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A pharmacokinetic-pharmacodynamic (PKPD) model-based analysis of tedizolid against enterococci using the hollow-fibre

K Iqbal1, H Rohde2, J Huang2

  • 1Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, Germany.

The Journal of Antimicrobial Chemotherapy
|June 13, 2022
PubMed
Abstract

Insights

The recommended dose of tedizolid (200 mg/day) was insufficient to inhibit bacterial growth in a simulated infection model. This highlights the need for caution when using tedizolid in immunocompromised patients.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Microbiology

Background:

  • Tedizolid is a novel oxazolidinone antibiotic with observed higher efficacy in immunocompetent models.
  • Its use is cautioned in immunocompromised patients due to potentially reduced effectiveness.

Purpose of the Study:

  • To assess the pharmacokinetic-pharmacodynamic (PKPD) relationship of tedizolid against Enterococcus species.
  • To evaluate tedizolid's efficacy in a simulated infection environment.

Main Methods:

  • Simulated unbound plasma concentration time profiles of tedizolid in a hollow-fibre infection model (HFIM).
  • Utilized a PKPD model linked to a population PK model to predict bacterial kinetics in plasma and tissues.
  • Tested against Enterococcus faecalis and vancomycin-resistant Enterococcus (VRE) isolates.

Main Results:

  • The PKPD model accurately described bacterial kill kinetics.
  • The standard human dose (200 mg/day) predicted bacterial growth in plasma and most tissues.
  • Bacterial stasis was only achieved at a higher dose (1200 mg/day), with resistance emerging at lower doses.
  • Epithelial lining fluid (ELF) showed some resistance to tedizolid's effects.

Conclusions:

  • The 200 mg/day dose of tedizolid is insufficient to suppress Enterococcus growth in the HFIM.
  • Clinical effectiveness may involve factors beyond the direct PKPD relationship.
  • Reinforces the recommendation to limit tedizolid use in immunocompromised individuals.

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