Combinations of R207910 with drugs used to treat multidrug-resistant tuberculosis have the potential to shorten treatment duration.
The objective of the present study was to identify the optimal R207910-containing regimen to administer to patients who cannot receive rifampin (RIF) and isoniazid (INH) because of multidrug-resistant tuberculosis (MDR-TB), concomitant use of antiretroviral drugs, or toxicity. Mice were infected intravenously with 5 x 10(6) CFU of the H37Rv strain and treated five times per week with R207910 alone or various combinations of R207910 with the second-line drugs amikacin (AMK), pyrazinamide (PZA), moxifloxacin (MXF), and ethionamide (ETH). All R207910-containing regimens were significantly more active than the non-R207910-containing regimens after 1 month of therapy. When given for 2 months, R207910 alone was more active than the WHO standard first-line regimen RIF-INH-PZA. When R207910 was combined with second-line drugs, the combinations were more active than the currently recommended regimen of MDR-TB AMK-ETH-MXF-PZA, and culture negativity of both the lungs and spleen was reached after 2 months of treatment in almost every case.
Lounis
Nacer
N
Tibotec Pharmaceuticals Ltd., Johnson & Johnson, Turnhoutseweg 30, 2340 Beerse, Belgium.
Veziris
Nicolas
N
Chauffour
Aurélie
A
Truffot-Pernot
Chantal
C
Andries
Koen
K
Jarlier
Vincent
V
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001372:Aza Compounds / Q000627:therapeutic use; D015169:Colony Count, Microbial; D064687:Diarylquinolines; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial; D005000:Ethionamide / Q000627:therapeutic use; D024841:Fluoroquinolones; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D000077266:Moxifloxacin; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011718:Pyrazinamide / Q000627:therapeutic use; D011804:Quinolines / Q000627:therapeutic use*; D012293:Rifampin / Q000627:therapeutic use; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D016019:Survival Analysis; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology
D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D001372:Aza Compounds; D064687:Diarylquinolines; D004338:Drug Combinations; D024841:Fluoroquinolones; D011804:Quinolines; D011718:Pyrazinamide; C493870:bedaquiline; D005000:Ethionamide; D000077266:Moxifloxacin; D012293:Rifampin