What is the recommended treatment for Enterococcus (E) faecalis endocarditis?

Treatment of Enterococcus faecalis Endocarditis

For Enterococcus faecalis endocarditis, the recommended first-line treatment is ampicillin 200 mg/kg/day IV in 4-6 divided doses plus gentamicin 3 mg/kg/day IV or IM in 1 dose for 6 weeks (for prosthetic valve endocarditis or symptoms >3 months) or 4 weeks (for uncomplicated native valve with symptoms <3 months). 1

Standard Treatment Regimens

First-line therapy (Beta-lactam and gentamicin-susceptible strains):

• Ampicillin 200 mg/kg/day IV in 4-6 divided doses for 6 weeks (for PVE or symptoms >3 months) or 4 weeks (for uncomplicated native valve with symptoms <3 months)
• PLUS Gentamicin 3 mg/kg/day IV or IM in 1 dose for 2-6 weeks 1

Alternative regimen (High-level aminoglycoside resistance):

• Ampicillin 200 mg/kg/day IV in 4-6 divided doses
• PLUS Ceftriaxone 4 g/day IV or IM in 2 doses
• Duration: 6 weeks 1

This combination is active against E. faecalis strains with and without high-level aminoglycoside resistance (HLAR) and is the combination of choice in patients with HLAR E. faecalis endocarditis.

For Penicillin-Allergic Patients

• Vancomycin 30 mg/kg/day IV in 2 divided doses
• PLUS Gentamicin 3 mg/kg/day IV or IM in 1 dose
• Duration: 6 weeks 1, 2

Special Considerations

Beta-lactamase producing strains:

• Replace ampicillin with ampicillin-sulbactam 1

Monitoring requirements:

• Renal function and serum gentamicin concentrations should be monitored once/week (twice/week in patients with renal failure) 1
• Serum trough vancomycin levels (Cmin) should be ≥10-20 mg/L 1

Duration considerations:

• 6-week therapy recommended for patients with prosthetic valve endocarditis (PVE) 1
• 4-week therapy may be considered for uncomplicated native valve with symptoms <3 months, though recent data suggests higher relapse rates with 4-week regimens 3

Management of Resistant Strains

For multidrug-resistant strains:

1. Daptomycin 10 mg/kg/day plus ampicillin 200 mg/kg/day IV in 4-6 doses
2. Linezolid 2 × 600 mg/day IV or orally for ≥8 weeks (monitor hematological toxicity)
3. Consultation with infectious disease specialists is strongly recommended 1, 4

Common Pitfalls and Caveats

1. Relapse risk: A 4-week course of antibiotic treatment might not be suitable for treating E. faecalis IE, as relapses are more frequent among patients treated for 4 weeks compared to 6 weeks (17% vs 2%) 3

2. Nephrotoxicity: The ampicillin plus ceftriaxone regimen demonstrates lower rates of nephrotoxicity compared to ampicillin plus gentamicin with similar efficacy and mortality outcomes 5

3. Cephalosporin ineffectiveness: Cephalosporins alone have minimal or no activity against enterococci and should not be used as monotherapy 4

4. Resistance testing: All enterococcal isolates should be tested for susceptibility to penicillin/ampicillin, vancomycin, and for high-level resistance to gentamicin to guide appropriate therapy 1

5. Cirrhotic patients: Higher relapse rates have been observed in cirrhotic patients, suggesting they may require longer treatment courses 3

The dual β-lactam therapy (ampicillin plus ceftriaxone) has emerged as a preferred option for high-level aminoglycoside resistant strains and for patients with renal impairment due to its reduced nephrotoxicity while maintaining similar efficacy to the traditional ampicillin plus gentamicin regimen 5.

For complicated cases with multidrug resistance, early consultation with infectious disease specialists is essential to optimize treatment outcomes 1, 4.