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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Translational Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1447511

In vitro elimination of antimicrobials during Advanced Organ Support (ADVOS) hemodialysis

Provisionally accepted
Christina König Christina König 1,2*Otto Frey Otto Frey 3*Susanne Himmelein Susanne Himmelein 4*Lisa Mulack Lisa Mulack 1*Alexander Brinkmann Alexander Brinkmann 3*Aritz Perez Ruiz de Garibay Aritz Perez Ruiz de Garibay 4Tobias Bingold Tobias Bingold 4*
  • 1 Department of Intensive Care Medicine, Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 2 Center of Anti-Infective Research and Development, Hartford Hospital, Hartford, United States
  • 3 Department of Pharmacy, General Hospital of Heidenheim, Heidenheim, Germany
  • 4 Other, Munich, Germany

The final, formatted version of the article will be published soon.

    Background: 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 in-vitro 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.Results: All studied drugs were removed during the in vitro ADVOS experiment. Clearance under ADVOS (CLADVOS) 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 CLADVOS 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.

    Keywords: Extracorporeal organ support, pharmacokinetics, antibiotic, Renal Replacement Therapy, Drug Monitoring

    Received: 11 Jun 2024; Accepted: 22 Nov 2024.

    Copyright: © 2024 König, Frey, Himmelein, Mulack, Brinkmann, Perez Ruiz de Garibay and Bingold. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Christina König, Department of Intensive Care Medicine, Medical Center Hamburg-Eppendorf, Hamburg, Germany
    Otto Frey, Department of Pharmacy, General Hospital of Heidenheim, Heidenheim, Germany
    Susanne Himmelein, Other, Munich, Germany
    Lisa Mulack, Department of Intensive Care Medicine, Medical Center Hamburg-Eppendorf, Hamburg, Germany
    Alexander Brinkmann, Department of Pharmacy, General Hospital of Heidenheim, Heidenheim, Germany
    Tobias Bingold, Other, Munich, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.