Brinkmann A, Röhr A C, Köberer A, Fuchs T, Preisenberger J, Krüger W A, Frey O R
Klinik für Anästhesie, operative Intensivmedizin und spezielle Schmerztherapie, Klinikum Heidenheim, Schlosshaustraße 100, 89522, Heidenheim, Deutschland.
Apotheke, Klinikum Heidenheim, Heidenheim, Deutschland.
Med Klin Intensivmed Notfmed. 2018 Mar;113(2):82-93. doi: 10.1007/s00063-016-0213-5. Epub 2016 Sep 13.
Pharmacokinetic variability of anti-infective drugs due to pathophysiological changes by severe sepsis and septic shock is a well-known problem for critically ill patients resulting in suboptimal serum and most likely tissue concentrations of these agents.To cover a wide range of potential pathogens, high concentrations of broad spectrum anti-infectives have to reach the site of infection. Microbiological susceptibility testing (susceptible, intermediate, resistant) don't take the pharmacokinetic variability into account and are based on data generated by non-critically ill patients. But inter-patient variability in distribution and elimination of anti-infective drugs in ICU patients is extremely high and also highly unpredictable. Drug clearance of mainly renally eliminated drugs and thus the required dose can differ up to 10-fold due to the variability in renal function in patients with severe infections. To assure a timely and adequate anti-infective regime, individual dosing and therapeutic drug monitoring (TDM) seem to be appropriate tools in the setting of pathophysiological changes in pharmacokinetics (PK) and pharmakodynamics (PD) due to severe sepsis. In the case of known minimal inhibitory concentration, PK/PD indices (time or peak concentration dependent activity) and measured serum level can provide an optimal target concentration for the individual drug and patient.Modern anti-infective management for ICU patients includes more than the choice of drug and prompt application. Individual dosing, optimized prolonged infusion time and TDM give way to new and promising opportunities in infection control.
由于严重脓毒症和感染性休克导致的病理生理变化，抗感染药物的药代动力学变异性是重症患者中一个众所周知的问题，会导致这些药物的血清浓度不理想，且很可能组织浓度也不理想。为了覆盖广泛的潜在病原体，必须使高浓度的广谱抗感染药物到达感染部位。微生物药敏试验（敏感、中介、耐药）未考虑药代动力学变异性，且基于非重症患者产生的数据。但重症监护病房（ICU）患者中抗感染药物分布和消除的个体间变异性极高，且极难预测。由于严重感染患者肾功能的变异性，主要经肾排泄药物的药物清除率以及所需剂量可能相差高达10倍。为确保及时且充分的抗感染治疗方案，在严重脓毒症导致药代动力学（PK）和药效学（PD）发生病理生理变化的情况下，个体化给药和治疗药物监测（TDM）似乎是合适的工具。在已知最低抑菌浓度的情况下，PK/PD指数（时间或峰浓度依赖性活性）和测得的血清水平可为个体药物和患者提供最佳目标浓度。ICU患者的现代抗感染管理不仅仅包括药物选择和及时应用。个体化给药、优化的延长输注时间和TDM为感染控制带来了新的且有前景的机会。
