What are the treatment options for Vancomycin-Resistant Enterococci (VRE) infections?

Treatment Options for Vancomycin-Resistant Enterococci (VRE) Infections

Linezolid 600 mg IV or PO every 12 hours is the first-line treatment for most VRE infections, with the treatment duration dependent on the site of infection and clinical response. 1

First-Line Treatment Options Based on Infection Site

Bloodstream Infections

• First choice: Linezolid 600 mg IV/PO every 12 hours (Strong recommendation) 1, 2
  • Treatment duration: 10-14 days
• Alternative: High-dose daptomycin 8-12 mg/kg/day IV (Weak recommendation) 1
  • Consider combination with β-lactams (penicillins, carbapenems, or cephalosporins except cefotaxime and cefazolin) for VRE with high daptomycin MIC (3-4 mg/mL) 1
  • Higher-dose daptomycin (≥9 mg/kg) shows better survival than lower-dose daptomycin (6-9 mg/kg) 3
  • Monitor CK levels when using higher doses of daptomycin 1

Intra-abdominal Infections

• First choice: Linezolid 600 mg IV/PO every 12 hours (Strong recommendation) 1
  • Treatment duration: 5-7 days
• Alternative: Tigecycline 100 mg IV loading dose, then 50 mg IV every 12 hours (Weak recommendation) 1
  • Particularly appropriate for polymicrobial infections 1

Urinary Tract Infections

• Complicated UTIs:

  • Linezolid 600 mg IV/PO every 12 hours (Strong recommendation) 1
  • Daptomycin 6-12 mg/kg IV daily (Weak recommendation) 1
  • Treatment duration: 5-7 days

• Uncomplicated UTIs:

  • Fosfomycin 3 g PO single dose or every other day (Weak recommendation) 1, 4
  • Nitrofurantoin 100 mg PO every 6 hours (Weak recommendation) 1, 4
  • High-dose ampicillin (18-30 g IV daily in divided doses) or amoxicillin 500 mg PO/IV every 8 hours for ampicillin-susceptible strains (Weak recommendation) 1, 4
  • Treatment duration: 3-7 days

Pneumonia

• Linezolid 600 mg IV/PO every 12 hours (Strong recommendation) 1
  • Treatment duration: At least 7 days
• Avoid daptomycin for pneumonia due to inactivation by pulmonary surfactant 1

Comparative Efficacy of Treatment Options

Linezolid vs. Daptomycin

• Linezolid has FDA approval for VRE infections with clinical cure rates of 67% for high-dose (600 mg) therapy 2
• Meta-analyses comparing daptomycin and linezolid for VRE bacteremia found:
  • Higher 30-day mortality with daptomycin compared to linezolid (OR 1.61; 95% CI 1.08-2.40) 5
  • Higher infection-related mortality with daptomycin (OR 3.61; 95% CI 1.42-9.20) 5
  • However, higher-dose daptomycin (≥9 mg/kg) shows comparable outcomes to linezolid 3

Clinical Considerations

• Tigecycline should not be used for VRE bacteremia due to low serum levels despite high tissue penetration 1
• Cardiac surgery combined with antimicrobial therapy should be considered for infective endocarditis 1
• Linezolid has both IV and oral formulations with 100% bioavailability, allowing for easy IV-to-oral switch 2

Common Pitfalls and Caveats

1. Differentiate colonization from true infection: Unnecessary treatment of VRE colonization or asymptomatic bacteriuria contributes to antimicrobial resistance 4

2. Daptomycin dosing: Standard doses (6 mg/kg) may be suboptimal for VRE bacteremia; higher doses (≥9 mg/kg) show better outcomes 3

3. Monitoring for adverse effects:

   • Linezolid: Monitor for thrombocytopenia with prolonged use (>14-21 days) 6
   • Daptomycin: Monitor CK levels for myopathy 1

4. Treatment duration: Should be individualized based on:

   • Site of infection
   • Source control
   • Underlying comorbidities
   • Initial response to therapy 1

5. Ampicillin susceptibility: Some VRE isolates remain susceptible to ampicillin and can be treated with high-dose ampicillin, particularly for UTIs 1

By following this evidence-based approach to treating VRE infections, clinicians can optimize outcomes while minimizing the risk of treatment failure and further antimicrobial resistance.