Standard Chemotherapy with Excluding Isoniazid in a Murine Model of Tuberculosis.
10.4046/trd.2008.65.3.177
- Author:
Tae Sun SHIM
1
;
Eun Gae LEE
;
Chang Min CHOI
;
Sang Bum HONG
;
Yeon Mok OH
;
Chae Man LIM
;
Sang Do LEE
;
Younsuck KOH
;
Woo Sung KIM
;
Dong Soon KIM
;
Sang Nae CHO
;
Won Dong KIM
Author Information
1. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Korea. shimts@amc.seoul.kr
- Publication Type:Original Article
- Keywords:
Tuberculosis;
Isoniazid;
Mouse
- MeSH:
Animals;
Ethambutol;
Isoniazid;
Lung;
Mice;
Pyrazinamide;
Rifampin;
Spleen;
Sprains and Strains;
Stem Cells;
Treatment Outcome;
Tuberculosis
- From:Tuberculosis and Respiratory Diseases
2008;65(3):177-182
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Isoniazid (INH, H) is a key drug of the standard first-line regimen for the treatment of tuberculosis (TB), yet some reports have suggested that treatment efficacy was maintained even though INH was omitted from the treatment regimen. METHODS: One hundred forty C57BL/6 mice were infected with the H37Rv strain of M. tuberculosis with using a Glas-Col aerosol generation device, and this resulted in depositing about 100 bacilli in the lung. Four weeks after infection, anti-TB treatment was initiated with varying regimens for 4-8 weeks; Group 1: no treatment (control), Group 2 (4HREZ): 4 weeks of INH, rifampicin (R), pyrazinamide (Z) and ethambutol (E), Group 3: 1HREZ/3REZ, Group 4: 4REZ, Group 5: 4HREZ/4HRE, Group 6: 1HREZ/3REZ/4RE, and Group 7: 4REZ/4RE. The lungs and spleens were harvested at several time points until 28 weeks after infection, and the colony-forming unit (CFU) counts were determined. RESULTS: The CFU counts increased steadily after infection in the control group. In the 4-week treatment groups (Group 2-4), even though the culture was negative at treatment completion, the bacilli grew again at the 12-week and 20-week time points after completion of treatment. In the 8-week treatment groups (Groups 5-7), the bacilli did not grow in the lung at 4 weeks after treatment initiation and thereafter. In the spleens of Group 7 in which INH was omitted from the treatment regimen, the culture was negative at 4-weeks after treatment initiation and thereafter. However, in Groups 5 and 6 in which INH was taken continuously or intermittently, the bacilli grew in the spleen at some time points after completion of treatment. CONCLUSION: TThe exclusion of INH from the standard first-line regimen did not affect the treatment outcome in a murine model of TB in the early stage of disease. Further studies using a murine model of chronic TB are necessary to clarify the role of INH in the standard first-line regimen for treating TB.
