• Tuberculosis and Respiratory Diseases
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• v.82 no.2
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• pp.151-157
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• 2019

Background: Tuberculosis (TB) is the most important disease screened for upon patient history review during preimmigration medical examinations as performed in South Korea in prospective immigrants to certain Western countries. In 2007, the U.S. Centers for Disease Control and Prevention (CDC) changed the TB screening protocol from a smear-based test to the complete Culture and Directly Observed Therapy Tuberculosis Technical Instructions (CDOT TB TI) for reducing the incidence of TB in foreign-born immigrants. Methods: This study evaluated the effect of the revised (as compared with the old) protocol in South Korea. Results: Of the 40,558 visa applicants, 365 exhibited chest radiographic results suggestive of active or inactive TB, and 351 underwent sputum tests (acid-fast bacilli smear and Mycobacterium tuberculosis culture). To this end, using the CDOT TB TI, 36 subjects (88.8 per $10^5$ of the population) were found to have TB, compared with only seven using the older U.S. CDC technical instruction (TI) (p<0.001). In addition, there were six drug-resistant cases which were identified (16.7 per $10^5$ of the population), two of whom had multidrug-resistance (5.6 per $10^5$ of the population). Conclusion: The culture-based 2007 TI identified a great deal of TB cases current to the individuals tested, as compared to older U.S. CDC TI.

• Tuberculosis and Respiratory Diseases
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• v.80 no.2
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• pp.159-168
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• 2017

Background: Streptomycin (SM) is recommended by the World Health Organization (WHO) as a part of standard regimens for retreating multidrug-resistant tuberculosis (MDR-TB) cases. The incidence of MDR-TB in retreatment cases was 19% in Thailand. To date, information on SM resistance (SMR) gene mutations correlated to the SMR of Mycobacterium tuberculosis Thai isolates is limited. In this study, the mutations in rpsL, rrs, gidB, and whiB7 were investigated and their association to SMR and the lineage of M. tuberculosis were explored. Methods: The lineages of 287 M. tuberculosis collected from 2007 to 2011 were identified by spoligotyping. Drug susceptibility profiles were evaluated by the absolute concentration method. Mutations in SMR genes of 46 SM-resistant and 55 SM-susceptible isolates were examined by DNA sequencing. Results: Three rpsL (Lys43Arg, Lys88Arg, and Lys88Thr) and two gidB (Trp45Ter and Gly69Asp) mutations were present exclusively in the SM resistant M. tuberculosis. Lys43Arg rpsL was the most predominant SMR mutations (69.6%) and prevailed among Beijing isolates (p<0.001). No SMR-related mutation in was found rrs. The combination of rpsL and gidB mutations provided 76.1% sensitivity for detecting SMR in M. tuberculosis Thai isolates. whiB7 was not responsible for SMR in SM resistant isolates lacking rpsL and rrs mutations. The significance of the three gidB mutations, 276A>C, 615A>G, and 330G>T, as lineage signatures for Beijing and EAI were underscored. This study identified 423G>A gidB as a novel sub-lineage marker for EAI6-BGD1. Conclusion: Our study suggested that the majority of SMR in M. tuberculosis Thai isolates were responsible by rpsL and gidB polymorphisms constantly providing the novel lineage specific makers.

• Tuberculosis and Respiratory Diseases
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• v.80 no.2
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• pp.143-152
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• 2017

Background: Fluoroquinolones are considered important substitutes for the treatment of tuberculosis. This study investigates the current status of fluoroquinolone for the treatment of tuberculosis. Methods: In 2009, a retrospective analysis was performed at one tertiary referral center for 953 patients diagnosed with tuberculosis. Results: A total of 226 patients (23.6%), who received fluoroquinolone at any time during treatment for tuberculosis, were enrolled in this study. The most common reasons for fluoroquinolone use were adverse events due to other anti-tuberculosis drugs (52.7%), drug resistance (23.5%), and underlying diseases (16.8%). Moxifloxacin (54.0%, 122/226) was the most commonly administered fluoroquinolone, followed by levofloxacin (36.3%, 82/226) and ofloxacin (9.7%, 22/226). The frequency of total adverse events from fluoroquinolone-containing anti-tuberculosis medication was 22.6%, whereas fluoroquinolone-related adverse events were estimated to be 2.2% (5/226). The most common fluoroquinolone-related adverse events were gastrointestinal problems (3.5%, 8/226). There were no significant differences in the treatment success rate between the fluoroquinolone and fluoroquinolone-$na{\ddot{i}}ve$ groups (78.3% vs. 78.4%, respectively). Conclusion: At our institution, fluoroquinolones are commonly used for the treatment of both multidrug-resistant tuberculosis and susceptible tuberculosis, especially as a substitute for adverse event-related drugs. Considering the low adverse event rates and the comparable treatment success rates, fluoroquinolones seem to be an invaluable drug for the treatment of tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.70 no.3
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• pp.251-256
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• 2011

The prevalence of multi-drug resistant tuberculosis (MDR-TB), which is resistant to isoniazid and rifampin, has been increasing in Korea. And the side effects of 2nd line anti-tuberculosis medications, including drug-induced hepatitis, are well known. Although prothionamide (PTH) is one of the most useful anti-TB medications and although TB medication-induced acute hepatitis is a severe complication, there are only a few published case reports about prothionamide induced hepatitis. In this case report, a 22 year old male was diagnosed with pulmonary MDR-TB and was administered 2nd line anti-TB mediations, including PTH. Afterwards, he had a spiking fever and his liver enzymes were more than 5 times greater than the upper limit of the normal range. He was then diagnosed with drug-induced hepatitis by liver biopsy. His symptoms and liver enzyme elevation were improved after stopping PTH. Accordingly, we report this case of an association between PTH and acute hepatitis.

• Tuberculosis and Respiratory Diseases
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• v.59 no.6
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• pp.613-618
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• 2005

Background : Recently, medical treatment of multi-drug resistant pulmonary tuberculosis has been unsuccessful. Through analyzing the cases with surgical treatment, we hope to provide some help in treating multi-drug resistant pulmonary tuberculosis in the future. Material and Method : A retrospective review was performed with 138cases of surgical treatment of multi-drug resistant tuberculosis during 10years from January 1994 to December 2003 at National Masan Hospital. Results : The ratio of men to women, 5.1:1 indicates that there were more incidences in men. The number of the resistant drugs was 5.3 with a mean age of 42.6 years. Cavitary lesions on the plain chest X-rays were seen in 94cases (68.1%). 128cases had positive sputum culture preoperatively. Types of operations were 24 pnemonectomies, 83 lobectomies, 10 bilobectomies, 19 lobectomies with segmentectomies or wedge resections, 1 wedge resection, and 1 carvenoplasty. There was no death after operation. There were 6cases of air leakage over a week, 6cases of postoperative bleeding, 8cases of bronchopleural fistula and empyema, 16cases of dead space, 1case of atelectasis, 1case of wound infection, 1case of cyst as postoperative complication. Postoperative complication showed higher long-term negative conversion rate of 92.8%. Conclusion : There has been many discussions about operative indications, postoperative drug regimens, length of postoperative chemotherapy. In our study, we showed higher long-term success rate of postoperative chemotherapy with pulmonary resection on multi-drug resistant pulmonary tuberculosis.

• Bulletin of the Korean Chemical Society
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• v.28 no.6
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• pp.947-952
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• 2007

Mycobacterium tuberculosis is a pathogen responsible for 2-3 million deaths every year worldwide. The emergence of drug-resistant and multidrug-resistant tuberculosis has increased the need to identify new antituberculosis targets. Acetohydroxy acid synthase, (AHAS, EC 2.2.1.6), an enzyme involved in branched-chain amino acid synthesis, has recently been identified as a potential anti-tuberculosis target. To assist in the search for new inhibitors and “receptor-based” design of effective inhibitors of tubercular AHAS (TbAHAS), we constructed four different structural models of TbAHAS and used one of the models as a target for virtual screening of potential inhibitors. The quality of each model was assessed stereochemically by PROCHECK and found to be reliable. Up to 89% of the amino acid residues in the structural models were located in the most favored regions of the Ramachandran plot, which indicates that the conformation of each residue in the models is good. In the models, residues at the herbicide-binding site were highly conserved across 39 AHAS sequences. The binding mode of TbAHAS with a sulfonylurea herbicide was characterized by 32 hydrophobic interactions, the majority of which were contributed by residue Trp516. The model based on the highest resolution X-ray structure of yeast AHAS was used as the target for virtual screening of a chemical database containing 8300 molecules with a heterocyclic ring. We developed a short list of molecules that were predicted to bind with high scores to TbAHAS in a conformation similar to that of sulfonylurea derivatives. Five sulfonylurea herbicides that were calculated to efficiently bind TbAHAS were experimentally verified and found to inhibit enzyme activity at micromolar concentrations. The data suggest that this time-saving and costeffective computational approach can be used to discover new TbAHAS inhibitors. The list of chemicals studied in this work is supplied to facilitate independent experimental verification of the computational approach.

• Tuberculosis and Respiratory Diseases
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• v.51 no.5
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• pp.409-415
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• 2001

Background : Multidrug-resistant tuberculosis(MDR-TB) in patients is mainly caused by acquired drug resistance. However, a small proportion of MDR-TB is caused by initial drug resistance(IDR), which may be somewhat different from acquired drug resistance. This study analyzed the clinical characteristics of IDR in MDR -TB patients to use the results as basic data in managing the disease. Methods : A retrospective study of 30 IDR cases in MDR-TB patients from Jan. 1995 to Dec. 1998 was performed. In order to analyze the clinical characteristics, the age, sex, family history, duration of negative conversion, number of resistant drugs, treatment regimens, duration of treatment, extent of disease and cavitary lesion on the chest X-ray was examined. In order to analyze the level of improvement, the extent of the disease and cavitary lesion on the chest X-ray, tested by Wilcoxon signed rank sum test, and the disease free interval rate of 1-year and 4-year was examined using the Kaplan-Meier method. Results : The mean age of the patients was 46.6 years and the sex ratio 1:1. Six(20%) patients had a family history. The mean negative conversion of the sputum AFB stain was 2.6 months. The number of resistant drugs was 7.6 and the number of used drugs 3.6. Twenty-three(67%) patients were treated for less than 12months and 28(93%) patients were treated with first-line drugs. The extent of the disease and the cavitary lesion on the chest X-ray improved after treatment(p<.05). Among 13 patients who were followed up for 22.6 months, 2(15%) patients relapsed and the disease free interval rate of I-year and 4-year was 85%. Conclusion: It is recommended that the duration of treatment of IDR in MDR-TB with first-line drugs be 9-12 months even if the extent of disease and cavitary lesion on the chest X-ray improves.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.842-851
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• 1996

Background : Rifampicin(RFP) is a key component of the antituberculous shon-course chemotherapy and the RFP-resistance is a marker of multi-drug resistant(MDR) M. tuberculosis. rpoB gene encodes the ${\beta}$-subunit of RNA polymerase of M. tuberculosis which is the target of RFP. Recent reports show that rpoB gene mutations are the cause of RFP resistance of M. tuberculosis and the main mechanism of rpoB gene mutation is point mutation. And PCR-SSCP is a rapid and easy method for detecting point mutations. So we performed PCR-SSCP of rpoB gene of M. tuberculosis and compared the result with traditional RFP sensitivity test. Method : The 27 RFP sensitive M. tuberculosis culture isolates and 25 RFP resistant isolates were evaluated. The RFP sensitivity test was done at the Korean Tuberculosis istitute. The DNA was extracted by bead beater method and was amplified with primers TR-8 and TR-9 in a 20ul PCR reaction containing 0.1ul(luCi) [${\alpha}-^{32}P$] - dCTP. After amplification, SSCP was done using non-denaturaring polyacrylamide gel electrophoresis. Then direct sequencing was done in cases of different eletrophoretic mobility compared with that of H37Rv. In 19 cases, we compared PCR-SSCP results with patient's clinical course and the results of traditional RFP sensitivity test. Results : 1) All 27 RFP sensitive M. tuberculosis isolates showed the same electrophoretic mobility compared with that of H37Rv. And all 25 RFP resistant M. tuberculosis isolates showed different electrophoretic mobility. 2) The mechanism of rpoB gene mutation of M. tuberculosis is mainly point mutation. 3) The PCR-SSCP results correlate well with traditional RFP sensitivity and patient's clinical response to antituberculous treatment. Conclusion: The PCR-SSCP of rpoB gene is a very sensitive and rapid mehod in detecting RFP- resistant M. tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.72 no.1
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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.

• Tuberculosis and Respiratory Diseases
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• v.73 no.1
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• pp.48-55
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• 2012

Background: The epidemiology of tuberculosis (TB) has been assessed based on the data of the analysis of TB patients notified to the surveillance system in Korea. However, the national status of TB is not validated through this surveillance system. The objective is to determine the epidemiology of TB and to understand the accurate status of TB patients treated in private institutions. Methods: Medical records of 53,579 patients who had been diagnosed with TB in 2008 were analyzed. Results: Among 53,579 patients, the number of sputum smear positive cases was 15,639(29.2%) and the number of new cases was 39,191 (73.1%). The drug resistance rate of new cases was 5.3%, while the rate stood at 13.3% for TB patients with treatment history. The number of multi-drug resistant TB (MDR-TB) patients was 2,472 (4.6%), which consists of 2.9% of new cases and 9.3% of TB patients with prior treatment history. The number of extensively drug-resistant TB patients was 749 (1.4%), consisting of 1.1% of new cases and 2.2% of TB patients with prior treatment history. In terms of treatment outcomes, 66.4% of all TB patients, 70.5% of new cases, 64.4% of relapse cases, and 46.8% of MDR-TB cases were cured or completed. It was inferred that in 2008, the total number of TB patients reached 70,767, 145.6 per 100,000 people (95% confidence interval, 145.5~145.7). Conclusion: We conclude that the medical records review of the Health Insurance Review and Assessment Service (HIRA) data can be very effective in promoting the understanding of the current status of TB in private institutions.