Moser Claus, Lerche Christian Johann, Thomsen Kim, Hartvig Tom, Schierbeck Jens, Jensen Peter Østrup, Ciofu Oana, Høiby Niels
Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
APMIS. 2019 May;127(5):361-371. doi: 10.1111/apm.12951.
The discovery of antibiotic drugs is considered one of the previous century's most important medical discoveries (Medicine's 10 greatest discoveries. New Haven, CT: Yale University Press, 1998: 263). Appropriate use of antibiotics saves millions of lives each year and prevents infectious complications for numerous people. Still, infections kill unacceptable many people around the world, even in developed countries with easy access to most antibiotic drugs. Optimal use of antibiotics is dependent on the identification of primary and secondary focus, and knowledge on which pathogens to expect in a specific infectious syndrome and information on general patterns of regional antibiotic resistance. Furthermore, sampling for microbiological analysis, knowledge of patient immune status and organ functions, travel history, pharmacokinetics and -dynamics of the different antibiotics and possible biofilm formation are among several factors involved in antibiotic therapy of infectious diseases. The present review aims at describing important considerations when using antibacterial antibiotics and to describe how this is becoming substantially more personalized. The parameters relevant in considering the optimal use of antibiotics to treat infections are shown in Fig. 1 - leading to the most relevant antibiotic therapy for that specific patient. To illustrate this subject, the present review's focus will be on challenges with optimal dosing of antibiotics and risks of underdosing. Especially, in cases highly challenging for achieving the aimed antibiotic effect against bacterial infections - this includes augmented renal clearance (ARC) in sepsis, dosing challenges of antibiotics in pregnancy and against biofilm infections.
抗生素药物的发现被认为是上个世纪最重要的医学发现之一（《医学的十大发现》。康涅狄格州纽黑文：耶鲁大学出版社，1998年：第263页）。合理使用抗生素每年挽救数百万人的生命，并预防无数人的感染并发症。然而，即使在大多数抗生素药物容易获取的发达国家，感染仍在全球造成了多得令人无法接受的死亡人数。抗生素的最佳使用取决于确定主要和次要病灶，了解特定感染综合征中可能出现的病原体，以及区域抗生素耐药性的一般模式信息。此外，进行微生物分析的采样、患者免疫状态和器官功能的知识、旅行史、不同抗生素的药代动力学和药效学以及可能的生物膜形成等都是传染病抗生素治疗中涉及的几个因素。本综述旨在描述使用抗菌抗生素时的重要注意事项，并描述其如何变得更加个性化。图1显示了在考虑最佳使用抗生素治疗感染时相关的参数——从而为该特定患者制定最相关的抗生素治疗方案。为了说明这个主题，本综述将重点关注抗生素最佳给药的挑战和给药不足的风险。特别是在实现针对细菌感染的目标抗生素效果极具挑战性的情况下——这包括脓毒症中的增强肾清除率（ARC）、孕期抗生素给药挑战以及针对生物膜感染的给药挑战。
