Jamal Janattul-Ain, Mueller Bruce A, Choi Gordon Y S, Lipman Jeffrey, Roberts Jason A
Burns Trauma and Critical Care Research Centre, The University of Queensland, Herston, QLD, Australia.
Department of Clinical Social and Administrative Sciences, College of Pharmacy University of MI, Ann Arbor, USA.
Diagn Microbiol Infect Dis. 2015 May;82(1):92-103. doi: 10.1016/j.diagmicrobio.2015.01.013. Epub 2015 Feb 2.
Determining appropriate antibiotic dosing for critically ill patients receiving renal replacement therapy (RRT) is complex. Worldwide unstandardized and heterogeneous prescribing of RRT as well as altered patient physiology and pathogen susceptibility all cause drug disposition to be much different to that seen in non-critically ill patients. Significant changes to pharmacokinetic parameters, including volume of distribution and clearance, could be expected, in particular, for antibiotics that are hydrophilic with low plasma protein binding and that are usually primarily eliminated by the renal system. Antibiotic clearance is likely to be significantly increased when higher RRT intensities are used. The combined effect of these factors that alter antibiotic disposition is that non-standard dosing strategies should be considered to achieve therapeutic exposure. In particular, an aggressive early approach to dosing should be considered and this may include administration of a 'loading dose', to rapidly achieve therapeutic concentrations and maximally reduce the inoculum of the pathogen. This approach is particularly important given the pharmacokinetic changes in the critically ill as well as the increased likelihood of less susceptible pathogens. Dose individualization that applies knowledge of the RRT and patient factors causing altered pharmacokinetics remains the key approach for ensuring effective antibiotic therapy for these patients. Where possible, therapeutic drug monitoring should also be used to ensure more accurate therapy. A lack of pharmacokinetic data for antibiotics during the prolonged intermittent RRT and intermittent hemodialysis currently limits evidence-based antibiotic dose recommendations for these patients.
为接受肾脏替代治疗（RRT）的重症患者确定合适的抗生素剂量很复杂。全球范围内RRT的处方不规范且存在差异，以及患者生理状态改变和病原体易感性变化，都导致药物处置与非重症患者有很大不同。预计药代动力学参数会发生显著变化，包括分布容积和清除率，特别是对于那些亲水性强、血浆蛋白结合率低且通常主要通过肾脏系统消除的抗生素。当采用更高的RRT强度时，抗生素清除率可能会显著增加。这些改变抗生素处置的因素共同作用的结果是，应考虑采用非标准的给药策略来实现治疗性暴露。特别是，应考虑采取积极的早期给药方法，这可能包括给予“负荷剂量”，以迅速达到治疗浓度并最大程度减少病原体接种量。鉴于重症患者的药代动力学变化以及不太敏感病原体的可能性增加，这种方法尤为重要。应用RRT知识和导致药代动力学改变的患者因素进行剂量个体化，仍然是确保这些患者有效抗生素治疗的关键方法。在可能的情况下，还应使用治疗药物监测来确保更准确的治疗。目前，在延长的间歇性RRT和间歇性血液透析期间缺乏抗生素的药代动力学数据，限制了为这些患者提供基于证据的抗生素剂量建议。
