Telacebec (Q203)-containing intermittent oral regimens sterilized mice infected with Mycobacterium ulcerans after only 16 doses
Buruli ulcer (BU), caused by Mycobacterium ulcerans, is currently treated with a daily combination of rifampin and either injectable streptomycin or oral clarithromycin. An intermittent oral regimen would facilitate treatment supervision. We first evaluated the bactericidal activity of newer antimic...
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| Format: | Journal Article |
| Language: | English |
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2021
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| Online Access: | https://hdl.handle.net/10356/148764 |
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| author | Chauffour, Aurélie Robert, Jérôme Veziris, Nicolas Aubry, Alexandra Pethe, Kevin Jarlier, Vincent |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Chauffour, Aurélie Robert, Jérôme Veziris, Nicolas Aubry, Alexandra Pethe, Kevin Jarlier, Vincent |
| author_sort | Chauffour, Aurélie |
| collection | NTU |
| description | Buruli ulcer (BU), caused by Mycobacterium ulcerans, is currently treated with a daily combination of rifampin and either injectable streptomycin or oral clarithromycin. An intermittent oral regimen would facilitate treatment supervision. We first evaluated the bactericidal activity of newer antimicrobials against M. ulcerans using a BU animal model. The imidazopyridine amine telacebec (Q203) exhibited high bactericidal activity whereas tedizolid (an oxazolidinone closely related to linezolid), selamectin and ivermectin (two avermectine compounds) and the benzothiazinone PBTZ169 were not active. Consequently, telacebec was evaluated for its bactericidal and sterilizing activities in combined intermittent regimens. Telacebec given twice a week in combination with a long-half-life compound, either rifapentine or bedaquiline, sterilized mouse footpads in 8 weeks, i.e. after a total of only 16 doses, and prevented relapse during a period of 20 weeks after the end of treatment. These results are very promising for future intermittent oral regimens which would greatly simplify BU treatment in the field. |
| first_indexed | 2025-02-19T03:28:02Z |
| format | Journal Article |
| id | ntu-10356/148764 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:28:02Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1487642023-03-05T16:49:50Z Telacebec (Q203)-containing intermittent oral regimens sterilized mice infected with Mycobacterium ulcerans after only 16 doses Chauffour, Aurélie Robert, Jérôme Veziris, Nicolas Aubry, Alexandra Pethe, Kevin Jarlier, Vincent Lee Kong Chian School of Medicine (LKCMedicine) School of Biological Sciences Science::Medicine Bedaquiline Imidazole Derivative Buruli ulcer (BU), caused by Mycobacterium ulcerans, is currently treated with a daily combination of rifampin and either injectable streptomycin or oral clarithromycin. An intermittent oral regimen would facilitate treatment supervision. We first evaluated the bactericidal activity of newer antimicrobials against M. ulcerans using a BU animal model. The imidazopyridine amine telacebec (Q203) exhibited high bactericidal activity whereas tedizolid (an oxazolidinone closely related to linezolid), selamectin and ivermectin (two avermectine compounds) and the benzothiazinone PBTZ169 were not active. Consequently, telacebec was evaluated for its bactericidal and sterilizing activities in combined intermittent regimens. Telacebec given twice a week in combination with a long-half-life compound, either rifapentine or bedaquiline, sterilized mouse footpads in 8 weeks, i.e. after a total of only 16 doses, and prevented relapse during a period of 20 weeks after the end of treatment. These results are very promising for future intermittent oral regimens which would greatly simplify BU treatment in the field. Published version 2021-05-17T08:39:55Z 2021-05-17T08:39:55Z 2020 Journal Article Chauffour, A., Robert, J., Veziris, N., Aubry, A., Pethe, K. & Jarlier, V. (2020). Telacebec (Q203)-containing intermittent oral regimens sterilized mice infected with Mycobacterium ulcerans after only 16 doses. PLoS Neglected Tropical Diseases, 14(8). https://dx.doi.org/10.1371/journal.pntd.0007857 1935-2727 https://hdl.handle.net/10356/148764 10.1371/journal.pntd.0007857 32866170 2-s2.0-85090520826 8 14 en PLoS Neglected Tropical Diseases © 2020 Chauffour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. application/pdf |
| spellingShingle | Science::Medicine Bedaquiline Imidazole Derivative Chauffour, Aurélie Robert, Jérôme Veziris, Nicolas Aubry, Alexandra Pethe, Kevin Jarlier, Vincent Telacebec (Q203)-containing intermittent oral regimens sterilized mice infected with Mycobacterium ulcerans after only 16 doses |
| title | Telacebec (Q203)-containing intermittent oral regimens sterilized mice infected with Mycobacterium ulcerans after only 16 doses |
| title_full | Telacebec (Q203)-containing intermittent oral regimens sterilized mice infected with Mycobacterium ulcerans after only 16 doses |
| title_fullStr | Telacebec (Q203)-containing intermittent oral regimens sterilized mice infected with Mycobacterium ulcerans after only 16 doses |
| title_full_unstemmed | Telacebec (Q203)-containing intermittent oral regimens sterilized mice infected with Mycobacterium ulcerans after only 16 doses |
| title_short | Telacebec (Q203)-containing intermittent oral regimens sterilized mice infected with Mycobacterium ulcerans after only 16 doses |
| title_sort | telacebec q203 containing intermittent oral regimens sterilized mice infected with mycobacterium ulcerans after only 16 doses |
| topic | Science::Medicine Bedaquiline Imidazole Derivative |
| url | https://hdl.handle.net/10356/148764 |
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