마우스 결핵 모델에서 Isoniazid를 제외한 표준치료의 예비 연구
Standard Chemotherapy with Excluding Isoniazid in a Murine Model of Tuberculosis
이은계 (연세대학교)
최창민 (울산대학교)
홍상범 (울산대학교)
오연목 (울산대학교)
임채만 (울산대학교)
이상도 (울산대학교)
고윤석 (울산대학교)
김우성 (울산대학교)
김동순 (울산대학교)
조상래 (연세의대 미생물학교실)
김원동 (울산대학교)
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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.
- keywords
- Tuberculosis, Isoniazid, Mouse
참고문헌
1. American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases Society of America. Treatment of tuberculosis. MMWR Recomm Rep 2003; 52:1-77.
2. Bai GH. Anti-tuberculosis drug resistance in Korea. Commun Dis Month Rep 2005;16:101-7.
3. Mitchison DA, Nunn AJ. Influence of initial drug resistance on the response to short-course chemotherapy of pulmonary tuberculosis. Am Rev Respir Dis 1986;133:423-30.
4. Lecoeur HF, Truffot-Pernot C, Grosset JH. Experimental short-course preventive therapy of tuberculosis with rifampin and pyrazinamide. Am Rev Respir Dis 1989;140:1189-93.
5. Grosset J, Truffot-Pernot C, Lacroix C, Ji B. Antagonism between isoniazid and the combination pyrazinamiderifampin against tuberculosis infection in mice. Antimicrob Agents Chemother 1992;36:548-51.
6. Jindani A, Dore CJ, Mitchison DA. Bactericidal and sterilizing activities of antituberculosis drugs during the first 14 days. Am J Respir Crit Care Med 2003;167:1348-54.
7. Nuermberger EL, Yoshimatsu T, Tyagi S, O'Brien RJ, Vernon AN, Chaisson RE, et al. Moxifloxacin-containing regimen greatly reduces time to culture conversion in murine tuberculosis. Am J Respir Crit Care Med 2004;169:421-6.
8. Rosenthal IM, Williams K, Tyagi S, Vernon AA, Peloquin CA, Bishai WR, et al. Weekly moxifloxacin and rifapentine s more active than the denver regimen in murine uberculosis. Am J Respir Crit Care Med 2005;172:1457-62.
9. Roberts AD, Cooper AM, Beslisle JT, Turner J, Gonzalez- Juarrero M, Orme IM. Murine model of tuberculosis. In: Kaufmann SHE, Kabelitz D, editors. Methods in microbiology, Vol. 32. New York: Elsevier Sciences; 2002. p. 433.
10. Nuermberger E, Rosenthal I, Tyagi S, Williams KN, Almeida D, Peloquin CA, et al. Combination chemotherapy with the nitroimidazopyran PA-824 and first-line drugs in a murine model of tuberculosis. Antimicrob Agents Chemother 2006;50:2621-5.
11. Centers for Disease Control and Prevention. Fatal and severe hepatitis associated with rifampin and pyrazinamide or the treatment of latent tuberculosis infection--New York and Georgia, 2000. MMWR Morb Mortal Wkly Rep 2001;50:289-91.
12. Centers for Disease Control and Prevention, American Thoracic Society. Update: adverse event data and revised American Thoracic Society/CDC recommendations against the use of rifampin and pyrazinamide for treatment of latent tuberculosis infection-United States, 2003. MMWR Morb Mortal Wkly Rep 2003;52:735-9.
13. Centers for Disease Control and Prevention. Update: Fatal and severe liver injuries associated with rifampin and pyrazinamide treatment for latent tuberculosis infection. MMWR Morb Mortal Wkly Rep 2002;51:998-9.
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