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. It was more potent than cefoperazone, cefamandole and ticarcillin in inhibiting Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, indole-positive Proteus spp. and Serratia marcescens). The MIC95 of ceftriaxone for these strains was 0.5 microgram/ml. The drug was less active against Staphylococcus aureus than cefamandole, cloxacillin and vancomycin, but most isolates were inhibited by 4 micrograms/ml. Against Pseudomonas aeruginosa, ceftriaxone was comparable in activity to ticarcillin (MIC95 = 64 micrograms/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 except Pseudomonas aeruginosa. Levels in bile, synovial and cerebro-spinal fluids were high.