• Tuberculosis and Respiratory Diseases
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• v.69 no.2
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• pp.95-102
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• 2010

Background: The increasing rate of drug-resistant tuberculosis (TB) is a threat to the public health and TB control. In Korea, about 75~80% of TB patients are treated in private hospitals and the rate has been continuously increasing since 2000. Methods: On a retrospective basis, we enrolled 170 newly diagnosed with or retreated for multidrug-resistant TB (MDR-TB) in 2004 from 21 private hospitals. We extracted the following demographics and treatment history from patient medical records: initial treatment outcomes, cumulative survival rates, treatment outcomes, and prognostic factors. Results: Of the 170 patients, the majority were male (64.1%), the mean age was 44.5 years old, and mean body-mass-index was $20.2kg/m^2$. None of the patients tested positive for HIV. Eleven (6.5%) were confirmed to have extensively drug-resistant TB (XDR-TB) at treatment initiation. Treatment success rates were not different between XDR-TB (36.4%, 4/11) and non-XDR MDR-TB (51.6%, 82/159). Default rate was high, 21.8% (37/170). Far advanced disease on X-ray was a significant negative predictor of treatment success; advanced disease and low BMI were risk factors for all-cause mortality. Conclusion: In private hospitals in Korea, the proportion of XDR-TB in MDR-TB was comparable to previous data. The treatment success rate of MDR-/XDR-TB remains poor and the failure rate was quite high. Adequate TB control policies should be strengthened to prevent the further development and spread of MDR-/XDR-TB in Korea.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.862-870
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• 1996

Background : Multidrug-resistant tuberculosis(MDR-Tb) has been increased not only in Asia but also in Western society, which may cause public health problems and reduce the efficacy of treatment of tuberculosis. In Western society HIV infection is believed to do a central role in increasing incidence of MDR tuberculosis, but MDR-Tb in Korea may be somewhat different about clinical features, underlying disorders, and prognosis. Goble et al reponed that overall treatment failure rate in MDR-Tb including resistance to isoniazid(INH) and rifampin (RFP) was 44 %. The aim of this study is to find the treatment result in Korea and the factors determining the prognosis. Methods: A retrospective study of pulmonary tuberculosis cultured M. tuberculosis from sputum or bronchial washing fluid between 1986 through 1992 was conducted in the Seoul Paik Hospital, Inje University. We reviewed clinical courses of 141 patients, who had a tuberculosis with resistance to 2 or more drugs including isoniazid(INH) and rifampin(RFP). One hundred and 4 patients of 141 patients had completed treatment and followed up for more than one year. Results: Of 104 (mean age $43.6{\pm}16.7$, M: F=63 : 41) patients with sufficient follow-up data, 73(84.6%) patients responded which is defined as negative Sputum cultures for at least 3 consecutive months. Seven patients(6.7%) had a failure in negative conversion and 9(8.7%) of the patients who initially responded relapsed. Overall treatment failure rate was 15.4%, Patients who were treated for less than 12 months had a higher relapse rate(12.3%) than 18 months(4.9%). And there was a statistically significant correlation between the relapse rate and the number of drugs to which isolates wera resistant(p<0.05). Conclusion : The treatment failure rate of MDR-Tb in Korea was lower than previous studies in western Country and the major determining factor of prognosis was the number of resistant drugs to M. tuberculosis at drug sensitivity test. For reducing the relapse rate, we recommend more than 12 months of treatment for MDR tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.77 no.4
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• pp.161-166
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• 2014

Since tuberculosis (TB) remains a major global health concern and the incidence of multi-drug resistant (MDR)-TB is increasing globally, new modalities for the detection of TB and drug resistant TB are needed to improve TB control. The Xpert MTB/RIF test can be a valuable new tool for early detection of TB and rifampicin resistance, with a high sensitivity and specificity. Late-generation fluoroquinolones, levofloxacin, and moxifloxacin, which are the principal drugs for the treatment of MDR-TB, show equally high efficacy and safety. Systemic steroids may reduce the overall TB mortality attributable to all forms of TB across all organ systems, although inhaled corticosteroids can increase the risk of TB development. Although fixed dose combinations were expected to reduce the risk of drug resistance and increase drug compliance, a recent meta-analysis found that they might actually increase the risk of relapse and treatment failure. Regarding treatment duration, patients with cavitation and culture positivity at 2 months of TB treatment may require more than 6 months of standard treatment. New anti-TB drugs, such as linezolid, bedaquiline, and delamanid, could improve the outcomes in drug-resistant TB. Nontuberculous mycobacterial lung disease has typical clinical and immunological phenotypes. Mycobacterial genotyping may predict disease progression, and whole genome sequencing may reveal the transmission of Mycobacterium abscessus. In refractory Mycobacterium avium complex lung disease, a moxifloxacin-containing regimen was expected to improve the treatment outcome.

• Journal of Microbiology and Biotechnology
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• v.25 no.6
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• pp.946-950
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• 2015

Recently, it has become a struggle to treat tuberculosis with the current commercial antituberculosis drugs because of the increasing emergence of multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis. We evaluated here the antimycobacterial activity of tamoxifen, known as a synthetic anti-estrogen, against eight drugsensitive or resistant strains of Mycobacterium tuberculosis (TB), and the active intracellular killing of tamoxifen on TB in macrophages. The results showed that tamoxifen had antituberculosis activity against drug-sensitive strains (MIC, 3.125-6.25 µg/ml) as well as drugresistant strains (MIC, 6.25 to 12.5 µg/ml). In addition, tamoxifen profoundly decreased the number of intracellular TB in macrophages in a dose-dependent manner.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.975-991
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• 1997

Background : Many patients with isoniazid and rifampin-resistant pulmonary tuberculosis have organisms that are also resistant to other first-line drugs. Despite of aggressive retreatment chemotherapy, the results are often unsuccessful, with a failure rate approaching 40%. Recently, there has been a revival of resectional surgery for the treatment of multidrug-resistant pulmonary tuberculosis. Methods : A retrospective analyses of the case records and radiographic findings were done. Between January 1991 and December 1995, 14 human immunodeficiency virus (HIV)-seronegative patients with multidrug-resistant pulmonary tuberculosis were selected for resection to supplement chemotherapy. All patients had organisms resistant to many of the first-line drugs, including both isoniazid and rifampin. Results : Despite of aggressive therapy for median duration of 9.5 months, 12 of the 14 patients (86%) were still sputum smear and/or culture positive at the time of surgery. The disease was generally extensive. Although main lesions of the disease including thick-walled cavities were localized in one lung, lesser amounts of contralateral disease were demonstrated in 10 of 14 (71%). Types of surgery performed were pneumonectomy including extrapleural pneumonectomy in six patients, lobectomy or lobectomy plus in six patients, and segmentectomy in two patients. The resected lung appeared to have poor function ; preoperative perfusion lung scan showed only 4.8% of the total perfusion to the resected portion of the lung. There were no operative deaths. Two patients had major postoperative complications including empyema with bronchopleural fistula and prolonged air leak, respectively. Of the 14 patients, 13 (93%) remained sputum-culture-negative for M. tuberculosis for a median duration of 23 months and one remained continuously sputum smear and culture positive for M. tuberculosis. Conclusion : On the basis of comparison with historical controls, adjunctive resectional surgery appears to play a significant beneficial role in the management of patients with multidrug-resistant pulmonary tuberculosis if the disease is localized and there are adequate reserve in pulmonary function.

• Journal of Microbiology and Biotechnology
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• v.31 no.12
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• pp.1632-1642
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• 2021

Tuberculosis is a highly contagious disease caused by Mycobacterium tuberculosis. It affects about 10 million people each year and is still one of the leading causes of death worldwide. About 2 to 3 billion people (equivalent to 1 in 3 people in the world) are infected with latent tuberculosis. Moreover, as the number of multidrug-resistant, extensively drug-resistant, and totally drug-resistant strains of M. tuberculosis continues to increase, there is an urgent need to develop new anti-tuberculosis drugs that are different from existing drugs to combat antibiotic-resistant M. tuberculosis. Against this background, we aimed to develop new anti-tuberculosis drugs using probiotics. Here, we report the anti-tuberculosis effect of Pediococcus acidilactici PMC202 isolated from young radish kimchi, a traditional Korean fermented food. Under coculture conditions, PMC202 inhibited the growth of M. tuberculosis. In addition, PMC202 inhibited the growth of drug-sensitive and -resistant M. tuberculosis- infected macrophages at a concentration that did not show cytotoxicity and showed a synergistic effect with isoniazid. In a 2-week, repeated oral administration toxicity study using mice, PMC202 did not cause weight change or specific clinical symptoms. Furthermore, the results of 16S rRNA-based metagenomics analysis confirmed that dysbiosis was not induced in bronchoalveolar lavage fluid after oral administration of PMC202. The anti-tuberculosis effect of PMC202 was found to be related to the reduction of nitric oxide. Our findings indicate that PMC202 could be used as an anti-tuberculosis drug candidate with the potential to replace current chemical-based drugs. However, more extensive toxicity, mechanism of action, and animal efficacy studies with clinical trials are needed.

• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.14-21
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• 1996

Objectives: Although outbreak of MDR Tb has been a recent problem in western countries, it has been a longstanding problem in Korea. The poor outcome of MDR Tb is mainly due to poor compliance, high rate of side reaction of secondary drugs, and limitation in number of available drugs. Thus, to improve the outcome of MDR Tb, it is crucial to make individualized adequate prescription based on the knowledge of the patterns of resistance to each drugs in the community as well as the natural history. The purpose of present study is to evaluate the clinical features of Korean MDR Tb patients including patterns of drug resistance and success rate of treatment which was prescribed according to the sensitivity tests. Methods: Retroscpective analysis of 71 Korean patients with MDR Tb was made. All strains isolated from patients showed resistence to at least two first line drugs. Patients profile, previous treatment history, patterns of drug resistance, outcome of treatment was analysed. Initial treatment regimen was selected according to the previous treatment history and was modified according to the sensitivity reports. The regimen was composed to include at least 4 sensitive drugs when possible. Results: The patients showed resistance to 4.1 drugs on average. 90% of them were resistant to INH and RFP. Among 71 patients, 35 patients(49%) had cavitary lesions in CXR. Treatment outcome was analysed in 55 patients. 35 patients(67%) were improved after treatment and 18 patients(33%) showed treatment failure. 5 patients showed primary resistance. Treatment outcome could be evaluated in 4 of them and all showed improvement after treatment. 14 patients(20%) had to change their regimens due to drug side effects. The most frequent side effect was elevation of liver enzymes(6 patients). Others included dizziness, hyperuricemia, tinnitus, skin rash, GI troubles. More than 50% of side effects developed within 3 months. In repeated drug sensitivity test, the concordance rate of resistance to INH was 100% and RFP 98%. EMB, PZA showed 80% concordance rate. But in the other drugs, the concordances were less than 50%. Operation was done in 5 patient - 1 patients as a adjunctive means of chemotherapy -. In that case, negative conversion of sputum AFB was done. Conclusion: 2/3 patients of multidrug-resistant tuberculosis were improved by appropriate prescription and regular medication suggesting that more aggressive management and monitoring is indicated in multidrug-resistant tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.60 no.4
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• pp.404-411
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• 2006

Purpose : Multidrug-resistant tuberculosis (MDR-TB) is an emerging threat to human beings. However, there is little data on the current status of MDR-TB in Korea. This study investigated the current status of MDR-TB in Korea using a survey of all the data from drug susceptibility tests (DST) performed across the country over the last three years. Method : The DST results between Jan. 2000 and Dec. 2002 from 7 laboratories, which were in charge of all antituberculous DSTs across the country as of March 2002, were collected and analyzed to determine the actual number of drug-resistant or MDR-TB patients, annual trend, degree and pattern of resistance against anti-TB drugs, etc. Results : Six laboratories used the absolute concentration method for DST and one used the proportional method. 59, 940 tests had been performed over the 3 year study period. The number of DST performed annually was 18,071, 19,950, and 21,919 in 2000-2002, respectively. The number of resistant tuberculosis patients (resistant against at least one anti-TB drug) had increased by 16.9% from 6,338 in 2000 to 7,409 in 2002. The rate of resistant tuberculosis among all DST results was 35.1% in 2000, 34.5% in 2001, and 33.8% in 2002. The number of MDR-TB patients (resistant against at least both isoniazid and rifampin) showed an increasing trend (14.5%) from 3,708 in 2000 to 4,245 in 2002. Conclusion : Approximately 4,000 MDR-TB cases are newly identified by DST annually and the number is showing an increasing trend. This study suggests that in order to cope with the current MDR-TB situation, the DST methods will need to be standardized and more aggressive measures will be required.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.251-263
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• 1997

Background : The emergence of multidrug-resistant strains of Mycobacterium tuberculosis presents a significant challange to the treatment and control of tuberculosis, and there is an urgent need to understand the mechanisms by which strains acquire multidrug resistance. Recent advances in molecular methods for the detection of M. tuberculosis genetic targets have approached the sensitivity of culture. Furthermore the prospect of determining resistance in mycobacteria at the nucleic acid level particulary to first-line drugs like rifampin, isoniazid has provided a glimps of the next generation of sensitivity test for M. tuberculosis. Previous studies in RMP resistant M. tuberculosis have shown that mutation in $\beta$subunit of RNA polymerase is main mechanism of resistance. Method : In this study, rpoB gene for the $\beta$subunit of RNA polymerase from M. tuberculosis of 42 cultured samples (32 were RMP resistant and 10 were sensitive cases) were isolated and characterised the mutations. Direct sequencing data were compared with the results of INNO-LiPA Line Probe Assay (LiPA, Innogenetics, Belgium), commercial RMP resistance detecting kit using reverse hybridization method. Results : All of the RMP resistant samples were revealed the presence of mutation by LiPA. In 22 samples (68.8%) out of 32 RMP resistant cases, the mutation types were confirmed by the positive signal at one of 4 mutation bands in the strip. The most frequent type was R5 (S531L) which were 17 cases (77.3%). Results of direct sequencing were identified the exact characteristics of 8 mutations which were not confirmed by LiPA. S522W type point mutation and 9 base pair deletion at codon 513~515 were new identified mutations for the first time. Conclusion : Mutations in rpoB gene is the main mechanism of RMP resistance in M. tuberculosis and LiPA is a very useful diagnostic tool for the early diagnosis of RMP resistance in M. tuberculosis.

• Journal of Preventive Medicine and Public Health
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• v.52 no.1
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• pp.66-70
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• 2019

Objectives: In the Republic of Korea (ROK), the notified incidence of tuberculosis in foreign-born individuals (NITFBI) has increased recently, as has the rate of multidrug-resistant (MDR) and rifampicin-resistant (RR) tuberculosis in foreigners staying in the ROK. As Jeju Province in ROK has a no-visa entry policy, control programs for NITFBI should be consolidated. The aim was to evaluate the status of NITFBI, with a focus on the distribution of MDR/RR tuberculosis by nationality. Methods: Data on tuberculosis incidence in individuals born in Jeju Province and in foreign-born individuals were extracted from the Korean Statistical Information Service of Statistics Korea, and the Infectious Disease Surveillance Web Statistics of the Korea Centers for Disease Control and Prevention, respectively. Results: Among all notified incident cases of tuberculosis, the proportion of NITFBI increased from 1.46% in 2011 to 6.84% in 2017. China- and Vietnam-born individuals accounted for the greatest proportion of the 95 cases of NITFBI. Seven cases of MDR/RR tuberculosis were found, all involving patients born in China. Conclusions: In Jeju Province, ROK, NITFBI might become more common in the near future. Countermeasures for controlling active tuberculosis in immigrants born in high-risk nations for tuberculosis should be prepared in Jeju Province, since it is a popular tourist destination.