What is the recommended treatment for a Vancomycin-Resistant Enterococcus (VRE) Urinary Tract Infection (UTI)?

Treatment of Vancomycin-Resistant Enterococcus (VRE) Urinary Tract Infection

For uncomplicated VRE urinary tract infections, a single dose of fosfomycin 3 g PO is recommended as first-line therapy. 1, 2

First-Line Treatment Options for VRE UTI

Uncomplicated VRE UTI

• Single dose of fosfomycin 3 g PO is recommended for uncomplicated urinary tract infections due to VRE 1
• Nitrofurantoin 100 mg PO every 6 hours is an effective alternative for uncomplicated VRE UTIs 1, 2
• High-dose ampicillin (18-30 g IV daily in divided doses) or amoxicillin 500 mg PO/IV every 8 hours can be used even for ampicillin-resistant VRE strains due to high urinary concentrations achieved 1

Complicated VRE UTI

• Linezolid 600 mg IV or PO every 12 hours is recommended for complicated VRE UTIs, with clinical cure rates of 63% reported in urinary tract infections 1, 3
• High-dose daptomycin (8-12 mg/kg IV daily) can be considered for complicated VRE UTIs, particularly when bacteremia is present 1, 2

Treatment Selection Based on Severity

Algorithm for VRE UTI Treatment

1. Determine if uncomplicated or complicated UTI:

   • Uncomplicated: Lower UTI symptoms in non-pregnant patients without structural/functional abnormalities 4
   • Complicated: Upper UTI, pregnancy, male gender, immunosuppression, or structural/functional abnormalities 4

2. For uncomplicated VRE UTI:

   • First choice: Fosfomycin 3 g PO single dose 1, 2
   • Second choice: Nitrofurantoin 100 mg PO every 6 hours 1, 4
   • Third choice: High-dose ampicillin or amoxicillin 1

3. For complicated VRE UTI:

   • First choice: Linezolid 600 mg IV or PO every 12 hours 1, 3
   • Second choice: High-dose daptomycin (≥9 mg/kg IV daily) 2, 5

Evidence Quality and Considerations

• The recommendations for VRE UTI treatment are based on weak to moderate quality evidence, with most recommendations carrying a "weak recommendation, very low quality of evidence" rating 1
• Clinical studies specifically evaluating VRE UTI treatments are limited, with most evidence coming from retrospective or small prospective studies 4, 6
• FDA data for linezolid shows a 63% cure rate for VRE urinary tract infections in clinical trials 3

Important Clinical Considerations

• Differentiate between VRE colonization, asymptomatic bacteriuria, and true UTI before initiating treatment to avoid unnecessary antibiotic use 1, 6
• Overtreatment of asymptomatic bacteriuria is common (58% of non-compliant cases in one study), leading to unnecessary antibiotic exposure 6
• Risk factors for clinical failure in VRE UTI treatment include weight ≥100 kg, renal disease, indwelling catheters, and concurrent VRE bloodstream infection 6
• For patients with concurrent VRE bacteremia, higher-dose daptomycin (≥9 mg/kg) has shown similar outcomes to linezolid 5

Monitoring and Duration

• For uncomplicated VRE UTI, single-dose fosfomycin or 5-7 days of nitrofurantoin is typically sufficient 1, 4
• For complicated VRE UTI, 7-14 days of therapy is generally recommended, with duration based on clinical response 1, 2
• Monitor for adverse effects:
  • Linezolid: Thrombocytopenia (especially with treatment >14 days), anemia, peripheral neuropathy 2, 7
  • Daptomycin: CPK elevation, myopathy 2, 5
  • Nitrofurantoin: Pulmonary reactions, peripheral neuropathy (avoid in renal impairment) 4

Common Pitfalls to Avoid

• Failing to distinguish between colonization and true infection 1, 6
• Using suboptimal daptomycin dosing (<9 mg/kg) for complicated VRE UTIs with bacteremia 5
• Using tigecycline for VRE UTI (not recommended due to low urinary concentrations) 1, 2
• Not removing urinary catheters when possible (indwelling catheters are associated with clinical failure) 6