Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis. / Bock, Magnus; Van Hasselt, Johan G C; Schwartz, Franziska; Wang, Hengzhuang; Høiby, Niels; Fuursted, Kurt; Ihlemann, Nikolaj; Gill, Sabine; Christiansen, Ulrik; Bruun, Niels Eske; Elming, Hanne; Povlsen, Jonas A; Køber, Lars; Høfsten, Dan E; Fosbøl, Emil L; Pries-Heje, Mia M; Christensen, Jens Jørgen; Rosenvinge, Flemming S; Torp-Pedersen, Christian; Helweg-Larsen, Jannik; Tønder, Niels; Iversen, Kasper; Bundgaard, Henning; Moser, Claus.

In: The Journal of antimicrobial chemotherapy, Vol. 78, No. 12, 2023, p. 2840–2848.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Bock, M, Van Hasselt, JGC, Schwartz, F, Wang, H, Høiby, N, Fuursted, K, Ihlemann, N, Gill, S, Christiansen, U, Bruun, NE, Elming, H, Povlsen, JA, Køber, L, Høfsten, DE, Fosbøl, EL, Pries-Heje, MM, Christensen, JJ, Rosenvinge, FS, Torp-Pedersen, C, Helweg-Larsen, J, Tønder, N, Iversen, K, Bundgaard, H & Moser, C 2023, 'Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis', The Journal of antimicrobial chemotherapy, vol. 78, no. 12, pp. 2840–2848. https://doi.org/10.1093/jac/dkad316

APA

Bock, M., Van Hasselt, J. G. C., Schwartz, F., Wang, H., Høiby, N., Fuursted, K., Ihlemann, N., Gill, S., Christiansen, U., Bruun, N. E., Elming, H., Povlsen, J. A., Køber, L., Høfsten, D. E., Fosbøl, E. L., Pries-Heje, M. M., Christensen, J. J., Rosenvinge, F. S., Torp-Pedersen, C., ... Moser, C. (2023). Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis. The Journal of antimicrobial chemotherapy, 78(12), 2840–2848. https://doi.org/10.1093/jac/dkad316

Vancouver

Bock M, Van Hasselt JGC, Schwartz F, Wang H, Høiby N, Fuursted K et al. Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis. The Journal of antimicrobial chemotherapy. 2023;78(12):2840–2848. https://doi.org/10.1093/jac/dkad316

Author

Bock, Magnus ; Van Hasselt, Johan G C ; Schwartz, Franziska ; Wang, Hengzhuang ; Høiby, Niels ; Fuursted, Kurt ; Ihlemann, Nikolaj ; Gill, Sabine ; Christiansen, Ulrik ; Bruun, Niels Eske ; Elming, Hanne ; Povlsen, Jonas A ; Køber, Lars ; Høfsten, Dan E ; Fosbøl, Emil L ; Pries-Heje, Mia M ; Christensen, Jens Jørgen ; Rosenvinge, Flemming S ; Torp-Pedersen, Christian ; Helweg-Larsen, Jannik ; Tønder, Niels ; Iversen, Kasper ; Bundgaard, Henning ; Moser, Claus. / Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis. In: The Journal of antimicrobial chemotherapy. 2023 ; Vol. 78, No. 12. pp. 2840–2848.

Bibtex

@article{c4218c2e6c0e475ea5fe9c3a291268ff,
title = "Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis",
abstract = "BACKGROUND: Linezolid in combination with rifampicin has been used in treatment of infective endocarditis especially for patients infected with staphylococci.OBJECTIVES: Because rifampicin has been reported to reduce the plasma concentration of linezolid, the present study aimed to characterize the population pharmacokinetics of linezolid for the purpose of quantifying an effect of rifampicin cotreatment. In addition, the possibility of compensation by dosage adjustments was evaluated.PATIENTS AND METHODS: Pharmacokinetic measurements were performed in 62 patients treated with linezolid for left-sided infective endocarditis in the Partial Oral Endocarditis Treatment (POET) trial. Fifteen patients were cotreated with rifampicin. A total of 437 linezolid plasma concentrations were obtained. The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and first-order elimination.RESULTS: We demonstrated a substantial increase of linezolid clearance by 150% (95% CI: 78%-251%), when combined with rifampicin. The final model was evaluated by goodness-of-fit plots showing an acceptable fit, and a visual predictive check validated the model. Model-based dosing simulations showed that rifampicin cotreatment decreased the PTA of linezolid from 94.3% to 34.9% and from 52.7% to 3.5% for MICs of 2 mg/L and 4 mg/L, respectively.CONCLUSIONS: A substantial interaction between linezolid and rifampicin was detected in patients with infective endocarditis, and the interaction was stronger than previously reported. Model-based simulations showed that increasing the linezolid dose might compensate without increasing the risk of adverse effects to the same degree.",
author = "Magnus Bock and {Van Hasselt}, {Johan G C} and Franziska Schwartz and Hengzhuang Wang and Niels H{\o}iby and Kurt Fuursted and Nikolaj Ihlemann and Sabine Gill and Ulrik Christiansen and Bruun, {Niels Eske} and Hanne Elming and Povlsen, {Jonas A} and Lars K{\o}ber and H{\o}fsten, {Dan E} and Fosb{\o}l, {Emil L} and Pries-Heje, {Mia M} and Christensen, {Jens J{\o}rgen} and Rosenvinge, {Flemming S} and Christian Torp-Pedersen and Jannik Helweg-Larsen and Niels T{\o}nder and Kasper Iversen and Henning Bundgaard and Claus Moser",
note = "{\textcopyright} The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.",
year = "2023",
doi = "10.1093/jac/dkad316",
language = "English",
volume = "78",
pages = "2840–2848",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "12",

}

RIS

TY - JOUR

T1 - Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis

AU - Bock, Magnus

AU - Van Hasselt, Johan G C

AU - Schwartz, Franziska

AU - Wang, Hengzhuang

AU - Høiby, Niels

AU - Fuursted, Kurt

AU - Ihlemann, Nikolaj

AU - Gill, Sabine

AU - Christiansen, Ulrik

AU - Bruun, Niels Eske

AU - Elming, Hanne

AU - Povlsen, Jonas A

AU - Køber, Lars

AU - Høfsten, Dan E

AU - Fosbøl, Emil L

AU - Pries-Heje, Mia M

AU - Christensen, Jens Jørgen

AU - Rosenvinge, Flemming S

AU - Torp-Pedersen, Christian

AU - Helweg-Larsen, Jannik

AU - Tønder, Niels

AU - Iversen, Kasper

AU - Bundgaard, Henning

AU - Moser, Claus

N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2023

Y1 - 2023

N2 - BACKGROUND: Linezolid in combination with rifampicin has been used in treatment of infective endocarditis especially for patients infected with staphylococci.OBJECTIVES: Because rifampicin has been reported to reduce the plasma concentration of linezolid, the present study aimed to characterize the population pharmacokinetics of linezolid for the purpose of quantifying an effect of rifampicin cotreatment. In addition, the possibility of compensation by dosage adjustments was evaluated.PATIENTS AND METHODS: Pharmacokinetic measurements were performed in 62 patients treated with linezolid for left-sided infective endocarditis in the Partial Oral Endocarditis Treatment (POET) trial. Fifteen patients were cotreated with rifampicin. A total of 437 linezolid plasma concentrations were obtained. The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and first-order elimination.RESULTS: We demonstrated a substantial increase of linezolid clearance by 150% (95% CI: 78%-251%), when combined with rifampicin. The final model was evaluated by goodness-of-fit plots showing an acceptable fit, and a visual predictive check validated the model. Model-based dosing simulations showed that rifampicin cotreatment decreased the PTA of linezolid from 94.3% to 34.9% and from 52.7% to 3.5% for MICs of 2 mg/L and 4 mg/L, respectively.CONCLUSIONS: A substantial interaction between linezolid and rifampicin was detected in patients with infective endocarditis, and the interaction was stronger than previously reported. Model-based simulations showed that increasing the linezolid dose might compensate without increasing the risk of adverse effects to the same degree.

AB - BACKGROUND: Linezolid in combination with rifampicin has been used in treatment of infective endocarditis especially for patients infected with staphylococci.OBJECTIVES: Because rifampicin has been reported to reduce the plasma concentration of linezolid, the present study aimed to characterize the population pharmacokinetics of linezolid for the purpose of quantifying an effect of rifampicin cotreatment. In addition, the possibility of compensation by dosage adjustments was evaluated.PATIENTS AND METHODS: Pharmacokinetic measurements were performed in 62 patients treated with linezolid for left-sided infective endocarditis in the Partial Oral Endocarditis Treatment (POET) trial. Fifteen patients were cotreated with rifampicin. A total of 437 linezolid plasma concentrations were obtained. The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and first-order elimination.RESULTS: We demonstrated a substantial increase of linezolid clearance by 150% (95% CI: 78%-251%), when combined with rifampicin. The final model was evaluated by goodness-of-fit plots showing an acceptable fit, and a visual predictive check validated the model. Model-based dosing simulations showed that rifampicin cotreatment decreased the PTA of linezolid from 94.3% to 34.9% and from 52.7% to 3.5% for MICs of 2 mg/L and 4 mg/L, respectively.CONCLUSIONS: A substantial interaction between linezolid and rifampicin was detected in patients with infective endocarditis, and the interaction was stronger than previously reported. Model-based simulations showed that increasing the linezolid dose might compensate without increasing the risk of adverse effects to the same degree.

U2 - 10.1093/jac/dkad316

DO - 10.1093/jac/dkad316

M3 - Journal article

C2 - 37823408

VL - 78

SP - 2840

EP - 2848

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 12

ER -

ID: 371014232