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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-08-01
|
| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://doi.org/10.1371/journal.pntd.0007857 |
| _version_ | 1818405992602271744 |
|---|---|
| author | Aurélie Chauffour Jérôme Robert Nicolas Veziris Alexandra Aubry Kevin Pethe Vincent Jarlier |
| author_facet | Aurélie Chauffour Jérôme Robert Nicolas Veziris Alexandra Aubry Kevin Pethe Vincent Jarlier |
| author_sort | Aurélie Chauffour |
| collection | DOAJ |
| 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 | 2024-12-14T09:04:51Z |
| format | Article |
| id | doaj.art-8e522c46fd8e4b0ab4ab206ec9764955 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-14T09:04:51Z |
| publishDate | 2020-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-8e522c46fd8e4b0ab4ab206ec97649552022-12-21T23:08:44ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352020-08-01148e000785710.1371/journal.pntd.0007857Telacebec (Q203)-containing intermittent oral regimens sterilized mice infected with Mycobacterium ulcerans after only 16 doses.Aurélie ChauffourJérôme RobertNicolas VezirisAlexandra AubryKevin PetheVincent JarlierBuruli 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.https://doi.org/10.1371/journal.pntd.0007857 |
| spellingShingle | Aurélie Chauffour Jérôme Robert Nicolas Veziris Alexandra Aubry Kevin Pethe Vincent Jarlier Telacebec (Q203)-containing intermittent oral regimens sterilized mice infected with Mycobacterium ulcerans after only 16 doses. PLoS Neglected Tropical Diseases |
| 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 |
| url | https://doi.org/10.1371/journal.pntd.0007857 |
| work_keys_str_mv | AT aureliechauffour telacebecq203containingintermittentoralregimenssterilizedmiceinfectedwithmycobacteriumulceransafteronly16doses AT jeromerobert telacebecq203containingintermittentoralregimenssterilizedmiceinfectedwithmycobacteriumulceransafteronly16doses AT nicolasveziris telacebecq203containingintermittentoralregimenssterilizedmiceinfectedwithmycobacteriumulceransafteronly16doses AT alexandraaubry telacebecq203containingintermittentoralregimenssterilizedmiceinfectedwithmycobacteriumulceransafteronly16doses AT kevinpethe telacebecq203containingintermittentoralregimenssterilizedmiceinfectedwithmycobacteriumulceransafteronly16doses AT vincentjarlier telacebecq203containingintermittentoralregimenssterilizedmiceinfectedwithmycobacteriumulceransafteronly16doses |