title: Efficacy of beta-lactam and inhibitor combinations in a diffusion chamber model in rabbits.
abstract: Using a diffusion chamber in rabbits, we evaluated therapy with the combination of ceftriaxone plus the beta-lactamase inhibitor tazobactam in comparison with ceftriaxone alone. One sensitive and one resistant strain of Escherichia coli, Enterobacter cloacae and Klebsiella pneumoniae were inoculated into one of the six diffusion chambers, implanted in the same animal. In order to simulate pharmacokinetics in humans, both substances were administered in decreasing doses. Ceftriaxone was given 0, 2, 4 and 6 h after infection in dosages of 45, 35, 25 and 15 mg/kg of body weight, while tazobactam was administered either in one dose at 0 h, or divided into two doses at 0 and 1 h or 0 and 4 h, or divided into three doses at 0, 1 and 4 h after infection. The ratio of ceftriaxone:tazobactam was fixed at 8:1. Ceftriaxone, in combination with tazobactam, given in one dose immediately after infection showed a significant reduction in bacterial count. All other combinations of ceftriaxone and tazobactam did not differ from ceftriaxone in monotherapy. Co-administration of the beta-lactamase inhibitor tazobactam significantly enhanced the activity of ceftriaxone against all three tested species.
authors.affiliation: University Clinic for Internal Medicine I, Clinical Department for Infectious Diseases and Chemotherapy, University of Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Georgopoulos
authors.forename: A
authors.initials: A
authors.lastname: Buxbaum
authors.forename: W
authors.initials: W
authors.lastname: Graninger
mesh_terms: D000818:Animals; D002443:Ceftriaxone / Q000494:pharmacology* / Q000627:therapeutic use; D018550:Cephalosporin Resistance; D002511:Cephalosporins / Q000494:pharmacology* / Q000627:therapeutic use; D015169:Colony Count, Microbial; D015194:Diffusion Chambers, Culture; D004359:Drug Therapy, Combination; D004754:Enterobacter / Q000187:drug effects; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000254:growth & development; D004756:Enterobacteriaceae Infections / Q000188:drug therapy / Q000382:microbiology; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D000078142:Tazobactam
chemical_list: D002511:Cephalosporins; D004791:Enzyme Inhibitors; D002443:Ceftriaxone; D010397:Penicillanic Acid; D000078142:Tazobactam