NEW INVITRO MODEL TO STUDY EFFECT OF ANTIBIOTIC CONCENTRATION AND RATE OF ELIMINATION ON ANTIBACTERIAL ACTIVITY
NEW INVITRO MODEL TO STUDY EFFECT OF ANTIBIOTIC CONCENTRATION AND RATE OF ELIMINATION ON ANTIBACTERIAL ACTIVITY
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DOI：
10.1128/aac.13.4.570
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发表时间：
1978-01-01
影响因子：
4.9
通讯作者：
TAMASSIA, V
中科院分区：
文献类型：
--
作者：
GRASSO, S;MEINARDI, G;TAMASSIA, V
本文介绍了一种用于研究抗生素体外抗菌活性随不同浓度时间曲线变化的新装置。该仪器可调节以模拟口服或注射后体内观察到的双指数血清水平曲线。初步研究了头孢菌素衍生物头孢唑林（cefazolin）对大肠埃希菌和克雷伯氏菌菌株的抑菌作用，模拟初始浓度为5、10和20 .mu。G /ml呈指数下降，半衰期分别为30,60和120min。每隔1小时对存活细胞进行计数，持续10小时。在所有测试的情况下，都有一个快速杀菌活性的初始阶段，随后是一个抑菌活性阶段，其长度取决于药物消除速度，但与初始浓度相对独立。当抗生素浓度低于药物对所测菌株的最低抑制浓度时，细菌就会再生。在含4%人白蛋白的培养基中，模拟人体注射1 g后的血清水平曲线，研究头孢唑林、头孢菌腈和头孢定对大肠杆菌和克雷伯氏菌的抑菌活性。对于头孢菌素来说，较长的半衰期可能比较高的峰值水平更有用。
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 i.m. 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 .mu.g/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 i.m. dose of 1 g. For cephalosporins a longer half-life might be more useful than higher peak levels.