소아 결핵 환자에서의 항결핵제 내성 Ⅱ = Drug resistance of Mycobacterium tuberculosis in children

다국어 초록 (Multilingual Abstract)

Purpose : The rate of drug-resistant tuberculosis (DR-TB) in children is an indicator of the effectiveness of TB control programs in the community. This study aimed to assess the prevalence of DR-TB in children and evaluate TB management.
Methods : Between January 1999 and July 2007, drug susceptibility tests for anti-TB drugs were employed for patients aged less than 19 years with culture-positive TB.
Results : A total of 607 cases (16.6%) were resistant to at least one anti-TB drug as follows: isoniazid (INH; 13.8%), rifampin (8.9%), pyrazinamide (4.2%), streptomycin (3.7%), ethambutol (EMB; 5.9%), and para-aminosalicylic acid (PAS; 1.9%). Multidrug-resistant (MDR) TB was found in 276 cases (7.6%); extensive drug resistant (XDR) TB, in 5 cases (0.2%). The rate of resistance to at least one anti-TB drug in children aged >15 years (16.1%) was significantly lower than that in children aged <15 years (20.5%) (P=0.016). The rate of resistance to at least one anti-TB drug and multidrug-resistance in this survey decreased significantly (P<0.001) as compared to the previous survey (1987-1995). The rate of resistance to INH, EMB, and PAS also significantly decreased (P<0.05).
Conclusion : The rate of DR-TB in children in Korea has decreased over time; however, it remains higher than that in other countries. MDR-TB and XDR-TB are the emerging problems in Korean children. Therefore, the selection of effective drugs through drug susceptibility tests and evaluating risk factors of resistant TB is essential to successful therapy and a decreased incidence of DR-TB.

국문 초록 (Abstract)

목 적 : 소아에서의 항결핵제 내성률은 지역 사회에서의 결핵 관리의 효율성을 파악하는 척도가 되나 국내외의 보고가 많지 않다. 이에 저자들은 소아청소년 결핵에서의 약제 내성률과 변화 경향을 조사하여 결핵 치료 및 예방적 화학요법 처방 선정에 도움을 얻고자 하였다.
방 법 : 1999년 1월부터 2007년 7월까지 대한결핵협회 결핵 연구원 미생물부(세계보건기구 지정 국제자문검사소)에 배양 및 감수성 검사가 의뢰되어 M. tuberculosis가 분리되어 항결핵제에 대한 감수성 검사가 실시된 예 중 19세 이하를 대상으로 항결핵제에 대한 감수성 검사를 실시하였다.
결 과 : 소아청소년에서 한 가지 이상의 약제에 대해 내성을 보인 균주는 607균주(16.6%)였고, IHN에 대해 내성을 보인 균주는 503균주(13.8%), RFP에 대해서는 326균주(8.9%), PZA에 대해서는 155균주(4.2%), SM에 대해서는 134균주(3.7%), EMB에 대해서는 215균주(5.9%), PAS에 대해서는 70균주(1.9%)였다. 다제내성결핵균은 276균주(7.6%)였고 광범위약제내성결핵균은 5균주(0.2%)였다. 15세 이하에서보다(20.5%) 15세 이상에서의 한 가지 이상의 약제에 대한 내성률(16.1%)이 유의하게 낮았고(P=0.016), 다제내성결핵이 차지하는 비율도 낮았으나(각각 8.7 %, 7.4%) 통계적으로 유의하지는 않았다. 본 조사 기간 동안 한 가지 이상의 결핵 약제에 대한 내성률과 다제내성결핵이 차지하는 비율은 유의하게 감소하였다(P<0.001). 이전 1987년부터 1995년까지의 조사와 비교해 보면, 한 가지 이상의 결핵 약제에 대한 내성률은 37.5%에서 20.5%로 유의하게 감소하였고(P=0.007), INH, EMB, PAS에 대한 내성률의 감소는 통계적으로 유의하였으며(P<0.05), 다제내성결핵이 차지하는 비율도 감소하였으나 통계적으로 유의하지는 않았다.
결 론 : 소아청소년 결핵에서의 약제 내성률은 과거에 비해 점차로 감소하는 양상을 보이고 있으나, 아직은 다른 나라보다 높고 다제내성결핵과 광범위약제내성결핵이 새로운 문제로 대두되고 있어 약제 감수성 검사와 내성균 감염 위험 요인 파악을 통한 효율적인 치료 약제 선정으로 치료 성공률을 높이면서 항결핵제 내성균의 증가를 막아야 할 것으로 사료된다.

참고문헌 (Reference)

• 1 Raviglione MC, "XDR tuberculosis implications for global public health" 356 : 656-659, 2007
• 2 Dye C, "Worldwide incidence of multidrug-resistant tuberculosis" 185 : 1197-1202, 2002
• 3 Starke J, "Tuberculosis in children" 23 : 861-881, 1996
• 4 de Pontual L, "Tuberculosis in adolescents: A French retrospective study of 52 cases" 25 : 930-932, 2006
• 5 Bai GH, "Trend of anti-tuberculosis drug resistance in Korea, 1994-2004" 11 : 571-576, 2007
• 6 Kwon KB, "The significance of bacteriologic examination in the childhood tuberculosis" 37 : 221-228, 1994
• 7 Corbett EL, "The growing burden of tuberculosis: global trends and interactions with the HIV epidemic" 163 : 1009-1021, 2003
• 8 Wane LG, "Simple pyrazinamidase and urease tests for routine identification of mycobacteria" 109 : 147-151, 1974
• 9 Torun T, "Side effects associated with the treatment of multidrug-resistant tuberculosis" 9 : 1373-1377, 2005
• 10 Ena J, "Short-course therapy with rifampin plus isoniazid compared with standard therapy with isoniazid, for latent tuberculosis infection: a meta-analysis" 40 : 670-676, 2005
• 11 Ormerod LP, "Rifampicin and isoniazid prophylactic chemotherapy for tuberculosis" 78 : 169-171, 1998
• 12 Centers for Disease Control and Prevention, "Revised definition of extensively drug-resistant tuberculosis" 55 : 1176-, 2006
• 13 Mukherjee JS, "Programmes and principles in treatment of multidrug-resistant tuberculosis" 363 : 474-481, 2004
• 14 Steiner M, "Primary tuberculosis in children : I. Incidence of primary drug resistant disease in 332 children observed between the years 1961 and 1964 at the Kings Country Medical Center of Brooklyn" 274 : 755-759, 1966
• 15 World Health Organization, "Guidelines for the programmatic management of drug-resistant tuberculosis. WHO/HTM/TB/ 2006.361. Geneva, Switzerland: WHO"
• 16 Korean Academy of Tuberculosis and Respiratory Diseases, "Guideline for the management of pulmonary tuberculosis"
• 17 World Health Organization, "Global tuberculosis control: suveillance, planning, financing. WHO/HTM/TB 2006. 362. Geneva, Switzerland: WHO"
• 18 Pablos-Mendez A, "Global surveillance for antituberculosis-drug resistance, 1994-1997" 338 : 1641-1649, 1998
• 19 World Health Organization, "Global map and information on XDR-TB"
• 20 Zignol M, "Global incidence of multidrug-resistant tuberculosis" 194 : 479-485, 2006
• 21 Nelson LJ, "Global epidemiology of childhood tuberculosis" 8 : 636-647, 2004
• 22 Schaaf HS, "Evaluation of young children in contact with adult multidrug-resistant pulmonary tuberculosis: a 30- month follow-up" 109 : 765-771, 2002
• 23 Nelson LJ, "Epidemiology of childhood tuberculosis in the united states, 19932001: The need for continued vgilance" 114 : 333-341, 2004
• 24 Aziz MA, "Epidemiology of anti-tuberculosis drug resistance (the global project on anti-tuberculosis drug resistance surveillance): an updated analysis" 368 : 2142-2154, 2006
• 25 Centers for Disease Control and Prevention (CDC), "Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drug-worldwide, 2000-2004" 55 : 301-305, 2006
• 26 Jang SH, "Drug-resistant tuberculosis in children" 40 : 818-824, 1997
• 27 Kim SJ, "Drug resistance of Mycobacterium tuberculosis in Korea" 38 : 99-107, 1991
• 28 Kim SJ, "Drug resistance of Mycobacterium tuberculosis in Korea" 1 : 302-308, 1997
• 29 Jae Chol Choi, "Drug Resistance Rates of Mycobacterium tuberculosis at a PrivateReferral Center in Korea" 대한의학회 22 (22): 677-681, 2007
• 30 American Thoracic Society/Center for Disease Control and Prevention, "Diagnostic standards and classification of tuberculosis in adults and children" 161 : 1376-1395, 2000
• 31 Schaaf HS, "Childhood drug-resistant tuberculosis in the Western Cape Province of South Africa" 95 : 523-528, 2006
• 32 World Health Organization, "Anti-tuberculosis drug resistance in the world: 3rd Report: the WHO/IUATLD global project on anti-tuberculosis drug resistance surveillance 1999-2002" WHO 2004
• 33 Bai GH, "Anti-tuberculosis drug resistance in Korea" 16 : 101-107, 2005
• 34 Ganetti G, "Advances in techniques of testing mycobacterial drug sensitivity, and the use of sensitivity tests in tuberculosis control programmes" 41 : 21-43, 1969
• 35 Hesseling A, "A critical review of diagnostic approaches used in the diagnosis of childhood tuberculosis" 6 : 1038-1045, 2002
• 36 British Thoracic Association, "A controlled trial of six months chemotherapy in pulmonary tuberculosis: first report: results during chemotherapy" 75 : 141-153, 1981
• 37 박영길, "2003~2005년도 민간 병의원 신환자에서 분리된 결핵균의 항결핵약제 내성률" 대한결핵및호흡기학회 64 (64): 87-94, 2008