What is the appropriate antibiotic therapy for a hospitalized or immunocompromised patient suspected of having an infection with Enterococcus faecium or faecalis, particularly those with a history of recent antibiotic use or vancomycin-resistant Enterococcus (VRE)?

Treatment of Enterococcus faecium and faecalis in Hospitalized/Immunocompromised Patients

For hospitalized or immunocompromised patients with suspected enterococcal infection, empiric anti-enterococcal therapy should target E. faecalis with ampicillin, piperacillin-tazobactam, or vancomycin based on susceptibility, while empiric coverage for vancomycin-resistant E. faecium (VRE) should be reserved only for very high-risk patients such as liver transplant recipients or those with known VRE colonization. 1

Risk Stratification for Empiric Coverage

When to provide empiric anti-enterococcal therapy:

• Healthcare-associated intra-abdominal infections 1
• Postoperative infections 1
• Prior cephalosporin or antimicrobial exposure selecting for Enterococcus 1
• Immunocompromised patients 1
• Valvular heart disease or prosthetic intravascular materials 1
• Recent antibiotic use or prolonged hospitalization 1
• ICU stay, severe underlying illness, invasive procedures, or gastrointestinal surgery 1

When to provide empiric VRE coverage (very selective):

• Liver transplant recipients with hepatobiliary tree infections 1
• Known VRE colonization 1
• Previous enterococcal infection or colonization 1
• Long ICU stay with recent vancomycin exposure 1

Species-Specific Treatment Approach

E. faecalis (Vancomycin-Susceptible)

Initial empiric therapy should be directed against E. faecalis, as it is the predominant species and most strains retain ampicillin susceptibility. 1

First-line options based on susceptibility testing:

• Ampicillin 2 g IV every 4-6 hours 1, 2, 3
• Piperacillin-tazobactam 4.5 g IV every 6 hours 1
• Vancomycin 25-30 mg/kg loading dose, then 15-20 mg/kg every 8 hours (only if β-lactam intolerant) 1

Critical distinction: Only 3% of E. faecalis strains are multidrug-resistant, and many vancomycin-resistant E. faecalis remain penicillin-susceptible. 4, 3 Ampicillin is superior to vancomycin for susceptible strains and should be preferred. 4, 3

E. faecium (Often Vancomycin-Resistant)

E. faecium has intrinsic penicillin resistance in most strains, making ampicillin ineffective as first-line therapy. 2, 3 Up to 95% of E. faecium strains express multidrug resistance to vancomycin, aminoglycosides, and penicillins. 3

For vancomycin-resistant E. faecium (VRE):

• Linezolid 600 mg IV/PO every 12 hours (preferred for monomicrobial infection) 1, 2
• Tigecycline 100 mg IV loading dose, then 50 mg IV every 12 hours (for polymicrobial infection) 1, 2
• High-dose daptomycin 10-12 mg/kg/day IV plus ampicillin (for bacteremia or endocarditis) 2, 3

The FDA label demonstrates linezolid achieved 67% cure rates for VRE infections at any site and 59% for VRE bacteremia. 5

Infection Site-Specific Considerations

Intra-Abdominal Infections

For healthcare-associated IAI in critically ill patients:

• Meropenem 1 g IV every 8 hours 1
• Plus vancomycin 25-30 mg/kg loading dose (if enterococcal coverage needed) 1
• Or linezolid 600 mg IV every 12 hours (if VRE risk) 1

For non-critically ill patients with healthcare-associated IAI:

• Piperacillin-tazobactam 4.5 g IV every 6 hours (provides enterococcal coverage) 1
• Add ampicillin 2 g IV every 6 hours if not using piperacillin-tazobactam or imipenem-cilastatin 1

Bacteremia and Endocarditis

For serious infections requiring bactericidal activity:

• Ampicillin 2 g IV every 4-6 hours plus gentamicin (for synergy in susceptible E. faecalis) 1, 3
• Native valve endocarditis: 4-6 weeks of therapy 1, 3
• Prosthetic valve endocarditis: minimum 6 weeks 1, 3

For aminoglycoside-resistant strains:

• Ampicillin 2 g IV every 4 hours plus ceftriaxone 2 g IV every 12 hours for 6 weeks 1

For VRE faecium endocarditis:

• Daptomycin 10 mg/kg/day plus ampicillin 200 mg/kg/day IV in 4-6 doses 2
• Or linezolid 600 mg IV/PO every 12 hours for ≥8 weeks 2

E. faecium bacteremia carries significantly higher mortality (62.5%) compared to E. faecalis (0%), particularly in immunosuppressed patients. 6

Catheter-Related Bloodstream Infections

The risk of endocarditis with enterococcal CRBSI is relatively low (1.5%). 1 However, persistent bacteremia >4 days is independently associated with mortality. 1

Treatment approach:

• Remove catheter if bacteremia persists despite appropriate antibiotics 1
• Evaluate for endocarditis with TEE if signs/symptoms present, persistent bacteremia, or prosthetic valve 1
• Combination therapy with gentamicin and ampicillin is more effective than monotherapy when catheter is retained 1

Critical Monitoring and Pitfalls

Monitoring requirements:

• Monitor CPK levels at least weekly with daptomycin (skeletal muscle toxicity risk) 2
• Monitor complete blood counts weekly with linezolid (bone marrow suppression risk, particularly with courses >14-21 days) 2
• Obtain repeat cultures if inadequate clinical response (monitor for daptomycin resistance development) 2

Common pitfalls to avoid:

• Never use cephalosporins alone for enterococcal coverage - they have no intrinsic activity despite in vitro synergy when combined with ampicillin 3
• Do not assume E. faecium has the same susceptibility profile as E. faecalis - E. faecium requires different empiric coverage due to intrinsic resistance 3
• Standard daptomycin doses (6 mg/kg/day) are inadequate for VRE faecium - higher doses (10-12 mg/kg/day) are required 2
• Source control is critical - failure to remove infected devices or drain abscesses will result in treatment failure regardless of antimicrobial choice 2
• Do not prescribe vancomycin empirically for E. faecalis - ampicillin is superior and vancomycin should be reserved for documented β-lactam allergy 4, 3

Antibiotic stewardship:

• Tailor broad-spectrum therapy when culture and susceptibility reports become available to reduce the number and spectra of administered agents 1
• Verify the antibiogram and adjust therapy when culture results are available 4, 3
• Consider resistance or alternative diagnosis if no clinical improvement after 48-72 hours 4, 3

Duration of Therapy

• Uncomplicated infections: 7-14 days 3
• Complicated infections or bacteremia: 14-28 days 5
• Endocarditis (native valve): 4-6 weeks 1, 3
• Endocarditis (prosthetic valve): minimum 6 weeks 1, 2, 3