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Exposure levels and target attainment of meropenem in adult patients admitted to the intensive care unit: a prospective observational study
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  • Ibrahim El-Haffaf,
  • Amélie Marsot,
  • Alice Paillault,
  • Viviane Giang,
  • Virginie Williams,
  • Marc-André Smith,
  • Martin Albert,
  • Michaël Chassé,
  • David Williamson
Ibrahim El-Haffaf
Université de Montréal Faculté de Pharmacie

Corresponding Author:ibrahim.el-haffaf@umontreal.ca

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Amélie Marsot
Université de Montréal
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Alice Paillault
Hôpital du Sacré-Coeur de Montréal Centre de Recherche
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Viviane Giang
Université de Montréal Faculté de Pharmacie
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Virginie Williams
Hôpital du Sacré-Coeur de Montréal Centre de Recherche
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Marc-André Smith
Hôpital du Sacré-Coeur de Montréal Centre de Recherche
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Martin Albert
Hôpital du Sacré-Coeur de Montréal Centre de Recherche
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Michaël Chassé
Centre Hospitalier de l'Universite de Montreal
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David Williamson
Hôpital du Sacré-Coeur de Montréal Centre de Recherche
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Abstract

Aim: Patients hospitalized in the intensive care units (ICU) with serious infections require rapid and optimal broad-spectrum antibiotic regimens to ensure favorable outcomes. The purpose of this study was to evaluate the exposure and pharmacokinetic/pharmacodynamic target attainment of meropenem in critically ill patients. Methods: We conducted a prospective observational study in two Canadian intensive care units (ICU) from January 2021 to December 2023. We included adult patients admitted in the ICU who received meropenem. On study day 1, 4 and 7 of antimicrobial therapy, three blood samples were collected: 1 h after meropenem dose administration, at the middle and at the end of the dosing interval. Samples were analyzed by ultra-high performance liquid chromatography with diode array detector. The pharmacokinetic profile of meropenem was evaluated, as well as the attainment of plasma concentrations above minimum inhibitory concentrations of 2, 4 and 8 mg/L at mid-point and at trough. Results: We enrolled twenty-eight patients and analyzed 167 meropenem concentrations. We observed large interindividual variability, with up to a 58-fold difference, but intra-patient variability was low. At mid-point, 52% of concentrations were below the target concentration of 8 mg/L, while this proportion increased to 73% for trough concentrations. Patients who failed to reach therapeutic concentrations all had normal to augmented renal clearance. Conclusion: The majority of ICU patients who received meropenem were underexposed for a target concentration of 8 mg/L, with significant interindividual variability. A more personalized approach such as TDM may help achieve optimal target concentration and potentially improve clinical outcomes.