TY - JOUR

T1 - Attainment of Target Antibiotic Levels by Oral Treatment of Left-sided Infective Endocarditis

T2 - A POET Substudy

AU - Bock, Magnus

AU - Theut, Anna Marie

AU - van Hasselt, Johan G. C.

AU - Wang, Hengzhuang

AU - Fuursted, Kurt

AU - Hoiby, Niels

AU - Lerche, Christian Johann

AU - Ihlemann, Nikolaj

AU - Gill, Sabine

AU - Christiansen, Ulrik

AU - Nielsen, Hans Linde

AU - Lemming, Lars

AU - Elming, Hanne

AU - Povlsen, Jonas A.

AU - Bruun, Niels Eske

AU - Hofsten, Dan

AU - Fosbøl, Emil L.

AU - Kober, Lars

AU - Schultz, Martin

AU - Pries-Heje, Mia M.

AU - Kristensen, Jonas Henrik

AU - Christensen, Jens Jørgen

AU - Rosenvinge, Flemming S.

AU - Pedersen, Christian Torp

AU - Helweg-Larsen, Jannik

AU - Tønder, Niels

AU - Iversen, Kasper

AU - Bundgaard, Henning

AU - Moser, Claus

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - infective endocarditis

KW - pharmacokinetics

KW - pharmacodynamics

KW - oral antibiotics

KW - target attainment

KW - ANTIMICROBIAL THERAPY

KW - PROTEIN-BINDING

KW - PHARMACOKINETICS

KW - PHARMACODYNAMICS

KW - MICE

U2 - 10.1093/cid/ciad168

DO - 10.1093/cid/ciad168

M3 - Journal article

C2 - 36947131

VL - 77

SP - 242

EP - 251

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 2

M1 - 168

ER -