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Bock, Magnus; Theut, Anna Marie; van Hasselt, Johan G C; Wang, Hengzhuang; Fuursted, Kurt; Høiby, Niels; Lerche, Christian Johann; Ihlemann, Nikolaj; Gill, Sabine; Christiansen, Ulrik; Nielsen, Hans Linde; Lemming, Lars; Elming, Hanne; Povlsen, Jonas A; Bruun, Niels Eske; Høfsten, Dan; Fosbøl, Emil L; Køber, Lars; Schultz, Martin; Pries-Heje, Mia M; Kristensen, Jonas Henrik; Christensen, Jens Jørgen; Rosenvinge, Flemming S; Pedersen, Christian Torp; [...]

Attainment of Target Antibiotic Levels by Oral Treatment of Left-Sided Infective Endocarditis: A POET Substudy

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  • Media type: E-Article
  • Title: Attainment of Target Antibiotic Levels by Oral Treatment of Left-Sided Infective Endocarditis: A POET Substudy
  • Contributor: Bock, Magnus; Theut, Anna Marie; van Hasselt, Johan G C; Wang, Hengzhuang; Fuursted, Kurt; Høiby, Niels; Lerche, Christian Johann; Ihlemann, Nikolaj; Gill, Sabine; Christiansen, Ulrik; Nielsen, Hans Linde; Lemming, Lars; Elming, Hanne; Povlsen, Jonas A; Bruun, Niels Eske; Høfsten, Dan; Fosbøl, Emil L; Køber, Lars; Schultz, Martin; Pries-Heje, Mia M; Kristensen, Jonas Henrik; Christensen, Jens Jørgen; Rosenvinge, Flemming S; Pedersen, Christian Torp; [...]
  • imprint: Oxford University Press (OUP), 2023
  • Published in: Clinical Infectious Diseases
  • Language: English
  • DOI: 10.1093/cid/ciad168
  • ISSN: 1058-4838; 1537-6591
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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%.</jats:p> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p> </jats:sec>