What are the treatment options for Enterococcus (E.) faecium urinary tract infections (UTIs)?

Treatment Options for Enterococcus faecium Urinary Tract Infections

For uncomplicated E. faecium UTIs, a single dose of fosfomycin 3g PO, nitrofurantoin 100mg PO every 6 hours, or high-dose ampicillin/amoxicillin (if susceptible) are the recommended first-line treatments. 1

First-Line Treatment Options for E. faecium UTIs

For Vancomycin-Susceptible E. faecium UTIs:

1. Uncomplicated UTIs:

   • Fosfomycin 3g PO single dose 1
   • Nitrofurantoin 100mg PO every 6 hours 1
   • Ampicillin 18-30g IV daily in divided doses (if susceptible) 1
   • Amoxicillin 500mg PO/IV every 8 hours (if susceptible) 1

2. Complicated UTIs:

   • Linezolid 600mg IV/PO every 12 hours 1
   • Daptomycin 8-12mg/kg IV daily (for systemic involvement) 1, 2

For Vancomycin-Resistant E. faecium (VRE) UTIs:

The prevalence of VRE has been increasing globally, with E. faecium being the predominant species of VRE with rates as high as 45% in some ICU settings 1. Treatment options include:

1. Uncomplicated VRE UTIs:

   • Fosfomycin 3g PO single dose 1
   • Nitrofurantoin 100mg PO every 6 hours 1
   • High-dose ampicillin or amoxicillin (if susceptible, despite vancomycin resistance) 1

2. Complicated VRE UTIs:

   • Linezolid 600mg IV/PO every 12 hours 1, 3
   • Daptomycin 8-12mg/kg IV daily (for systemic involvement) 1, 2

Treatment Selection Algorithm

1. Determine if UTI is uncomplicated or complicated:

   • Uncomplicated: No structural/functional abnormalities, not pregnant, non-diabetic, immunocompetent patient
   • Complicated: Presence of structural abnormalities, pregnancy, diabetes, immunocompromised state, or systemic symptoms

2. Obtain urine culture and susceptibility testing:

   • Check for susceptibility to ampicillin/amoxicillin
   • Check for vancomycin resistance
   • Check for high-level aminoglycoside resistance (HLAR)

3. For uncomplicated UTIs:

   • If outpatient management is possible, prefer oral options:
     • Fosfomycin 3g PO single dose (convenient dosing)
     • Nitrofurantoin 100mg PO every 6 hours (if normal renal function)
     • Amoxicillin 500mg PO every 8 hours (if susceptible)

4. For complicated UTIs:

   • Consider hospitalization and IV therapy initially:
     • Linezolid 600mg IV/PO every 12 hours
     • Daptomycin 8-12mg/kg IV daily (for systemic involvement)
   • Consider combination therapy for severe infections

Important Clinical Considerations

Susceptibility Testing

E. faecium has higher rates of resistance compared to E. faecalis. Studies show that while E. faecalis generally maintains good susceptibility to ampicillin (96%), E. faecium has much lower susceptibility rates (32%) 4. Therefore, susceptibility testing is crucial before selecting definitive therapy.

Vancomycin Resistance

The prevalence of vancomycin-resistant E. faecium has increased significantly, from 8.1% in 2012 to 19% in 2018 in European countries, and up to 45% in some ICU settings 1. This highlights the importance of considering alternative agents like linezolid, daptomycin, fosfomycin, and nitrofurantoin.

Common Pitfalls to Avoid

1. Do not use cephalosporins: Enterococci have intrinsic resistance to cephalosporins.
2. Do not rely on fluoroquinolones: High resistance rates have been reported (86% of E. faecium isolates resistant to ciprofloxacin in some studies) 4, 5.
3. Do not treat asymptomatic bacteriuria: Treatment is not recommended unless the patient is pregnant or undergoing urologic procedures 6.
4. Do not forget to remove indwelling catheters if present, as this is a crucial step in management 6.
5. Do not use aminoglycosides as monotherapy: High-level aminoglycoside resistance is common in E. faecium 5.

Duration of Therapy

• Uncomplicated UTIs: 5-7 days (except single-dose fosfomycin)
• Complicated UTIs: 10-14 days
• Adjust based on clinical response and resolution of symptoms

Evidence Quality Assessment

The recommendations for treating E. faecium UTIs are based primarily on guidelines with low to very low quality evidence 1. Most recommendations carry weak recommendation strength (2C or 2D level), reflecting the limited high-quality clinical trials specifically addressing E. faecium UTIs. The strongest recommendation is for linezolid (1C) for enterococcal infections, though this is not specific to UTIs 1.