Heavner Mojdeh S, Claeys Kimberly C, Masich Anne M, Gonzales Jeffrey P
Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, Maryland, USA.
Curr Infect Dis Rep. 2018 Apr 5;20(5):10. doi: 10.1007/s11908-018-0614-0.
We provide an overview of antimicrobials that are considered last resort for the treatment of resistant gram-negative infections in adult critically ill patients. The role in therapy, pharmacodynamic (PD) goals, and pharmacokinetic (PK) changes in critical illness for aminoglycosides, polymyxins, tigecycline, fosfomycin, and fluoroquinolones are summarized.
Altered PK in septic patients in the intensive care unit (ICU) is observed with many of our agents of last resort. Based on the available literature, dosage adjustments may be required to optimize PK parameters and meet PD targets for most effective bacterial killing. Data is limited, studies are conducted in heterogeneous patient populations, and conclusions are frequently conflicting. Strategic dosing regimens such as high-dose extended interval dosing of aminoglycosides or loading doses with colistin and polymyxin B are examples of ways to optimize antibiotic PK in critically ill patients. Benefits of these strategies must be balanced with risks of increased toxicity. Patients with resistant gram-negative infections may present with septic shock in the ICU. Sepsis can significantly alter the PK of antibiotics and require dosage adjustments to attain optimal drug levels. An understanding of PK and PD properties of these agents of last resort will help to maximize therapeutic efficacy while minimizing toxic effects.
我们概述了在成年重症患者中被视为治疗耐药革兰氏阴性菌感染的最后手段的抗菌药物。总结了氨基糖苷类、多粘菌素、替加环素、磷霉素和氟喹诺酮类药物在治疗中的作用、药效学（PD）目标以及危重病中的药代动力学（PK）变化。
我们的许多最后手段药物在重症监护病房（ICU）的脓毒症患者中观察到PK改变。根据现有文献资料，可能需要调整剂量以优化PK参数并达到最有效杀灭细菌的PD目标。数据有限，研究在异质性患者群体中进行，结论常常相互矛盾。氨基糖苷类的高剂量延长给药间隔方案或多粘菌素和多粘菌素B的负荷剂量等策略性给药方案是优化重症患者抗生素PK的方法示例。这些策略的益处必须与毒性增加的风险相平衡。耐药革兰氏阴性菌感染患者在ICU中可能出现脓毒症休克。脓毒症可显著改变抗生素的PK，需要调整剂量以达到最佳药物水平。了解这些最后手段药物的PK和PD特性将有助于在使毒性作用最小化的同时最大化治疗效果。
