What is the recommended treatment for Enterococcus faecium with Zyvox (linezolid)?

Treatment of Enterococcus faecium with Linezolid (Zyvox)

Linezolid 600 mg IV or PO every 12 hours is strongly recommended as first-line therapy for Enterococcus faecium infections, particularly vancomycin-resistant strains, with treatment duration dependent on the site of infection and clinical response. 1

Dosing Recommendations

• For adults and adolescents (≥12 years):

  • 600 mg IV or oral every 12 hours 2
  • Duration: 10-14 days for skin/soft tissue infections; 14-28 days for bacteremia and more serious infections 2

• For pediatric patients (birth through 11 years):

  • 10 mg/kg IV or oral every 8 hours 2
  • Neonates <7 days (especially premature): Start with 10 mg/kg every 12 hours; consider increasing to every 8 hours by 7 days of life 2

Clinical Efficacy

Linezolid has demonstrated excellent efficacy against E. faecium, including vancomycin-resistant strains:

• Microbiological cure rates of 86.4% and clinical cure rates of 81.4% in patients with VRE infections 1
• Particularly effective for:
  • Complicated skin/soft tissue infections (87.5% cure rate)
  • Bacteremia (90.9-100% cure rate)
  • Intra-abdominal infections (91.7% cure rate) 3

Advantages of Linezolid for E. faecium

1. FDA-approved specifically for vancomycin-resistant E. faecium infections 2
2. 100% oral bioavailability allowing seamless IV-to-oral transition without dose adjustment 4
3. Active against both vancomycin-resistant E. faecium (MIC₉₀ = 2-4 μg/ml) and E. faecalis 3
4. Potential for reduced hospital stays compared to vancomycin due to oral availability 4

Monitoring and Adverse Effects

• Thrombocytopenia: More common with longer treatment courses (>14-21 days); monitor complete blood counts weekly 3, 5
• Myelosuppression: Risk increases with duration of therapy 5
• Gastrointestinal effects: Nausea, vomiting, diarrhea are common 3
• Neuropathy: Risk increases with higher exposures and longer treatment 5

Therapeutic Drug Monitoring Considerations

• Consider therapeutic drug monitoring (TDM) for:
  • Patients with renal insufficiency
  • Patients on renal replacement therapy
  • Pediatric patients
  • Patients on medications that interact with linezolid
  • Treatment courses >14 days 5

Alternative Therapies for E. faecium

If linezolid cannot be used or resistance develops:

1. Daptomycin: 8-12 mg/kg/day IV (higher doses for bacteremia)

   • Consider combination with β-lactams for synergy 1
   • Not FDA-approved for VRE but shows good in vitro activity 1

2. For uncomplicated urinary tract infections only:

   • Fosfomycin: 3 g PO single dose 1, 6
   • Nitrofurantoin: 100 mg PO every 6 hours 1, 6
   • High-dose ampicillin: 18-30 g IV daily in divided doses (if susceptible) 1

3. For intra-abdominal infections:

   • Tigecycline: 100 mg IV loading dose, then 50 mg IV every 12 hours 1

Resistance Concerns

• Linezolid resistance in enterococci remains rare (≤0.8% in surveillance programs) but is emerging 7
• Risk factors for developing resistance:
  • Prior linezolid exposure (mean treatment duration ~23-30 days) 7
  • Prolonged therapy 8
  • Hospital transmission of resistant strains 8
• Resistance mechanisms include:
  • 23S rRNA (G2576T) mutations (most common: 80.5% of resistant E. faecium) 7
  • Presence of transferable resistance genes (cfr, optrA) 7

Key Practice Points

• Always obtain cultures and susceptibility testing before initiating therapy when possible
• Consider infectious disease consultation for complex cases, especially for vancomycin-resistant strains 1
• Switch from IV to oral therapy when clinically appropriate to reduce hospital stay 2, 4
• For severe infections, consider combination therapy or alternative agents if clinical response is inadequate
• Monitor for thrombocytopenia and other hematologic effects with weekly complete blood counts