Mouton J W, Vinks A A
Department of Clinical Microbiology, Erasmus University Hospital Rotterdam, The Netherlands.
J Antimicrob Chemother. 1996 Jul;38(1):5-15. doi: 10.1093/jac/38.1.5.
The most important pharmacodynamic parameter for beta-lactam antibiotics has been shown to be the time above the MIC, which is used as an argument to administer beta-lactam antibiotics by continuous infusion. Studies in vitro and in laboratory animals comparing efficacy of continuous and intermittent infusion of beta-lactam antibiotics generally show continuous infusion to be more efficacious. While comparative trials in humans are scarce and a significant difference was only found in subgroup analysis in one study, several case-reports support the use of continuous infusion. Arguments in favour and against continuous infusion are discussed. Although dose-ranging studies have not yet been performed in humans, the results from in-vitro and in-vivo experiments indicate that 4 x MIC for the infecting bacterium would be the target concentration. Pharmacokinetic studies which have been performed in humans during continuous infusion show that serum concentrations can be predicted from total clearance or, using population pharmacokinetic modelling, the elimination rate constant as obtained during intermittent infusion. A nomogram is presented which allows calculation of the daily dose to obtain the target steady state blood concentrations suggested by the susceptibility of the infecting bacterium, usually 4 x MIC. For bacteria with a low MIC, the daily dose may be substantially lower than that used in conventional dosing regimens, while in infections which are difficult to treat as a result of more resistant bacteria, continuous infusion may be more effective than an equivalent bolus dose.
β-内酰胺类抗生素最重要的药效学参数已被证明是高于最低抑菌浓度（MIC）的时间，这被用作持续输注β-内酰胺类抗生素的一个依据。体外和实验动物研究比较β-内酰胺类抗生素持续输注和间歇输注的疗效，通常显示持续输注更有效。虽然人体中的比较试验很少，且仅在一项研究的亚组分析中发现了显著差异，但一些病例报告支持持续输注的使用。本文讨论了支持和反对持续输注的观点。尽管尚未在人体中进行剂量范围研究，但体外和体内实验结果表明，针对感染细菌的4倍MIC将是目标浓度。在持续输注期间对人体进行的药代动力学研究表明，血清浓度可以根据总清除率预测，或者使用群体药代动力学模型，根据间歇输注期间获得的消除速率常数进行预测。本文给出了一个列线图，可据此计算每日剂量，以获得由感染细菌的药敏结果建议的目标稳态血药浓度，通常为4倍MIC。对于MIC较低的细菌，每日剂量可能远低于传统给药方案中使用的剂量，而在因细菌耐药性更强而难以治疗的感染中，持续输注可能比等量的推注剂量更有效。
