What is the best antibiotic for Enterococcus (E.) faecalis infections?

Best Antibiotic Treatment for Enterococcus faecalis Infections

For Enterococcus faecalis infections, the combination of ampicillin plus ceftriaxone is the preferred first-line treatment, especially for infective endocarditis and in patients with renal impairment or high-level aminoglycoside resistance. 1

First-Line Treatment Options

Ampicillin-Ceftriaxone Combination

• Dosing:
  • Ampicillin 2g IV every 4 hours
  • Ceftriaxone 2g IV every 12 hours
• Duration: 4-6 weeks for endocarditis; 10-14 days for other infections 1
• Key advantages:
  • No nephrotoxicity compared to aminoglycoside-containing regimens
  • Effective for high-level aminoglycoside-resistant strains
  • Suitable for elderly patients and those with renal impairment
  • Demonstrated efficacy in both native and prosthetic valve endocarditis

Alternative First-Line: Ampicillin-Gentamicin Combination

• Dosing:
  • Ampicillin 2g IV every 4 hours
  • Gentamicin 3 mg/kg/day IV in 3 divided doses
• Duration: Consider short-course (2 weeks) gentamicin therapy to reduce nephrotoxicity risk 1
• Caution: 23% of patients develop nephrotoxicity with this regimen

Treatment Algorithm Based on Clinical Scenario

For Uncomplicated E. faecalis UTIs:

1. First choice: Ampicillin (if susceptible)
2. Alternative: Vancomycin (if penicillin-resistant) 2

For E. faecalis Endocarditis:

1. First choice: Ampicillin-ceftriaxone for 4-6 weeks 1
2. Alternative if ampicillin-susceptible but high-level aminoglycoside resistance:
   • Ampicillin-ceftriaxone for 6 weeks
3. For penicillin-resistant strains:
   • Vancomycin plus gentamicin for 6 weeks 1, 3

For Multi-Drug Resistant E. faecalis:

1. Consider: Linezolid or daptomycin 1
2. Recent evidence suggests: Ampicillin plus daptomycin shows robust activity against strains with decreased ampicillin-ceftriaxone susceptibility 4

Special Considerations

Penicillin-Resistant E. faecalis

• Treatment: Vancomycin 30 mg/kg/day IV in 2 divided doses plus gentamicin 3 mg/kg/day IV in 3 divided doses for 6 weeks 1
• Note: Intrinsic penicillin resistance is uncommon in E. faecalis (unlike E. faecium) 1

Beta-lactamase Producing Strains

• Treatment: Ampicillin-sulbactam plus aminoglycoside or vancomycin plus gentamicin 1

High-Level Aminoglycoside Resistance

• Best option: Ampicillin-ceftriaxone combination therapy 1
• This regimen has shown similar success rates to ampicillin-gentamicin in multiple studies

Monitoring and Pitfalls

Key Monitoring Parameters:

• For aminoglycoside regimens:
  • Serum peak (3-4 μg/mL) and trough (<1 μg/mL) concentrations
  • Renal function
  • Hearing assessment
• For vancomycin regimens:
  • Serum trough concentrations (10-20 μg/mL)

Common Pitfalls:

1. Failure to identify high-level aminoglycoside resistance - Always test for this before starting aminoglycoside therapy
2. Prolonged aminoglycoside therapy - Consider short-course (2 weeks) to reduce nephrotoxicity
3. Inadequate treatment duration - Endocarditis requires 4-6 weeks of therapy
4. Failure to recognize β-lactamase production - Rare in E. faecalis but requires specific treatment
5. Missing endocarditis - E. faecalis has higher risk of endocarditis than E. faecium; consider echocardiography in persistent bacteremia 1

Evidence Quality Assessment

The recommendations are primarily based on the 2015 American Heart Association guidelines for infective endocarditis 1, which include large observational studies comparing ampicillin-ceftriaxone with ampicillin-gentamicin therapy. While not randomized controlled trials, these studies included substantial patient numbers (43 and 272 patients) and demonstrated comparable efficacy with significantly less nephrotoxicity in the ampicillin-ceftriaxone group.

Recent research (2025) suggests that ampicillin plus daptomycin may be effective against strains with decreased ampicillin-ceftriaxone susceptibility 4, which could be considered for difficult-to-treat cases.