Management of Vancomycin-Resistant Bacteria
For vancomycin-resistant Enterococcus faecium (VRE) infections, linezolid 600 mg IV or PO every 12 hours is the first-line treatment, while daptomycin 8-12 mg/kg IV daily serves as the preferred alternative for bacteremia. 1
Species Identification is Critical
Before initiating therapy, you must distinguish between E. faecium and E. faecalis because treatment options differ significantly:
- Quinupristin-dalfopristin is NOT active against E. faecalis (MIC₉₀ = 16 mcg/mL), making species identification essential before selecting this agent 1, 2
- E. faecium accounts for the majority of vancomycin-resistant enterococcal infections and responds to all approved VRE agents 2
- E. faecalis VRE is less common but requires linezolid or daptomycin specifically 1
Primary Treatment Algorithm for VRE Faecium
First-Line Therapy
- Linezolid 600 mg IV or PO every 12 hours for 10-14 days (bacteremia) or 7-14 days (other sites) 1, 3
- This recommendation has strong guideline support with FDA approval and demonstrated 67% cure rate in documented VRE infections 1, 3
- Linezolid has the advantage of excellent oral bioavailability, allowing IV-to-PO conversion 3
Alternative for Bacteremia
- Daptomycin 8-12 mg/kg IV daily for 10-14 days is the preferred alternative specifically for bloodstream infections 1
- Higher doses (8-12 mg/kg) are recommended rather than the standard 6 mg/kg dose used for other indications 1
Additional Option for E. Faecium Only
- Quinupristin-dalfopristin 7.5 mg/kg IV every 8 hours demonstrated 70.5% clinical response in bacteriologically evaluable patients and 65.8% overall response 4, 2
- This agent is bacteriostatic with MIC₉₀ = 2 mcg/mL against E. faecium 2
- Major limitation: myalgia/arthralgia is the most common treatment-limiting adverse effect 4, 2
Site-Specific Considerations
Intra-Abdominal Infections
For critically ill patients with healthcare-associated intra-abdominal infections at risk for VRE:
- Linezolid 600 mg every 12 hours as part of combination therapy with appropriate gram-negative coverage 5
- Tigecycline 100 mg loading dose, then 50 mg IV every 12 hours for 5-7 days is an alternative for intra-abdominal infections specifically 1
- Critical pitfall: Do NOT use tigecycline for VRE bacteremia due to inadequate serum concentrations despite in vitro activity 1
Complicated Skin and Soft Tissue Infections
- Linezolid 600 mg every 12 hours for 14-28 days demonstrated 83% cure rate in diabetic foot infections 3
- Treatment duration of 7-14 days is typically sufficient for non-diabetic complicated skin infections 1
Urinary Tract Infections
- Linezolid achieves adequate urinary concentrations and demonstrated 63% cure rate for VRE urinary infections 3
Critical Pitfalls to Avoid
Distinguish Colonization from Infection
- Do not treat VRE colonization - antimicrobial therapy is indicated only for documented invasive infection 1
- VRE commonly colonizes the gastrointestinal tract without causing disease 1
- Positive cultures from non-sterile sites require clinical correlation with signs/symptoms of infection 1
Tigecycline Limitations
- Never use tigecycline monotherapy for bacteremia - serum levels are inadequate despite in vitro susceptibility 1
- Reserve tigecycline for intra-abdominal infections where tissue penetration is adequate 1
Monitoring for Adverse Effects
- Linezolid: Monitor for thrombocytopenia, particularly with treatment courses exceeding 14-21 days 2
- Common adverse effects include gastrointestinal symptoms (nausea, vomiting, diarrhea), headache, and taste alteration 2
- Quinupristin-dalfopristin: Anticipate arthralgias/myalgias which may limit therapy 4, 2
Emerging Combination Strategies for Refractory Cases
When monotherapy fails in severe VRE infections:
- Linezolid plus fosfomycin may be considered, though evidence remains limited 1
- Double beta-lactam combinations (imipenem plus ampicillin, or cephalosporins plus ampicillin) have shown synergistic bactericidal activity against some E. faecalis strains 1
- Combination therapy with quinupristin-dalfopristin plus ampicillin or doxycycline has shown enhanced killing in vitro, but clinical use remains unestablished 2, 6
Infection Control Measures
Beyond antimicrobial therapy, preventing VRE transmission requires:
- Immediate implementation of contact precautions for all patients with VRE infection or colonization 5
- Hand hygiene before and after every patient contact 5
- Early detection and prompt reporting by the microbiology laboratory 5
- Education of hospital staff regarding vancomycin resistance 5
- Prudent vancomycin use to prevent selection pressure for resistance 5