• Journal of Microbiology and Biotechnology
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• v.29 no.9
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• pp.1401-1411
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• 2019

Mycobacterial cell walls comprise thick and diverse lipids and glycolipids that act as a permeability barrier to antibiotics or other chemical agents. The use of OH radicals from a non-thermal plasma jet (NTPJ) for the inactivation of mycobacteria in aqueous solution was adopted as a novel approach. Addition of water vapor in a nitrogen plasma jet generated OH radicals, which converted to hydrogen peroxide ($H_2O_2$) that inactivated non-pathogenic Mycobacterium smegmatis and pathogenic Mycobacterium tuberculosis H37Rv. A stable plasma plume was obtained from a nitrogen plasma jet with 1.91 W of power, killing Escherichia coli and mycobacteria effectively, whereas addition of catalase decreased the effects of the former. Mycobacteria were more resistant than E. coli to NTPJ treatment. Plasma treatment enhanced intracellular ROS production and upregulation of genes related to ROS stress responses (thiolrelated oxidoreductases, such as SseA and DoxX, and ferric uptake regulator furA). Morphological changes of M. smegmatis and M. tuberculosis H37Rv were observed after 5 min treatment with $N_2+H_2O$ plasma, but not of pre-incubated sample with catalase. This finding indicates that the bactericidal efficacy of NTPJ is related to the toxicity of OH and $H_2O_2$ radicals in cells. Therefore, our study suggests that NTPJ treatment may effectively control pulmonary infections caused by M. tuberculosis and nontuberculous mycobacteria (NTM) such as M. avium or M. abscessus in water.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.76 no.1
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• pp.30-33
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• 2014

We report the first Korean case of lung diseases caused by Mycobacterium abscessus subsp. bolletii in a previously healthy male, except for a previous history of pulmonary tuberculosis and bronchiectasis. All serial isolates are identified as M. abscessus subsp. bolletii by multi-locus sequence analysis based on the hsp65, rpoB, and 16S rRNA fragments. At the genetic level, the isolate has the erm(41) gene with a T28 sequevar, associated with clarithromycin resistance, and no rrl mutation. The isolate is resistant to clarithromycin. Although the symptoms and radiographic findings have improved after combination of antibiotics, the follow-up sputum cultures are persistently positive.

• The Journal of Internal Korean Medicine
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• v.41 no.5
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• pp.856-867
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• 2020

Objectives: The purpose of this case study was to report the effect of Korean Medicine treatment on a patient diagnosed with nontuberculous mycobacterial lung disease. Methods: A 61-year-old female patient with nontuberculous mycobacterial lung disease was admitted to the clinic from October 15th, 2018 to November 7th, 2018. The patient was treated using Korean medical treatments of Jinhae-tang-gami, Ssanghwa-tang-gami, Haeyeol-tang, Jinhae-tang plus Ssanghwa-tang-gami, and Jinhae-tang plus Bojungikgi-tang-gami. We evaluated the improvement of symptoms by a numeric rating scale (NRS) score, C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and body temperature. Results: After Korean medicine treatment, the patient's cough and sputum amounts were decreased as measured by the NRS score. CRP levels and ESR were also decreased and fever was relieved. Conclusion: This study suggested that Korean medicine treatment might be effective in treating patients diagnosed with nontuberculous mycobacterial lung disease.

• Journal of Microbiology and Biotechnology
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• v.19 no.3
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• pp.323-330
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• 2009

Nontuberculous mycobacteria (NTM) are a major cause of opportunistic infections in immunocompromised patients, making the reliable and rapid identification of NTM to the species level very important for the treatment of such patients. Therefore, this study evaluated the usefulness of the novel target genes tuf and tmRNA for the identification of NTM to the species level, using a PCRrestriction fragment length polymorphism analysis (PRA). A total of 44 reference strains and 17 clinical isolates of the genus Mycobacterium were used. The 741 bp or 744 bp tuf genes were amplified, restricted with two restriction enzymes (HaeIII/MboI), and sequenced. The tuf gene-PRA patterns were compared with those for the tmRNA (AvaII), hsp65 (HaeIII/HphI), rpoB (MspI/HaeIII), and 16S rRNA (HaeIII) genes. For the reference strains, the tuf gene-PRA yielded 43 HaeIII patterns, of which 35 (81.4%) showed unique patterns on the species level, whereas the tmRNA, hsp65, rpoB, and 16S rRNA-PRAs only showed 10 (23.3%), 32 (74.4%), 19 (44.2%), and 3 (7%) unique patterns after single digestion, respectively. The tuf gene-PRA produced a clear distinction between closely related NTM species, such as M. abscessus (557-84-58) and M. chelonae (477-84-80-58), and M. kansasii (141-136-80-63-58-54-51) and M. gastri (141-136-117-80-58-51). No difference was observed between the tuf-PRA patterns for the reference strains and clinical isolates. Thus, a diagnostic algorithm using a tuf gene-targeting PRA is a promising tool with more advantages than the previously used hsp65, rpoB, and 16S rRNA genes for the identification of NTM to the species level.

• Biomedical Science Letters
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• v.26 no.3
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• pp.170-178
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• 2020

Mycobacterium tuberculosis (MTB) continues to be one of the main causative agents of tuberculosis (TB); moreover, the incidence of nontuberculous mycobacteria (NTM) infections has been rising gradually in both immunocompromised and immunocompetent patients. Precise and rapid detection and identification of MTB and NTM in respiratory specimens are thus important for MTB infection control. Molecular diagnostic methods based on the nucleic acid amplification test (NAAT) are known to be rapid, sensitive, and specific compared to the conventional acid-fast bacilli (AFB) smear and mycobacterial culture methods. In the present study, the clinical performances of three commercial molecular diagnostic assays, namely TB/NTM PCR (Biocore), MolecuTech Real MTB-ID^® (YD Diagnostics), and REBA Myco-ID^® (YD Diagnostics), were evaluated with a total of 92 respiratory specimens (22 AFB smear positives and 67 AFB smear negatives). The sensitivity and specificity of TB/NTM PCR were 100% and 75.81%, respectively. The corresponding values of MolecuTech Real MTB-ID^® and REBA Myco-ID^® were 56.52% and 90.32%, and 56.52% and 82.26%, respectively. TB/NTM PCR showed the highest sensitivity; however, the concordant rate was 10% compared with sequence analysis. Although MolecuTech Real MTB-ID^® showed lower sensitivity, its specificity was the highest among the three methods. REBA Myco-ID^® allowed accurate classification of NTM species; therefore, it was the most specific diagnostic method. Of the three PCR-based methods, MolecuTech Real MTB-ID^® showed the best performance. This method is expected to enable rapid and accurate identification of MTB and NTM.

• Tuberculosis and Respiratory Diseases
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• v.67 no.3
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• pp.199-204
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• 2009

Background: To examine the recovery rate of nontuberculous mycobacteria (NTM) from respiratory specimens and the clinical course of NTM pulmonary disease at a 700-bed secondary hospital. Methods: This study analyzed the results of 843 acid-fast bacilli (AFB) culture-positive respiratory specimens from 650 subjects collected between May 2003 and April 2008. In addition, the clinical course of NTM pulmonary disease, diagnosed using criteria established by the American Thoracic Society, was examined. Results: There were 67 (7.9%) NTM isolates recovered from 52 (8.0%) subjects. Among the 535 AFB smear-positive specimens, 34 (6.3%) NTM isolates were recovered. There were 33 (10.7%) NTM isolates were recovered from 308 AFB smear-negative specimens. Of 52 subjects with isolated NTM, M. intracellulare was the most common species at 73.1% (n=33), followed by M. kansassi (n=7), M. abscessus (n=2), M. fortuitum (n=2), and M. avium (n=1). Sixteen (30.8%) patients had NTM pulmonary disease and the most common causative organism was M. intracellulare (n=14, 87.5%). Of these, 6 cases attained negative conversion in culture, 4 cases failed to attain negative conversion because of poor cooperation or expiration from complicated underlying lung disease, and 5 cases were transferred to a higher-grade hospital. Conclusion: The recovery rate of NTM from respiratory specimens was relatively low and the most common species was M. intracellulare. Patients with NTM pulmonary disease showed variable clinical outcomes.

• Tuberculosis and Respiratory Diseases
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• v.54 no.3
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• pp.283-294
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• 2003

Introduction : Rapidly growing nontuberculous mycobacteria (RGM) can produce numerous types of manifestations including a pulmonary infection. Managing a pulmonary infection due to RGM is unusually difficult to treat because the organism is invariably resistant to traditional antituberculous drugs and has a varying susceptibility to other antibiotics. The experiences of treatments for a RGM pulmonary infection with various antibiotics are also limited. This study evaluated the clinical manifestations, treatment, and the therapeutic outcomes of a RGM pulmonary infection. Subjects and method : Fifty-four cases with RGM from respiratory specimens were identified between November of 1996 and September of 2002 in the Asan medical center. The medical records and radiographic findings in 20 patients who fulfilled the diagnostic criteria of nontuberculous mycobacteria (NTM) pulmonary disease by ATS guidelines. The clinical, laboratory, and radiological parameters between subgroups. Results : Of the 20 patients, 15 were female. The mean age was 57.7 yrs (${\pm}7.5$), and all of the patients had a history of pulmonary tuberculosis. Most (90%) had an underlying lung disease. The majority of the isolates (80%) were M. abscessus. Chest radiography showed bilateral involvement in 80% of the patients. Bronchiectasis and multiple nodules were the main findings. Cavitation was present in 35% of the patients. Even though 70 % of the patients received antituberculous drugs prior to the correct diagnosis, all of the patients eventually received antibiotics. A mean of 3.5 antibiotics were given for an average of 439 days(${\pm}168$). After completing treatment, nine patients showed improvement after a mean 591(${\pm}311$) days of treatment, whereas the antibiotic treatment was unsuccessful in 2 patients. Conclusion : Many patients with a RGM pulmonary infection show an atypical pattern of radiological findings (bronchiectasis and multiple centrilobular nodules). It is very important to differentiate between M. tuberculosis and NTM and to identify the causative organisms among the NTM because a misdiagnosis can lead to an inappropriate and prolonged treatment. Combined antibiotic treatment yielded promising results, and is recommended for treating patients with a RGM pulmonary infection.

• The Journal of Internal Korean Medicine
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• v.42 no.5
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• pp.1148-1159
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• 2021

Objectives: This study investigated the effect of combined Korean medical treatment and antibiotics on a patient diagnosed with nontuberculous mycobacterial lung disease. Methods: The patient had been treated with antibiotics since July 2020 concurrently with Maekmoondong-tang, Banhasasim-tang, Gwakhyangjunggi-san and Bojungikgi-tang. The improvement of symptoms was evaluated using scores for the numerical rating scale (NRS), the Medical Research Council (MRC) dyspnea scale, C-reactive protein (CRP) levels, and computed tomography (CT). Results: Following treatment, the NRS, MRC dyspnea scale and CT images significantly improved. Also, CRP levels remained in the normal range during treatment. Conclusions: Traditional Korean medical treatment combined with antibiotics could be effective for treating patients with nontuberculous mycobacterial lung disease.

• Tuberculosis and Respiratory Diseases
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• v.72 no.3
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• pp.275-283
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• 2012

Background: Healthy individuals who develop nontuberculous mycobacteria (NTM) lung disease are likely to have specific susceptibility factors which can lead to a NTM infection. The aim of the present study was to investigate the mechanism underlying innate immune responses, including the role of mitogen-activated protein kinase (MAPK), in Mycobacterium abscessus lung disease. Methods: Extracellular signal-regulated kinase (ERK1/2) and p38 MAPK expression in monocytes from peripheral blood mononuclear cells were measured by Western blot analysis after stimulation by Mycobacterium avium in five patients with M. abscessus lung disease and seven healthy controls. A M. avium-induced cytokine assay was performed after inhibition of ERK1/2 and p38 MAPK pathways. Results: Mycobacterium avium induced p38 and ERK1/2 expression in monocytes from healthy controls and subsequently upregulated tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and IL-10 production. In monocytes from patients with M. abscessus lung disease, however, induction of p38 and ERK1/2 expression, and the production of TNF-${\alpha}$, IL-6, and IL-10 were significantly lower. Conclusion: Decreased activity of MAPK and cytokine secretion in monocytes from patients with M. abscessus lung disease may provide an explanation regarding host susceptibility to these uncommon infections.