What is the best antibiotic therapy for Vancomycin-Resistant Enterococci (VRE) infections?

Best Antibiotic Therapy for VRE Infections

Linezolid 600 mg IV or PO every 12 hours is the first-line treatment for VRE infections, with strong recommendation from current guidelines and demonstrated clinical cure rates of 81.4% and microbiological cure rates of 86.4%. 1, 2

Site-Specific Treatment Recommendations

VRE Bacteremia

• Linezolid 600 mg IV or PO every 12 hours remains first-line therapy for VRE bacteremia, including both E. faecium and E. faecalis 2, 3
• High-dose daptomycin 8-12 mg/kg/day (particularly ≥9 mg/kg) is an effective alternative, especially when linezolid cannot be used 1, 2
• For bacteremia specifically, linezolid achieved cure rates of 59% in patients with associated bacteremia and 50% in bacteremia of unknown origin in FDA trials 3
• Daptomycin combined with β-lactams (penicillins, cephalosporins, or carbapenems) may improve outcomes for difficult-to-treat bacteremia 1, 2
• Meta-analyses show conflicting mortality data, but microbiological cure rates are comparable between daptomycin (93%) and linezolid (91%) 2

Uncomplicated Urinary Tract Infections

For uncomplicated VRE UTIs, you have three excellent oral options:

• Fosfomycin 3 g PO as a single dose (first-line recommendation) 1, 4
• Nitrofurantoin 100 mg PO every 6 hours for 5-7 days 1, 4
• High-dose ampicillin (18-30 g IV daily in divided doses) or amoxicillin 500 mg PO/IV every 8 hours—effective even for ampicillin-resistant strains due to high urinary concentrations 1, 4

Complicated Urinary Tract Infections

• Linezolid 600 mg IV or PO every 12 hours for 7-14 days, with 63% clinical cure rates reported 4
• High-dose daptomycin (8-12 mg/kg IV daily) when bacteremia is present 4

Wound/Skin and Soft Tissue Infections

• Linezolid 600 mg IV or PO every 12 hours for 5-7 days (strong recommendation, 1C) 5
• High-dose daptomycin 8-12 mg/kg IV daily as alternative, particularly combined with β-lactams for difficult infections 5
• Tigecycline 100 mg IV loading dose, then 50 mg IV every 12 hours for complicated wound infections 5

Intra-Abdominal Infections

• Tigecycline 100 mg IV loading dose followed by 50 mg IV every 12 hours, with duration based on clinical response 1
• Linezolid 600 mg IV or PO every 12 hours achieved 85% cure rates for "other" infections including hepatic abscess, biliary sepsis, and pericolonic abscess 3

Comparative Efficacy Evidence

The FDA approval trial for linezolid in VRE showed dose-dependent efficacy:

• High-dose linezolid (600 mg every 12 hours): 67% cure rate (39/58 patients) 3
• Low-dose linezolid (200 mg every 12 hours): 52% cure rate (24/46 patients) 3
• This difference was not statistically significant but clinically meaningful 3

Critical Clinical Considerations

Distinguish Colonization from Infection

• VRE is part of normal colonizing flora—do not treat colonization or asymptomatic bacteriuria 2, 5
• Only treat documented infections with clinical signs and symptoms 2

Source Control

• Remove central venous catheters or other potential sources of persistent infection 2
• Surgical intervention may be necessary for abdominal sources 1

Drug-Specific Pitfalls

Tigecycline limitations:

• Never use tigecycline for VRE bacteremia—it achieves low serum levels due to large volume of distribution 2, 5
• Not recommended for VRE UTI due to low urinary concentrations 4
• Reserved for intra-abdominal infections and complicated wound infections only 1, 5

Linezolid toxicity monitoring:

• Thrombocytopenia occurs in approximately 2% of patients, particularly with courses >14-21 days 6, 7
• Monitor complete blood counts weekly for prolonged therapy 7
• Plasma trough concentrations ≥9 μg/mL are associated with hematologic toxicity 8

Resistance concerns:

• Linezolid resistance remains rare (1.8% in one large series) but can emerge during therapy, particularly in transplant patients receiving protracted courses 9, 10
• Perform susceptibility testing at therapy initiation and if clinical failure occurs 10

Dosing Optimization for Critically Ill Patients

For critically ill patients with VRE isolates having MICs ≤1 μg/mL:

• Standard 1,200 mg/day (600 mg every 12 hours) achieves optimal PK/PD targets with acceptable toxicity rates <15% 8
• For VRE with MIC of 2 μg/mL, consider combination therapy to achieve PK/PD targets and prevent resistance 8

Pediatric Considerations

• Linezolid 10 mg/kg IV or PO every 8 hours for children birth through 11 years 3
• Cure rate of 75% (6/8) for vancomycin-resistant E. faecium in pediatric trials 3
• Linezolid is favored as first-line therapy in children due to activity against both E. faecalis and E. faecium, oral availability, and lower resistance concerns compared to alternatives 7