Lipman J
Intensive Care Unit, Royal Brisbane Hospital and University of Queensland, Brisbane, Queensland.
Crit Care Resusc. 2000 Dec;2(4):282-9.
To review the recent pharmacokinetic and pharmacodynamic reports of some of the commonly used antibiotics in critically ill patients and recommend alterations in their administration to improve their efficacy.
Relevant articles and published reviews on aminoglycoside, third and fourth generation cephalosporins, vancomycin and ciprofloxacin dosing in critically ill patients.
Antibiotic regimens are derived from non-critically ill volunteers. To optimise antibiotic administration in the intensive care unit, the different 'kill-characteristics' of the antibiotic classes and the altered drug pharmacokinetics in critically ill patients should be considered together to re-evaluate the currently recommended regimens. Aminoglycosides require high peak levels to be most effective, hence large single daily doses are important. With the increased clearances in the critically ill patient, particularly those who have normal renal function, a more frequent administration than single daily dosing may be optimal (e.g. 18-hourly). Increased clearances of beta-lactam antibiotics result in low troughs causing a reduced duration of antibiotic levels above the minimum inhibitory concentration (i.e. the suggested pharmacological target for these drugs). In critically ill patients frequent dosing or even continuous infusions of the beta-lactam antibiotics may increase their effectiveness by maintaining blood levels above the minimum inhibitory concentration (MIC) for longer periods. Vancomycin has a high volume of distribution in the critically ill patient, thus the currently recommended maximum daily dose may lead to inadequate serum levels. Suggested targets for quinolone therapy involve more than just high peak levels. A ratio of Area Under (serum) Concentration (AUC) time curve to MIC of >125 has been shown to correlate with better clinical outcomes. Ciprofloxacin when given intravenously at 400 mg 8-hourly should achieve this, which is a regimen that has been shown to be safe.
Applying pharmacokinetic and pharmacodynamic principles to critically ill patients will lead to better antibiotic use and hopefully a better outcome.
回顾近期关于危重症患者常用抗生素的药代动力学和药效学报告，并建议调整其给药方式以提高疗效。
有关危重症患者氨基糖苷类、第三代和第四代头孢菌素、万古霉素及环丙沙星给药的相关文章和已发表的综述。
抗生素治疗方案源自非危重症志愿者。为优化重症监护病房的抗生素给药，应综合考虑不同抗生素类别的“杀菌特性”以及危重症患者改变的药物药代动力学，以重新评估当前推荐的治疗方案。氨基糖苷类抗生素需要高血药峰浓度才能达到最佳疗效，因此每日单次大剂量给药很重要。危重症患者，尤其是肾功能正常者，清除率增加，每日单次给药可能并非最佳，更频繁给药（如每18小时一次）可能更优。β-内酰胺类抗生素清除率增加导致谷浓度降低，使抗生素浓度高于最低抑菌浓度的持续时间缩短（即这些药物的建议药理学靶点）。在危重症患者中，频繁给药甚至持续输注β-内酰胺类抗生素可能通过使血药浓度在更长时间内维持在最低抑菌浓度（MIC）以上而提高其疗效。万古霉素在危重症患者中的分布容积很大，因此目前推荐的最大日剂量可能导致血清浓度不足。喹诺酮类治疗的建议靶点不仅仅是高血药峰浓度。（血清）浓度-时间曲线下面积（AUC）与MIC之比>125已被证明与更好的临床结局相关。环丙沙星静脉滴注400mg，每8小时一次应能达到这一目标，该方案已被证明是安全的。
将药代动力学和药效学原理应用于危重症患者将导致更好地使用抗生素，并有望带来更好的治疗结果。
