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

Treatment for Vancomycin-Resistant Enterococci (VRE) Infections

Linezolid 600 mg IV or PO every 12 hours is the first-line treatment for VRE infections, with treatment duration dependent on the site of infection and clinical response. 1, 2

First-Line Treatment Options Based on Infection Site

VRE Bacteremia

• Linezolid 600 mg IV or PO every 12 hours is strongly recommended as first-line therapy with microbiological and clinical cure rates of 86.4% and 81.4%, respectively 1, 2, 3
• High-dose daptomycin (8-12 mg/kg/day IV) is an effective alternative, particularly at doses ≥9 mg/kg 1, 2, 4
• Daptomycin in combination with β-lactams (including penicillins, cephalosporins, or carbapenems) may improve outcomes for VRE bacteremia 1, 2

Intra-abdominal VRE Infections

• Tigecycline 100 mg IV loading dose followed by 50 mg IV every 12 hours is recommended 1, 2
• Treatment duration should be based on clinical response 1

Uncomplicated VRE Urinary Tract Infections

• A single dose of fosfomycin 3 g PO is recommended 1, 5
• Nitrofurantoin 100 mg PO every 6 hours is an effective alternative 1, 5
• High-dose ampicillin (18-30 g IV daily in divided doses) or amoxicillin 500 mg PO/IV every 8 hours can be used even for some ampicillin-resistant strains due to high urinary concentrations achieved 1, 5

Comparative Efficacy of Treatment Options

• FDA-approved clinical trials for linezolid showed 67% cure rates for VRE infections across all sites 3
• For VRE bacteremia specifically, linezolid demonstrated 59% cure rates in patients with associated bacteremia 3
• Meta-analyses comparing linezolid and daptomycin have shown conflicting results:
  • Some studies suggest linezolid is associated with lower mortality than daptomycin 6, 7
  • Other studies show similar efficacy between daptomycin and linezolid when daptomycin is dosed appropriately 8, 4
• Higher-dose daptomycin (≥9 mg/kg) appears to have comparable outcomes to linezolid, while lower-dose daptomycin (6-9 mg/kg) is associated with higher mortality 4

Important Clinical Considerations

• Differentiate between VRE colonization and true infection before initiating treatment 2, 5
• Remove central venous catheters or other potential sources of persistent infection when treating VRE bacteremia 2
• Avoid using tigecycline for VRE bacteremia due to large volume of distribution and low serum levels 2
• Implement appropriate infection control measures to prevent VRE transmission 2
• For complicated VRE UTIs, 7-14 days of therapy is generally recommended, with duration based on clinical response 5

Monitoring and Adverse Effects

• Monitor for thrombocytopenia with linezolid, which occurs in approximately 2% of patients 9
• Common adverse events with linezolid include diarrhea, headache, nausea, and vomiting 9
• For daptomycin, monitor creatine phosphokinase (CPK) levels weekly to detect potential myopathy 2
• Consider therapeutic drug monitoring when using high-dose daptomycin regimens 2

Treatment Algorithm

1. Identify the site of infection and confirm VRE through appropriate cultures
2. For bacteremia: Start linezolid 600 mg IV/PO q12h or high-dose daptomycin ≥9 mg/kg/day IV 1, 2, 4
3. For intra-abdominal infections: Use tigecycline 100 mg IV loading dose followed by 50 mg IV q12h 1, 2
4. For uncomplicated UTIs: Use fosfomycin 3 g PO single dose, nitrofurantoin 100 mg PO q6h, or high-dose ampicillin/amoxicillin 1, 5
5. Adjust therapy based on clinical response and susceptibility testing results 1
6. Continue treatment until clinical and microbiological cure, with duration dependent on infection site 1, 2