What are the treatment options for a urinary tract infection (UTI) caused by vancomycin-resistant Enterococcus faecalis (VRE)?

Treatment Options for Vancomycin-Resistant Enterococcus faecalis UTI

For uncomplicated urinary tract infections caused by vancomycin-resistant Enterococcus faecalis, a single dose of fosfomycin 3 g PO is recommended as the first-line treatment option due to its effectiveness, convenience, and minimal risk of resistance development. 1

First-Line Treatment Options (in order of preference)

1. Fosfomycin 3 g PO (single dose)

   • Recommended for uncomplicated VRE UTIs
   • Convenient single-dose administration
   • High urinary concentrations
   • Weak recommendation, very low quality of evidence 1

2. Nitrofurantoin 100 mg PO every 6 hours

   • Effective alternative for uncomplicated VRE UTIs
   • Good urinary concentrations
   • Requires multiple daily dosing
   • Weak recommendation, very low quality of evidence 1

3. High-dose ampicillin or amoxicillin

   • Ampicillin 18-30 g IV daily in divided doses, or
   • Amoxicillin 500 mg PO/IV every 8 hours
   • May be effective even against ampicillin-resistant VRE in UTIs due to high urinary concentrations
   • Weak recommendation, very low quality of evidence 1

Second-Line Treatment Options

1. Linezolid 600 mg PO/IV every 12 hours

   • Strong recommendation for enterococcal infections in general 1
   • FDA-approved for VRE infections 2
   • Clinical cure rate of 63% specifically for VRE UTIs 2
   • Despite limited urinary excretion, appears effective for mild VRE UTIs 3
   • Monitor for thrombocytopenia with prolonged use (>14-21 days) 4

2. Daptomycin (high-dose)

   • 8-12 mg/kg/day IV
   • Alternative for complicated UTIs with bacteremia
   • Monitor CK levels during therapy
   • Weak recommendation, low quality of evidence 1

Treatment Algorithm Based on UTI Classification

For Uncomplicated Lower UTI (Cystitis):

1. First choice: Fosfomycin 3 g PO (single dose)
2. Second choice: Nitrofurantoin 100 mg PO every 6 hours for 5-7 days
3. Third choice: Amoxicillin 500 mg PO every 8 hours for 5-7 days

For Complicated UTI without Bacteremia:

1. First choice: Linezolid 600 mg PO/IV every 12 hours for 7-14 days
2. Second choice: High-dose ampicillin (if susceptible) 18-30 g IV daily in divided doses for 7-14 days

For UTI with Bacteremia:

1. First choice: Linezolid 600 mg IV every 12 hours for 14 days
2. Second choice: High-dose daptomycin 8-12 mg/kg IV daily for 14 days

Important Clinical Considerations

• Differentiate colonization from true infection: Many patients with VRE in urine are merely colonized rather than infected. In one study, 64% of patients with positive VRE urine cultures had asymptomatic bacteriuria 3.

• Susceptibility testing: Always perform susceptibility testing to guide therapy, as resistance patterns can vary significantly.

• Duration of therapy:

  • Uncomplicated cystitis: Single dose (fosfomycin) or 5-7 days
  • Complicated UTI: 7-14 days
  • UTI with bacteremia: Minimum 14 days

• Monitoring for adverse effects:

  • Linezolid: Monitor for thrombocytopenia, especially with treatment >14 days
  • Daptomycin: Monitor CK levels
  • Nitrofurantoin: Avoid in patients with CrCl <30 mL/min

• Resistance concerns: Linezolid resistance has been reported in E. faecium strains, particularly in transplant patients receiving prolonged therapy 5, 6. Resistance developed in approximately 1 in 45 patients treated with linezolid 5.

By following this evidence-based approach, clinicians can effectively manage VRE UTIs while minimizing unnecessary antibiotic use and reducing the risk of treatment failure and resistance development.