In vitro elimination of antimicrobials during ADVanced Organ Support hemodialysis

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 a...

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Bibliographic Details
Published in:Frontiers in pharmacology 2024, Vol.15, p.1447511
Main Authors: König, Christina, Frey, Otto, Himmelein, Susanne, Mulack, Lisa, Brinkmann, Alexander, Perez Ruiz de Garibay, Aritz, Bingold, Tobias
Format: Article
Language:English
Subjects:
antibiotic
drug monitoring
extracorporeal organ support
pharmacokinetics
Pharmacology
renal replacement therapy
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Summary: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.
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2024.1447511