Abstract：
Antimicrobial prescription in critically ill patients represents a complex challenge due to the difficult balance between infection treatment and toxicity prevention. Underexposure to antibiotics and therapeutic failure or, conversely, drug overexposure and toxicity may both contribute to a worse prognosis. Moreover, changes in organ perfusion and dysfunction often lead to unpredictable pharmacokinetics. In critically ill patients, interindividual and intraindividual real-time β-lactam antibiotic dose adjustments according to the patient\'s condition are critical. The continuous infusion of β-lactams and the therapeutic monitoring of their concentration have both been proposed to improve their efficacy, but strong data to support their use are still lacking. The knowledge of the pharmacokinetic/pharmacodynamic targets is poor and is mostly based on observational data. In patients with renal or hepatic failure, selecting the right dose is even more tricky due to changes in drug clearance, distribution, and the use of extracorporeal circuits. Intermittent usage may further increase the dosing conundrum. Recent data have emerged linking overexposure to β-lactams to central nervous system toxicity, mitochondrial recovery delay, and microbiome changes. In addition, it is well recognized that β-lactam exposure facilitates resistance selection and that correct dosing can help to overcome it. In this review, we discuss recent data regarding real-time β-lactam antibiotic dose adjustment, options in special populations, and the impacts on mitochondria and the microbiome.
摘要：
由于感染治疗和毒性预防之间的困难平衡，重症患者的抗菌处方代表了一个复杂的挑战。缺乏抗生素和治疗失败或，相反,药物过度暴露和毒性均可能导致预后较差。此外，器官灌注和功能障碍的变化通常会导致无法预测的药代动力学。在危重病人,个体间和个体间根据患者病情实时调整β-内酰胺抗生素剂量至关重要.β-内酰胺的连续输注和对其浓度的治疗监测都被提出来提高其疗效，但仍然缺乏强有力的数据来支持它们的使用。药代动力学/药效学目标的知识很差，并且主要基于观察数据。在肾功能衰竭或肝功能衰竭的患者中，由于药物清除率的变化，选择正确的剂量更加棘手，分布，以及体外回路的使用。间歇使用可能会进一步增加剂量难题。最近的数据已经出现，过度接触β-内酰胺与中枢神经系统毒性有关，线粒体恢复延迟，和微生物组的变化。此外,众所周知,β-内酰胺暴露有助于抗性选择,正确的给药有助于克服抗性选择.在这次审查中,我们讨论有关实时β-内酰胺抗生素剂量调整的最新数据，特殊人群的选择，以及对线粒体和微生物组的影响。
