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


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 two oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for one antibiotic. One patient did not reach target for any of the two antibiotics.

CONCLUSION: For the individual orally administered antibiotic, the majority of patients reached the target level. Patients with sub-target levels were compensated by the administration of two different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis.

Original languageEnglish
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Publication statusE-pub ahead of print - 2023


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