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Meropenem PK/PD Variability and Renal Function: "We Go Together"
Jacopo Angelini1,2, Simone Giuliano3, Sarah Flammini3
1Clinical Pharmacology and Toxicology Institute, University Hospital Friuli Centrale ASUFC, 33100 Udine, Italy.
Background:
Meropenem is a carbapenem antibiotic widely employed for serious bacterial infections. Therapeutic drug monitoring (TDM) is a strategy to optimize dosing, especially in critically ill patients. This study aims to show how TDM influences the management of meropenem in a real-life setting, not limited to intensive care units.
Methods:
From December 2021 to February 2022, we retrospectively analyzed 195 meropenem serum concentrations (Css). We characterized patients according to meropenem exposure, focusing on the renal function impact.
Results:
A total of 36% (n = 51) of the overall observed patients (n = 144) were in the therapeutic range (8-16 mg/L), whereas 64% (n = 93) required a meropenem dose modification (37 patients (26%) underexposed; 53 (38%) overexposed). We found a strong relationship between renal function and meropenem concentrations (correlation coefficient = -0.7; p-value < 0.001). We observed different dose-normalized meropenem exposure (Css/D) among renal-impaired (severe and moderate), normal, and hyperfiltrating patients, with a median (interquartile range) of 13.1 (10.9-20.2), 7.9 (6.1-9.5), 3.8 (2.6-6.0), and 2.4 (1.6-2.7), respectively (p-value < 0.001).
Conclusions:
Meropenem TDM in clinical practice allows modification of dosing in patients inadequately exposed to meropenem to maximize antibiotic efficacy and minimize the risk of antibiotic resistance, especially in renal alterations despite standard dose adaptations.
Insights
Therapeutic drug monitoring (TDM) for meropenem optimizes dosing in real-world settings. TDM identified significant meropenem dose adjustments needed in 64% of patients, particularly those with renal impairment, to improve outcomes.
Area of Science:
- Pharmacology
- Infectious Diseases
- Clinical Pharmacy
Background:
- Meropenem is a critical carbapenem antibiotic for severe bacterial infections.
- Therapeutic drug monitoring (TDM) is essential for optimizing meropenem dosing, especially in critically ill patients.
- This study evaluates meropenem TDM's impact on clinical management outside intensive care units.
Purpose of the Study:
- To assess the influence of meropenem therapeutic drug monitoring (TDM) on dosing strategies in a real-world clinical setting.
- To investigate the relationship between meropenem exposure and patient renal function.
- To identify patient subgroups requiring meropenem dose adjustments.
Main Methods:
- Retrospective analysis of 195 meropenem serum concentrations (Css) from December 2021 to February 2022.
- Patient characterization based on meropenem exposure levels (therapeutic, underexposed, overexposed).
- Correlation analysis between renal function and meropenem Css, including dose-normalized exposure (Css/D) across different renal function categories.
Main Results:
- Only 36% of patients achieved therapeutic meropenem Css (8-16 mg/L); 64% required dose modification.
- Significant correlation (r = -0.7, p < 0.001) found between renal function and meropenem concentrations.
- Dose-normalized meropenem exposure (Css/D) varied significantly with renal function (p < 0.001), with higher exposure in impaired renal function.
Conclusions:
- Meropenem TDM in clinical practice facilitates necessary dosing adjustments for patients with inadequate exposure.
- Optimizing meropenem dosing via TDM can enhance antibiotic efficacy and mitigate resistance risks.
- Renal function significantly impacts meropenem exposure, necessitating TDM even with standard dose adjustments.
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