Bactericidal potencies of new regimens are not predictive of their sterilizing potencies in a murine model of tuberculosis.
TMC207, rifapentine, and moxifloxacin are in clinical testing for the treatment of tuberculosis. Five experimental regimens with various combinations of TMC207, rifapentine, moxifloxacin, and pyrazinamide were tested for their bactericidal and sterilizing potencies in Swiss mice intravenously inoculated with Mycobacterium tuberculosis bacilli. TMC207 had the strongest bactericidal efficacy, while rifapentine was the strongest contributor to sterilizing efficacy. The rank order of sterilizing potencies was different from the rank order of bactericidal potencies, underlining the importance of prioritizing new regimens designed to shorten the treatment duration by their sterilizing potencies rather than by their bactericidal potencies. Both 3 months of treatment with a regimen combining TMC207, pyrazinamide, and rifapentine and 5 months of treatment with a regimen combining TMC207, pyrazinamide, and moxifloxacin resulted in relapse rates similar to the rate obtained by 6 months of treatment with rifampin-isoniazid-pyrazinamide.
Andries
Koen
K
Tibotec BVBA, Turnhoutseweg 30, Beerse, Belgium. kandries@its.jnj.com
Gevers
Tom
T
Lounis
Nacer
N
D000818:Animals; D000904:Antibiotics, Antitubercular / Q000494:pharmacology / Q000627:therapeutic use*; D001372:Aza Compounds / Q000627:therapeutic use; D064687:Diarylquinolines; D004195:Disease Models, Animal; D005260:Female; D024841:Fluoroquinolones; D051379:Mice; D000077266:Moxifloxacin; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000472:pathogenicity; D011718:Pyrazinamide / Q000627:therapeutic use; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use; D012293:Rifampin / Q000031:analogs & derivatives / Q000627:therapeutic use; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology*
D000904:Antibiotics, Antitubercular; D001372:Aza Compounds; D064687:Diarylquinolines; D024841:Fluoroquinolones; D011804:Quinolines; D011718:Pyrazinamide; C493870:bedaquiline; D000077266:Moxifloxacin; D012293:Rifampin; C018421:rifapentine