Craig W A
Department of Medicine, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, USA.
Diagn Microbiol Infect Dis. 1995 May-Jun;22(1-2):89-96. doi: 10.1016/0732-8893(95)00053-d.
The broad-spectrum cephalosporins exhibit time-dependent bactericidal activity and produce prolonged postantibiotic effects only with staphylococci. The duration of time that serum levels exceed the minimum inhibitory concentration (MIC) is the important pharmacodynamic parameter correlating with efficacy for these drugs. Maximal efficacy for cephalosporins in several animal infection models is approached when serum levels are above the MIC for 60%-70% of the dosing interval for Enterobacteriaceae and streptococci and for 40%-50% of the dosing interval for Staphylococcus aureus. Based on MIC90 values of 0.5 microgram/ml for enteric bacilli and 4 micrograms/ml for S. aureus, these time above MIC goals can be easily met in infected and/or elderly patients following 1-2 g of cefotaxime at 12-h intervals. Full knowledge of the interrelationships between pharmacokinetics and pharmacodynamics is important for determining effective dosage regimens for the broad-spectrum cephalosporins.
广谱头孢菌素呈现时间依赖性杀菌活性，且仅对葡萄球菌产生延长的抗生素后效应。血清水平超过最低抑菌浓度（MIC）的持续时间是与这些药物疗效相关的重要药效学参数。当血清水平在给药间隔的60%-70%高于MIC时，对于肠杆菌科细菌和链球菌，以及在给药间隔的40%-50%高于MIC时，对于金黄色葡萄球菌，在几种动物感染模型中可达到头孢菌素的最大疗效。基于肠道杆菌的MIC90值为0.5微克/毫升，金黄色葡萄球菌的MIC90值为4微克/毫升，在感染和/或老年患者中，每12小时给予1-2克头孢噻肟后，上述高于MIC的时间目标很容易实现。全面了解药代动力学和药效学之间的相互关系对于确定广谱头孢菌素的有效给药方案很重要。
