Efficacy of ampicillin combined with ceftriaxone and gentamicin in the treatment of experimental endocarditis due to Enterococcus faecalis with no high-level resistance to aminoglycosides

J Antimicrob Chemother. 2003 Sep;52(3):514-7. doi: 10.1093/jac/dkg360. Epub 2003 Aug 13.

Abstract

Objective: This study tests the usefulness of ceftriaxone combined with ampicillin as an alternative to ampicillin plus gentamicin for the treatment of experimental endocarditis due to Enterococcus faecalis without high-level resistance to aminoglycosides. It also determines whether adding ceftriaxone to ampicillin and gentamicin increases the effectiveness against experimental enterococcal endocarditis resulting from E. faecalis.

Methods: Animals with catheter-induced endocarditis were infected intravenously with 108 cfu of the EF91 strain of E. faecalis and were treated for 3 days with ampicillin 2 g every 4 h administered as 'human-like' (H-L) pharmacokinetics, plus gentamicin 1 mg/kg every 8 h H-L, or ceftriaxone 2 g every 12 h H-L alone or combined with gentamicin 6 mg/kg every 24 h administered subcutaneously.

Results: The results of therapy for experimental endocarditis resulting from EF91 showed that the combination of ampicillin plus ceftriaxone was as effective as ampicillin plus gentamicin. The triple combination did not improve on the overall efficacies of the two-drug combinations.

Conclusions: Because of its lower nephrotoxicity, ampicillin plus ceftriaxone may be a useful alternative therapy for E. faecalis endocarditis in selected patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoglycosides / pharmacology*
  • Ampicillin / pharmacokinetics
  • Ampicillin / therapeutic use*
  • Animals
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / therapeutic use*
  • Area Under Curve
  • Ceftriaxone / pharmacokinetics
  • Ceftriaxone / therapeutic use*
  • Cephalosporins / pharmacokinetics
  • Cephalosporins / therapeutic use*
  • Drug Resistance, Bacterial
  • Drug Synergism
  • Drug Therapy, Combination / pharmacokinetics
  • Drug Therapy, Combination / therapeutic use*
  • Endocarditis, Bacterial / drug therapy*
  • Endocarditis, Bacterial / microbiology
  • Enterococcus faecalis / drug effects*
  • Gentamicins / pharmacokinetics
  • Gentamicins / therapeutic use*
  • Half-Life
  • Humans
  • Microbial Sensitivity Tests
  • Penicillins / pharmacokinetics
  • Penicillins / therapeutic use*
  • Rabbits

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Cephalosporins
  • Gentamicins
  • Penicillins
  • Ceftriaxone
  • Ampicillin