What is the recommended management, including source control and empiric antimicrobial therapy, for a hospital‑acquired Enterococcus faecium infection, and how should treatment be adjusted based on susceptibility results?

Management of Hospital-Acquired Enterococcus faecium Infection

For hospital-acquired E. faecium infections, initiate empiric anti-enterococcal therapy with vancomycin or linezolid while awaiting susceptibility results, ensure aggressive source control including removal of infected catheters, and adjust therapy based on resistance patterns—using high-dose daptomycin (10-12 mg/kg/day) plus ampicillin or ceftaroline for vancomycin-resistant or panresistant strains. 1, 2

Empiric Therapy Selection

When to Cover Enterococci Empirically

Empiric anti-enterococcal therapy is mandatory for: 1

• Healthcare-associated intra-abdominal infections, particularly postoperative infections
• Patients with prior cephalosporin or broad-spectrum antibiotic exposure (selects for E. faecium)
• Immunocompromised patients
• Patients with valvular heart disease or prosthetic intravascular materials
• Patients known to be colonized with VRE

Initial Empiric Agent Choice

• Target E. faecalis initially unless high VRE risk: Use ampicillin, piperacillin-tazobactam, or vancomycin 1
• For suspected vancomycin-resistant E. faecium (VREfm): Use linezolid 600 mg IV/PO every 12 hours as first-line empiric therapy 2, 3
• Do NOT empirically cover VREfm unless the patient is at very high risk (liver transplant with hepatobiliary source, known VRE colonization) 1

Source Control—Critical First Step

Source control is non-negotiable and often determines treatment success or failure: 2, 4

• Remove all short-term intravascular catheters immediately when infected with enterococci 4
• Remove long-term catheters if there is insertion site infection, pocket infection, suppurative thrombophlebitis, sepsis, or bacteremia persisting >72 hours despite appropriate therapy 2, 4
• If long-term catheter must be retained, use antibiotic lock therapy plus systemic antibiotics 4
• Drain all abscesses and debride infected tissue—failure to achieve source control will result in treatment failure regardless of antibiotic choice 2

Definitive Therapy Based on Susceptibility

For Ampicillin-Susceptible E. faecium (Rare)

• Ampicillin is preferred if susceptible 4
• Note: E. faecium has intrinsic penicillin resistance, making this scenario uncommon 5

For Vancomycin-Susceptible E. faecium

• Vancomycin 30 mg/kg/day IV in 2 divided doses (target trough 15-20 mg/L) 5

For Vancomycin-Resistant E. faecium (VREfm)

First-line options: 2, 3

• Linezolid 600 mg IV/PO every 12 hours—FDA-approved for VREfm infections including bacteremia 3
• Daptomycin 8-12 mg/kg/day IV—alternative option 2, 5

For Panresistant E. faecium

This requires aggressive combination therapy: 2

• High-dose daptomycin (10-12 mg/kg/day) PLUS ampicillin or ceftaroline—strongly recommended as backbone therapy 2
• Combination therapy prevents emergence of resistance and provides synergistic activity 2, 6
• Never use daptomycin monotherapy—associated with treatment failures and resistance development 2

Treatment Duration Algorithm

Uncomplicated Bacteremia (Catheter-Related, Source Removed)

• 7-14 days if catheter removed or source controlled 2, 4
• Obtain follow-up blood cultures to document clearance 2

Complicated Bacteremia or Endocarditis

• Minimum 6 weeks of high-dose daptomycin plus ampicillin/ceftaroline 2
• Obtain transesophageal echocardiography (TEE) if: 2, 4
  • Signs/symptoms of endocarditis present
  • Bacteremia persists >72 hours despite appropriate therapy
  • Prosthetic valves or endovascular foreign bodies present
  • Bacteremia persists >4 days (independently associated with increased mortality) 4

Intra-Abdominal Infections

• Tailor therapy based on culture results from intra-abdominal sources 1
• Ensure adequate source control with surgical drainage/debridement 1

Special Clinical Scenarios

Respiratory Isolation of E. faecium

• Usually represents colonization, not infection—consider alternative diagnoses first 5
• Only treat if true pneumonia confirmed with clinical/radiographic evidence 5
• Never treat colonization—promotes further resistance without benefit 5

Urinary Tract Infections

Alternative agents for VRE cystitis: 2

• Fosfomycin 3 g PO (single dose)
• Nitrofurantoin 100 mg PO every 6 hours
• High-dose ampicillin (18-30 g IV daily in divided doses) if susceptible

Critical Pitfalls to Avoid

Antibiotic Selection Errors: 2, 5

• Never use standard-dose daptomycin (6 mg/kg/day)—inadequate for E. faecium; requires 10-12 mg/kg/day
• Never use cephalosporins alone—no intrinsic activity against enterococci despite potential in vitro synergy
• Never use aminoglycosides as monotherapy—enterococci have intrinsic low-level resistance

Clinical Management Errors: 2, 4

• Do not assume E. faecium has same susceptibility as E. faecalis—E. faecium requires different empiric coverage (up to 95% multidrug-resistant)
• Do not fail to remove infected catheters when indicated—most common cause of persistent bacteremia
• Do not miss endocarditis—perform TEE when bacteremia persists or high-risk features present

Monitoring Errors: 2, 3

• Monitor CBC weekly with linezolid—risk of bone marrow suppression with prolonged use
• Monitor for daptomycin resistance development—especially with monotherapy
• Verify clinical improvement within 48-72 hours—if no improvement, consider resistance or alternative diagnosis

Antimicrobial Stewardship

• De-escalate therapy daily once susceptibilities available to prevent superinfection with C. difficile, Candida, or further resistant organisms 1
• Narrow spectrum when possible after pathogen identification 1
• Multidisciplinary team management recommended for panresistant E. faecium—include infectious diseases, cardiology, cardiovascular surgery, and clinical pharmacy 2

Monitoring Treatment Response

• Obtain follow-up blood cultures to document bacteremia clearance 2, 4
• Persistent bacteremia >72 hours should prompt immediate catheter removal and evaluation for metastatic foci 2, 4
• Linezolid therapy: Monitor complete blood counts weekly due to bone marrow suppression risk 2
• Linezolid is bacteriostatic—may limit effectiveness in endovascular infections; consider daptomycin-based regimens for these scenarios 2