EX-VIVO PHARMACODYNAMIC STUDY OF PIPERACILLIN ALONE AND IN COMBINATION WITH TAZOBACTAM, COMPARED WITH TICARCILLIN PLUS CLAVULANIC ACID

Ten volunteers received piperacillin (4 g), piperacillin (4 g) plus ta zobactam (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 infus ion to measure by (high-pressure liquid chromatography) the concentrat ion and bactericidal titers against 70 gram-negative bacilli. Serum ti me-kill curves were done against 35 strains to measure killing rates a nd area under the time-kill curve. Using the measure of serum bacteric idal activity, ticarcillin-clavulanic acid and piperacillin-tazobactam were equally effective against Pseudomonas aeruginosa, Escherichia co li, Enterobacter cloacae, Serratia marcescens, and Bacteroides fragili s. 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-kil l curve, piperacillin-tazobactam was equivalent to ticarcillin-clavula nic acid against piperacillin-susceptible strains; piperacillin-tazoba ctam was significantly more active than piperacillin against piperacil lin-resistant strains and was more active than ticarcillin-clavulanic acid when the sample obtained 3 h after the end of infusion to volunte ers was considered. Serum piperacillin concentrations (mean +/- standa rd 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 piperacil lin-tazobactam. Serum tazobactam concentrations (in milligrams per lit er) were 13.1 +/- 1.4 at 0.5 h and 1.2 +/- 0.2 at 3 h. The piperacilli n-tazobactam ratio was 8 +/- 0.3 at 0.5 h and 6.2 +/- 0.5 at 3 h. Pipe racillin-tazobactam appears promising against beta-lactamase-producing gram-negative bacilli.