Van der Auwera P, Duchateau V, Lambert C, Husson M, Kinzig M, Sörgel F
Clinique des Maladies Infectieuses et Laboratoire de Microbiologie, Institut Jules Bordet, Bruxelles, Belgium.
Antimicrob Agents Chemother. 1993 Sep;37(9):1860-8. doi: 10.1128/AAC.37.9.1860.
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.
10名志愿者按照交叉双盲方案，在30分钟内静脉输注哌拉西林（4克）、哌拉西林（4克）加他唑巴坦（0.5克）（特治星）以及替卡西林（3克）加克拉维酸（0.2克）（替门汀）。在输注结束后0.5小时和3小时采集血样，通过高压液相色谱法测定针对70株革兰氏阴性杆菌的浓度和杀菌效价。针对35株菌株绘制血清时间-杀菌曲线，以测定杀菌率和时间-杀菌曲线下面积。采用血清杀菌活性测定法，替卡西林-克拉维酸和哌拉西林-他唑巴坦对铜绿假单胞菌、大肠埃希菌、阴沟肠杆菌、粘质沙雷菌和脆弱拟杆菌同样有效。哌拉西林-他唑巴坦对耐哌拉西林的肺炎克雷伯菌（4至16倍）和粘质沙雷菌（2至4倍）优于替卡西林-克拉维酸。通过时间-杀菌曲线下面积测定，哌拉西林-他唑巴坦对哌拉西林敏感菌株与替卡西林-克拉维酸相当；对耐哌拉西林菌株，哌拉西林-他唑巴坦比哌拉西林活性显著更高，且在考虑志愿者输注结束后3小时采集的样本时，比替卡西林-克拉维酸活性更高。单独给予哌拉西林后，0.5小时血清哌拉西林浓度（平均值±平均标准误；单位为毫克/升）为115±13，3小时为7.4±1.4；给予哌拉西林-他唑巴坦后，0.5小时为105.5±12.6，3小时为7.7±1.6。血清他唑巴坦浓度（单位为毫克/升）0.5小时为13.1±1.4，3小时为1.2±0.2。哌拉西林-他唑巴坦比值0.5小时为8±0.3，3小时为6.2±0.5。哌拉西林-他唑巴坦对产β-内酰胺酶的革兰氏阴性杆菌似乎很有前景。
