Treatment of Vancomycin-Resistant Enterococcus faecalis
First-Line Treatment
Linezolid 600 mg IV or PO every 12 hours is the preferred first-line treatment for vancomycin-resistant E. faecalis infections, with FDA approval and strong guideline support from the Infectious Diseases Society of America. 1, 2
- Linezolid demonstrated a 67% cure rate in the high-dose arm (600 mg q12h) versus 52% in the low-dose arm for documented VRE infections in FDA clinical trials 2
- For bacteremia with associated infection, cure rates reached 59% compared to 29% with lower doses 2
- Treatment duration is typically 10-14 days for bloodstream infections 1
Alternative Agents
High-Dose Daptomycin
- Daptomycin 8-12 mg/kg IV daily is the recommended alternative for VRE faecalis bacteremia, particularly when linezolid is contraindicated or has failed 1
- Higher doses (10-12 mg/kg/day) may be more effective for serious infections like endocarditis 3
- One case report demonstrated successful treatment of vancomycin-tolerant E. faecalis bacteremia with daptomycin 12 mg/kg IV q24h after vancomycin failure 4
Site-Specific Recommendations
Bloodstream Infections
- Linezolid 600 mg IV/PO every 12 hours for 10-14 days 1
- Daptomycin 8-12 mg/kg IV daily for 10-14 days as alternative 1
- Remove central venous catheters and other infection sources 5
Intra-Abdominal Infections
- Tigecycline 100 mg IV loading dose, then 50 mg IV every 12 hours for 5-7 days 1
- This is a weak recommendation with very low quality evidence 1
Urinary Tract Infections (Uncomplicated)
- Fosfomycin 3 g PO single dose or every other day for resistant strains 3
- Nitrofurantoin 100 mg PO every 6 hours for 3-7 days 3, 2
- High-dose ampicillin (18-30 g IV daily in divided doses) if susceptibility testing shows sensitivity 3
Critical Pitfalls to Avoid
Species Identification is Mandatory
- Quinupristin-dalfopristin is NOT active against E. faecalis (MIC₉₀ = 16 mcg/mL), only against E. faecium 1, 6
- This makes species identification essential before selecting therapy 1
Tigecycline Limitations
- Do NOT use tigecycline for VRE bacteremia due to inadequate serum concentrations despite in vitro activity 1, 5
- Tigecycline is only appropriate for intra-abdominal infections 1, 5
Colonization vs. Infection
- Differentiate colonization from true infection before initiating anti-VRE therapy 1, 5
- Treatment of colonization is not indicated 1
Emerging Combination Strategies
Linezolid Plus Fosfomycin
- Consider this combination for severe VRE infections where monotherapy has failed 1
- A 2021 hollow fiber model study demonstrated that linezolid (12 mg/L steady-state) combined with fosfomycin (8 g IV q8h) produced sustained bactericidal effect of 3-4 log₁₀ CFU/mL over 72 hours and completely eradicated resistant subpopulations 7
- Neither agent alone prevented amplification of resistant subpopulations 7
Double Beta-Lactam Combinations
- Imipenem plus ampicillin or cephalosporins plus ampicillin have shown synergistic bactericidal activity against some E. faecalis strains 1
- Clinical evidence remains limited for these combinations 1
Monitoring and Adverse Effects
Linezolid Monitoring
- Monitor for bone marrow suppression and neuropathy with prolonged use (>14-21 days) 3
- Thrombocytopenia appears limited to patients receiving longer courses 6
- Common adverse effects include gastrointestinal symptoms (nausea, vomiting, diarrhea), headache, and taste alteration 6
Daptomycin Monitoring
- Monitor creatine phosphokinase (CPK) levels for myopathy 4
- Higher doses (8-12 mg/kg) require closer monitoring 1