Grasso S, Meinardi G, de Carneri I, Tamassia V
Antimicrob Agents Chemother. 1978 Apr;13(4):570-6. doi: 10.1128/AAC.13.4.570.
A new apparatus is described which serves to investigate the in vitro antibacterial activity of antibiotics as a function of different concentration time curves. The apparatus can be adjusted to simulate the biexponential serum level curves observed in vivo after oral or intramuscular administration. Preliminary studies were carried out with a cephalosporin derivative, cefazolin, against Escherichia coli and Klebsiella sp. strains simulating initial concentrations of 5, 10, and 20 mug/ml that decreased exponentially with half-lives of 30, 60, and 120 min. Surviving cells were counted at 1-h intervals for 10 h. In all the situations tested there was an initial phase of rapid bactericidal activity followed by a phase of bacteriostatic activity, whose length depended on the drug elimination rate but was relatively independent of the initial concentrations. Bacterial regrowth occurred when the antibiotic concentration fell below the minimum inhibitory concentration of the drug against the strains tested. The antibacterial activity of cefazolin, cephacetrile, and cephradine against E. coli and Klebsiella strains was also investigated, in a medium containing 4% human albumin, simulating the serum level curves observed in humans after an intramuscular dose of 1 g. The results obtained suggest that, for cephalosporins, a longer half-life might be more useful than higher peak levels.
本文描述了一种新装置，该装置用于研究抗生素的体外抗菌活性与不同浓度-时间曲线的关系。该装置可进行调节，以模拟口服或肌肉注射后在体内观察到的双指数血清水平曲线。使用头孢菌素衍生物头孢唑林对大肠杆菌和克雷伯菌属菌株进行了初步研究，模拟初始浓度为5、10和20μg/ml，其浓度以30、60和120分钟的半衰期呈指数下降。在10小时内每隔1小时对存活细胞进行计数。在所有测试情况下，均存在一个快速杀菌活性的初始阶段，随后是一个抑菌活性阶段，其持续时间取决于药物消除率，但相对独立于初始浓度。当抗生素浓度降至低于该药物对测试菌株的最低抑菌浓度时，细菌会重新生长。还在含有4%人白蛋白的培养基中研究了头孢唑林、头孢乙腈和头孢拉定对大肠杆菌和克雷伯菌菌株的抗菌活性，模拟了1g肌肉注射剂量后在人体中观察到的血清水平曲线。所得结果表明，对于头孢菌素类药物，较长的半衰期可能比较高的峰值水平更有用。
