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Fully weekly antituberculosis regimen: a proof-of-concept study

Fatma Kort, Laure Fournier Le Ray, Aurélie Chauffour, Vincent Jarlier, Nacer Lounis, Koen Andries, Alexandra Aubry, Lorenzo Guglielmetti, Nicolas Veziris
European Respiratory Journal 2020 56: 1902502; DOI: 10.1183/13993003.02502-2019
Fatma Kort
1Sorbonne Université, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, équipe 13, Paris, France
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Laure Fournier Le Ray
1Sorbonne Université, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, équipe 13, Paris, France
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Aurélie Chauffour
1Sorbonne Université, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, équipe 13, Paris, France
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  • ORCID record for Aurélie Chauffour
Vincent Jarlier
1Sorbonne Université, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, équipe 13, Paris, France
2APHP, Groupe Hospitalier Universitaire Sorbonne Université, Hôpital Pitié-Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France
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Nacer Lounis
3Janssen R&D, Beerse, Belgium
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Koen Andries
3Janssen R&D, Beerse, Belgium
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Alexandra Aubry
1Sorbonne Université, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, équipe 13, Paris, France
2APHP, Groupe Hospitalier Universitaire Sorbonne Université, Hôpital Pitié-Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France
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Lorenzo Guglielmetti
1Sorbonne Université, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, équipe 13, Paris, France
2APHP, Groupe Hospitalier Universitaire Sorbonne Université, Hôpital Pitié-Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France
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Nicolas Veziris
1Sorbonne Université, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, équipe 13, Paris, France
2APHP, Groupe Hospitalier Universitaire Sorbonne Université, Hôpital Pitié-Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France
4APHP, Groupe Hospitalier Universitaire Sorbonne Université, Hôpital Saint-Antoine, Département de Bactériologie, Paris, France
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  • For correspondence: nicolas.veziris@sorbonne-universite.fr
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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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Fully weekly antituberculosis regimen: a proof-of-concept study
Fatma Kort, Laure Fournier Le Ray, Aurélie Chauffour, Vincent Jarlier, Nacer Lounis, Koen Andries, Alexandra Aubry, Lorenzo Guglielmetti, Nicolas Veziris
European Respiratory Journal Sep 2020, 56 (3) 1902502; DOI: 10.1183/13993003.02502-2019

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Fully weekly antituberculosis regimen: a proof-of-concept study
Fatma Kort, Laure Fournier Le Ray, Aurélie Chauffour, Vincent Jarlier, Nacer Lounis, Koen Andries, Alexandra Aubry, Lorenzo Guglielmetti, Nicolas Veziris
European Respiratory Journal Sep 2020, 56 (3) 1902502; DOI: 10.1183/13993003.02502-2019
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