Drusano G L, Craig W A
Department of Medicine, Albany Medical College, New York 12208, USA.
J Chemother. 1997 May;9 Suppl 3:38-44.
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.
将体内各系统抗生素浓度与其作用联系起来的药效学原理直到最近才得以阐明。动物实验结果现已得到临床研究的证实，结果表明，对于β-内酰胺类抗生素而言，血清浓度超过病原体最低抑菌浓度（MIC）值的时间是预测临床和细菌学治疗成功的关键参数。大环内酯类抗生素的情况则不太明确；高于MIC的时间是可能与红霉素和克拉霉素疗效最密切相关的动态变量，但对于阿奇霉素而言，似乎是血浆浓度-时间曲线下面积与MIC的比值。不同的抗生素适用于社区获得性呼吸道感染的主要病原体。对于肺炎链球菌，阿莫西林/克拉维酸有效，不同的给药方案可使血清浓度高于MIC90的时间约为40%，相比之下，口服头孢菌素和大环内酯类抗生素的血清浓度不会超过MIC90。对于流感嗜血杆菌，阿莫西林/克拉维酸和头孢克肟是合适的抗生素，而大环内酯类抗生素的活性有限。除阿莫西林外，本文所综述的所有β-内酰胺类和大环内酯类抗生素对卡他莫拉菌的抗菌效果均优于对其他两种主要的社区获得性呼吸道病原体，且有多种合适的药物可供选择。了解不同抗生素的药效学相关变量有助于优化给药方案，并对同一变量的不同药物进行直接比较。
