• The Korean journal of internal medicine
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• 제39권4호
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• pp.640-649
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• 2024

Background/Aims: This study aimed to investigate the timing and predictors of death during treatment among patients with multidrug/rifampin-resistant tuberculosis (MDR/RR-TB) in South Korea. Methods: This was a retrospective cohort study that included MDR/RR-TB cases notified between 2011 and 2017 in South Korea. Results: Among 7,226 MDR/RR-TB cases, 699 (9.7%) died at a median of 167 days (IQR 51-358 d) from the initiation of MDR-TB treatment. The cumulative proportion of all-cause death was 35.5% at 90 days and 52.8% at 180 days from treatment initiation. TB-related deaths occurred at a median of 133 days (IQR 32-366 d), which was significantly earlier than the median of 184 days (IQR 68-356 d) for non-TB-related deaths (p = 0.002). In a multivariate analysis, older age was the factor most strongly associated with death, with those aged ≥ 75 years being 68 times more likely to die (aHR 68.11, 95% CI 21.75-213.26), compared those aged ≤ 24 years. In addition, male sex, comorbidities (cancer, human immunodeficiency virus, and end stage renal disease), the lowest household income class, and TB-specific factors (previous history of TB treatment, smear positivity, and fluoroquinolone resistance) were identified as independent predictors of all-cause death. Conclusions: This nationwide study highlights increased deaths during the intensive phase and identifies high-risk groups including older people and those with comorbidities or socioeconomic vulnerabilities. An integrated and comprehensive strategy is required to reduce mortality in patients with MDR/RR-TB, particularly focusing on the early stages of treatment and target populations.

• Tuberculosis and Respiratory Diseases
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• 제83권1호
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• pp.20-30
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• 2020

Tuberculosis (TB) remains a threat to public health and is the leading cause of death globally. Isoniazid (INH) is an important first-line agent for the treatment of TB considering its early bactericidal activity. Resistance to INH is now the most common type of resistance. Resistance to INH reduces the probability of treatment success and increases the risk of acquiring resistance to other first-line drugs such as rifampicin (RIF), thereby increasing the risk of multidrug-resistant-TB. Studies in the 1970s and 1980s showed high success rates for INH-resistant TB cases receiving regimens comprised of first-line drugs. However, recent data have indicated that INH-resistant TB patients treated with only firs-tline drugs have poor outcomes. Fortunately, based on recent systematic meta-analyses, the World Health Organization published consolidated guidelines on drug-resistant TB in 2019. Their key recommendations are treatment with RIF-ethambutol (EMB)-pyrazinamide (PZA)-levofloxacin (LFX) for 6 months and no addition of injectable agents to the treatment regimen. The guidelines also emphasize the importance of excluding resistance to RIF before starting RIF-EMB-PZA-LFX regimen. Additionally, when the diagnosis of INH-resistant TB is confirmed long after starting the first-line TB treatment, the clinician must decide whether to start a 6-month course of RIF-EMB-PZA-LFX based on the patient's condition. However, these recommendations are based on observational studies, not randomized controlled trials, and are thus conditional and based on low certainty of the effect estimates. Therefore, further work is needed to optimize the treatment of INH-resistant TB.

• Tuberculosis and Respiratory Diseases
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• 제50권6호
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• pp.686-692
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• 2001

배 경 : 다제내성 폐결핵의 발생은 약제선택의 제한성과장기간의 항결핵제의 복용으로 인한 부작용 등으로 인하여 치료 성공율을 감소시킨다. 본 연구는 치료 실패인자들을 알아내어 다제내성 폐결핵의 치료 성공율을 향상시키는데 기초자료로 삼고자 하였다. 대상 및 방법 : 1996년 1월부터 1998년 12월까지 입원치료를 시행한 다제내성 폐결핵 환자 111명을 대상으로 하였다. 다제내성 폐결핵 치료의 실패에 관계되는 인자들을 분석하기 위하여 치료에 성공한 군(I군)과 실패한 군(II군)으로 나누어 각 인자들을 독립표본 T-검정, $X^2$ 검정 그리고 Fisher의 정확확률 검정으로 비교 분석하였다. 결 과 : I군과 II군을 비교한 결과, 폐결핵 과거력의 유무, 흉부방사선 검사상 공동이 있는 경우와 과거의 치료 횟수, 내성 약제의 개수 그리고 치료약제의 개수에서 통계적 유의성을 관찰할 수 있었다(p<0.05). 결 론 : 다제내성 폐결핵 치료 실패의 위험인자는 과거의 치료력, 흉부방사선상 공동이 있는 경우, 내성약제의 개수가 많은 것임을 알 수 있었다. 따라서 다제내성 폐결핵의 치료 효과를 향상시키기 위하여 초치료 폐결핵관리를 보다 철저히 하여 항결핵제에 대한 약제 내성발생을 억제하는데 노력을 하여야 할 것으로 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제59권2호
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• pp.179-185
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• 2005

배 경 : 다제내성 폐결핵환자에서 폐병소의 근치절제술 후 일차 항결핵제로 구성된 처방으로 치료하였을 때의 성적을 알아보고자 하였다. 방 법 : 전향적 연구로 국립마산결핵병원에서 1998년 2월부터 2004년 12월 사이에 다제내성 폐결핵으로 수술전 HRCT에서 공동을 포함하는 국소적 병소인 것과 수술 중에 절제부위 이외에 잔존병소가 없다고 판단 된 환자 17명에게 수술 후 3HERZS/3HERS/6HER로 투약하고 그 임상적 경과를 살펴보았다. 결 과 : 대상환자들은 약제감수성검사에서 INH, RFP이외에 평균 4가지 항결핵제에 내성을 보였으며, 술 후 균음전은 평균 2일째 이루어졌다. 평균 39개월의 추구관찰 기간 동안 치료를 중단한 1명을 제외한 94%(15/16) 환자에서 치유되었으며 균음전에 실패한 1명과 치료종결하고 약 7년 후에 재발된 1명은 본원의 처방지침에 따라 이차 항결핵제로 처방을 변경 투약하여 모두 균음전에 성공하였다. 결 론 : 국소적 병변을 가진 다제내성결핵 환자에서 병소의 근치절제후 일차 항결핵제로 구성된 처방으로도 양호한 치료성적을 얻을 수 있었다. 하지만 이러한 경험을 일반화하기 위해서는 더 많은 경험과 병소별 결핵균 주의 특성에 관한 연구 등이 필요할 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제79권3호
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• pp.134-142
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• 2016

In recent years, in spite of medical advancement, tuberculosis (TB) remains a worldwide health problem. Although many laboratory methods have been developed to expedite the diagnosis of TB, delays in diagnosis remain a major problem in the clinical practice. Because of the slow growth rate of the causative agent Mycobacterium tuberculosis, isolation, identification, and drug susceptibility testing of this organism and other clinically important mycobacteria can take several weeks or longer. During the past several years, many methods have been developed for direct detection, species identification, and drug susceptibility testing of TB. A good understanding of the effectiveness and practical limitations of these methods is important to improve diagnosis. This review summarizes the currently-used advances in non-molecular and molecular diagnostics.

• Tuberculosis and Respiratory Diseases
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• 제84권3호
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• pp.237-244
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• 2021

Background: The emergence of drug-resistant tuberculosis (TB), is a major menace to cast off TB worldwide. Line probe assay (LPA; GenoType MTBDRplus ver. 2) and Xpert MTB/RIF assays are two rapid molecular TB detection/diagnostic tests. To compare the performance of LPA and Xpert MTB/RIF assay for early diagnosis of rifampicin-resistant (RR) TB in acid-fast bacillus (AFB) smear-positive and negative sputum samples. Methods: A total 576 presumptive AFB patients were selected and subjected to AFB microscopy, Xpert MTB/RIF assay and recent version of LPA (GenoType MTBDRplus assay version 2) tests directly on sputum samples. Results were compared with phenotypic culture and drug susceptibility testing (DST). DNA sequencing was performed with rpoB gene for samples with discordant rifampicin susceptibility results. Results: Among culture-positive samples, Xpert MTB/RIF assay detected Mycobacterium tuberculosis (Mtb) in 97.3% (364/374) of AFB smear-positive samples and 76.5% (13/17) among smear-negative samples, and the corresponding values for LPA test (valid results with Mtb control band) were 97.9% (366/374) and 58.8% (10/17), respectively. For detection of RR among Mtb positive molecular results, the sensitivity of Xpert MTB/RIF assay and LPA (after resolving discordant phenotypic DST results with DNA sequencing) were found to be 96% and 99%, respectively. Whereas, specificity of both test for detecting RR were found to be 99%. Conclusion: We conclude that although Xpert MTB/RIF assay is comparatively superior to LPA in detecting Mtb among AFB smear-negative pulmonary TB. However, both tests are equally efficient in early diagnosis of AFB smear-positive presumptive RR-TB patients.

• 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.

• Journal of Microbiology and Biotechnology
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• 제27권9호
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• pp.1549-1558
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• 2017

Despite significant efforts to improve the treatment of tuberculosis (TB), it remains a prevalent infectious disease worldwide owing to the limitations of current TB therapeutic regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors may be beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs may be more effective than the currently approved TB drugs, which are limited by the long durations of treatment needed and the emergence of drug-resistant strains. Targets of HDTs include host factors such as cytokines, immune checkpoints, immune cell functions, and essential enzyme activities. This review article discusses examples of potentially promising HDTs and introduces novel approaches for their development.

• Tuberculosis and Respiratory Diseases
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• 제82권2호
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• pp.143-150
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• 2019

Background: The purpose of this study was to analyze the relationship between the gene mutation patterns by the GenoType MTBDRplus (MTBDRplus) assay and the phenotypic drug susceptibility test (pDST) results of isoniazid (INH) and prothionamide (Pto). Methods: A total of 206 patients whose MTBDRplus assay results revealed katG or inhA mutations were enrolled in the study. The pDST results were compared to mutation patterns on the MTBDRplus assay. Results: The katG and inhA mutations were identified in 68.0% and 35.0% of patients, respectively. Among the 134 isolated katG mutations, three (2.2%), 127 (94.8%) and 11 (8.2%) were phenotypically resistant to low-level INH, high-level INH, and Pto, respectively. Among the 66 isolated inhA mutations, 34 (51.5%), 18 (27.3%) and 21 (31.8%) were phenotypically resistant to low-level INH, high-level INH, and Pto, respectively. Of the 34 phenotypic Pto resistant isolates, 21 (61.8%), 11 (32.4%), and two (5.9%) had inhA, katG, and both gene mutations. Conclusion: It is noted that Pto may still be selected as one of the appropriate multidrug-resistant tuberculosis regimen, although inhA mutation is detected by the MTBDRplus assay until pDST confirms a Pto resistance. The reporting of detailed mutation patterns of the MTBDRplus assay may be important for clinical practice, rather than simply presenting resistance or susceptibility test results.

• 대한임상검사과학회지
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• 제54권2호
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• pp.125-132
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• 2022

다제내성결핵과 광범위내성결핵은 결핵 치료의 문제가 되고 있으며 발생빈도 역시 증가하고 있다. 본 연구는 2010년 1월부터 2019년 12월까지 녹십자의료재단 의뢰된 환자를 대상으로 Löwenstein-Jensen 고체배지와 pyrazinamide for pyrazinamidase를 이용하여 약물감수성시험(DST)을 시행하여 내성으로 전환되는 항결핵제 패턴과 평균 추적 기간을 분석하였다. 항결핵제 중 1개 이상의 항결핵제 내성을 보인 증례들에서 초기 의뢰 시 INH 항결핵제에 내성인 경우가 55명(33.1%)으로 가장 높은 비율로 나타났으며, 내성으로 전환된 항결핵제는 EMB 17명(26.6%), RFP 14명(21.9%), QUI 14명(21.9%), PZA 12명(10.9%) 순으로 조사되었다. 10개의 항결핵제에 모두 감수성인 증례들에서는 INH 항결핵제에 대한 내성 전환은 43명(7.2%)으로 가장 빈도가 높았으며, 평균 추적 기간은435.6일로 조사되었으며, 내성으로 전환되는 항결핵제의 내성전환율은 INH 43명(7.2%), RFP 23명(3.9%), SM 11명(1.9%), QUI 4명(0.7%), AMK 3명(0.5%), EMB 3명(0.5%)이었다. 이에 본 연구는 항결핵제에 대한 감수성에서 내성으로의 전환은 특히 다제내성결핵과 광범위 내성결핵의 전환되는 환자에게 매우 중요한 자료가 될 것으로 보이며, 결핵 치료에서 환자 치료에 도움이 될 것으로 사료된다.