Exposure levels and target attainment of meropenem in adult patients
admitted to the intensive care unit: a prospective observational study
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.