Svensson Margareta, Nilsson Lennart E, Ström Magnus, Nilsson Maud, Sörberg Mikael
Division of Clinical Microbiology and Gastroenterology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, SE-581 85 Linköping, Sweden.
Antimicrob Agents Chemother. 2002 Jul;46(7):2244-8. doi: 10.1128/AAC.46.7.2244-2248.2002.
Pharmacodynamic studies of Helicobacter pylori exposed to metronidazole and tinidazole alone and in combination with clarithromycin were performed by bioluminescence assay of intracellular ATP. The pharmacodynamic parameter control-related effective regrowth time (CERT) was used. CERT is defined as the time required for the resumption of logarithmic growth and a return of the level of growth to the preexposure inoculum in the test culture minus the corresponding time in the control culture. CERT measures the combined effects of the initial level of killing and postantibiotic effect. The incubation times and drug concentrations were chosen according to their half-lives and their clinically achievable concentrations. The study shows that the parameter CERT is useful for the testing of antibiotic combinations. The CERTs induced by clarithromycin, metronidazole, and tinidazole alone and in the combinations tested were concentration dependent, with no maximum response, indicating that the use of high doses may be preferable. The combinations with the highest concentrations induced synergistic effects and prevented regrowth. The use of tinidazole in combination with clarithromycin proved to give the longest CERTs, indicating that this is the most effective combination.
通过细胞内ATP的生物发光测定法,对单独暴露于甲硝唑和替硝唑以及与克拉霉素联合暴露的幽门螺杆菌进行了药效学研究。使用了药效学参数对照相关有效再生长时间(CERT)。CERT定义为测试培养物中恢复对数生长并使生长水平恢复到暴露前接种量所需的时间减去对照培养物中的相应时间。CERT衡量初始杀灭水平和抗生素后效应的综合作用。根据它们的半衰期和临床可达到的浓度选择孵育时间和药物浓度。研究表明,参数CERT可用于测试抗生素组合。单独使用克拉霉素、甲硝唑和替硝唑以及在所测试的组合中诱导的CERT呈浓度依赖性,没有最大反应,这表明使用高剂量可能更可取。最高浓度的组合诱导了协同效应并阻止了再生长。事实证明,替硝唑与克拉霉素联合使用可产生最长的CERT,表明这是最有效的组合。