What is the treatment for Vancomycin-resistant Enterococcus faecalis?

Treatment of Vancomycin-Resistant Enterococcus faecalis

Linezolid 600 mg IV or PO every 12 hours is the first-line treatment for vancomycin-resistant E. faecalis infections, with strong guideline support and FDA approval for this indication. 1, 2

Primary Treatment Algorithm

First-Line Therapy

• Linezolid 600 mg IV or PO every 12 hours is recommended as the preferred agent for all VRE infections including E. faecalis (Strong recommendation, low quality evidence) 1
• This is the only agent with FDA approval specifically for vancomycin-resistant E. faecium infections, including concurrent bacteremia 2
• Clinical cure rates of 67% were demonstrated in the FDA registration trial for documented VRE infections 2

Alternative Systemic Therapies

• High-dose daptomycin 8-12 mg/kg IV daily is recommended as an alternative for VRE bacteremia (Weak recommendation, low quality evidence) 1
• Daptomycin at 10-12 mg/kg/day may be more effective for serious infections like endocarditis 3
• Daptomycin plus beta-lactam combination (ampicillin, cephalosporins, or carbapenems) should be considered for VRE bacteremia with high daptomycin MIC (3-4 mg/mL) 1, 3

Site-Specific Treatment Recommendations

Bloodstream Infections

• Linezolid 600 mg IV/PO every 12 hours for 10-14 days 1, 3, 4
• Daptomycin 8-12 mg/kg IV daily for 10-14 days as alternative 1, 3, 4
• Remove central venous catheters and other infection sources 4
• For endocarditis: extend treatment to at least 6 weeks and consider cardiac surgery 1, 3

Intra-Abdominal Infections

• Tigecycline 100 mg IV loading dose, then 50 mg IV every 12 hours for 5-7 days (Weak recommendation, very low quality evidence) 1
• Linezolid 600 mg IV/PO every 12 hours for 5-7 days as alternative 1, 3
• Duration based on clinical response and source control 1, 3

Pneumonia

• Linezolid 600 mg IV every 12 hours for at least 7 days 1, 3

Complicated Urinary Tract Infections

• Linezolid 600 mg IV/PO every 12 hours for 5-7 days 1, 3
• Daptomycin 6-12 mg/kg IV daily for 5-7 days as alternative 1

Uncomplicated Urinary Tract Infections

• Fosfomycin 3 g PO single dose (Weak recommendation, very low quality evidence) 1, 3
• Nitrofurantoin 100 mg PO every 6 hours for 3-7 days (Weak recommendation, very low quality evidence) 1, 3
• High-dose ampicillin 18-30 g IV daily in divided doses for 3-7 days if susceptible (Weak recommendation, very low quality evidence) 1, 3
• Amoxicillin 500 mg PO/IV every 8 hours for 3-7 days if susceptible 1, 3

Critical Pitfalls and Caveats

Species Identification is Mandatory

• Quinupristin-dalfopristin is NOT active against E. faecalis (only E. faecium), making species identification essential before selecting this agent 3, 5, 6
• E. faecalis is typically vancomycin-sensitive in antibiotic-naive patients, so confirm vancomycin resistance before using alternative agents 7

Tigecycline Limitations

• Do NOT use tigecycline for VRE bacteremia due to inadequate serum concentrations despite in vitro activity 4
• Tigecycline is appropriate only for intra-abdominal infections 1, 4

Linezolid Monitoring

• Monitor for bone marrow suppression (thrombocytopenia) with treatment courses >14-21 days 3, 5
• Monitor for peripheral and optic neuropathy with prolonged use 3
• Resistance can develop via 23S ribosome binding site mutations 5

Daptomycin Considerations

• Higher doses (10-12 mg/kg/day) are preferred for serious infections and endocarditis 3, 7
• Combination with beta-lactams may provide synergistic effects for resistant strains 1, 3

Emerging Combination Strategies

Linezolid Plus Fosfomycin

• The combination of linezolid with fosfomycin produced sustained bactericidal effect and completely eradicated resistant subpopulations in hollow fiber models 8
• This combination may be considered for severe VRE infections where monotherapy has failed 8

Double Beta-Lactam Combinations

• Imipenem plus ampicillin or cephalosporins plus ampicillin have shown synergistic bactericidal activity against some E. faecalis strains 3

Colonization vs. Infection

• Differentiate colonization from true infection before initiating anti-VRE therapy, as treatment of colonization is not indicated 4
• VRE can colonize without causing invasive disease, particularly in the gastrointestinal tract 1, 5