External evaluation of population pharmacokinetic models of vancomycin in large cohorts of intensive care patients

Tingjie Guo, Reinier M van Hest, Luca F Roggeveen, Lucas M Fleuren, Patrick J Thoral, Rob J Bosman, Peter H J van der Voort, Armand R J Girbes, Ron A A Mathot, Paul W G Elbers

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Dosing of vancomycin is often guided by therapeutic drug monitoring and population pharmacokinetic models in the intensive care unit (ICU). Validity of these models is crucial as ICU patients have marked pharmacokinetic variability. Therefore, we set out to evaluate the predictive performance of published population pharmacokinetic models of vancomycin in ICU patients. The PubMed database was used for searching population pharmacokinetic models of vancomycin in adult ICU patients. Identified models were evaluated in two independent datasets which were collected from two large hospitals in the Netherlands (Amsterdam UMC, Location VUmc and OLVG Oost). We also tested a one-compartment model with fixed values for clearance and volume of distribution, in which a clinical standard dosage regimen (SDR) was mimicked to assess its predictive performance. Prediction error was calculated to assess the predictive performance of the models. Six models plus the SDR model were evaluated. The model of Roberts et al. performed satisfactorily, with mean and median values of prediction error of 5.1% and -7.5% for Amsterdam UMC, Location VUmc patients, and -12.6% and -17.2% for OLVG Oost patients. The other models including the SDR model yielded high mean values (-49.7% to 87.7%) and median values (-56.1% to 66.1%) for both populations. In conclusion, only the model of Roberts et al. was able to validly predict the concentrations of vancomycin for our data, whereas other models and standard dosing were largely inadequate. Extensive evaluation should precede the adoption of any model in clinical practice for ICU patients.

Original languageEnglish
JournalAntimicrobial Agents and Chemotherapy
DOIs
Publication statusE-pub ahead of print - 4 Mar 2019

Cite this

@article{d0e110841e2243cbb552ed26662f2636,
title = "External evaluation of population pharmacokinetic models of vancomycin in large cohorts of intensive care patients",
abstract = "Dosing of vancomycin is often guided by therapeutic drug monitoring and population pharmacokinetic models in the intensive care unit (ICU). Validity of these models is crucial as ICU patients have marked pharmacokinetic variability. Therefore, we set out to evaluate the predictive performance of published population pharmacokinetic models of vancomycin in ICU patients. The PubMed database was used for searching population pharmacokinetic models of vancomycin in adult ICU patients. Identified models were evaluated in two independent datasets which were collected from two large hospitals in the Netherlands (Amsterdam UMC, Location VUmc and OLVG Oost). We also tested a one-compartment model with fixed values for clearance and volume of distribution, in which a clinical standard dosage regimen (SDR) was mimicked to assess its predictive performance. Prediction error was calculated to assess the predictive performance of the models. Six models plus the SDR model were evaluated. The model of Roberts et al. performed satisfactorily, with mean and median values of prediction error of 5.1{\%} and -7.5{\%} for Amsterdam UMC, Location VUmc patients, and -12.6{\%} and -17.2{\%} for OLVG Oost patients. The other models including the SDR model yielded high mean values (-49.7{\%} to 87.7{\%}) and median values (-56.1{\%} to 66.1{\%}) for both populations. In conclusion, only the model of Roberts et al. was able to validly predict the concentrations of vancomycin for our data, whereas other models and standard dosing were largely inadequate. Extensive evaluation should precede the adoption of any model in clinical practice for ICU patients.",
author = "Tingjie Guo and {van Hest}, {Reinier M} and Roggeveen, {Luca F} and Fleuren, {Lucas M} and Thoral, {Patrick J} and Bosman, {Rob J} and {van der Voort}, {Peter H J} and Girbes, {Armand R J} and Mathot, {Ron A A} and Elbers, {Paul W G}",
note = "Copyright {\circledC} 2019 American Society for Microbiology.",
year = "2019",
month = "3",
day = "4",
doi = "10.1128/AAC.02543-18",
language = "English",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",

}

External evaluation of population pharmacokinetic models of vancomycin in large cohorts of intensive care patients. / Guo, Tingjie; van Hest, Reinier M; Roggeveen, Luca F; Fleuren, Lucas M; Thoral, Patrick J; Bosman, Rob J; van der Voort, Peter H J; Girbes, Armand R J; Mathot, Ron A A; Elbers, Paul W G.

In: Antimicrobial Agents and Chemotherapy, 04.03.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - External evaluation of population pharmacokinetic models of vancomycin in large cohorts of intensive care patients

AU - Guo, Tingjie

AU - van Hest, Reinier M

AU - Roggeveen, Luca F

AU - Fleuren, Lucas M

AU - Thoral, Patrick J

AU - Bosman, Rob J

AU - van der Voort, Peter H J

AU - Girbes, Armand R J

AU - Mathot, Ron A A

AU - Elbers, Paul W G

N1 - Copyright © 2019 American Society for Microbiology.

PY - 2019/3/4

Y1 - 2019/3/4

N2 - Dosing of vancomycin is often guided by therapeutic drug monitoring and population pharmacokinetic models in the intensive care unit (ICU). Validity of these models is crucial as ICU patients have marked pharmacokinetic variability. Therefore, we set out to evaluate the predictive performance of published population pharmacokinetic models of vancomycin in ICU patients. The PubMed database was used for searching population pharmacokinetic models of vancomycin in adult ICU patients. Identified models were evaluated in two independent datasets which were collected from two large hospitals in the Netherlands (Amsterdam UMC, Location VUmc and OLVG Oost). We also tested a one-compartment model with fixed values for clearance and volume of distribution, in which a clinical standard dosage regimen (SDR) was mimicked to assess its predictive performance. Prediction error was calculated to assess the predictive performance of the models. Six models plus the SDR model were evaluated. The model of Roberts et al. performed satisfactorily, with mean and median values of prediction error of 5.1% and -7.5% for Amsterdam UMC, Location VUmc patients, and -12.6% and -17.2% for OLVG Oost patients. The other models including the SDR model yielded high mean values (-49.7% to 87.7%) and median values (-56.1% to 66.1%) for both populations. In conclusion, only the model of Roberts et al. was able to validly predict the concentrations of vancomycin for our data, whereas other models and standard dosing were largely inadequate. Extensive evaluation should precede the adoption of any model in clinical practice for ICU patients.

AB - Dosing of vancomycin is often guided by therapeutic drug monitoring and population pharmacokinetic models in the intensive care unit (ICU). Validity of these models is crucial as ICU patients have marked pharmacokinetic variability. Therefore, we set out to evaluate the predictive performance of published population pharmacokinetic models of vancomycin in ICU patients. The PubMed database was used for searching population pharmacokinetic models of vancomycin in adult ICU patients. Identified models were evaluated in two independent datasets which were collected from two large hospitals in the Netherlands (Amsterdam UMC, Location VUmc and OLVG Oost). We also tested a one-compartment model with fixed values for clearance and volume of distribution, in which a clinical standard dosage regimen (SDR) was mimicked to assess its predictive performance. Prediction error was calculated to assess the predictive performance of the models. Six models plus the SDR model were evaluated. The model of Roberts et al. performed satisfactorily, with mean and median values of prediction error of 5.1% and -7.5% for Amsterdam UMC, Location VUmc patients, and -12.6% and -17.2% for OLVG Oost patients. The other models including the SDR model yielded high mean values (-49.7% to 87.7%) and median values (-56.1% to 66.1%) for both populations. In conclusion, only the model of Roberts et al. was able to validly predict the concentrations of vancomycin for our data, whereas other models and standard dosing were largely inadequate. Extensive evaluation should precede the adoption of any model in clinical practice for ICU patients.

U2 - 10.1128/AAC.02543-18

DO - 10.1128/AAC.02543-18

M3 - Article

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

ER -