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Background <p>This study aimed to describe vancomycin concentrations in critically ill children undergoing continuous renal replacement therapy (CRRT) and to identify factors impacting vancomycin concentrations.</p> Methods <p>Monocentric retrospective study. Children under 18&#xa0;years of age, who underwent CRRT from 2020 to 2023 and received vancomycin with at least one concentration measurement on CRRT were included. Patients receiving ECMO were excluded. Demographic, clinical and biological data were collected from the patients’ medical records, including CRRT modalities and flow rate parameters. Regarding vancomycin, we collected dosing regimen, times and duration of infusions, duration of treatment, times of sampling, and plasma concentrations. Associations between vancomycin concentrations and each covariate were analyzed using a linear mixed modelling approach including a random effect on patient and adjusted on the dosing regimen and infusion modality.</p> Results <p>Forty-two patients were included with a total of 512 vancomycin samples. Dialysate and effluent flow rates were set at 63.1 (0–308) mL/h/kg and 65.5 (0–327) mL/h/kg, respectively, corresponding to a high intensity. Vancomycin underexposure was more frequent for patients on CRRT than off CRRT (<i>n</i> = 172/320, 54% versus <i>n</i> = 71/192, 37%, <i>p</i> &lt; 0.001), with lower concentrations on CRRT compared to off CRRT (18.5 (0.5–89.9) vs. 21.3 (0.5–73) mg/L, <i>p</i> &lt; 0.001). The factors decreasing vancomycin exposure were a lower body weight, higher effluent flow rate (EFR), residual urine output and lower hematocrit.</p> Conclusions <p>Within the limitations of this retrospective study, lacking standardized vancomycin administration and therapeutic drug monitoring (TDM) protocols, the present study suggests that critically ill children receiving vancomycin and on CRRT are at higher risk of underexposure than those off CRRT. Vancomycin concentrations are impacted by CRRT flow rates, particularly effluent flow rate (EFR), reflecting CRRT intensity, with more frequent underexposure observed at very high clearance rates. Considering the large inter- and intraindividual variability and the narrow therapeutic range, TDM and population pharmacokinetic modelling could be helpful to optimize and individualize vancomycin dosing in children undergoing CRRT.</p> Graphical Abstract <p></p>

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Vancomycin exposure in critically ill children undergoing high intensity continuous renal replacement therapy

  • 期刊论文

  • 发表日期：

    2026年7月7日

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  • Victor Belliard,
  • Naim Bouazza,
  • Baptiste Grenier,
  • Mathilde Grapin,
  • Valérie Nivet-Antoine,
  • Noémie de Cacqueray,
  • Jean-Marc Treluyer,
  • Romain Berthaud,
  • Sylvain Renolleau,
  • Mehdi Oualha,
  • Agathe Béranger

摘要

Background

This study aimed to describe vancomycin concentrations in critically ill children undergoing continuous renal replacement therapy (CRRT) and to identify factors impacting vancomycin concentrations.

Methods

Monocentric retrospective study. Children under 18 years of age, who underwent CRRT from 2020 to 2023 and received vancomycin with at least one concentration measurement on CRRT were included. Patients receiving ECMO were excluded. Demographic, clinical and biological data were collected from the patients’ medical records, including CRRT modalities and flow rate parameters. Regarding vancomycin, we collected dosing regimen, times and duration of infusions, duration of treatment, times of sampling, and plasma concentrations. Associations between vancomycin concentrations and each covariate were analyzed using a linear mixed modelling approach including a random effect on patient and adjusted on the dosing regimen and infusion modality.

Results

Forty-two patients were included with a total of 512 vancomycin samples. Dialysate and effluent flow rates were set at 63.1 (0–308) mL/h/kg and 65.5 (0–327) mL/h/kg, respectively, corresponding to a high intensity. Vancomycin underexposure was more frequent for patients on CRRT than off CRRT (n = 172/320, 54% versus n = 71/192, 37%, p < 0.001), with lower concentrations on CRRT compared to off CRRT (18.5 (0.5–89.9) vs. 21.3 (0.5–73) mg/L, p < 0.001). The factors decreasing vancomycin exposure were a lower body weight, higher effluent flow rate (EFR), residual urine output and lower hematocrit.

Conclusions

Within the limitations of this retrospective study, lacking standardized vancomycin administration and therapeutic drug monitoring (TDM) protocols, the present study suggests that critically ill children receiving vancomycin and on CRRT are at higher risk of underexposure than those off CRRT. Vancomycin concentrations are impacted by CRRT flow rates, particularly effluent flow rate (EFR), reflecting CRRT intensity, with more frequent underexposure observed at very high clearance rates. Considering the large inter- and intraindividual variability and the narrow therapeutic range, TDM and population pharmacokinetic modelling could be helpful to optimize and individualize vancomycin dosing in children undergoing CRRT.

Graphical Abstract