Cephalosporin antibiotics in therapy of experimental Streptococcus pneumoniae and Haemophilus influenzae meningitis in rabbits

Abstract

Six cephalosporin antibiotics (cefamandole, cefazolin, cephacetrile, cephalothin, cephaloridine, and cephradine) and two penicillin (ampicillin and penicillin G) were evaluated in vitro and in a rabbit model of experimental meningitis due to Haemophilus influenzae or Streptococcus pneumoniae. The percentage penetration ([concentration in cerebrospinal fluid/concentration in serum] X 100%) of these antibiotics varied from 0.7% for cephalothin to 17% for cephaloridine. The penetration varied inversely with binding to serum proteins. The bactericidal rate of all of the cephalosporin antibiotics was similar in vitro and in vivo to that of penicillin G. However, as demonstrated with cephalothin, concentrations considerably above the minimal bactericidal concentration (as determined in broth) were necessary to initiate the bactericidal effect. Cefamandole was found to be as effective as ampicillin in the therapy of H. influenzae meningitis in rabbits.