• 제목/요약/키워드: Anti-tuberculosis drug

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다제내성결핵 균주에서 Reverse Hybridization Assay를 이용한 Fluoroquinolone, Kanamycin 신속 내성 검사의 유용성 (Evaluation of Reverse Hybridization Assay for Detecting Fluoroquinolone and Kanamycin Resistance in Multidrug-Resistance Mycobacterium tuberculosis Clinical Isolates)

  • 박진수;성낙문;황수희;전재현;원영섭;민진홍;김천태;강형석
    • Tuberculosis and Respiratory Diseases
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    • 제72권1호
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    • pp.44-49
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    • 2012
  • Background: 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$^{(R)}$ and REBA MTB-KM$^{(R)}$ (M&D, Wonju, Korea) were evaluated for rapid detection of FQ and kanamycin (KM) resistance in MDR-TB clinical isolates. Methods: 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$^{(R)}$ and REBA MTB-KM$^{(R)}$, 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. Results: Sensitivity and specificity of REBA MTB-FQ$^{(R)}$ 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$^{(R)}$ for detecting KM resistance were 66%, 94%, 70%, and 95%, respectively. Conclusion: REBA MTB-FQ$^{(R)}$ and REBA MTB-KM$^{(R)}$ 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.

일개 국립결핵병원에 입원치료를 받은 폐결핵환자의 임상양태에 관한 연구 - 1995년과 2002년 비교연구 - (Clinical Observational study of Pulmonary Tuberculosis for admitted patients at a National Tuberculosis Hospital - Comparison with the previous results in 1995 -)

  • 박승규;이인희;김병주
    • Tuberculosis and Respiratory Diseases
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    • 제58권4호
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    • pp.392-398
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    • 2005
  • 배 경 : 1995년 제7차 전국 결핵실태조사가 마지막으로 시행된 이 후 2000년 6월 결핵정보감시체계가 도입되었다. 결핵정보감시체계에서는 기존의 전국결핵실태조사에 포함된 균양성 유병율, 약제내성율 등 중요한 역학적 지표를 알 수 없는 한계를 가지고 있다. 본 연구의 목적은 1995년 12월과 2002년도 12월 국립마산결핵병원에 입원치료중인 환자의 임상양태를 조사 비교함으로 우리나라의 다제내성 결핵을 포함한 결핵실태추이의 한 단면을 알아보고자 함이었다. 방 법 : 2002년 12월 현재 국립마산결핵병원에 입원치료 중인 결핵환자 중 NTM으로 최종 확인된 6명을 제외한 331명을 대상으로 임상양태를 조사하고 이를 1995년에 보고된 자료와 비교조사 하였다. 결 과 : 1995년 자료와 비교할 때 평균연령은 3.6세 많았으며, 결핵치료 과거력과 이전 사용 약제 수는 각각 $2.0{\pm}1.7$회, $6.1{\pm}2.3$제에서 $1.7{\pm}1.8$회, $4.6{\pm}3.6$제로 감소하였다(각각 p<0.05, p<0.001). 전체적인 약제내성율은 비슷하였으나(81.0% vs 77.6%), 초회내성율과 초회다제내성율은 각각 10.5%와 2.4%에서 21.4%와 16.5%로 현저히 증가하였다(각각 p=0.012, p=0.001). 또한 1995년도에는 보건소에서 진단을 받은 경우가 65%였으나 2002년도에는 40.5%로 크게 감소하였다(p<0.001). 결 론 : 초회 내성율이 증가하고, 민간의료기관에서 진료하는 환자의 비중이 증가하는 등 우리나라의 결핵관리상황이 이전과 다르게 변해가고 있으므로 이에 대처할 수 있는 민간 및 공공의료기관이 협력할 수 있는 국가결핵관리프로그램의 수정 및 보완이 필요할 것으로 생각된다.

An International Collaborative Program To Discover New Drugs from Tropical Biodiversity of Vietnam and Laos

  • Soejarto, Djaja D.;Pezzuto, John M.;Fong, Harry H.S.;Tan, Ghee Teng;Zhang, Hong Jie;Tamez, Pamela;Aydogmus, Zeynep;Chien, Nguyen Quyet;Franzblau, Scott G.;Gyllenhaal, Charlotte;Regalado, Jacinto C.;Hung, Nguyen Van;Hoang, Vu Dinh;Hiep, Nguyen Tien;Xuan, Le Thi;Hai, Nong Van;Cuong, Nguyen Manh;Bich, Truong Quang;Loc, Phan Ke;Vu, Bui Minh;Southavong, Boun Hoong
    • Natural Product Sciences
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    • 제8권1호
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    • pp.1-15
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    • 2002
  • An International Cooperative Biodiversity Group (ICBG) program based at the University of Illinois at Chicago initiated its activities in 1998, with the following specific objectives: (a) inventory and conservation of of plants of Cuc Phuong National Park in Vietnam and of medicinal plants of Laos; (b) drug discovery (and development) based on plants of Vietnam and Laos; and (c) economic development of communities participating in the ICBG project both in Vietnam and Laos. Member-institutions and an industrial partner of this ICBG are bound by a Memorandum of Agreement that recognizes property and intellectual property rights, prior informed consent for access to genetic resources and to indigenous knowledge, the sharing of benefits that may arise from the drug discovery effort, and the provision of short-term and long-term benefits to host country institutions and communities. The drug discovery effort is targeted to the search for agents for therapies against malaria (antimalarial assay of plant extracts, using Plasmodium falciparum clones), AIDS (anti-HIV-l activity using HOG.R5 reporter cell line (through transactivation of the green fluorescent protein/GFP gene), cancer (screening of plant extracts in 6 human tumor cell lines - KB, Col-2, LU-l, LNCaP, HUVEC, hTert-RPEl), tuberculosis (screening of extracts in the microplate Alamar Blue assay against Mycobacterium tuberculosis $H_{37}Ra\;and\;H_{37}Rv),$ all performed at UIC, and CNS-related diseases (with special focus on Alzheimer's disease, pain and rheumatoid arthritis, and asthma), peformed at Glaxo Smith Kline (UK). Source plants were selected based on two approaches: biodiversity-based (plants of Cuc Phuong National Park) and ethnobotany-based (medicinal plants of Cuc Phuong National Park in Vietnam and medicinal plants of Laos). At mc, as of July, 2001, active leads had been identified in the anti-HIV, anticancer, antimalarial, and anti- TB assay, after the screening of more than 800 extracts. At least 25 biologically active compounds have been isolated, 13 of which are new with anti-HIV activity, and 3 also new with antimalarial activity. At GSK of 21 plant samples with a history of use to treat CNS-related diseases tested to date, a number showed activity against one or more of the CNS assay targets used, but no new compounds have been isolated. The results of the drug discovery effort to date indicate that tropical plant diversity of Vietnam and Laos unquestionably harbors biologically active chemical entities, which, through further research, may eventually yield candidates for drug development. Although the substantial monetary benefit of the drug discovery process (royalties) is a long way off, the UIC ICBG program provides direct and real-term benefits to host country institutions and communities.

노인 폐결핵의 특징 (Characteristics of Pulmonary Tuberculosis in Elderly People)

  • 신지영;정선영;이정은;박지원;유수진;박희선;김주옥;김선영
    • Tuberculosis and Respiratory Diseases
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    • 제69권3호
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    • pp.163-170
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    • 2010
  • Background: Pulmonary tuberculosis remains a health concern in Korea despite major progress in the development of new strategies for diagnosing and treating tuberculosis. In particular, the diagnosis of newly developed pulmonary tuberculosis is on the rise in elderly persons. The aim of this study was to investigate the clinical, radiographic characteristics, and treatment outcomes of pulmonary tuberculosis in the elderly. Methods: The medical records of 113 young (<65 years old) and 112 elderly (${\geq}65$ years old) pulmonary tuberculosis patients diagnosed at Chungnam National University hospital between January 2007 and December 2008 were reviewed. Results: There was no difference in the prevalence of typical symptoms between the younger and the elderly group. Dypsnea was the only symptom that occurred more frequently in the elderly group (16.8% vs 5.5%, p=0.008). On radiological study, pneumonic infiltration type was more common in the elderly group (28.6% vs 16.8%, p=0.035). Sputum Acid fast bacilli smear positivity rate was similar between the 2 groups. Elderly patients with anti-tuberculosis medication had more frequent adverse drug reactions; however, there was no significant difference between the 2 groups in the number of patients required to stop medication due to an adverse drug reaction. There were more patients lost to follow-up in the elderly group (22/112, 19.6% vs 11/113, 9.7%, p=0.036). Conclusion: The majority of elderly patients did not complete the treatment, resulting in a poorer outcome. Therefore, we need to make an effort to support the continued screening of elderly patients by making this economically feasible.

Isoniazid를 포함한 항결핵약제 투여 후 발생한 여성형 유방 증례 1예 (A Case of Bilateral Gynecomastia Associated with Isoniazid)

  • 허은영;정인아;이재석;이창훈;정희순;김덕겸
    • Tuberculosis and Respiratory Diseases
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    • 제65권4호
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    • pp.308-312
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    • 2008
  • 저자들은 폐결핵으로 진단받고 결핵 약제를 복용하던 환자에서 발생한 여성형 유방에 대하여 검사를 시행한 결과 Isoniazid를 포함한 항결핵약제를 복용 후 발생한 여성형 유방 사례를 경험하였기에 문헌 고찰과 함께 보고하는 바이다.

한국인의 항결핵제에 의한 간독성 위험인자 예측 (Prediction of the Hepatotoxicity Risk Factor Induced by Antituberculosis Agents in Koreans)

  • 이지선;김현아;조은;이옥상;임성실
    • 약학회지
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    • 제55권4호
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    • pp.352-360
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    • 2011
  • Standard combination chemotherapy including isoniazid, rifampin, pyrazinamide, and ethambutol is very effective against tuberculosis. But, these medicines can cause hepatotoxicity which is the main reason for treatment interruption or change in drug regimen. In order to identify risk factors associated with hepatotoxcity in Koreans and assess elevated baseline LFTs' contributions to hepatotoxicity, a retrospective case control study was performed. The medical records of 277 patients who diagnosed with tuberculosis at a community hospital from January 1st, 2007 to June 30th, 2010 were reviewed. Patients were categorized into 3 groups (non toxic group, patients without increase in LFT levels; mild to moderate hepatotoxic group and severe hepatotoxic group). And the correlation between risk factors and hepatotoxicity was analyzed by using SPSS program. The overall incidence of hepatotoxicity was 18% and 8.7% of patients developed severe toxicity. Patients in the severe toxic group had the longest treatment period among the three groups. In 75% of severe toxic group, hepatotoxicity occurred within 18.3 days after starting medication. Hypoalbuminemia (serum albumin <3 g/dl) was a significant risk factor for development of severe toxicity. Elevated baseline transaminase (except ALT), total bilirubin, and preexisting hepatitis were also risk factors which were more than twice as likely to increase risk of severe hepatotoxicity (p>0.05). In conclusion, hypoalbuminemia (serum albumin level <3 g/dl) was a significant risk factor for anti-tuberculosis druginduced severe toxicity. Therefore, before starting antituberculosis chemotherapy, serum albumin level should be assessed at baseline. In high-risk patients (hypoalbuminemia, elevated LFTs) for hepatotoxicty, liver function should be closely monitored up to at least 21 days after taking medication.

Chemotherapy for Lung Cancer in the Era of Personalized Medicine

  • Lee, Seung Hyeun
    • Tuberculosis and Respiratory Diseases
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    • 제82권3호
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    • pp.179-189
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    • 2019
  • Although recent advances in molecular targeted therapy and immuno-oncology have revolutionized the landscape of lung cancer therapeutics, cytotoxic chemotherapy remains an essential component of lung cancer treatment. Extensive evidence has demonstrated the clinical benefit of chemotherapy, either alone or in combination with other treatment modalities, on survival and quality of life of patients with early and advanced lung cancer. Combinational approaches with other classes of anti-neoplastic agents and new drug-delivery systems have revealed promising data and are areas of active investigation. Chemotherapy is recommended as a standard of care in patients that have progressed after tyrosine kinase inhibitors or immune checkpoint inhibitors. Chemotherapy remains the fundamental means of lung cancer management and keeps expanding its clinical implication. This review will discuss the current position and future role of chemotherapy, and specific consideration for its clinical application in the era of precision medicine.

Afatinib Mediates Autophagic Degradation of ORAI1, STIM1, and SERCA2, Which Inhibits Proliferation of Non-Small Cell Lung Cancer Cells

  • Kim, Mi Seong;Kim, So Hui;Yang, Sei-Hoon;Kim, Min Seuk
    • Tuberculosis and Respiratory Diseases
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    • 제85권2호
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    • pp.147-154
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    • 2022
  • Background: The expression of calcium signaling pathway molecules is altered in various carcinomas, which are related to the proliferation and altered characteristics of cancer cells. However, changes in calcium signaling in anti-cancer drug-resistant cells (bearing a T790M mutation in epidermal growth factor receptor [EGFR]) remain unclear. Methods: Afatinib-mediated changes in the level of store-operated Ca2+ entry (SOCE)-related proteins and intracellular Ca2+ level in non-small cell lung cancer cells with T790M mutation in the EGFR gene were analyzed using western blot and ratiometric assays, respectively. Afatinib-mediated autophagic flux was evaluated by measuring the cleavage of LC3B-II. Flow cytometry and cell proliferation assays were conducted to assess cell apoptosis and proliferation. Results: The levels of SOCE-mediating proteins (ORAI calcium release-activated calcium modulator 1 [ORAI1], stromal interaction molecule 1 [STIM1], and sarco/endoplasmic reticulum Ca2+ ATPase [SERCA2]) decreased after afatinib treatment in non-small cell lung cancer cells, whereas the levels of SOCE-related proteins did not change in gefitinib-resistant non-small cell lung cancer cells (PC-9/GR; bearing a T790M mutation in EGFR). Notably, the expression level of SOCE-related proteins in PC-9/GR cells was reduced also responding to afatinib in the absence of extracellular Ca2+. Moreover, extracellular Ca2+ influx through the SOCE was significantly reduced in PC-9 cells pre-treated with afatinib than in the control group. Additionally, afatinib was found to decrease the level of SOCE-related proteins through autophagic degradation, and the proliferation of PC-9GR cells was significantly inhibited by a lack of extracellular Ca2+. Conclusion: Extracellular Ca2+ plays important role in afatinib-mediated autophagic degradation of SOCE-related proteins in cells with T790M mutation in the EGFR gene and extracellular Ca2+ is essential for determining anti-cancer drug efficacy.

다제내성 결핵에 의한 횡단척수염 1예 (A case of Transverse Myelitis due to Multidrug-Resistant Tuberculosis)

  • 이광하;나승원;박이내;최혜숙;정훈;전규락;심태선
    • Tuberculosis and Respiratory Diseases
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    • 제60권3호
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    • pp.353-356
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    • 2006
  • 폐결핵 치료중 흉부엑스선상 악화 및 갑자기 발생한 하지 마비와 감각이상으로 자기공명영상 촬영후 급성 횡단척수염 진단 및 객담 검사상 다제내성 결핵균 검출로 2차 결핵약제와 스테로이드 병합치료를 시행하여 부분적으로 호전을 보였던 증례이다. 급성 횡단척수염은 매우 드문 질환이며 균주의 직접 침범이나 면역학적 기전으로 발생하나 후자가 더 가능성 있는 기전으로 생각되어지고 있다. 아직도 결핵 및 다제내성 결핵의 유병률이 높은 국내 상황에서 드물게 결핵이 원인으로 추정된 급성 횡단척수염의 증례를 보고하는 바이다.

Rifampin 내성 결핵의 진단에서 INNO-LiPA 검사법의 임상적 의미 (Clinical Meaning of INNO-LiPA Test in the Diagnosis of Rifampin Resistant Tuberculosis)

  • 장윤수;김영;이창률;최종락;김형중;안철민;김성규
    • Tuberculosis and Respiratory Diseases
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    • 제55권4호
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    • pp.344-352
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    • 2003
  • 연구배경 : Isoniazid와 rifampin에 내성인 다제내성 결핵의 유병률은 1995년 세계적으로 5.3%이며 이의 지속적인 증가는 공중보건의 중요한 문제로 대두 되고 있다. 결핵 치료의 중요한 약물의 하나인 RFP에 대한 내성은 불량한 예후를 초래한다. 이에 RFP내성을 조기에 정확하게 진단하는 임상적으로 중요하다. 최근 PCR 방법을 이용하여 약제 (RFP) 내성을 초래하는 변이를 신속하게 진단하는 방법이 가능하게 되었다. 본 연구는 결핵 초치료군, 치료 실패군 및 재발군에서 INNO-LiPA 검사법을 이용하여 RFP내성 유병률을 확인하고 기존의 약제 감수성 검사법을 이용하여 얻은 결과를 비교하여 INNO-LiPA검사의 유용성을 연구하였다. 방 법 : 1998년부터 2002년까지 본원에 내원하여 객담 도말 검사상 양성 소견으로 폐결핵으로 진단받은 46명을 대상으로 하였으며 환자는 초치료, 초치료 실패, 및 재발 환자군으로 분류하였다. RPF 내성은 INNO-LiPA Rif.TB kit을 이용하여 검사하였으며 이를 결핵균 배양을 이용한 약제 감수성 결과와 비교 분석하였다. 결 과 : 46명의 환자중에 21명이 결핵으로 처음 진단받은 환자였으며 17명이 초치료 실패한 환자이었으며 8명이 재발한 환자이었다. 배양 검사를 이용한 약제 감수성 검사법을 기준으로 하여 비교시 INNO-LiPA 검사법을 이용한 RFP 저항성의 양성 예측률은 85.7% 이었으여 음성 예측률은 76.0% 이었다. INNO-LiPA 검사 결과 초치료 실패한 및 재발한 환자 25명의 환자중 20예 (80.0%)에서 rpoB gene의 변이를 보였으며 처음 결핵으로 진단받은 21명의 환자중 4예 (19.0%)에서 rpoB gene의 변이를 보였다. 결 론 : INNO-LiPA 검사는 비교적 신속하고 정확하게 RFP 약제 내성 정보를 제공하여 2차 항결핵 약제의 선택에 도움을 준다. 아울러 기존의 배양 검사를 이용한 약제 감수성 검사법과 함께 상호 보완적으로 사용하면 다제 내성결핵의 치료에 있어 그 유용성은 매우 클 것으로 사료된다.