the VRE is causing actual infection rather than just colonization 1
• Monitor for adverse effects: Watch for thrombocytopenia with linezolid, especially with treatment courses >14 days 5
• Combination therapy: Consider combination therapy with beta-lactams for severe infections, though this approach is better established for bacteremia than wound infections 1
• Susceptibility testing: Confirm susceptibility patterns to guide therapy, especially if considering alternatives to linezolid 1

Common Pitfalls to Avoid

1. Don't assume penicillin sensitivity means Zosyn is preferred: Despite in vitro sensitivity, penicillins are not optimal for VRE
2. Don't use inadequate dosing: Use the full recommended dose of linezolid (600 mg q12h)
3. Don't treat colonization: Ensure the VRE is causing actual infection before initiating therapy
4. Don't forget source control: Surgical debridement or drainage may be necessary alongside antibiotic therapy
5. Don't continue unnecessarily long courses: Base duration on clinical response and resolution of infection

Linezolid's specific activity against VRE, strong guideline support, and excellent bioavailability make it the optimal choice for VRE wound infections, even when penicillin sensitivity is reported.