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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Impact of Molecular Adsorbent Recirculating System Therapy on Piperacillin Concentration in Critically Ill Patients:
Clément Monet1,2, Lucas Allegre1, Alina Kozoriz1
1Department of Anesthesia and Intensive Care Unit, Regional University Hospital of Montpellier, St-Eloi Hospital, University of Montpellier, Montpellier, Cedex 5, France.
Objectives:
To assess the impact of Molecular Adsorbent Recirculating System (MARS) therapy on total plasma piperacillin concentrations in critically ill patients with acute liver failure or acute-on-chronic liver failure.
Design:
Retrospective, single-center observational cohort study.
Setting:
University ICU.
Patients:
Consecutive adult patients treated with MARS therapy and piperacillin-tazobactam between March 2023 and June 2025.
Interventions:
MARS therapy was delivered as 8-hour sessions for up to three consecutive days. Piperacillin-tazobactam was administered by continuous infusion following a loading dose.
Measurements And Main Results:
Venous blood samples were collected immediately before and after each MARS session. Total piperacillin concentrations were quantified using ultrahigh-performance liquid chromatography. The primary endpoint was the relative reduction in plasma piperacillin concentration induced by MARS therapy. Thirty patients (121 piperacillin measurements across 77 sessions) were analyzed. Seventy-three percent had cirrhosis (median Model for End-Stage Liver Disease Score 31 [23-38]). The mean relative reduction in piperacillin concentration per session was 34% (± 7.9%; p < 0.05). In univariable mixed-effects analysis, MARS session (β -47.49 mg/L; p < 0.001) and creatinine clearance (β -0.37 mg/L per mL/min; p < 0.001) were associated with lower concentrations. In multivariable modeling, higher creatinine clearance was independently associated with greater intra-session piperacillin loss (p < 0.001), whereas higher bilirubin levels were associated with reduced drug loss (p = 0.01). Overall, 31.6% of post-session concentrations were less than 80 mg/L, and 38% of patients had at least one concentration outside the predefined target range.
Conclusions:
MARS therapy was associated with a one-third reduction in total plasma piperacillin concentrations per session. These findings support systematic therapeutic drug monitoring and individualized antibiotic dose adjustment during MARS therapy.
Insights
Molecular Adsorbent Recirculating System (MARS) therapy significantly reduced piperacillin plasma concentrations by one-third per session. This highlights the need for drug monitoring and dose adjustments in critically ill patients undergoing MARS treatment.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Nephrology
Background:
- Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are critical conditions requiring intensive care.
- The Molecular Adsorbent Recirculating System (MARS) is used to support liver function in these patients.
- Antibiotic dosing requires careful consideration in critically ill patients with liver dysfunction.
Purpose of the Study:
- To evaluate the impact of MARS therapy on total plasma piperacillin concentrations.
- To determine the extent of piperacillin reduction during MARS sessions in critically ill patients.
Main Methods:
- A retrospective, single-center observational cohort study was conducted.
- Consecutive adult patients receiving MARS therapy and piperacillin-tazobactam were analyzed.
- Plasma piperacillin concentrations were measured before and after MARS sessions using ultrahigh-performance liquid chromatography.
Main Results:
- MARS therapy resulted in a mean reduction of 34% in plasma piperacillin concentrations per session.
- Higher creatinine clearance was associated with greater piperacillin loss, while higher bilirubin levels correlated with reduced drug loss.
- A significant proportion of patients had post-session piperacillin concentrations below the target range.
Conclusions:
- MARS therapy significantly reduces total plasma piperacillin concentrations.
- Systematic therapeutic drug monitoring and individualized antibiotic dosing are recommended during MARS therapy for critically ill patients.
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