AUTHOR=König Christina , Frey Otto , Himmelein Susanne , Mulack Lisa , Brinkmann Alexander , Perez Ruiz de Garibay Aritz , Bingold Tobias TITLE=In vitro elimination of antimicrobials during ADVanced Organ Support hemodialysis JOURNAL=Frontiers in Pharmacology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1447511 DOI=10.3389/fphar.2024.1447511 ISSN=1663-9812 ABSTRACT=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.

Methods

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).

Conclusion

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.