What is the recommended treatment for Vancomycin-Resistant Enterococci (VRE) endocarditis?

Treatment of Vancomycin-Resistant Enterococci (VRE) Endocarditis

For VRE endocarditis, the recommended treatment is linezolid 600 mg IV every 12 hours combined with cardiac surgery for valve replacement when indicated. 1

First-line Treatment Options

• Linezolid 600 mg IV every 12 hours is the strongly recommended first-line therapy for VRE endocarditis with strong evidence (Level 1C) 1
• Cardiac surgery combined with antimicrobial therapy should be considered for the treatment of infective endocarditis 1
• Treatment duration should be individualized according to clinical response, but typically requires at least 10-14 days of therapy, often longer for endocarditis 1

Alternative Treatment Options

• Daptomycin 8-12 mg/kg IV daily is an alternative option (Level 2C), with higher doses (≥11 mg/kg) showing improved survival in patients with VRE bloodstream infections, particularly for isolates with higher MICs 1, 2
• Combination therapy with daptomycin plus beta-lactams may be considered for VRE bloodstream infections with high daptomycin MIC (3-4 mg/mL) 1
• Beta-lactams that can be used in combination include penicillins and carbapenems (except cefotaxime and cefazolin) 1

Special Considerations for Daptomycin

• Higher daptomycin doses (≥11 mg/kg) have shown improved survival rates compared to lower doses (8-<11 mg/kg) for VRE with higher MICs (≥2 mg/L) 2
• Monitor creatine kinase levels when using higher doses of daptomycin, as doses ≥11 mg/kg are associated with a higher rate (3.9%) of significantly elevated creatine kinase (>2000 U/L) 1, 2

Salvage Therapy Options

• For multi-drug resistant VRE endocarditis with treatment failure, combination therapy may be necessary 3
• Reported successful combinations include:
  • Daptomycin with chloramphenicol 3
  • Daptomycin with ampicillin and gentamicin 1
  • Linezolid with tigecycline 1

Treatment Duration and Monitoring

• Definitive treatment duration should be individualized according to infection site, source control, underlying comorbidities, and initial response to therapy 1
• For endocarditis, longer treatment courses (4-6 weeks) are typically required 1
• Infectious disease specialist consultation is strongly recommended for VRE endocarditis due to the complexity of management 1

Clinical Efficacy Data

• In clinical trials, linezolid demonstrated a 67% cure rate in the high-dose arm for documented VRE infections 4, 5
• For VRE with bacteremia, linezolid showed a 59% cure rate when associated with bacteremia 4
• Pediatric data shows linezolid has a 75% cure rate for VRE infections 5

Important Pitfalls to Avoid

• Tigecycline should not be used for the treatment of VRE bacteremia or endocarditis due to its large volume of distribution and low serum levels 1
• Avoid monotherapy with cephalosporins as they have poor activity against enterococci 1
• Do not delay cardiac surgery evaluation in patients with VRE endocarditis, as combined medical and surgical therapy often provides the best outcomes 1
• Recognize that VRE endocarditis has a high mortality rate and early aggressive therapy is essential 1