Sterilizing activity of second-line regimens containing TMC207 in a murine model of tuberculosis.

<h4>Rationale</h4>The sterilizing activity of the regimen used to treat multidrug resistant tuberculosis (MDR TB) has not been studied in a mouse model.<h4>Objective and methods</h4>Swiss mice were intravenously inoculated with 6 log10 of Mycobacterium tuberculosis (TB) strai...

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Autores principales:	Nicolas Veziris, Murad Ibrahim, Nacer Lounis, Koen Andries, Vincent Jarlier
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Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b41338aa1a849aea4a30571471ea535
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spelling	oai:doaj.org-article:5b41338aa1a849aea4a30571471ea5352021-11-18T06:57:48ZSterilizing activity of second-line regimens containing TMC207 in a murine model of tuberculosis.1932-620310.1371/journal.pone.0017556https://doaj.org/article/5b41338aa1a849aea4a30571471ea5352011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21408613/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Rationale</h4>The sterilizing activity of the regimen used to treat multidrug resistant tuberculosis (MDR TB) has not been studied in a mouse model.<h4>Objective and methods</h4>Swiss mice were intravenously inoculated with 6 log10 of Mycobacterium tuberculosis (TB) strain H37Rv, treated with second-line drug combinations with or without the diarylquinoline TMC207, and then followed without treatment for 3 more months to determine relapse rates (modified Cornell model).<h4>Measurements</h4>Bactericidal efficacy was assessed by quantitative lung colony-forming unit (CFU) counts. Sterilizing efficacy was assessed by measuring bacteriological relapse rates 3 months after the end of treatment.<h4>Main results</h4>The relapse rate observed after 12 months treatment with the WHO recommended MDR TB regimen (amikacin, ethionamide, pyrazinamide and moxifloxacin) was equivalent to the relapse rate observed after 6 months treatment with the recommended drug susceptible TB regimen (rifampin, isoniazid and pyrazinamide). When TMC207 was added to this MDR TB regimen, the treatment duration needed to reach the same relapse rate dropped to 6 months. A similar relapse rate was also obtained with a 6-month completely oral regimen including TMC207, moxifloxacin and pyrazinamide but excluding both amikacin and ethionamide.<h4>Conclusions</h4>In this murine model the duration of the WHO MDR TB treatment could be reduced to 12 months instead of the recommended 18-24 months. The inclusion of TMC207 in the WHO MDR TB treatment regimen has the potential to further shorten the treatment duration and at the same time to simplify treatment by eliminating the need to include an injectable aminoglycoside.Nicolas VezirisMurad IbrahimNacer LounisKoen AndriesVincent JarlierPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 3, p e17556 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicolas Veziris Murad Ibrahim Nacer Lounis Koen Andries Vincent Jarlier Sterilizing activity of second-line regimens containing TMC207 in a murine model of tuberculosis.
description	<h4>Rationale</h4>The sterilizing activity of the regimen used to treat multidrug resistant tuberculosis (MDR TB) has not been studied in a mouse model.<h4>Objective and methods</h4>Swiss mice were intravenously inoculated with 6 log10 of Mycobacterium tuberculosis (TB) strain H37Rv, treated with second-line drug combinations with or without the diarylquinoline TMC207, and then followed without treatment for 3 more months to determine relapse rates (modified Cornell model).<h4>Measurements</h4>Bactericidal efficacy was assessed by quantitative lung colony-forming unit (CFU) counts. Sterilizing efficacy was assessed by measuring bacteriological relapse rates 3 months after the end of treatment.<h4>Main results</h4>The relapse rate observed after 12 months treatment with the WHO recommended MDR TB regimen (amikacin, ethionamide, pyrazinamide and moxifloxacin) was equivalent to the relapse rate observed after 6 months treatment with the recommended drug susceptible TB regimen (rifampin, isoniazid and pyrazinamide). When TMC207 was added to this MDR TB regimen, the treatment duration needed to reach the same relapse rate dropped to 6 months. A similar relapse rate was also obtained with a 6-month completely oral regimen including TMC207, moxifloxacin and pyrazinamide but excluding both amikacin and ethionamide.<h4>Conclusions</h4>In this murine model the duration of the WHO MDR TB treatment could be reduced to 12 months instead of the recommended 18-24 months. The inclusion of TMC207 in the WHO MDR TB treatment regimen has the potential to further shorten the treatment duration and at the same time to simplify treatment by eliminating the need to include an injectable aminoglycoside.
format	article
author	Nicolas Veziris Murad Ibrahim Nacer Lounis Koen Andries Vincent Jarlier
author_facet	Nicolas Veziris Murad Ibrahim Nacer Lounis Koen Andries Vincent Jarlier
author_sort	Nicolas Veziris
title	Sterilizing activity of second-line regimens containing TMC207 in a murine model of tuberculosis.
title_short	Sterilizing activity of second-line regimens containing TMC207 in a murine model of tuberculosis.
title_full	Sterilizing activity of second-line regimens containing TMC207 in a murine model of tuberculosis.
title_fullStr	Sterilizing activity of second-line regimens containing TMC207 in a murine model of tuberculosis.
title_full_unstemmed	Sterilizing activity of second-line regimens containing TMC207 in a murine model of tuberculosis.
title_sort	sterilizing activity of second-line regimens containing tmc207 in a murine model of tuberculosis.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/5b41338aa1a849aea4a30571471ea535
work_keys_str_mv	AT nicolasveziris sterilizingactivityofsecondlineregimenscontainingtmc207inamurinemodeloftuberculosis AT muradibrahim sterilizingactivityofsecondlineregimenscontainingtmc207inamurinemodeloftuberculosis AT nacerlounis sterilizingactivityofsecondlineregimenscontainingtmc207inamurinemodeloftuberculosis AT koenandries sterilizingactivityofsecondlineregimenscontainingtmc207inamurinemodeloftuberculosis AT vincentjarlier sterilizingactivityofsecondlineregimenscontainingtmc207inamurinemodeloftuberculosis
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Sterilizing activity of second-line regimens containing TMC207 in a murine model of tuberculosis.

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