Superior Efficacy of a Bedaquiline, Delamanid, and Linezolid Combination Regimen in a Mouse Tuberculosis Model

Elise D. Pieterman, Lina Keutzer, Aart Van Der Meijden, Sanne Van Den Berg, Han Wang, Matthew D. Zimmerman, Ulrika S.H. Simonsson, Hannelore I. Bax, Jurriaan E.M. De Steenwinkel*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)

Abstract

Background: The treatment success rate of drug-resistant (DR) tuberculosis is alarmingly low. Therefore, more effective and less complex regimens are urgently required. Methods: We compared the efficacy of an all oral DR tuberculosis drug regimen consisting of bedaquiline (25 mg/kg), delamanid (2.5 mg/kg), and linezolid (100 mg/kg) (BDL) on the mycobacterial load in the lungs and spleen of tuberculosis-infected mice during a treatment period of 24 weeks. This treatment was compared with the standard regimen of isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE). Relapse was assessed 12 weeks after treatment. Two logistic regression models were developed to compare the efficacy of both regimens. Results: Culture negativity in the lungs was achieved at 8 and 20 weeks of treatment with BDL and HRZE, respectively. After 14 weeks of treatment only 1 mouse had relapse in the BDL group, while in the HRZE group relapse was still observed at 24 weeks of treatment. Predictions from the final mathematical models showed that a 95% cure rate was reached after 20.5 and 28.5 weeks of treatment with BDL and HRZE, respectively. Conclusion: The BDL regimen was observed to be more effective than HRZE and could be a valuable option for the treatment of DR tuberculosis.

Original languageEnglish
Pages (from-to)1039-1047
Number of pages9
JournalJournal of Infectious Diseases
Volume224
Issue number6
Early online date27 Jan 2021
DOIs
Publication statusPublished - 15 Sept 2021

Bibliographical note

Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.

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