El-Najjar Nahed, Jantsch Jonathan, Gessner André
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Clin Chem Lab Med. 2017 Aug 28;55(9):1246-1261. doi: 10.1515/cclm-2016-0700.
Cancer remains a leading cause of mortality and morbidity worldwide. In addition to organ failure, the most frequent reasons for admission of cancer patients to intensive care units (ICU) are: infections and sepsis. As critically ill, the complexity of the health situation of cancer patients renders the standard antimicrobial regimen more complex and even inadequate which results in increased mortality rates. This is due to pathophysiological changes in the volume of distribution, increased clearance, as well as to organ dysfunction. While in the former cases a decrease in drug efficacy is observed, the hallmark of the latter one is overdosing leading to increased toxicity at the expense of efficacy. Furthermore, an additional risk factor is the potential drug-drug interaction between antibiotics and antineoplastic agents. Therefore, therapeutic drug monitoring (TDM) is a necessity to improve the clinical outcome of antimicrobial therapy in cancer patients. To be applied in routine analysis the method used for TDM should be cheap, fast and highly accurate/sensitive. Furthermore, as ICU patients are treated with a cocktail of antibiotics the method has to cover the simultaneous analysis of antibiotics used as a first/second line of treatment. The aim of the current review is to briefly survey the pitfalls in the current antimicrobial therapy and the central role of TDM in dose adjustment and drug-drug interaction's evaluation. A major section is dedicated to summarize the currently published analytical methods and to shed light on the difficulties and potential problems that can be encountered during method development.
癌症仍然是全球范围内导致死亡和发病的主要原因。除器官衰竭外，癌症患者入住重症监护病房（ICU）最常见的原因是感染和败血症。作为重症患者，癌症患者健康状况的复杂性使得标准抗菌方案更加复杂甚至不足，从而导致死亡率上升。这是由于分布容积的病理生理变化、清除率增加以及器官功能障碍所致。在前一种情况下，观察到药物疗效下降，而在后一种情况下，其特征是用药过量导致毒性增加而疗效受损。此外，另一个风险因素是抗生素与抗肿瘤药物之间潜在的药物相互作用。因此，治疗药物监测（TDM）对于改善癌症患者抗菌治疗的临床结果是必要的。为了应用于常规分析，用于TDM的方法应该便宜、快速且高度准确/灵敏。此外，由于ICU患者接受多种抗生素联合治疗，该方法必须涵盖对一线/二线治疗所用抗生素的同时分析。本综述的目的是简要概述当前抗菌治疗中的陷阱以及TDM在剂量调整和药物相互作用评估中的核心作用。一个主要部分致力于总结当前已发表的分析方法，并阐明在方法开发过程中可能遇到的困难和潜在问题。
