What antibiotics (ABX) are used to treat vancomycin-resistant infections?

Antibiotics for Vancomycin-Resistant Infections

Linezolid is the drug of choice for vancomycin-resistant enterococcal infections, with daptomycin as an alternative for bloodstream infections, and tigecycline for intra-abdominal infections. 1

First-Line Treatment Options by Infection Type

Bloodstream Infections

• Linezolid 600 mg IV q12h is strongly recommended as first-line therapy for VRE bacteremia 1
• High-dose daptomycin (8-12 mg/kg IV daily) is an effective alternative, especially when combined with beta-lactams for synergistic effect 1
• Treatment duration is typically 10-14 days, depending on source control and clinical response 1

Complicated Intra-abdominal Infections

• Linezolid 600 mg IV q12h is the primary recommendation 1
• Tigecycline (100 mg IV loading dose, then 50 mg IV q12h) is specifically recommended for intra-abdominal infections due to VRE 1
• Treatment duration is typically 5-7 days, adjusted based on source control and clinical response 1

Urinary Tract Infections

• For complicated UTIs: Linezolid 600 mg IV q12h or daptomycin 6-12 mg/kg IV daily 1
• For uncomplicated UTIs, several options are available:
  • Fosfomycin 3 g PO as a single dose or every other day 1
  • Nitrofurantoin 100 mg PO four times daily 1
  • High-dose ampicillin (18-30 g IV daily in divided doses) or amoxicillin 500 mg PO/IV q8h may be effective even against ampicillin-resistant VRE due to high urinary concentrations 1

Pneumonia

• Linezolid 600 mg IV q12h is the recommended treatment for VRE pneumonia 1
• Treatment duration should be at least 7 days 1

Mechanism of Action and Efficacy

• Linezolid works by inhibiting bacterial protein synthesis at the pre-translational initiation complex formation 1
• It has bacteriostatic activity against both vancomycin-resistant E. faecium and E. faecalis (MIC₉₀ = 2-4 μg/ml) 2
• Clinical cure rates with linezolid have been reported as high as 92.6% across various infection sites 2
• Daptomycin exhibits bactericidal activity, making it particularly valuable for bloodstream infections 1

Special Considerations

Combination Therapy

• For VRE bloodstream infections with high daptomycin MIC (3-4 μg/mL), combination with beta-lactams (including penicillins, carbapenems, or cephalosporins) may be beneficial 1
• Linezolid shows synergistic activity with beta-lactam antibiotics against VRE infections 3

Monitoring and Adverse Effects

• Monitor complete blood count when using linezolid for >2 weeks due to potential hematologic toxicity (thrombocytopenia) 1, 3
• Daptomycin requires monitoring for myopathy and rhabdomyolysis with weekly CPK levels 4
• Tigecycline may cause nausea, vomiting, and has been associated with increased mortality in some studies 1

Emerging Options

• Newer agents with activity against VRE include:
  • Eravacycline for intra-abdominal infections 1
  • Ceftaroline has in vitro activity against gram-positive organisms but poor activity against enterococci and should not be used empirically for VRE infections 1, 5

Clinical Pitfalls to Avoid

• Distinguish between colonization and true infection before initiating anti-VRE therapy 1
• Avoid empiric vancomycin use in neutropenic patients with persistent fever if culture results remain negative after 72-96 hours 1
• Do not use ceftaroline empirically for VRE infections despite its activity against other gram-positive organisms 1
• For VRE endocarditis, cardiac surgery combined with antimicrobial therapy should be considered for optimal outcomes 1

By following these evidence-based recommendations and considering the specific infection site, patient factors, and local resistance patterns, clinicians can effectively manage vancomycin-resistant infections and improve patient outcomes.