What is the recommended treatment for vancomycin‑resistant Enterococcus (VRE) infection?

Treatment of Vancomycin-Resistant Enterococcus (VRE)

Linezolid 600 mg IV or PO every 12 hours is the first-line treatment for most serious VRE infections including pneumonia, bacteremia, and complicated intra-abdominal infections, with strong guideline support and demonstrated clinical cure rates of 81.4% and microbiological cure rates of 86.4%. 1

Site-Specific Treatment Algorithm

Uncomplicated VRE Cystitis (Lower UTI)

• Fosfomycin 3 g PO as a single dose is the preferred first-line oral agent, achieving high urinary concentrations that reliably eradicate VRE 1, 2
• Nitrofurantoin 100 mg PO every 6 hours for 5-7 days is an effective alternative oral option 1, 2
• High-dose ampicillin (18-30 g IV daily in divided doses) or amoxicillin 500 mg PO/IV every 8 hours can be used even against ampicillin-resistant VRE strains because urinary concentrations exceed the MIC 1, 2
• Duration: 3-7 days 1

Complicated VRE UTI or Pyelonephritis

• Linezolid 600 mg IV or PO every 12 hours is the preferred systemic agent (strong recommendation, 1C evidence) 1
• Daptomycin 6-12 mg/kg IV once daily is an alternative option (weak recommendation, 2D evidence) 1
• Duration: 5-7 days 1

VRE Bacteremia

• High-dose daptomycin ≥9 mg/kg/day (optimally 10-12 mg/kg) is associated with significantly lower mortality compared to standard dosing (adjusted OR 0.26,95% CI 0.09-0.74) 2
• Linezolid 600 mg IV or PO every 12 hours is an equally acceptable first-line option with mortality rates of 32.8% versus 35.7% for daptomycin (RR 1.24,95% CI 1.02-1.50) 1
• Combination therapy with daptomycin plus β-lactam (ampicillin 2 g IV every 4-6 hours, ceftaroline, or meropenem) reduces 30-day mortality by approximately 77% when daptomycin MIC is ≤2 mg/L 2
• Duration: 10-14 days for uncomplicated bacteremia; 4-6 weeks for persistent bacteremia, endocarditis, or metastatic infection 1, 2

VRE Pneumonia

• Linezolid 600 mg IV every 12 hours is the recommended agent (strong recommendation, 1C evidence) 1
• Duration: At least 7 days 1

VRE Complicated Intra-Abdominal Infections

• Linezolid 600 mg IV every 12 hours (strong recommendation, 1C evidence) 1
• Tigecycline 100 mg IV loading dose, then 50 mg IV every 12 hours is an alternative (weak recommendation, 2D evidence) 1
• Duration: 5-7 days based on clinical response and source control 1

Critical Safety Monitoring Requirements

For Linezolid

• Monitor for serotonin syndrome every 4-6 hours during the first 72 hours, particularly in patients on SSRIs, SNRIs, tricyclic antidepressants, or bupropion 2, 3
• Symptoms include neuromuscular hyperactivity, autonomic instability, and mental status changes 3
• Obtain informed consent before initiating linezolid in patients on serotonergic medications 3
• Monitor for thrombocytopenia in patients receiving >14-21 days of therapy 4

For Daptomycin

• Monitor creatine kinase (CK) levels for rhabdomyolysis, though meta-analysis showed no significantly increased risk with high-dose regimens 2
• Monitor for neuropathy and eosinophilic pneumonia 2

Essential Pre-Treatment Considerations

Differentiate Colonization from Infection

• Do not treat VRE colonization or asymptomatic bacteriuria, as unnecessary treatment drives resistance and increases costs 2, 5, 6
• Obtain susceptibility testing—approximately 60% of E. faecium are vancomycin-resistant with variable ampicillin susceptibility 2, 5

Source Control

• Remove central venous catheters or other foreign bodies when present 2, 5
• Ensure adequate surgical drainage of closed-space infections (abscesses, peritonitis) 5, 7
• For VRE endocarditis, cardiac surgery consultation is mandatory with a minimum of 6 weeks of combination antimicrobial therapy 1, 2

Critical Pitfalls to Avoid

Tigecycline Misuse

• Never use tigecycline for VRE bacteremia or suspected upper tract infection despite in vitro susceptibility, as it yields poor serum concentrations and is linked to treatment failures in bloodstream infections 2, 5
• Tigecycline is appropriate only for intra-abdominal VRE infections without bacteremia 1, 2

Inadequate Daptomycin Dosing

• Standard-dose daptomycin (6 mg/kg) is insufficient for VRE bacteremia; doses of 10-12 mg/kg are required for optimal outcomes 2

Persistent Bacteremia

• If blood cultures remain positive after 72 hours of appropriate therapy, extend treatment to at least 4-6 weeks and perform transesophageal echocardiography to rule out endocarditis 2

Special Populations

Immunocompromised/Transplant Patients

• Profound immunosuppression warrants prolonged therapy (4-6 weeks minimum) analogous to treatment in other immunocompromised hosts 2
• For lung transplant recipients on ECMO with VRE bacteremia, high-dose daptomycin (10-12 mg/kg IV once daily) is recommended as first-line with a minimum of 14 days and strong consideration for 4-6 weeks 2

Patients on Serotonergic Medications

• Daptomycin 8-12 mg/kg/day is preferred over linezolid to avoid serotonin syndrome risk 3
• If linezolid is unavoidable, explicit risk-benefit discussion and informed consent are required 3