Relevance of pharmacokinetics and pharmacodynamics in the selection of antibiotics for respiratory tract infections.
Relevance of pharmacokinetics and pharmacodynamics in the selection of antibiotics for respiratory tract infections.
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发表时间：
1997
影响因子：
1.8
通讯作者：
G. Drusano;W. Craig
中科院分区：
文献类型：
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作者：
G. Drusano;W. Craig
将抗生素在体内的浓度与其影响联系起来的药效学原理直到最近才被阐明。目前已被临床研究证实的动物研究表明，对于β-内酰胺类抗生素，血清浓度超过病原体最小抑菌浓度(MIC)值的时间是预测成功的临床和细菌学结果的关键参数。大环内酯类药物的情况不太清楚；超过MIC的时间是动态变量，可能与红霉素和克拉霉素的疗效最密切相关，但对于阿奇霉素，它似乎是血药浓度-时间曲线下的面积：MIC比率。不同的抗生素适用于社区获得性呼吸道感染的主要病原菌。对于肺炎链球菌，阿莫西林/克拉维酸在不同剂量方案下是有效的，其MIC90以上的时间约为40%，而口服头孢菌素和大环内酯类药物的血清浓度不超过MIC90。对于流感嗜血杆菌，阿莫西林/克拉维酸和头孢克辛是合适的抗生素，而大环内酯类抗生素的活性有限。除阿莫西林外，本文综述的所有β-内酰胺类和大环内酯类抗生素对卡他莫拉菌的效果均好于对其他两种主要的社区获得性呼吸道病原体的效果，并且有广泛的适当药物选择。了解不同抗生素的药效学相关变量可以优化给药方案，并对相同变量的不同药剂进行直接比较。
The pharmacodynamic principles that link the concentrations of antibiotics within body systems and their effects have been elucidated only recently. Animal work, now confirmed by clinical studies, has shown that for beta-lactam antibiotics, the time that the serum concentration exceeds the minimum inhibitory concentration (MIC) value of the pathogen is a key parameter in predicting a successful clinical and bacteriological outcome. The situation with the macrolides is less clear; time above MIC is the dynamic variable likely to be most closely linked to efficacy for erythromycin and clarithromycin but for azithromycin it appears to be the area under the plasma concentration-time curve: MIC ratio. Different antibiotics are appropriate for the key pathogens in community-acquired respiratory tract infections. For Streptococcus pneumoniae, amoxycillin/clavulanate is effective with varying dosage regimens providing around 40% time above the MIC90, in contrast to the oral cephalosporins and the macrolides for which serum concentrations do not exceed the MIC90. For Haemophilus influenzae, amoxycillin/clavulanate and cefixime are suitable antibiotics whereas macrolides have limited activity. With the exception of amoxycillin, all the beta-lactam and macrolide antibiotics reviewed here perform better against Moraxella catarrhalis than against the other two principal community-acquired respiratory tract pathogens and there is a wide choice of appropriate agents. Knowledge of the pharmacodynamically-linked variables for different antibiotics allows optimization of dosage regimens and direct comparisons across agents for the same variables.