Evidence map›Paper›PMID 34403127›Full record

ArticleEuropean journal of drug metabolism and pharmacokinetics2021

Population Pharmacokinetics and Pharmacodynamics of Meropenem in Critically Ill Patients: How to Achieve Best Dosage Regimen According to the Clinical Situation.

Amaury O'Jeanson, Romaric Larcher, Cosette Le Souder, Nassim Djebli, Sonia Khier

Registry-linked trialOpen access · greenAbstract read
PubMed Publisher
In one paragraph

Article in European journal of drug metabolism and pharmacokinetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07681544 (Meropenem Dosing in Critically Ill Patients), which is not on this map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.8field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07681544 nacompletednot on this mapstarted 2024, after this paper: background citation

Meropenem Dosing in Critically Ill Patients: Early Evaluation of Plasma Concentrations and Minimum Inhibitory Concentration

TypeinterventionalSponsorHospital Italiano de Buenos AiresRan2024 to 2025Enrolled26ConditionsEmpirical Antimicrobial Therapy, Critically Ill, Meropenem, Pharmacokinetics and PharmacodynamicsArmsBlood extraction
3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 17 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Amaury O'JeansonPharmacokinetic Modeling Department, UFR Pharmacie, Montpellier University (School of Pharmacy), 15 Avenue Charles Flahault, 34000, Montpellier, France.
Romaric LarcherIntensive Care Unit Department, Montpellier University Hospital (CHU Lapeyronie), Montpellier, France.
Cosette Le SouderToxicology and Target Drug Monitoring Department, Montpellier University Hospital (CHU Lapeyronie), Montpellier, France.
Nassim DjebliRoche Innovation Center Basel, Roche Pharma Research and Early Development, Basel, Switzerland.
Sonia KhierPharmacokinetic Modeling Department, UFR Pharmacie, Montpellier University (School of Pharmacy), 15 Avenue Charles Flahault, 34000, Montpellier, France. sonia.khier@umontpellier.fr.ORCID http://orcid.org/0000-0001-6712-8461
Université de Montpellier · FRCentre National de la Recherche Scientifique · FRRoche (Switzerland) · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesMeropenem is frequently used for the treatment of severe bacterial infections in critically ill patients. Because critically ill patients are more prone to pharmacokinetic variability than other patients, ensuring an effective blood concentration can be complex. Therefore, describing this variability to ensure a proper use of this antibiotic drug limits the rise and dissemination of antimicrobial resistance, and helps preserve the current antibiotic arsenal. The aims of this study were to describe the pharmacokinetics of meropenem in critically ill patients, to identify and quantify the patients' characteristics responsible for the observed pharmacokinetic variability, and to perform different dosing simulations in order to determine optimal individually adapted dosing regimens.

methodsA total of 58 patients hospitalized in the medical intensive care unit and receiving meropenem were enrolled, including 26 patients with renal replacement therapy. A population pharmacokinetic model was developed (using NONMEM software) and Monte Carlo simulations were performed with different dosing scenarios (bolus-like, extended, and continuous infusion) exploring the impact of clinical categories of residual diuresis (anuria, oliguria, and preserved diuresis) on the probability of target attainment (MIC: 1-45 mg/L).

resultsThe population pharmacokinetic model included five covariates with a significant impact on clearance: glomerular filtration rate, dialysis (continuous and semi-continuous), renal function status, and volume of residual diuresis. The clearance for a typical patient in our population is 4.20 L/h and volume of distribution approximately 44 L. Performed dosing regimen simulations suggested that, for equivalent doses, the continuous infusion mode (with loading dose) allowed the obtaining of the pharmacokinetic/pharmacodynamic target for a larger number of patients (100% for MIC ≤ 20 mg/L). Nevertheless, for the treatment of susceptible bacteria (MIC ≤ 2 mg/L), differences in the probability of target attainment between bolus-like, extended, and continuous infusions were negligible.

conclusionsIdentified covariates in the model are easily accessible information in patient health records. The model highlighted the importance of considering the patient's overall condition (renal function and dialysis) and the pathogen's characteristics (MIC target) during the establishment of a patient's dosing regimen.

Indexed as

Models, BiologicalAdolescentAdultAgedAged, 80 and overAnti-Bacterial AgentsBacterial InfectionsCritical IllnessDrug Administration ScheduleFemaleHumansIntensive Care UnitsMaleMeropenemMicrobial Sensitivity TestsMiddle AgedAnti-Bacterial AgentsMeropenem

Identifiers

PMID34403127
OpenAlexW3194223471

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.