title: Ex vivo pharmacodynamic study of piperacillin alone and in combination with tazobactam, compared with ticarcillin plus clavulanic acid.
abstract: Ten volunteers received piperacillin (4 g), piperacillin (4 g) plus tazobactam (0.5 g) (Tazocin), and ticarcillin (3 g) plus clavulanic acid (0.2 g) (Timentin) intravenously over 30 min in a cross-over blinded scheme. Blood samples were obtained 0.5 and 3 h after the end of infusion to measure by (high-pressure liquid chromatography) the concentration and bactericidal titers against 70 gram-negative bacilli. Serum time-kill curves were done against 35 strains to measure killing rates and area under the time-kill curve. Using the measure of serum bactericidal activity, ticarcillin-clavulanic acid and piperacillin-tazobactam were equally effective against Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, Serratia marcescens, and Bacteroides fragilis. Piperacillin-tazobactam was superior to ticarcillin-clavulanic acid against piperacillin-resistant Klebsiella pneumoniae (4 to 16 times) and S. marcescens (2 to 4 times). By using the area under the time-kill curve, piperacillin-tazobactam was equivalent to ticarcillin-clavulanic acid against piperacillin-susceptible strains; piperacillin-tazobactam was significantly more active than piperacillin against piperacillin-resistant strains and was more active than ticarcillin-clavulanic acid when the sample obtained 3 h after the end of infusion to volunteers was considered. Serum piperacillin concentrations (mean +/- standard error of the mean; in mg/liter) were 115 +/- 13 at 0.5 h and 7.4 +/- 1.4 at 3 h after the administration of piperacillin alone and 105.5 +/- 12.6 (0.5 h) and 7.7 +/- 1.6 after the administration of piperacillin-tazobactam. Serum tazobactam concentrations (in milligram per liter) were 13.1 +/- 1.4 at 0.5 h and 1.2 +/- 0.2 at 3 h. The piperacillin-tazobactam ratio was 8 +/- 0.3 at 0.5 h and 6.2 +/- 0.5 at 3 h. Piperacillin-tazobactam appears promising against beta-lactamase-producing gram-negative bacilli.
authors.affiliation: Clinique des Maladies Infectieuses et Laboratoire de Microbiologie, Institut Jules Bordet, Bruxelles, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Van der Auwera
authors.forename: V
authors.initials: V
authors.lastname: Duchateau
authors.forename: C
authors.initials: C
authors.lastname: Lambert
authors.forename: M
authors.initials: M
authors.lastname: Husson
authors.forename: M
authors.initials: M
authors.lastname: Kinzig
authors.forename: F
authors.initials: F
authors.lastname: Sörgel
mesh_terms: D000328:Adult; D001681:Biological Assay; D002851:Chromatography, High Pressure Liquid; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000493:pharmacokinetics; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D010878:Piperacillin / Q000493:pharmacokinetics; D015610:Serum Bactericidal Test; D000078142:Tazobactam; D013982:Ticarcillin / Q000493:pharmacokinetics; D065093:beta-Lactamase Inhibitors
chemical_list: D002969:Clavulanic Acids; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid; D010397:Penicillanic Acid; D013982:Ticarcillin; D000078142:Tazobactam; D010878:Piperacillin