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

In this study, we evaluate the exposure and pharmacokinetic/pharmacodynamic target attainment of meropenem in critically ill patients. We conducted a prospective observational study in two Canadian intensive care units (ICUs) from January 2021 to December 2023. We included adult patients admitted in the ICU who received meropenem. On study days 1, 4, and 7 of antimicrobial therapy, three blood samples were collected: 1 h after end of infusion, 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 serum concentrations above minimum inhibitory concentrations of 2, 4, and 8 mg/L at midpoint and at trough. We enrolled 28 patients and analyzed 167 meropenem concentrations. We observed large interindividual variability, but intraindividual variability was low. At midpoint, 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 increased renal function. The majority of ICU patients who received meropenem were underexposed for a target concentration of 8 mg/L, with notable interindividual variability but low intraindividual variability. More aggressive dosing administration protocols are warranted to facilitate target attainment of meropenem.