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다제내성결핵 균주에서 Reverse Hybridization Assay를 이용한 Fluoroquinolone, Kanamycin 신속 내성 검사의 유용성
박진수 ( Chin Su Park ),성낙문 ( Nack Moon Sung ),황수희 ( Soo Hee Hwang ),전재현 ( Jae Hyun Jeon ),원영섭 ( Young Sub Won ),민진홍 ( Jin Hong Min ),김천태 ( Cheon Tae Kim ),강형석 ( Hyung Seok Kang ) 대한결핵 및 호흡기학회 2012 Tuberculosis and Respiratory Diseases Vol.72 No.1
Multidrug-resistant tuberculosis (MDR-TB) is an increasing public health problem and poses a serious threat to global TB control. Fluoroquinolone (FQ) and aminoglycoside (AG) are essential anti-TB drugs for MDR-TB treatment. REBA MTB-FQ? and REBA MTB-KM? (M&D, Wonju, Korea) were evaluated for rapid detection of FQ and kanamycin (KM) resistance in MDR-TB clinical isolates. M. tuberculosis (n=67) were isolated and cultured from the sputum samples of MDR-TB patients for extracting DNA of the bacilli. Mutations in genes, gyrA and rrs, that have been known to be associated with resistance to FQ and KM were analyzed using both REBA MTB-FQ? and REBA MTB-KM?, respectively. The isolates were also utilized for a conventional phenotypic drug susceptibility test (DST) as the gold standard of FQ and KM resistance. The molecular and phenotypic DST results were compared. Sensitivity and specificity of REBA MTB-FQ? were 77 and 100%, respectively. Positive predictive value and negative predictive value of the assay were 100 and 95%, respectively, for FQ resistance. Sensitivity, specificity, positive predictive value and negative predictive value of REBA MTB-KM? for detecting KM resistance were 66%, 94%, 70%, and 95%, respectively. REBA MTB-FQ? and REBA MTB-KM? evaluated in this study showed excellent specificities as 100 and 94%, respectively. However, sensitivities of the assays were low. It is essential to increase sensitivity of the rapid drug resistance assays for appropriate MDR-TB treatment, suggesting further investigation to detect new or other mutation sites of the associated genes in M. tuberculosis is required.
객담 전처리 방법에 따른 객담 항산균 도말 및 배양 양성률 비교연구
강형석 ( Hyung Seok Kang ),성낙문 ( Nack Moon Sung ),이선숙 ( Sun Sook Lee ),김도형 ( Do Hyung Kim ),전두수 ( Doo Soo Jeon ),황수희 ( Soo Hee Hwang ),민진홍 ( Jin Hong Min ),김진희 ( Jin Hee Kim ),원영섭 ( Young Sub Won ),박승규 ( 대한결핵 및 호흡기학회 2008 Tuberculosis and Respiratory Diseases Vol.65 No.5
연구배경: NaOH (sodium hydroxide) 기법을 이용한 전처리 객담과 NALC-NaOH (N-acetyl-L-cysteine-sodium hydroxide) 기법을 이용한 객담의 항산균 도말 및 결핵균 배양 양성률 그리고 배지 오염률을 비교하여 실험실 검사과정 중의 일부분을 개선함으로써 검사 결과의 개선이 가능한 지 확인하고자 하였다. 방법: 2007년 6월부터 2008년 6월까지 국립마산병원에서 객담 검사가 시행된 환자를 대상으로 환자에게서 객담배출 요령을 충분히 교육한 후 두개의 객담 검체를 채취하여 통상적인 NaOH 기법과 NALC-NaOH 기법을 각각 적용한 후 도말 및 배양 결과 그리고 배지 오염률을 비교하였다(n=436). 결과: 항산균 도말 검사에서는 NaOH 기법에 비하여 NALC-NaOH 기법이 다소 높은 양성률(33.0% vs. 39.0%)을 보였으나 통계적인 유의성은 없었다(p=0.078). 결핵균 배양 검사에서는 배지 오염률(culture contamination)은 각각 3.2%와 3.0%로 유의한 차이는 보이지 않았다. 배양 양성률은 NALC-NaOH 기법이 통계적으로 유의하게 높은 배양 양성률(39.7% vs. 28.0%, p=0.0003)을 보였으며, 배양 결과를 도말 검사 결과와 연관 지어 분석하였을 때 도말 검사상 음성인 경우 NaOH 기법과 NALC-NaOH 기법은 각각 7.2%와 15.8% (p=0.0017), scanty를 보인 객담의 경우 각각 42.9%와 60.8% (p=0.036)의 배양 양성률을 보여 통계적으로 의미 있는 차이를 보였다. 결론: 도말 검사에서 음성이나 scanty를 보여 상대적으로 결핵균의 수가 적은 객담의 경우 NALC-NaOH를 이용함으로써 배양 양성률을 개선 시킬 수 있었으며 이는 임상적으로 폐결핵의 진단과 치료 경과 관찰에 직접적인 도움을 줄 수 있음을 보여주었다. Background: Sputum decontamination with NALC-NaOH (N-acetyl-L-cysteine-sodium hydroxide) is known to better detect Mycobacterium tuberculosis (M. tb) by culture than that with using NaOH, which is widely used in Korean hospitals. In this report, sputum samples collected from pulmonary tuberculosis (TB) patients were treated with either NaOH or NALC-NaOH, and we compared the results of smear and culture positivity to determine whether the NALC-NaOH treatment method improves culture positivity in the sputum samples, and especially for those sputum samples that are smear negative and scanty. Methods: For each decontamination method, 436 sputum samples from pulmonary TB patients in the National Masan Tuberculosis Hospital were collected for this study. Sputum from a patient was collected two times for the first and second day of sampling time, and these samples were employed for the decontamination process by performing the 4% NaOH and NALC-2% NaOH treatment methods, respectively, for detecting M. tb by an AFB (Acid Fast Bacilli) smear and also by culture in solid Ogawa medium. Results: The NaOH and NALC-NaOH treatment methods did not significantly affect the AFB smear positivity of the sputum samples (33.0% vs 39.0%, respectively, p=0.078). However, the culture positive percents of M. tb in the Ogawa medium treated with NALC-NaOH and NaOH were 39.7% and 28.0%, respectively, which was a significantly different (p=0.0003). This difference in culture was more prominent in the sputum samples that were smear negative (the positive percents with NALC-NaOH and NaOH were 15.8% and 7.2%, respectively, p=0.0017) and scanty (NALC-NaOH and NaOH were 60.8% and 42.9%, respectively, p=0.036), but not for a smear that was 1+ or higher (p>0.05). Conclusion: NALC-NaOH treatment is better than NaOH treatment for the detection of M. tb by culture, but not by smear, and especially when the AFB smear is negative and scanty. (Tuberc Respir Dis 2008;65:379-384)
일개 결핵병원에서 다제내성결핵과 광범위내성결핵의 추이, 2001~2005
전두수 ( Doo Soo Jeon ),신동옥 ( Dong Ok Shin ),강형석 ( Hyung Seok Kang ),성낙문 ( Nack Moon Sung ),권경순 ( Kyung Soon Kweon ),신은 ( Eun Shin ),김경순 ( Kyung Soon Kim ),이명희 ( Myung Hee Lee ),박승규 ( Seung Kyu Park ) 대한결핵 및 호흡기학회 2008 Tuberculosis and Respiratory Diseases Vol.64 No.3
연구배경: 다제내성결핵과 광범위내성결핵은 전세계적으로 결핵 치료에 큰 위협으로 등장하고 있지만 이에 대한 국내의 정확한 실태 및 추이는 잘 알려져 있지 않다. 일개 결핵병원에서 다제내성결핵과 광범위내성결핵의 빈도 및 추이를 살펴봄으로써 국내 실태를 간접적으로 파악하고자 하였다. 방법: 2001년부터 2005년 사이에 국립마산병원에 입원하여 배양양성 결핵으로 진단된 환자를 대상으로 약제 감수성검사 결과와 의무기록을 후향적으로 분석하였다. 결과: 2001년부터 2005년 사이에, 다제내성결핵은 신환자에서 9.2%, 13.8%, 16.9%, 23%, 27.0%로 의미있게 증가하였고(p<0.001 for trend) 재치료환자에서 9.1%, 15.7%, 17.3%, 19.9%, 19.1%로 의미있게 증가하였다 (p=0.002 for trend). 광범위내성결핵은 신환자에서 0%, 2.3%, 3.1%, 2.5%, 6.3%로 의미있게 증가하였고(p=0.005 for trend) 재치료환자에서 9.1%, 15.7%, 17.3%, 19.9%, 19.1%로 의미있게 증가하였다(p<0.001 for trend). 결론: 다제내성결핵과 광범위내성결핵은 신환자와 재치료환자 모두에서 증가하는 추이를 보였다. 국내의 정확한 실태 파악을 위하여 공공 및 민간의료기관을 포괄하는 통합적인 약제내성실태 조사가 필요할 것으로 사료된다. Background: Multidrug-resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) are serious threats to worldwide tuberculosis control, but the national burden and the trends of infectious spread are largely unknown. Methods: We retrospectively reviewed the results of drug sensitivity tests and medical records of patients that were diagnosed with culture-confirmed pulmonary tuberculosis and were admitted to the National Masan Tuberculosis Hospital between 2001 and 2005. Results: From 2001 to 2005, the proportion of MDR-TB among new cases was 9.2%, 13.8%, 16.9%, 23% and 27.0% in 2001, 2002, 2003, 2004 and 2005, respectively, and the proportion of MDR-TB among previously treated cases was 58.5%, 60.2%, 62.7%, 61.7% and 71.3% in 2001, 2002, 2003, 2004 and 2005, respectively. A significant increasing trend could be discerned for MDR-TB among both new and previously treated cases (p<0.001, p=0.002 for trend, respectively). The proportion of XDR-TB among new cases was 0%, 2.3%, 3.1%, 2.5% and 6.3% in 2001, 2002, 2003, 2004 and 2005, respectively, and the proportion of XDR-TB among previously treated cases was 9.1%, 15.7%, 17.3%, 19.9% and 19.1% in 2001, 2002, 2003, 2004 and 2005, respectively. A significant increasing trend could be discerned for XDR-TB among both new and previously treated cases (p=0.005, p<0.001 for trend, respectively). Conclusion: Both MDR-B and XDR-TB were gradually increased among both new and previously treated cases. Integrated national surveillance, including the public and private sectors, will be needed to estimate the exact status of antituberculous drug resistance. (Tuberc Respir Dis 2008;64:187-193)
김선영 ( Sun Young Kim ),김희진 ( Hee Jin Kim ),김창기 ( Chang Ki Kim ),윤혜령 ( Hye Ryung Yoon ),배혜경 ( Hye Gyung Bae ),이선화 ( Sun Hwa Lee ),성낙문 ( Nack Moon Sung ),김대연 ( Dae Yeon Kim ),이강영 ( Gang Young Lee ),조영수 ( 대한결핵 및 호흡기학회 2010 Tuberculosis and Respiratory Diseases Vol.68 No.3
Background: The increasing incidence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) has become a serious worldwide problem. However, there is insufficient data regarding the current status of MDR-TB and XDR-TB in Korea. This study examined the recent status of MDR- and XDR-TB using the data from 7 laboratories, in which almost all drug susceptibility tests (DST) for Mycobacterium tuberculosis were performed. Methods: The patients` identification data and DST results were collected from all 7 laboratories from 2001 to 2006 and the number of patients with MDR-TB and XDR-TB were calculated. Results: The number of DSTs was 140,638 for 6 years with an increasing incidence each year (p<0.001). The number of DST with MDR results was 18,510 and personal identifying information was obtained in 16,640 (89.9%) tests. The number of MDR-TB patients from 2001 to 2006 was 2,329, 2,496, 2,374, 2,300, 2,354, and 2,178, respectively, when counting the duplications in a year as one patient. The number of MDR-TB patients when counting the duplications in 6 years as one patient was 2,281, 1,977, 1,620, 1,446, 1,512, and 1,373, respectively. When the same method was adopted, the number of XDR-TB patients was 191, 238, 282, 260, 272, and 264, respectively, and 189, 150, 130, 90, 122, and 110 patients, respectively. Conclusion: Despite the national efforts to control TB, there are still a large number of MDR- and XDR-TB patients in Korea.