Abstract
Background The World Health Organization recommends supervising the treatment of tuberculosis. Intermittent regimens have the potential to simplify the supervision and improve compliance. Our objective was to analyse the sterilising activity of once-weekly regimens based on drugs with a long half-life, bedaquiline and rifapentine, in a murine model of tuberculosis.
Methods 300 Swiss mice were infected intravenously infected with ×10−6 CFU Mycobacterium tuberculosis H37Rv. Mice were treated once weekly with regimens containing: 1) bedaquiline, rifapentine and pyrazinamide (BPZ); 2) BPZ plus moxifloxacin (BPZM); 3) BPZM plus clofazimine (BPZMC); 4) the standard daily regimen of tuberculosis. All regimens were given for 4 or 6 months. Bactericidal and sterilising activity were assessed.
Results After 2 months of treatment, the mean count in lungs was 0.76±0.60 log10 CFU in mice treated with the daily control regimen and negative in all mice treated with once-weekly regimens (p<0.05 compared to the daily control). All mice had negative lung cultures on completion of either 4 or 6 months of treatment, whereas 3 months after 4 and 6 months of treatment, respectively, the relapse rate was 64% and 13% in the standard daily regimen, 5% and 0% in BPZ, 0% and 0% in BPMZ and 0% and 5% in BPMZC (p<0.05 for all once-weekly regimens versus 4-month daily control; p>0.05 for all once-weekly regimens versus 6-month daily control).
Conclusions BPZ-based once-weekly regimens have higher sterilising activity than the standard daily regimen and could greatly simplify treatment administration and possibly shorten the duration of tuberculosis treatment.
Abstract
Bedaquiline–rifapentine–pyrazinamide-based once-weekly regimens have higher sterilising activity than the standard daily regimen of tuberculosis and could thus greatly simplify treatment of tuberculosis https://bit.ly/2W8yx2r
Footnotes
This article has an editorial commentary: https://doi.org/10.1183/13993003.02510-2020
This article has supplementary material available from erj.ersjournals.com
Conflict of interest: F. Kort reports grants from Janssen, during the conduct of the study.
Conflict of interest: L. Fournier Le Ray reports grants from Janssen, during the conduct of the study.
Conflict of interest: A. Chauffour reports grants from Janssen, during the conduct of the study.
Conflict of interest: V. Jarlier reports grants from Janssen, during the conduct of the study.
Conflict of interest: N. Lounis reports grants from Janssen, during the conduct of the study; and is an employee of Janssen.
Conflict of interest: K. Andries reports grants from Janssen, during the conduct of the study; is a former employee of Janssen; and has a patent WO 2004/011436 licensed, a patent WO 2005/117875 licensed, and a patent WO 2006/035051 issued.
Conflict of interest: A. Aubry reports grants from Janssen, during the conduct of the study.
Conflict of interest: L. Guglielmetti reports grants from Janssen, during the conduct of the study.
Conflict of interest: N. Veziris reports grants from Janssen, during the conduct of the study.
Support statement: This work was supported by a grant from “Fonds de dotation Recherche en Santé Respiratoire” and by a grant from Janssen. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received December 30, 2019.
- Accepted April 20, 2020.
- The content of this work is copyright of the authors or their employers. Design and branding are copyright ©ERS 2020
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