Synergistic activity of ceftriaxone combined with netilmicin administered once daily for treatment of experimental streptococcal endocarditis

Antimicrob Agents Chemother. 1993 Feb;37(2):207-12. doi: 10.1128/AAC.37.2.207.


We have conducted experiments to determine if one daily injection of netilmicin (NET) would be synergistic with the broad-spectrum cephalosporin ceftriaxone (CRO) in the treatment of experimentally induced endocarditis. Rats with catheter-induced aortic vegetations were infected intravenously with 3 x 10(7) CFU of a beta-lactam-sensitive strain of Streptococcus sanguis or a beta-lactam-resistant strain of Streptococcus mitis. Treatment with the antibiotics alone (CRO, 10 mg/kg of body weight every 8 h; NET, 18 mg/kg every 24 h) or in combinations which had proved synergistic in in vitro time-kill curves was commenced 48 h postinfection and continued for 72 h. The results show that the combination was markedly effective against S. sanguis and moderately effective against S. mitis, while, with the protocol used here, the agents alone were not. The results suggest that CRO-NET should be an effective combination for treating streptococcal endocarditis in humans and may permit a shorter duration of treatment and once-a-day dosing to be used.

MeSH terms

  • Animals
  • Ceftriaxone / pharmacokinetics
  • Ceftriaxone / pharmacology*
  • Drug Resistance, Microbial
  • Drug Synergism
  • Drug Therapy, Combination / pharmacokinetics
  • Drug Therapy, Combination / pharmacology
  • Endocarditis, Bacterial / drug therapy*
  • Endocarditis, Bacterial / microbiology
  • Female
  • Microbial Sensitivity Tests
  • Netilmicin / pharmacokinetics
  • Netilmicin / pharmacology*
  • Rats
  • Rats, Wistar
  • Serum Bactericidal Test
  • Streptococcal Infections / drug therapy*
  • Streptococcal Infections / microbiology
  • Streptococcus sanguis
  • Streptococcus*


  • Netilmicin
  • Ceftriaxone