Is ceftriaxone (Ceftriaxone) effective for treating Enterococcus faecalis infections?

Ceftriaxone is Not Effective as Monotherapy for Enterococcus faecalis Infections

Ceftriaxone should not be used as monotherapy for Enterococcus faecalis infections as enterococci have intrinsic resistance to cephalosporins. 1

Enterococcal Resistance to Cephalosporins

• E. faecalis demonstrates intrinsic resistance to cephalosporins, including ceftriaxone
• When used alone, ceftriaxone has minimal or no in vitro activity against enterococci 1
• Most strains of E. faecalis are inhibited but not killed by penicillin or ampicillin alone, showing relative resistance to beta-lactam antibiotics as well 1

Recommended Treatment Options for E. faecalis Infections

First-line Treatment

• The standard treatment for E. faecalis infections is a combination of ampicillin/penicillin + gentamicin, which provides synergistic bactericidal activity 1
• For native valve endocarditis, treatment duration is typically 4-6 weeks 2
• For prosthetic valve endocarditis, treatment duration is at least 6 weeks 2

Alternative Treatment Option: Ampicillin + Ceftriaxone

• While ceftriaxone alone is ineffective, the combination of ampicillin and ceftriaxone shows synergistic activity against E. faecalis by saturating different penicillin-binding proteins 1
• This combination is particularly valuable for high-level aminoglycoside-resistant (HLAR) E. faecalis strains 1
• Recommended dosage:
  • Ampicillin: 200 mg/kg/day IV, divided into 4-6 doses
  • Ceftriaxone: 4 g/day IV, divided into 2 doses 1
• Multiple studies have shown this combination to be as effective as ampicillin-gentamicin for E. faecalis infective endocarditis 1, 3, 4

Important Clinical Considerations

• The ampicillin-ceftriaxone combination is not effective against E. faecium 1

• For outpatient parenteral antimicrobial therapy (OPAT), various regimens have been studied:

  • Standard regimen: ampicillin 2g/4h plus ceftriaxone 2g/12h 3
  • Alternative regimen: ampicillin 2g/4h plus ceftriaxone 4g/24h 3, 4
  • Co-diluted regimen: ampicillin and ceftriaxone jointly administered in bolus every 4h 4

• Caution with once-daily high-dose ceftriaxone (4g) regimens: A pharmacokinetic study showed that only 25% of patients maintained adequate synergistic concentrations with twice-daily dosing, and none with once-daily dosing 5

• Higher relapse rates (29.4%) have been observed with once-daily ceftriaxone regimens compared to twice-daily dosing 4

Treatment for Special Populations

• For orthopedic infections due to E. faecalis, ampicillin-ceftriaxone combination has shown promising results with 90% cure rates in a small pilot study 6
• For patients unable to tolerate β-lactam therapy, vancomycin is an effective substitute, often combined with gentamicin 2

Key Pitfalls to Avoid

1. Never use ceftriaxone as monotherapy for E. faecalis infections
2. Do not assume that once-daily ceftriaxone dosing provides adequate synergistic concentrations throughout the dosing interval
3. Monitor renal function when using aminoglycoside-containing regimens
4. Be aware that ampicillin-ceftriaxone combination is specific for E. faecalis and not effective for E. faecium
5. Consider infectious disease specialist consultation for management of enterococcal infections, especially in complicated cases