A Retrospective Study for Relapse Rate According to the Discontinuance of Para-aminosalicylic acid(PAS) after Bacteriological Conversion during the Course of Chemotherapy for Multidrug- Resistant Tuberculosis(MDR-TB)

Para-aminosalicylic acid(PAS)가 포함된 처방으로 치료한 다제내성 결핵환자에서 치료경과 중 균음전 후 PAS 중단시 재발율에 관한 조사

  • 박승규 (국제결핵연구센터) ;
  • 김병주 (국제결핵연구센터) ;
  • 신동옥 (국립마산결핵병원 임상연구소) ;
  • 전병률 (국립마산결핵병원 임상연구소)
  • Received : 2005.12.20
  • Accepted : 2006.02.02
  • Published : 2006.02.28

Abstract

Background : Para-aminosalicylic acid(PAS) is a 2nd-line drug that can cause severe adverse reactions leading to poor patient compliance. This study evaluated the relapse rate according to the discontinuance of PAS at a certain point after bacteriological conversion during the course of chemotherapy for multidrug-resistant tuberculosis(MDR-TB). Methods : 42 out of 452 MDR-TB patients were enrolled in this study. All subjects were receiving chemotherapy including PAS at National Masan TB Hospital between Jan. 1, 2000 and Dec. 31, 2001. The relapse rate was evaluated after the discontinuance of PAS from their initial regimen as a result of the severe adverse reactions at a certain point after the bacteriological conversion during the course of chemotherapy for MDR-TB. Results : The male to female ratio was 2.5:1, and the mean age was 47.2 years old. The average number of past histories, used drugs and resistant drugs was 1.2, 3.9 and 4.3. The mean number of sensitive drugs included in the inirial regimen was 3.9. The mean time for bacteriological conversion and discontinuance of the PAS was 2.3 months after initiating treatment and 6 months after bacteriological conversion, respectively. There was no relapse after discontinuing PAS during a mean follow up period of 31.6 months. Conclusion : PAS may be discontinued in the cases of serious gastrointestinal problems approximately 6 months after bacteriological conversion without concern about relapse.

배경: 다제내성 결핵환자에서 이차약제로 구성된 처방 복약시 특히 PAS는 심한 위장장애 등의 부작용으로 환자의 치료순응도 저하에 중요한 요인이 되므로 균음전 후 PAS를 처방에서 제외한 경우의 치료경과 특히, 치료종결 후 재발율에 대한 조사를 통해 치료경과 중에 적절한 시점에 처방에서 PAS제외 가능성에 대하여 평가하고자 하였다. 방법: 2000년 1월 1일부터 2001년 12월 31일 동안에 국립마산결핵병원에서 입원 혹은 외래치료를 받았던 452명의 다제내성 결핵환자 중에서 처방에 PAS가 포함된 194명 중 심한 위장장애 등의 부작용 때문에 PAS를 중단한 환자 중 균음전 후 PAS를 제외한 처방을 12개월 이상 유지할 수 있었던 42명을 대상으로 임상적 특성 및 치료종결 후 재발율을 분석하였다. 결과: 대상환자의 남녀성비는 2.5:1, 평균나이는 56.2세였다. 1.2회의 과거치료력이 있었으며, 사용한 약제는 평균 3.9제였다. 내성약제수는 평균 4.3제였으며 처방에 포함된 감수성약제수는 평균 3.9제였다. 치료가 시작된 후 균음전시기는 평균 2.3개월째였으며, PAS 중단 시기는 균음전 후 평균 6개월째였다. 31.6개월의 추구관찰 기간 중 재발환자는 없었다. 결론: 새로운 항결핵제의 개발이 요원하고, 다제내성 결핵에 사용가능한 약제가 제한된 현 상황에서 치료순응도 개선방안을 강구하는 것은 치료효율을 높일 수 있는 최선의 방법 중 하나라고 생각되며, 다제내성 결핵환자에서 PAS가 포함된 처방으로 균음전이 되고 환자가 PAS복약에 따른 부작용을 호소하여 치료순응도가 나빠질 것으로 염려가 되면 균음전 후 6개월 즈음에는 PAS를 처방에서 제외할 수 있을 것으로 판단되었다.

Keywords

References

  1. Kritski AL, Rodrigues de Jesus LS, Andrade MK, Werneck-Barroso E, Vieira MA, Haffner A, et al. Retreatment tuberculosis cases: factors associated with drug resistance and adverse outcomes. Chest 1997;111:1162-7 https://doi.org/10.1378/chest.111.5.1162
  2. Bechan S, Connolly C, Short GM, Standing E, Wilkinson D. Directly observed therapy for tuberculosis given twice weekly in the workplace in urban South Africa. Trans R Soc Trop Med Hyg 1997;9 1:704-7
  3. Goble M, Iseman MD, Madsen LA, Waite D, Ackerson L, Horsburgh CR Jr. Treatment of 171 patients with pulmonary tuberculosis resistant to isoniazid and rifampin. N Engl J Med 1993;328:527-32 https://doi.org/10.1056/NEJM199302253280802
  4. Weis SE, Slocum PC, Blais FX, King B, Nunn M, Matney GB, et al. The effect of directly observed therapy on the rates of drug resistance and relapse in tuberculosis. N Engl J Med 1994;330:1179-84 https://doi.org/10.1056/NEJM199404283301702
  5. Pearce SJ, Horne NW. Follow-up of patients with pulmonary tuberculosis adequately treated by chemotherapy:is this really necessary? Lancet 1974;2:641-3
  6. Singapore Tuberculosis Service/Birtish Medical Research Council. Five-year follow-up of a clinical trial of three 6-month regimens of chemotherapy given intermittently in the continuation phase in the treatment of pulmonary tuberculosis. Am Rev Respir Dis 1988;137:1147-50 https://doi.org/10.1164/ajrccm/137.5.1147
  7. Kopanoff DE, Snider DE Jr, Johnson M. Recurrent tuberculosis: why do patients develop disease again- Am J Public Health 1988;78:30-3 https://doi.org/10.2105/AJPH.78.1.30
  8. Burman WJ, Cohn DL, Rietmeijer CA, Judson FN, Sbarbaro JA, Reves RR. Noncompliance with directly observed therapy for tuberculosis: epidemiology and effect on the outcome of treatment. Chest 1997;111:1168-73 https://doi.org/10.1378/chest.111.5.1168
  9. Jarvis B, Lamb HM. Rifapentine. Drugs 1998;56:607-16 https://doi.org/10.2165/00003495-199856040-00008
  10. Addington WW. Patient compliance: the most serious remaining problem in the control of tuberculosis in the United States. Chest 1979;76:741-3 https://doi.org/10.1378/chest.76.6_Supplement.741
  11. Davidson PT, Le HQ. Drug treatment of tuberculosis:1992. Drugs 1992;43:651-73 https://doi.org/10.2165/00003495-199243050-00003
  12. Kilpatrick GS. Compliance in relation to tuberculosis. Tubercle 1987;68:31-2 https://doi.org/10.1016/S0041-3879(87)80018-1
  13. Cueno WD, Snider DE Jr. Enhancing patient compliance with tuberculosis therapy. Clin Chest Med 1989;10:375-80
  14. Snider DE Jr, Roper WL. The new tuberculosis. N Engl J Med 1992;326:703-5 https://doi.org/10.1056/NEJM199203053261011
  15. Bloch AB, Cauthen GM, Simone PM, Kelly GD, Dansbury KG, Castro KG. Completion of tuberculosis therapy for patients reported in the United States in 1993. Int J Tuberc Lung Dis 1999;3:273-80
  16. American Thoracic Society, CDC, Infectious Diseases Society of America. Treatment of tuberculosis. MMWR Recomm Rep 2003;52:1-77
  17. Centers for Disease Control. Patients with recurrent tuberculosis. MMWR Morb Mortal Wkly Rep 1982;30:645-7
  18. la Raja M, Screm C, Talmassons G, Pasquadibisceglie A, Pitzalis G, Pitzus E. Antituberculosis drug-resistance surveillance as a tool for tuberculosis control programmes. Monaldi Arch Chest Dis 1997;52:450-4
  19. Strull GE, Dym H. Tuberculosis: diagnosis and treatment of resurgent disease. J Oral Maxillofac Surg 1995;53:1334-40 https://doi.org/10.1016/0278-2391(95)90597-9
  20. Canetti G, Froman S, Grosset J, Hauduroy P, Langerova M, Mahler HT, et al. Mycobacteria: laboratory methods for testing drug sensitivity and resistance. Bull World Health Organ 1963;29:565-78
  21. Park SK, Lee WC, Lee DH, Mitnick CD, Han L, Seung KJ. Self-administered, standardized regimens for multidrug-resistant tuberculosis in South Korea. Int J Tuberc Lung Dis 2004;8:361-8
  22. Kim HK, Hong YP, Kim SJ, Lew WJ, Lee EG. Ambulatory treatment of multidrug-resistant tuberculosis patients at a chest clinic. Int J Tuberc Lung Dis 2001;5:1129-36
  23. Volmink J, Matchaba P, Garner P. Directly observed therapy and treatment adherence. Lancet 2000;355:1345-50 https://doi.org/10.1016/S0140-6736(00)02124-3
  24. Mangura B, Napoltano E, Pascannante M, Sarrel M, McDonald R, Galanowsky K, et al. Directly observed therapy(DOT) is not the entire answer: an operational cohort analysis. Int J Tuberc Lung Dis 2002;6:654-61
  25. Bernheim F. Effect of salicylates on oxygen uptake of tubercle bacillus. Science 1940;92:204
  26. Lehman J. Para-aminosalicylic acid in the treatment of tuberculosis. Lancet 1946;250:15-6
  27. Lorian V. Antibiotics in laboratory medicine. 2nd ed. Baltimore: Williams & Wilkins; 1986
  28. Rengarajan J, Sassetti CM, Naroditskaya V, Sloutsky A, Bloom BR, Rubin EJ. The folate pathway is a target for resistance to the drug para-aminosalicylic acid (PAS) in mycobacteria. Mol Microbiol 2004;53:275-82 https://doi.org/10.1111/j.1365-2958.2004.04120.x
  29. Kucers A, Bennett N. The use of antibiotics. 3rd ed. London: Heinemann; 1979
  30. Pfuetze K, de la Huerga J, Frakis A. Out-patient acceptance of PAS: transactions of the 20th research conference in pulmonary diseases. Washington, DC:Veterans Administration Department of Medicine and Surgery; 1961
  31. Ormerod LP. Multidrug-resistant tuberculosis(MDR-T B): epidemiology, prevention and treatment. Br Med Bull 2005;73:17-24 https://doi.org/10.1093/bmb/ldh047