Does ceftriaxone cover Enterococcus faecalis?

Ceftriaxone Does Not Cover Enterococcus faecalis as Monotherapy

Ceftriaxone alone does not provide adequate coverage for Enterococcus faecalis infections, as this organism is naturally resistant to cephalosporins. 1 However, the combination of ceftriaxone with ampicillin demonstrates synergistic activity against E. faecalis and is an effective treatment option.

Intrinsic Resistance of Enterococci to Cephalosporins

• E. faecalis has intrinsic resistance to cephalosporins, including ceftriaxone
• Most strains of E. faecalis are inhibited but not killed by penicillin or ampicillin alone 2
• Cephalosporins have minimal or no in vitro activity against enterococci when used as monotherapy 2

Effective Treatment Options for E. faecalis

Traditional Approach: Beta-lactam + Aminoglycoside

• Historically, the standard treatment for E. faecalis infections has been a combination of:
  • Ampicillin/penicillin + gentamicin
  • This combination provides synergistic bactericidal activity
  • Duration typically 6 weeks for endocarditis 2

Alternative Approach: Ampicillin + Ceftriaxone

• The combination of ampicillin and ceftriaxone shows synergistic activity against E. faecalis 2, 1
• This combination works by saturating different penicillin-binding proteins 2
• Recommended dosing per European Society of Cardiology guidelines 2:
  • Ampicillin: 200 mg/kg/day IV in 4-6 doses
  • Ceftriaxone: 4 g/day IV or IM in 2 doses

Clinical Evidence Supporting Ampicillin-Ceftriaxone Combination

• Large multicenter studies have shown that ampicillin-ceftriaxone is as effective as ampicillin-gentamicin for E. faecalis infective endocarditis 2
• The ampicillin-ceftriaxone combination is particularly valuable for:
  • High-level aminoglycoside-resistant (HLAR) E. faecalis strains 2, 1
  • Patients at risk for aminoglycoside-associated nephrotoxicity 3
• Clinical cure rates of up to 100% have been reported in patients who completed the full treatment course 3

Important Clinical Considerations

• The ampicillin-ceftriaxone combination is not effective against E. faecium 2, 4
• For orthopedic infections due to E. faecalis, ampicillin-ceftriaxone has shown promising results with 90% cure rates in a pilot study 5
• In vitro studies have confirmed synergistic effects of penicillin/ceftriaxone against E. faecalis isolates with ceftriaxone MICs ≤ 256 mg/L 6

Treatment Pitfalls to Avoid

• Never use ceftriaxone as monotherapy for E. faecalis infections
• Do not assume that the ampicillin-ceftriaxone combination will be effective against E. faecium
• When treating serious E. faecalis infections, ensure adequate dosing of both agents to achieve synergistic effects
• For patients with renal impairment, the ampicillin-ceftriaxone combination offers advantages over aminoglycoside-containing regimens

In conclusion, while ceftriaxone alone does not cover E. faecalis, its combination with ampicillin provides an effective treatment option that is particularly valuable for patients with HLAR strains or those at risk for aminoglycoside-related toxicity.