What is the recommended treatment for Vancomycin-Resistant Enterococci (VRE) urinary tract infections (UTIs)?

Treatment for Vancomycin-Resistant Enterococci (VRE) Urinary Tract Infections

For uncomplicated VRE UTIs, a single dose of fosfomycin 3 g PO is recommended as first-line therapy. 1

First-Line Treatment Options for Uncomplicated VRE UTIs

The 2022 guidelines provide several treatment options for uncomplicated VRE UTIs, all with weak recommendations but supported by clinical evidence:

1. Fosfomycin 3 g PO single dose 1

   • Advantages: Single-dose therapy, good compliance
   • Achieves high urinary concentrations

2. Nitrofurantoin 100 mg PO every 6 hours 1

   • Good in vitro activity against VRE
   • Appropriate for lower UTIs only (achieves inadequate tissue concentrations)
   • Contraindicated in patients with CrCl <30 mL/min

3. High-dose ampicillin or amoxicillin (if susceptible) 1

   • 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 urinary tract due to high urinary concentrations

Treatment Algorithm for VRE UTIs

Step 1: Confirm True Infection vs. Colonization

• Differentiate between colonization, asymptomatic bacteriuria, and true infection 2
• Treat only symptomatic patients with pyuria and significant bacteriuria
• Unnecessary treatment of colonization contributes to antimicrobial resistance

Step 2: Determine Infection Severity and Location

• Uncomplicated lower UTI (cystitis):

  • Fosfomycin 3 g PO single dose (first-line) 1
  • Nitrofurantoin 100 mg PO every 6 hours (alternative) 1
  • Duration: Single dose for fosfomycin; 5-7 days for nitrofurantoin

• Complicated UTI or pyelonephritis:

  • Linezolid 600 mg IV/PO every 12 hours 1, 3
  • Duration: 7-14 days based on clinical response

Step 3: Special Considerations

• For bacteremic VRE UTI:
  • High-dose daptomycin (8-12 mg/kg/day) 1, 4
  • Consider combination with β-lactams for synergy
  • Duration: At least 14 days

Evidence for Treatment Efficacy

Linezolid has FDA approval for VRE infections with documented clinical efficacy. In the FDA trial for VRE infections, linezolid 600 mg q12h showed a 63% cure rate specifically for urinary tract infections, compared to 60% with the lower dose 3. The overall microbiological and clinical cure rates using linezolid were 86.4% and 81.4%, respectively 1.

Higher-dose daptomycin (≥9 mg/kg) has been associated with better survival than lower-dose daptomycin (6-9 mg/kg) for VRE bacteremia 4. However, daptomycin should be reserved for bacteremic UTIs due to its pharmacokinetic properties.

Common Pitfalls and Caveats

1. Overtreatment of colonization: Studies show that 58% of VRE-positive urine cultures represent colonization or asymptomatic bacteriuria rather than true infection 5. Avoid treating these cases.

2. Underdosing daptomycin: If using daptomycin for bacteremic VRE UTI, doses ≥9 mg/kg are associated with significantly better outcomes than lower doses 4.

3. Monitoring for adverse effects:

   • Linezolid: Monitor for thrombocytopenia, especially with courses >14 days
   • Daptomycin: Monitor CK levels regularly
   • Nitrofurantoin: Avoid in patients with renal impairment (CrCl <30 mL/min)

4. Risk factors for clinical failure include:

   • Weight ≥100 kg
   • Renal disease
   • Indwelling catheter
   • Concurrent VRE bloodstream infection 5

5. Susceptibility testing: Always base definitive therapy on susceptibility results, as resistance patterns vary.

By following this evidence-based approach, clinicians can effectively manage VRE UTIs while minimizing unnecessary antibiotic use and optimizing patient outcomes.