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Exploring the Impact of Model-Informed Precision Dosing on Procalcitonin Concentrations in Critically Ill Patients: A

Sarah Dräger1,2,3, Tim M J Ewoldt1,2,4, Alan Abdulla1,2

  • 1Department of Hospital Pharmacy, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands.

Pharmaceutics
|February 24, 2024
PubMed

Insights

Model-informed precision dosing (MIPD) did not significantly alter procalcitonin (PCT) levels in critically ill patients. However, PCT levels were highest in patients exceeding the pharmacodynamic target (PDT) at day one.

Area of Science:

  • Critical Care Medicine
  • Pharmacology
  • Infectious Diseases

Background:

  • Model-informed precision dosing (MIPD) aims to optimize antibiotic therapy.
  • Procalcitonin (PCT) serves as a biomarker for infection severity and treatment response.
  • Understanding PCT dynamics in relation to dosing strategies is crucial for critically ill patients.

Purpose of the Study:

  • To evaluate the effect of MIPD on procalcitonin (PCT) levels in critically ill patients.
  • To investigate the association between PCT concentrations and pharmacodynamic target (PDT) attainment.
  • To analyze PCT trends in relation to patient outcomes and dosing strategies.

Main Methods:

  • Secondary analysis of the multicentre, open-label, randomized controlled DOLPHIN trial.
  • Inclusion of critically ill patients with PCT measurements at days 1, 3, and 5 post-randomization.
  • Comparison of PCT concentrations between MIPD and standard antibiotic dosing groups.

Main Results:

  • No statistically significant difference in PCT concentrations was observed between MIPD and standard dosing groups at any time point (T1, T3, T5).
  • PCT concentrations were highest in patients exceeding 10x the pharmacodynamic target (PDT) at T1.
  • PCT levels decreased significantly from T1 to T3 in non-survivors and those exceeding PDT, but plateaued thereafter.

Conclusions:

  • MIPD did not significantly impact PCT concentrations in this cohort of critically ill patients.
  • PCT levels correlate with exceeding the pharmacodynamic target, suggesting its utility as a severity indicator.
  • Further research is warranted to explore the role of PCT in guiding antibiotic dosing strategies.
Keywords:
antibioticsbiomarkercritically illinflammationmodel-informed precision dosingpharmacodynamic target attainmentprocalcitonin

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