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

Treatment of Vancomycin-Resistant Enterococci (VRE) in Urine

For uncomplicated urinary tract infections due to VRE, a single dose of fosfomycin 3 g PO is recommended as first-line therapy, with nitrofurantoin 100 mg PO every 6 hours as an effective alternative. 1, 2

First-Line Treatment Options for VRE UTIs

Uncomplicated VRE UTIs

1. Fosfomycin 3 g PO single dose (Weak recommendation, very low quality of evidence) 1

   • FDA approved for UTIs caused by E. faecalis
   • Achieves high urinary concentrations
   • Convenient single-dose administration

2. Nitrofurantoin 100 mg PO every 6 hours (Weak recommendation, very low quality of evidence) 1, 2

   • Good in vitro activity against VRE
   • Achieves high urinary concentrations
   • Typically used for 5-7 days

3. High-dose ampicillin (18-30 g IV daily in divided doses) or amoxicillin 500 mg PO/IV every 8 hours (Weak recommendation, very low quality of evidence) 1

   • May be effective even against ampicillin-resistant VRE in urine due to high urinary concentrations 3
   • One retrospective study reported clinical and microbiological eradication rates of 88.1% and 86%, respectively 1

Treatment for Complicated or Systemic VRE Infections

For patients with complicated UTIs, pyelonephritis, or bacteremia:

1. Linezolid 600 mg IV or PO every 12 hours (Strong recommendation, low quality of evidence) 1, 4

   • FDA-approved for VRE infections
   • Microbiological and clinical cure rates of 86.4% and 81.4%, respectively 1
   • Effective for urinary tract infections with 63% cure rate 4

2. High-dose daptomycin 8-12 mg/kg IV daily (Weak recommendation, low quality of evidence) 1, 5

   • Higher doses (≥9 mg/kg) associated with better outcomes than lower doses 5
   • Consider in combination with β-lactams for synergistic effect 1
   • Not FDA-approved for VRE infections but has better in vitro bactericidal activity than other agents 1

Important Clinical Considerations

• Differentiate colonization from true infection before initiating treatment 1, 3

  • Assess for symptoms (dysuria, frequency, urgency)
  • Absence of vaginal discharge
  • Pyuria on urinalysis

• Obtain susceptibility testing to guide definitive therapy 1, 2

  • Some VRE isolates may retain susceptibility to ampicillin

• Treatment duration:

  • Uncomplicated UTI: Single dose for fosfomycin; 5-7 days for nitrofurantoin
  • Complicated UTI: 7-14 days based on clinical response

• Avoid unnecessary treatment of asymptomatic bacteriuria, especially in elderly patients 2, 3

Special Situations

• For patients with renal impairment:

  • Avoid nitrofurantoin if CrCl <30 mL/min
  • Adjust daptomycin dosing in severe renal impairment

• For patients with hepatic impairment:

  • Monitor closely if using linezolid due to potential for hepatotoxicity

• For pregnant patients:

  • Fosfomycin is generally considered safe in pregnancy
  • Avoid linezolid and daptomycin

Monitoring

• For linezolid:

  • Monitor for thrombocytopenia with prolonged use (>14 days) 6
  • Watch for serotonin syndrome if used with serotonergic agents

• For daptomycin:

  • Monitor CPK levels weekly
  • Watch for myopathy symptoms

Common Pitfalls

1. Underdosing daptomycin: Studies show that higher doses (≥9 mg/kg) are associated with better outcomes than standard doses 5

2. Treating asymptomatic bacteriuria: Unnecessary antibiotic use contributes to resistance development 2, 3

3. Using tigecycline for UTIs: Poor urinary concentrations make it unsuitable for UTIs despite in vitro activity 1

4. Failing to remove urinary catheters: Foreign body removal is essential to successful treatment 7

5. Not considering oral step-down therapy: Early transition to oral therapy when appropriate can reduce hospital stay and complications