Standard chemotherapy with excluding isoniazid in a murine model of tuberculosis

Sun Shim Tae, Gae Lee Eun, Min Choi Chang, Sang Bum Hong, Yeon Mok Oh, Chae Man Lim, Do Lee Sang, Younsuck Koh, Sung Kim Woo, Soon Kim Dong, Sang Nae Cho, Dong Kim Won

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)177-182
Number of pages6
JournalTuberculosis and Respiratory Diseases
Volume65
Issue number3
DOIs
Publication statusPublished - 2008 Sep 1

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Isoniazid
Tuberculosis
Drug Therapy
Bacillus
Spleen
Therapeutics
Lung
Stem Cells
Pyrazinamide
Ethambutol
Control Groups
Rifampin
Infection Control
Infection
Aerosols
Inbred C57BL Mouse
Equipment and Supplies
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Infectious Diseases

Cite this

Tae, S. S., Eun, G. L., Chang, M. C., Hong, S. B., Oh, Y. M., Lim, C. M., ... Won, D. K. (2008). Standard chemotherapy with excluding isoniazid in a murine model of tuberculosis. Tuberculosis and Respiratory Diseases, 65(3), 177-182. https://doi.org/10.4046/trd.2008.65.3.177
Tae, Sun Shim ; Eun, Gae Lee ; Chang, Min Choi ; Hong, Sang Bum ; Oh, Yeon Mok ; Lim, Chae Man ; Sang, Do Lee ; Koh, Younsuck ; Woo, Sung Kim ; Dong, Soon Kim ; Cho, Sang Nae ; Won, Dong Kim. / Standard chemotherapy with excluding isoniazid in a murine model of tuberculosis. In: Tuberculosis and Respiratory Diseases. 2008 ; Vol. 65, No. 3. pp. 177-182.
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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.",
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Tae, SS, Eun, GL, Chang, MC, Hong, SB, Oh, YM, Lim, CM, Sang, DL, Koh, Y, Woo, SK, Dong, SK, Cho, SN & Won, DK 2008, 'Standard chemotherapy with excluding isoniazid in a murine model of tuberculosis', Tuberculosis and Respiratory Diseases, vol. 65, no. 3, pp. 177-182. https://doi.org/10.4046/trd.2008.65.3.177

Standard chemotherapy with excluding isoniazid in a murine model of tuberculosis. / Tae, Sun Shim; Eun, Gae Lee; Chang, Min Choi; Hong, Sang Bum; Oh, Yeon Mok; Lim, Chae Man; Sang, Do Lee; Koh, Younsuck; Woo, Sung Kim; Dong, Soon Kim; Cho, Sang Nae; Won, Dong Kim.

In: Tuberculosis and Respiratory Diseases, Vol. 65, No. 3, 01.09.2008, p. 177-182.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Standard chemotherapy with excluding isoniazid in a murine model of tuberculosis

AU - Tae, Sun Shim

AU - Eun, Gae Lee

AU - Chang, Min Choi

AU - Hong, Sang Bum

AU - Oh, Yeon Mok

AU - Lim, Chae Man

AU - Sang, Do Lee

AU - Koh, Younsuck

AU - Woo, Sung Kim

AU - Dong, Soon Kim

AU - Cho, Sang Nae

AU - Won, Dong Kim

PY - 2008/9/1

Y1 - 2008/9/1

N2 - 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.

AB - 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.

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