What are the treatment options for Enterococcus infections?

Treatment of Enterococcus Infections

For community-acquired enterococcal infections, routine anti-enterococcal coverage is not necessary, but for healthcare-associated infections, antimicrobial therapy targeting enterococci should be given when these organisms are recovered from cultures. 1

When to Treat Enterococci

Community-Acquired Infections

• Anti-enterococcal therapy is NOT routinely required for community-acquired intra-abdominal infections, as multiple randomized trials comparing regimens with and without enterococcal coverage showed no clinical advantage 1
• The pathogenicity of enterococci in community-acquired biliary infections has not been demonstrated 1

Healthcare-Associated Infections

• Antimicrobial therapy for enterococci MUST be given when recovered from healthcare-associated infections 1
• Empiric anti-enterococcal therapy is specifically recommended for: 1
  • Postoperative infections
  • Patients who previously received cephalosporins or other agents selecting for Enterococcus
  • Immunocompromised patients
  • Patients with valvular heart disease or prosthetic intravascular materials
  • Liver transplant recipients with hepatobiliary infections
  • Patients known to be colonized with vancomycin-resistant enterococci

First-Line Treatment by Species and Susceptibility

Enterococcus faecalis (Most Common Species)

For ampicillin-susceptible E. faecalis, ampicillin is the preferred first-line agent. 2, 3

Uncomplicated Infections (UTI, Bacteremia without Endocarditis)

• Ampicillin (if susceptible): Standard dosing for 7-14 days 2
• Piperacillin-tazobactam: Alternative if ampicillin-susceptible 1, 3
• Vancomycin 30 mg/kg/day IV divided into two doses: For ampicillin-resistant strains 1, 2

Complicated Infections (Endocarditis, Persistent Bacteremia)

• Ampicillin 200 mg/kg/day IV in 4-6 divided doses PLUS gentamicin 3 mg/kg/day IV in 2-3 doses for 4-6 weeks (if gentamicin MIC <500 mg/L) 1, 4
• For penicillin-allergic patients: Vancomycin 30 mg/kg/day IV in two doses PLUS gentamicin for 6 weeks 1
• For aminoglycoside-resistant strains: Ampicillin 2 g IV every 4 hours PLUS ceftriaxone 2 g IV every 12 hours for 6 weeks 4

Enterococcus faecium (More Resistant Species)

For vancomycin-susceptible E. faecium, use ampicillin or piperacillin-tazobactam if susceptible; for vancomycin-resistant E. faecium (VRE), linezolid is first-line. 1, 3

Vancomycin-Susceptible E. faecium

• Ampicillin (if MIC ≤8 mg/L): Preferred agent 3
• Piperacillin-tazobactam: Alternative if susceptible 3
• Vancomycin: If ampicillin-resistant 3

Vancomycin-Resistant E. faecium (VRE)

Linezolid 600 mg IV/PO every 12 hours is the first-line treatment for VRE infections. 1, 3, 5

Treatment by Site:

• Bacteremia/Endocarditis: 1, 3

  • First-line: Linezolid 600 mg IV/PO every 12 hours for 10-14 days (bacteremia) or ≥8 weeks (endocarditis)
  • Alternative: High-dose daptomycin 8-12 mg/kg IV daily (consider adding β-lactam if daptomycin MIC 3-4 mg/mL)
  • For multiresistant VRE endocarditis: Daptomycin 10 mg/kg/day PLUS ampicillin 200 mg/kg/day IV in 4-6 doses

• Pneumonia: 1

  • Linezolid 600 mg IV/PO every 12 hours for at least 7 days

• Intra-abdominal Infections: 1

  • Linezolid 600 mg IV/PO every 12 hours for 5-7 days
  • Alternative: Tigecycline 100 mg IV loading dose, then 50 mg IV every 12 hours

• Complicated Urinary Tract Infections: 1

  • Linezolid 600 mg IV/PO every 12 hours for 5-7 days
  • Alternative: Daptomycin 6-12 mg/kg IV daily

• Uncomplicated Urinary Tract Infections: 1

  • Fosfomycin 3 g PO single dose (preferred for simple cystitis)
  • Nitrofurantoin 100 mg PO four times daily for 3-7 days
  • High-dose ampicillin 18-30 g/day IV in divided doses (if susceptible)

Critical Pitfalls to Avoid

Dosing Errors

• Standard daptomycin doses (6 mg/kg/day) are inadequate for VRE bacteremia/endocarditis—use 8-12 mg/kg/day 1, 3
• Monitor CPK levels at least weekly with daptomycin due to skeletal muscle toxicity risk 3
• Monitor complete blood counts weekly with linezolid, especially for courses >14-21 days, due to bone marrow suppression risk 3, 6

Source Control Failures

• Remove infected intravascular catheters when enterococci are isolated—short-term catheters should always be removed 2
• Long-term catheters require removal if there is insertion site infection, suppurative thrombophlebitis, or sepsis 2
• Failure to drain abscesses or remove infected devices will result in treatment failure regardless of antimicrobial choice 3

Diagnostic Oversights

• Perform transesophageal echocardiography (TEE) if enterococcal bacteremia persists >4 days or if there is concern for endovascular infection 4, 2
• Never perform prostatic massage in acute bacterial prostatitis, as this can precipitate bacteremia 4
• High-level aminoglycoside resistance (gentamicin MIC >500 mg/L) eliminates synergistic bactericidal effect—test for this before using combination therapy 1, 7

Empiric Therapy Mistakes

• Do NOT provide empiric coverage for vancomycin-resistant E. faecium unless the patient is at very high risk (e.g., liver transplant recipient with hepatobiliary infection or known VRE colonization) 1
• Cephalosporins have no activity against enterococci and select for enterococcal superinfection 1, 8

Treatment Duration Guidelines

• Uncomplicated bacteremia: 7-14 days when catheter removed or with antibiotic lock therapy 2
• Complicated bacteremia/endocarditis: 4-6 weeks minimum 1, 4
• Prostatitis: 4-6 weeks 4
• Intra-abdominal infections: 5-7 days with adequate source control 1
• Urinary tract infections: 5-7 days (complicated), 3-7 days (uncomplicated) 1