Attainment of target antibiotic levels by oral treatment of left-sided infective endocarditis: a POET substudy

Magnus Bock, Anna Marie Theut, Johan G. C. van Hasselt, Hengzhuang Wang, Kurt Fuursted, Niels Høiby, Christian Johann Lerche, Nikolaj Ihlemann, Sabine Gill, Ulrik Christiansen, Hans Linde Nielsen, Lars Lemming, Hanne Elming, Jonas A. Povlsen, Niels Eske Bruun, Dan Høfsten, Emil L. Fosbøl, Lars Køber, Martin Schultz, Mia M. Pries-HejeJonas Henrik Kristensen, Jens Jørgen Christensen, Flemming S. Rosenvinge, Christian Torp Pedersen, Jannik Helweg-Larsen, Niels Tønder, Kasper Iversen, Henning Bundgaard, Claus Moser*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

11 Citations (Scopus)

Abstract

Background: In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs). Methods: Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated. Results: A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%-100%. For moxifloxacin and rifampicin, the PTAs were 71%-100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%-17%. Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics. Conclusions: For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-Target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis.

Original languageEnglish
Article numberciad168
JournalClinical Infectious Diseases
Volume77
Issue number2
Pages (from-to)242-251
Number of pages10
ISSN1058-4838
DOIs
Publication statusPublished - 15 Jul 2023

Bibliographical note

© The Author(s) 2023. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: [email protected].

Keywords

  • Amoxicillin
  • Anti-Bacterial Agents/pharmacology
  • Dicloxacillin/therapeutic use
  • Endocarditis, Bacterial/drug therapy
  • Endocarditis/drug therapy
  • Humans
  • Linezolid/therapeutic use
  • Microbial Sensitivity Tests
  • Moxifloxacin/therapeutic use
  • Rifampin/therapeutic use
  • pharmacodynamics
  • target attainment
  • infective endocarditis
  • oral antibiotics
  • pharmacokinetics

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