• The Journal of the Korean life insurance medical association
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• v.28 no.1_2
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• pp.15-18
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• 2009

Background: Recent emergence of drug-resistant tuberculosis such as multidrug-resistant tuberculosis(MDR-TB) or extensively drug-resistant tuberculosis(XDR-TB) has become important health care problems. It has also became grave issues for insurance industries in determining medical risks. We have therefore strived to analyze the comparative mortality rates for drug-resistant tuberculosis through utilization of results from previous articles. Methods: Comparative mortality was calculated from source articles using mortality analysis methods. Results: Mortality ratio of MDR-TB was estimate to 1200%, and excess death rate was 110 per 1,000. Comparative mortality between MDR-TB and XDR-TB by Korean $study^{(1)}$ were 1750, 382, 405, 443, 1025, and 357%, for each 10 months study intervals, respectively. Total mortality ratio was 594% and total excess death rate was 60 per 1,000person. It was determined that the risk of XDR-TB was much greater than MDR-TB. Discussion; Pending the development of a novel anti-tuberculosis drug, it would be prudent to steer clear insuring XDR-TB during underwriting phase due to high medical cost that it creates.

• Tuberculosis and Respiratory Diseases
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• v.64 no.6
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• pp.414-421
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• 2008

Background: Recently, in addition to multi-drug resistant tuberculosis (MDR-TB), extensively drug-resistant tuberculosis (XDR-TB) has become rapidly growing public health threat. This study examined the clinical differences between pulmonary TB patients with extensively drug resistance (XDR) and multi-drug resistance (MDR) at the National Medical Center in Korea in order to determine the clinical characteristics associated more with XDR-TB than MDR-TB. Methods: Patients who received a diagnosis of culture-confirmed pulmonary TB and a drug sensitivity test (DST) for anti-TB drugs at the National Medical Center between January 2000 and August 2007 were enrolled in this study. The patients were identified into the XDR-TB or MDR-TB group according to the DST results. The clinical characteristics were reviewed retrospectively from the medical records. Statistical analysis for the comparisons was performed using a ${\chi}^2$-test, independent samples t-test or binary logistic regression where appropriate. Results: A total 314 patients with culture-confirmed pulmonary TB were included. Among them, 18 patients (5.7%) had XDR-TB and 69 patients (22%) had MDR-TB excluding XDR-TB. A comparison of the clinical characteristics, revealed the XDR-TB group to have a higher frequency of a prior pulmonary resection for the treatment of TB (odds ratio [OR], 3.974; 95% confidence interval [CI], 1.052~15.011; P value 0.032) and longer average previous treatment duration with anti-TB drugs, including a treatment interruption period prior to the diagnosis of XDR, than the MDR-TB group (XDR-TB group, 72.67 months; MDR-TB group, 13.09 months; average treatment duration difference between two groups, 59.582 months; 95% CI, 31.743~87.420; P value, 0.000). In addition, a longer previous treatment duration with anti-TB drugs was significantly associated with XDR-TB (OR, 1.076; 95% CI, 1.038~1.117; P value, 0.000). A comparison of the other clinical characteristics revealed the XDR-TB group to have a higher frequency of male gender, diabetes mellitus (DM), age under 45, treatment interruption history, cavitations on simple chest radiograph and positive result of sputum AFB staining at the time of diagnosis of XDR. However, the association was not statistically significant. Conclusion: Pulmonary TB patients with XDR have a higher frequency of a prior pulmonary resection and longer previous treatment duration with anti-TB drugs than those with MDR. In addition, a longer previous treatment duration with anti-TB drugs is significantly associated with XDR-TB.

• Tuberculosis and Respiratory Diseases
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• v.68 no.3
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• pp.146-154
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• 2010

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.

• Tuberculosis and Respiratory Diseases
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• v.85 no.3
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• pp.256-263
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• 2022

Background: Mycobacterium tuberculosis (Mtb) is resistant to the β-lactam antibiotics due to a non-classical transpeptidase in the cell wall with β-lactamase activity. A recent study showed that meropenem combined with clavulanate, a β-lactamase inhibitor, was effective in multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). However, in Korea, clavulanate can only be used as drugs containing amoxicillin. In this study, we investigated the susceptibility and genetic mutations of drug-resistant Mtb isolates to amoxicillin-clavulanate and meropenem-clavulanate to improve the diagnosis and treatment of drug-resistant TB patients. Methods: The minimum inhibitory concentration (MIC) of amoxicillin-clavulanate and meropenem-clavulanate was examined by resazurin microtiter assay. We used 82 MDR and 40 XDR strains isolated in Korea and two reference laboratory strains. Mutations of drug targets blaC, blaI, ldtA, ldtB, dacB2, and crfA were analyzed by polymerase chain reaction and DNA sequencing. Results: The MIC₉₀ values of amoxicillin/clavulanate and meropenem/clavulanate in drug-resistant Mtb isolates were 64/2.5 and 16/2.5 mg/L, respectively. Gene mutations related to amoxicillin/clavulanate and meropenem/clavulanate resistance could not be identified, but T448G mutation was found in the blaC gene related to β-lactam antibiotics' high susceptibility. Conclusion: Our results provide clinical consideration of β-lactams in treating drug-resistant TB and potential molecular markers of amoxicillin-clavulanate and meropenem-clavulanate susceptibility.

• Annals of Laboratory Medicine
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• v.38 no.6
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• pp.563-568
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• 2018

Background: Delamanid, bedaquiline, and linezolid have recently been approved for the treatment of multidrug- and extensively drug-resistant (MDR and XDR, respectively) tuberculosis (TB). To use these drugs effectively, drug susceptibility tests, including rapid molecular techniques, are required for accurate diagnosis and treatment. Furthermore, mutation analyses are needed to assess the potential for resistance. We evaluated the minimum inhibitory concentrations (MICs) of these three anti-TB drugs for Korean MDR and XDR clinical strains and mutations in genes related to resistance to these drugs. Methods: MICs were determined for delamanid, bedaquiline, and linezolid using a microdilution method. The PCR products of drug resistance-related genes from 420 clinical Mycobacterium tuberculosis strains were sequenced and aligned to those of M. tuberculosis H37Rv. Results: The overall MICs for delamanid, bedaquiline, and linezolid ranged from ${\leq}0.025$ to >1.6 mg/L, ${\leq}0.0312$ to >4 mg/L, and ${\leq}0.125$ to 1 mg/L, respectively. Numerous mutations were found in drug-susceptible and -resistant strains. We did not detect specific mutations associated with resistance to bedaquiline and linezolid. However, the Gly81Ser and Gly81Asp mutations were associated with resistance to delamanid. Conclusions: We determined the MICs of three anti-TB drugs for Korean MDR and XDR strains and identified various mutations in resistance-related genes. Further studies are needed to determine the genetic mechanisms underlying resistance to these drugs.

• Tuberculosis and Respiratory Diseases
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• v.64 no.3
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• pp.187-193
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• 2008

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.

• 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.85 no.2
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• pp.111-121
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• 2022

Multidrug-resistant tuberculosis (MDR-TB) is caused by an organism that is resistant to both rifampicin and isoniazid. Extensively drug-resistant TB, a rare type of MDR-TB, is caused by an organism that is resistant to quinolone and one of group A TB drugs (i.e., linezolid and bedaquiline). In 2018, the World Health Organization revised the groupings of TB medicines and reclassified linezolid as a group A drug for the treatment of MDR-TB. Linezolid is a synthetic antimicrobial agent in the oxazolidinone class. Although linezolid has a good efficacy, it can cause substantial adverse events, especially hematologic toxicity. In both TB infection and linezolid mechanism of action, mitochondrial dysfunction plays an important role. In this concise review, characteristics of linezolid as an anti-TB drug are summarized, including its efficacy, pathogenesis of hematologic toxicity highlighting mitochondrial dysfunction, and the monitoring and management of hematologic toxicity.

• Microbiology and Biotechnology Letters
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• v.51 no.4
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• pp.517-525
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• 2023

The emergence and spread of multidrug-resistant Pseudomonas aeruginosa (MRPA) have become a serious problem worldwide. The involvement of metallo-β-lactamases (MBLs) in inducing carbapenem resistance is particularly acute. However, unlike other members of the Enterobacteriaceae genus, new clones of P. aeruginosa are constantly emerging and rapidly replacing previously prevalent dominant clones. Therefore, this study aimed to perform antimicrobial resistance gene analysis, integron gene cassette analysis using DNA sequencing, and plasmid transfer analysis by conjugation to investigate the antimicrobial resistance dynamics of 18 P. aeruginosa strains isolated from various medical samples at a general hospital in Busan from September 2017 to September 2019. All 18 strains showed extensively drug-resistant (XDR) phenotype and were resistant to most antibiotics, except colistin (100%) but were susceptible to aztreonam (22.2%) and ceftazidime (16.6%). Approximately 66.7% of the strains had Class 1 integrons showing various antimicrobial resistances. Notably, IMP-6 ST235 (66.7%), VIM-2 ST357 (16.7%), and IMP-1 ST446(16.7%) were identified. The identification of IMP-1-producing ST446, previously unreported in Korea, is noteworthy considering the emergence and prevalence of another MRPA high-risk clone.

• 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.