König Christina, Frey Otto, Himmelein Susanne, Mulack Lisa, Brinkmann Alexander, Perez Ruiz de Garibay Aritz, Bingold Tobias
Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, United States.
Front Pharmacol. 2024 Dec 16;15:1447511. doi: 10.3389/fphar.2024.1447511. eCollection 2024.
Acute kidney injury (AKI) requiring continuous renal replacement therapy is common in critically ill patients. The ADVanced Organ Support (ADVOS) system is a novel hemodialysis machine that uses albumin enriched dialysate which allows the removal of protein-bound toxins and drugs. To date, data on antimicrobial removal under ADVOS has not yet been reported.
An study was conducted using whole porcine blood and continuous infusions of different antimicrobial agents to investigate the effect of ADVOS on drug exposure. Drugs with varying protein binding, molecular weights and renal clearances, anidulafungin, cefotaxime, daptomycin, fluconazole, ganciclovir, linezolid, meropenem and piperacillin were studied.
All studied drugs were removed during the ADVOS experiment. Clearance under ADVOS (CL) for low protein-bound drugs, such as cefotaxime, fluconazole, ganciclovir, linezolid, meropenem and piperacillin ranged from 2.74 to 3.4 L/h at a blood flow of 100 mL/min. With a doubling of flow rate CL for these drugs increased. Although efficiently removed, this effect was not seen for CL in high protein-bound substances such as daptomycin (1.36 L/h) and anidulafungin (0.84 L/h).
The ADVOS system effectively removed protein-bound and unbound antimicrobials to a significant extent indicating that dose adjustments are required. Further, clinical studies are necessary to comprehensively assess the impact of ADVOS on antimicrobial drug removal. Until clinical data are available, therapeutic drug monitoring should guide antimicrobial dosing under ADVOS.
需要持续肾脏替代治疗的急性肾损伤（AKI）在重症患者中很常见。先进器官支持（ADVOS）系统是一种新型血液透析机，它使用富含白蛋白的透析液，能够清除与蛋白质结合的毒素和药物。迄今为止，尚未有关于ADVOS对抗菌药物清除作用的数据报道。
使用全猪血并持续输注不同抗菌药物进行一项研究，以调查ADVOS对药物暴露的影响。研究了具有不同蛋白质结合率、分子量和肾脏清除率的药物，包括阿尼芬净、头孢噻肟、达托霉素、氟康唑、更昔洛韦、利奈唑胺、美罗培南和哌拉西林。
在ADVOS实验过程中，所有研究的药物均被清除。在血流速度为100 mL/min时，ADVOS（CL）对低蛋白结合药物（如头孢噻肟、氟康唑、更昔洛韦、利奈唑胺、美罗培南和哌拉西林）的清除率范围为2.74至3.4 L/h。随着流速加倍，这些药物的CL增加。尽管能有效清除，但对于高蛋白结合物质（如达托霉素（1.36 L/h）和阿尼芬净（0.84 L/h））的CL未观察到这种影响。
ADVOS系统在很大程度上有效清除了与蛋白质结合和未结合的抗菌药物，这表明需要进行剂量调整。此外，有必要进行临床研究以全面评估ADVOS对抗菌药物清除的影响。在获得临床数据之前，治疗药物监测应指导ADVOS下的抗菌药物给药。
