抗生素合理应用课总结.ppt

* This slide represents key factors involved in antimicrobial therapy. Once the dose is administered, pharmacokinetic parameters then describe what happens to the drug once it enters the body. Absorption from the GI tract is essential for oral therapy. Once in the blood stream critical factors for success include distribution of the drug into the infected tissues. How long a drug remains in the blood stream is determined by half-life (metabolism or excretion) The distribution and metabolism of the drug can have an impact on safety (hepatic metabolites) or efficacy (urine excretion unchanged for UTI). The degree of protein binding can impact the microbiologic activity Pharmacodynamics represents the relationship between the pharmacologic activity (MIC) and pharmacokinetics (AUC or peak concentrations). The pharmacologic activity of an antibiotic can be defined by whether they are time-dependent, (effect can be predicted by time above the MIC, or concentration dependent - higher the concentration the greater the bacterial killing) as defined by peak:MIC or AUC:MIC ratios. In addition, post antibiotic effect (PAE) or the continued bacterial killing when the antibiotic blood level fall below the MIC can also impact efficacy. Pharmacologic effect can be determined by a decline in bacterial colony counts which is typically observed in in vitro models. Mortality rates in animal studies is another endpoint and finally in human trials, resolution of signs and symptoms of an infection typically determines clinical success rates. * 不同的抗生素的抗菌效力参照的药动学/药效学参数不一样。 青、头孢、碳青烯、氨曲、大环，克林，参照 (TMIC) 氨基糖苷、氟喹酮、阿奇，参照24hr AUC/MIC 四环、万古、链阳、氨基糖苷、氟喹酮，参照峰值/MIC 名词解释： TMIC:血浆浓度高于细菌MIC值的时间 24hrAUC/MIC:24小时浓度时间曲线下面积与MIC比值 峰值/MIC：血浆峰浓度与MIC比值 * 抗生素按杀菌活性可分成二类： 时间依赖型 浓度依赖型 * 时间依赖型的抗生素主要的一大类就是b -内酰胺类 (青霉素类、头孢菌素、氨曲南、碳烯类)，克林和大环(红、克、阿奇)、四环、链、万古，是目前临床上应用最多的一些抗生素 它有以下特点： 持续后效应-无或轻、中度 在MIC4-5倍时杀菌率即处于饱和 杀菌范围主要依赖于接触时间 血药浓度超过MIC时间是与临床疗效相关的主要参数 * 名词解释： TMIC:血浆浓度高于细菌MIC值的时间 TMIC%：血浆浓度高于细菌MIC值的时间与该药给药间