Pharmacokinetic and microbial susceptibility studies of ceftriaxone

The in vitro activity of ceftriaxone, a new parenteral cephalosporin, was tested against 450 strains isolated from blood cultures and compared with that of various other antibiotics. The compound was comparable to cefotaxime for all species tested. Its was more potent than cefoperazone, cefamandole and ticarcillin in inhibitingEnterobacteriaceae (Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, indole-positiveProteus spp. andSerratia marcescens). The MIC₉₅ of ceftriaxone for these strains was 0.5Μg/ml. The drug was less active againstStaphylococcus aureus than cefamandole, cloxacillin and vancomycin, but most isolates were inhibited by 4Μg/ml. AgainstPseudomonas aeruginosa, ceftriaxone was comparable in activity to ticarcillin (MIC₉₅=64Μg/ml), and inferior to cefoperazone, ceftazidime and cefsulodine. Levels of ceftriaxone in serum and various body fluids were determined by bio-assays. Due to its very long half-life (8 h), ceftriaxone serum levels 24 h after i.v. or i.m. injection of 1 and 2 g were still above the MIC₉₅ of all strains tested exceptPseudomonas aeruginosa. Levels in bile, synovial and cerebro-spinal fluids were high.