What is the treatment for Vancomycin-Resistant Enterococci (VRE) in the urine?

Treatment of Vancomycin-Resistant Enterococci (VRE) in the Urine

Fosfomycin (3g single oral dose) is the first-line treatment for VRE urinary tract infections, as recommended by the Infectious Diseases Society of America (IDSA) and American Urological Association (AUA). 1

First-Line Treatment Options for VRE UTIs

• Fosfomycin (3g single oral dose)

  • First-line therapy for uncomplicated VRE cystitis
  • High clinical and microbiological eradication rates
  • Convenient single-dose administration
  • Recommended by IDSA and AUA guidelines 1

• Nitrofurantoin (100mg twice daily for 5-7 days)

  • Effective alternative for lower UTIs caused by VRE
  • Good in vitro activity against VRE isolates
  • Contraindicated if CrCl <30 mL/min 1, 2

• High-dose ampicillin or amoxicillin

  • Despite in vitro resistance, high urinary concentrations may overcome resistance
  • Clinical and microbiological eradication rates of 88.1% and 86%, respectively
  • Ampicillin 18-30g IV daily or amoxicillin 500mg PO/IV every 8 hours 3, 1

Second-Line Options

• Linezolid (600mg IV or PO every 12 hours)

  • Reserve for complicated or upper tract VRE UTIs when first-line options have failed
  • FDA-approved for VRE infections with clinical cure rates of 63% for urinary tract infections 1, 4
  • Monitor for adverse effects: thrombocytopenia (especially with >14 days of therapy), myelosuppression, and serotonergic interactions 4

• Daptomycin (≥8-10 mg/kg daily)

  • Consider for complicated VRE UTIs when other options have failed
  • Higher doses (≥9 mg/kg) associated with better outcomes than lower doses 5
  • Not FDA-approved specifically for UTIs but has activity against VRE 3

Important Clinical Considerations

1. Differentiate colonization from true infection

   • Do not treat asymptomatic bacteriuria, even if VRE is isolated 1
   • Treatment is indicated only for symptomatic UTI

2. Antimicrobial stewardship

   • Reserve linezolid and daptomycin for serious infections to prevent resistance development 1
   • Use local antibiogram data when available to guide therapy

3. Duration of therapy

   • Uncomplicated lower UTI: Single dose for fosfomycin, 5-7 days for other agents
   • Complicated UTI: 10-14 days 1

4. Combination therapy considerations

   • Daptomycin combined with other antimicrobials may be considered for complex infections
   • Synergistic combinations (e.g., daptomycin with β-lactams) have shown enhanced killing effects against VRE in vitro 3

Treatment Algorithm

1. Uncomplicated lower UTI (cystitis):

   • First choice: Fosfomycin 3g single oral dose
   • Alternatives: Nitrofurantoin 100mg twice daily for 5-7 days or high-dose ampicillin/amoxicillin

2. Complicated UTI or pyelonephritis:

   • First choice: High-dose ampicillin (if susceptible) 18-30g IV daily
   • Alternatives: Linezolid 600mg IV/PO every 12 hours or daptomycin ≥9 mg/kg daily

3. Treatment failure or severe infection:

   • Consider combination therapy (e.g., daptomycin plus β-lactam)
   • Consult infectious disease specialist

Pitfalls and Caveats

• Avoid treating asymptomatic bacteriuria with VRE to prevent unnecessary antibiotic use and resistance development
• Nitrofurantoin should not be used for upper UTIs or in patients with CrCl <30 mL/min
• Monitor for thrombocytopenia with prolonged linezolid use (>14 days)
• Tigecycline should not be used for UTIs due to low urinary concentrations 3
• Ensure adequate hydration to promote urinary flow and antibiotic efficacy 1

By following this evidence-based approach, clinicians can effectively manage VRE urinary tract infections while practicing good antimicrobial stewardship.