Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia.
Lancet Infect Dis. 2014 Jun;14(6):498-509. doi: 10.1016/S1473-3099(14)70036-2. Epub 2014 Apr 24.
Infections in critically ill patients are associated with persistently poor clinical outcomes. These patients have severely altered and variable antibiotic pharmacokinetics and are infected by less susceptible pathogens. Antibiotic dosing that does not account for these features is likely to result in suboptimum outcomes. In this Review, we explore the challenges related to patients and pathogens that contribute to inadequate antibiotic dosing and discuss how to implement a process for individualised antibiotic therapy that increases the accuracy of dosing and optimises care for critically ill patients. To improve antibiotic dosing, any physiological changes in patients that could alter antibiotic concentrations should first be established; such changes include altered fluid status, changes in serum albumin concentrations and renal and hepatic function, and microvascular failure. Second, antibiotic susceptibility of pathogens should be confirmed with microbiological techniques. Data for bacterial susceptibility could then be combined with measured data for antibiotic concentrations (when available) in clinical dosing software, which uses pharmacokinetic/pharmacodynamic derived models from critically ill patients to predict accurately the dosing needs for individual patients. Individualisation of dosing could optimise antibiotic exposure and maximise effectiveness.
危重症患者的感染与持续不良的临床结局相关。这些患者的抗生素药代动力学发生了严重且多变的改变，并且受到了耐药性较低的病原体的感染。不考虑这些特征的抗生素剂量给药可能导致治疗效果不理想。在这篇综述中，我们探讨了与导致抗生素剂量不足的患者和病原体相关的挑战，并讨论了如何实施个体化抗生素治疗的流程，以提高剂量给药的准确性并优化危重症患者的治疗。为了改善抗生素剂量给药，首先应该确定任何可能改变抗生素浓度的患者生理变化；这些变化包括液体状态改变、血清白蛋白浓度变化、肾功能和肝功能改变以及微血管衰竭。其次，应使用微生物学技术确认病原体的抗生素敏感性。然后，可以将细菌药敏数据与临床剂量给药软件中（当有数据时）测量的抗生素浓度数据相结合，该软件使用从危重症患者中获得的药代动力学/药效学衍生模型来准确预测个体患者的剂量需求。个体化剂量给药可以优化抗生素暴露并最大限度地提高疗效。
