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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
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Predictors for non-attainment of meropenem target concentrations when treating infections in critically ill patients


Shao Jun Zheng, Yifan Xu, Nai Dong Chen

    International Journal of Clinical Pharmacology and Therapeutics
    |November 16, 2023
    PubMed
    Abstract

    Insights

    Augmented renal clearance (ARC) is a key factor in achieving target meropenem concentrations in critically ill patients. Increased creatinine clearance raises the risk of sub-therapeutic levels, necessitating careful monitoring.

    Area of Science:

    • Pharmacokinetics and Pharmacodynamics
    • Critical Care Medicine
    • Infectious Diseases

    Background:

    • Sub-therapeutic beta-lactam antibiotic concentrations are common in critically ill patients.
    • High doses of meropenem may not achieve target concentrations.
    • Identifying risk factors for non-attainment is crucial for optimizing therapy.

    Purpose of the Study:

    • To identify risk factors for failing to reach target meropenem concentrations.
    • To investigate predictors of sub-therapeutic meropenem levels in intensive care unit (ICU) patients.
    • To inform dosing strategies for meropenem in critically ill populations.

    Main Methods:

    • Retrospective study of adult ICU patients receiving meropenem via intravenous infusion.
    • Therapeutic drug monitoring (TDM) used to measure meropenem trough concentrations (Cmin).
    • UPLC-MS analysis of blood samples; logistic regression used to identify risk factors.

    Main Results:

    • 19.5% of patients (41/210) did not attain target meropenem concentrations.
    • Multivariate analysis identified age, dosage, and augmented renal clearance (ARC) as predictors of non-attainment.
    • Higher creatinine clearance correlated with an increased risk of sub-therapeutic meropenem levels.

    Conclusions:

    • Augmented renal clearance (ARC) is a significant predictor of meropenem target concentration non-attainment.
    • Age and dosage also contribute to the risk of sub-therapeutic levels.
    • Clinicians should consider ARC and creatinine clearance when dosing meropenem in critically ill patients to ensure efficacy.

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