title: Sterilizing activity of second-line regimens containing TMC207 in a murine model of tuberculosis.
abstract: BACKGROUND
  The sterilizing activity of the regimen used to treat multidrug resistant tuberculosis (MDR TB) has not been studied in a mouse model.
  
  
  OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: UPMC Université Paris 06, EA 1541, laboratoire de Bactériologie-Hygiène, Paris, France. nicolas.veziris@upmc.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Veziris
authors.forename: Murad
authors.initials: M
authors.lastname: Ibrahim
authors.forename: Nacer
authors.initials: N
authors.lastname: Lounis
authors.forename: Koen
authors.initials: K
authors.lastname: Andries
authors.forename: Vincent
authors.initials: V
authors.lastname: Jarlier
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D064687:Diarylquinolines; D004195:Disease Models, Animal; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D012008:Recurrence; D013154:Spleen / Q000473:pathology; D013242:Sterilization; D016019:Survival Analysis; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D064687:Diarylquinolines; D011804:Quinolines; C493870:bedaquiline