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. 2025 Oct;53(5):2103-2110.
doi: 10.1007/s15010-025-02554-4. Epub 2025 May 21.

Meropenem plasma concentrations in critically ill patients treated with the novel multi organ replacement therapy ADVOS

David Totschnig  1 , Theresa Mader  1 , Thomas Stimpfl  2 , Klaus Breinbauer  3 , Cristina Groza  3 , David Stücklschwaiger  3 , Stephanie Neuhold  1 , Emanuela Friese  1 , Johannes Holbik  1 , Martina Delivuk  1 , Tom Ripplinger  1 , Marcell Leber  1 , Clemens Ott  1 , Wolfgang Hoepler  1 , Aritz Perez Ruiz de Garibay  4 , Christoph Wenisch  1 , Otto Frey  5 , Alexander Zoufaly  3 , Marianna Traugott  6
Affiliations

Meropenem plasma concentrations in critically ill patients treated with the novel multi organ replacement therapy ADVOS

David Totschnig et al. Infection. 2025 Oct.

Abstract

Background: Optimal dosing of antibiotics in critically ill patients treated with the novel multi organ replacement therapy ADVOS (ADVanced Organ Support) based on albumin dialysis is unclear. This study aims to provide real life data on meropenem plasma concentrations after prolonged infusion in patients treated with ADVOS and a critically ill control group with and without continuous veno-venous hemodiafiltration (CVVHDF).

Methods: We retrospectively analyzed plasma concentrations of meropenem obtained as part of our standard of care therapeutic drug monitoring in the intensive care unit. Meropenem was administered as a prolonged infusion over 3 h. We measured peak and trough levels, pre-and post-filter levels of meropenem using high performance liquid chromatography. We calculated the meropenem clearance and compared the measured clearance with predicted clearance based on creatinine, calculated by the MeroEasy tool.

Results: In total, 159 measurements across 16 patients were analyzed. Meropenem trough concentrations were highest in the CVVHDF group with a median of 23.5 mg/L, followed by the ADVOS (median 9.3 mg/L) and control group (median 7.6 mg/L). No trough levels were below the lower limit of 2 mg/L in the CVVHDF and ADVOS groups. Meropenem machine clearance by CVVHDF was calculated to be 1.8 (± 0.5) L/h and 3.5 (± 1) L/h for ADVOS.

Conclusion: Our results suggest that ADVOS treatment in critically ill patients receiving a high dose meropenem regimen (2 g IV q8h) does not lead to underdosing. Some trough values were even within potentially toxic levels, especially in the CVVHDF group, highlighting the importance of therapeutic drug monitoring.

Keywords: ADVOS; Calculated vs. measured values; Meropenem; Multi organ replacement therapy; TDM; Therapeutic drug monitoring.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. AP was employed by ADVITOS GmbH at the time of writing this manuscript. DT, SN and OF received lecture fees by ADVITOS GmbH. Ethical approval and consent to participate: Ethics approval was obtained (EK 24–066-VK), consent to participate is not applicable since we only performed a retrospective data analysis.

Figures

Graph 1
Graph 1
Analysis of meropenem trough levels, A Min to max Boxplot of trough levels in the control, CVVHDF- and ADVOS group. B Scatterplot of all trough levels. The green area highlights the target range of trough levels of 2 – 8 mg/L (20), the red line shows nephrotoxic levels of 44 mg/L (6). The percentages at the top show the fraction of values in the target range area. CVVHDF continuous veno-venous hemodiafiltration, ADVOS ADVanced Organ Support
Graph 2
Graph 2
Analysis of meropenem clearance, A Bar graph of calculated meropenem clearance (CLpatient) based on trough levels. B Bar graph of calculated machine clearance (CLADVOS and CLCVVHDF), based on measured pre- and post-dialyzer levels. C Bar graph showing the fraction of total clearance achieved by the respective machine clearance. Striped areas represent the machine clearance. Estimated values by subtracting the machine clearance (CLADVOS and CLCVVHDF), (B) from the total clearance (CLpatient) (A). CVVHDF continuous veno-venous hemodiafiltration; ADVOS ADVanced Organ Support
Graph 3
Graph 3
Analysis of creatinine as a surrogate marker, A Bar graph of calculated meropenem clearance, based on trough levels (CLpatient). B Bar graph of estimated meropenem clearance, based on creatinine values (CLestimated). C Correlation plot of the measured meropenem clearance (A) and estimated meropenem clearance (B). CVVHDF continuous veno-venous hemodiafiltration, ADVOS ADVanced Organ Support
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