Exposure levels and target attainment of meropenem in adult patients admitted to the intensive care unit: a prospective observational study
Bibliographic record
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".