Activity of KRM-1648 in combination with isoniazid against Mycobacterium tuberculosis in a murine model.
AUTOR(ES)
Klemens, S P
RESUMO
The activity of KRM-1648, alone and in combination with isoniazid, was compared with those of isoniazid, rifampin, and the combination of rifampin plus isoniazid in a murine model of tuberculosis. Four-week-old female CD-1 mice were infected intravenously with approximately 10(7) viable Mycobacterium tuberculosis ATCC 35801 organisms. Treatment was started 1 week postinfection and was given by gavage 5 days per week. The duration of the treatment phase was 12 weeks, with groups of mice sacrificed at 2, 4, 6, 8, and 12 weeks. For the observation phase, additional groups of treated mice were sacrificed at 4, 8, 16, and 24 weeks after the cessation of treatment. Viable cell counts were determined from homogenates of the spleens and the right lungs. KRM-1648 was the most active single agent evaluated and resulted in no detectable CFUs in the spleens and lungs by the end of 6 weeks of treatment. Neither rifampin nor isoniazid reduced cell counts to undetectable levels, even after 12 weeks of treatment. The combination of KRM-1648 plus isoniazid was much more active than rifampin plus isoniazid. KRM-1648 plus isoniazid resulted in the apparent sterilization of organs at 6 months following the cessation of treatment. The promising activity of KRM-1648 may allow for ultrashort-course therapy of tuberculosis, i.e., treatment regimens of 4 months or less.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=163105Documentos Relacionados
- Activity of KRM-1648, a new benzoxazinorifamycin, against Mycobacterium tuberculosis in a murine model.
- In vitro and in vivo activities of the benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis.
- Bacteriostatic and bactericidal activities of benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis and Mycobacterium avium in human macrophages.
- Activity of KRM-1648 alone or in combination with both ethambutol and kanamycin or clarithromycin against Mycobacterium intracellulare infections in beige mice.
- Activity of KRM 1648 alone or in combination with ethambutol or clarithromycin against Mycobacterium avium in beige mouse model of disseminated infection.
