• The Korean Journal of Medicine
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• v.93 no.6
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• pp.509-517
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• 2018

A small number of viable tuberculosis bacilli can reside in an individual with latent tuberculosis infection (LTBI) without obvious clinical symptoms or abnormal chest radiographs. Diagnosis and treatment of LTBI are important for tuberculosis (TB) control in public and private healthcare facilities, particularly in high-risk populations. The updated 2017 Korean guidelines for TB recommend that tuberculin skin tests, interferon-gamma release assays, or a combination of them can be used for the diagnosis of LTBI, depending on the age and immune status of the patient as well as their TB contact history. For diagnosis of LTBI, exclusion of active TB is essential, and the possibility of healed TB in those without a history of treatment for TB but at risk of its development must be considered. The treatment options for LTBI include isoniazid, rifampicin, isoniazid/rifampicin, and isoniazid/rifapentine. The benefits and risks of these agents based on the age of the patient and their hepatotoxicity must be considered when selecting the appropriate drug. Standardized diagnosis and treatment of LTBI based on the updated 2017 guidelines will contribute to the control of TB in Korea as well as to further revisions of the guidelines.

• Clinical and Experimental Pediatrics
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• v.65 no.5
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• pp.214-221
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• 2022

Diagnosing and treating latent tuberculosis infection (LTBI) is an important part of efforts to combat tuberculosis (TB). The Korean guidelines for TB published in 2020 recommend 2 LTBI regimens for children and adolescents: 9 months of daily isoniazid (9H) and 3 months of daily isoniazid plus rifampicin. Isoniazid for 6-12 months has been used to effectively treat LTBI in children for over 50 years. However, a long treatment period results in poor patient compliance. This review summarizes pediatric data on the treatment completion rate, safety, and efficacy of 4 months of daily rifampicin (4R) and evaluates the pharmacokinetics and pharmacodynamics of rifampicin in children. The 4R regimen has a higher treatment completion rate than the 9H regimen and equivalent safety in children. The efficacy of preventing TB is also consistent with that of 9H when summarizing reports published to date. A shorter treatment period could increase patient compliance and, therefore, prevent TB in more patients. By using an effective, safe, and highly compliant regimen for the treatment of children with LTBI, we would become one step closer to our goal of eradicating TB.

• Tuberculosis and Respiratory Diseases
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• v.59 no.6
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• pp.619-624
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• 2005

Background : The drug resistance rate in tuberculosis patients with history of chemotherapy is an important indicator of for evaluation of appropriateness of treatment regimens and compliance of patients. This study examined the long-term changes in the drug resistance rates among TB patients failed in treatment or reactivated. Methods : The results of drug susceptibility testing data from patients registered in health centers from 1981 to 2004 were analyzed. Results : The rate of resistance to isoniazid decreased from 90% to 20%, and the resistance to ethambutol decreased from 45% to 6%. The rate of resistance to rifampicin varied from 13% to 28% and the resistance to pyrazinamide was 5% to 10%. Multidrug resistance was about 2-3% lower than any rifampicin resistance rates. The second-line drug resistance was ranged from 1% to 3%. There was no difference between patients' genders. Patient numbers per 100,000 population increased with age. The regional distribution was even at 4-6 patients per 100,000 population, and drug resistance rates were significantly lower in big city areas than in small towns and rural areas. Conclusion : The rates of resistance of Mycobacterium tuberculosis isolated from TB patients with history of chemotherapy to isoniazid, rifampin, ethambutol, and isoniazid plus rifampin were significantly decreased during over two decades.

• Tuberculosis and Respiratory Diseases
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• v.78 no.2
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• pp.56-63
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• 2015

A small number of viable tuberculosis bacilli can reside in an individual with latent tuberculosis infection (LTBI) without obvious clinical symptoms or abnormal chest radiographs. Diagnosis and treatment for LTBI are important for tuberculosis (TB) control in public and private health, especially in high-risk populations. The updated 2014 Korean guidelines for TB recommend that tuberculin skin tests, interferon-gamma release assays, or a combination of the two can be used for LTBI diagnosis according to age and immune status of the host as well as TB contact history. The regimens for LTBI treatment include isoniazid, rifampicin, or isoniazid/rifampicin. However, results of drug susceptibility test from the index case must be considered in selecting the appropriate drug for recent contacts. Standardized LTBI diagnosis and treatment based on the new 2014 guidelines will contribute to the effective TB control in Korea as well as to the establishment of updated guidelines.

• Tuberculosis and Respiratory Diseases
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• v.83 no.1
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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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• v.80 no.3
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• pp.255-264
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• 2017

Background:N-acetyl transferase (NAT) inactivates the pro-drug isoniazid (INH) to N-acetyl INH through a process of acetylation, and confers low-level resistance to INH in Mycobacterium tuberculosis (MTB). Similar to NAT of MTB, NAT2 in humans performs the same function of acetylation. Rapid acetylators, may not respond to INH treatment efficiently, and could be a potential risk factor, for the development of INH resistance in humans. Methods: To understand the contribution of NAT of MTB and NAT2 of humans in developing INH resistance using in silico approaches, in this study, the wild type (WT) and mutant (MT)-NATs of MTB, and humans, were modeled and docked, with substrates and product (acetyl CoA, INH, and acetyl INH). The MT models were built, using templates 4BGF of MTB, and 2PFR of humans. Results: On the basis of docking results of MTB-NAT, it can be suggested that in comparison to the WT, binding affinity of MT-G207R, was found to be lower with acetyl CoA, and higher with acetyl-INH and INH. In case of MT-NAT2 from humans, the pattern of score with respect to acetyl CoA and acetyl-INH, was similar to MT-NAT of MTB, but revealed a decrease in INH score. Conclusion: In MTB, MT-NAT revealed high affinity towards acetyl-INH, which can be interpreted as increased formation of acetyl-INH, and therefore, may lead to INH resistance through inactivation of INH. Similarly, in MT-NAT2 (rapid acetylators), acetylation occurs rapidly, serving as a possible risk factor for developing INH resistance in humans.

• Korean Journal of Clinical Pharmacy
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• v.28 no.2
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• pp.95-100
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• 2018

Background: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that can affect many organs of the body but usually affects the lungs. The prevalence of TB in Korea is considerably higher than that in other countries with similar economic levels, and is much higher in elderly people. Pharmacotherapy is important in the treatment of TB and requires relatively high compliance for a prolonged duration. Methods: We analyzed sample data of elderly patients obtained from the Health Insurance Review and Assessment Service. We used logistic regression analysis and frequency analysis to identify factors that could affect prevalence of TB in elderly patients, compliance with prescribed medication regimes in these patients, and use of medical institutions. Korean Standard Classification of Diseases, version 7 (KCD-7) was used to diagnose pulmonary TB, and medications were analyzed using Korean standardized drug classification codes. Results: 1,276,331 patients were analyzed in the sample of the elderly population, and 16,658 TB patients were included in the study. The mean age of the TB patients was 76.19 years (SD 6.899). A total of 699 patients were prescribed isoniazid, rifampicin, ethambutol, or pyrazinamide at least once. Of these, 352 (50.4%) were prescribed all four medications and 101 (14.4%) were prescribed only isoniazid, rifampicin, and ethambutol. The mean duration of prescription was 28.75 days (SD 36.13). Conclusion: In the elderly population, old age and poor socioeconomic conditions correlated with TB prevalence. Most patients did not meet the criteria for effective pharmacotherapy of TB.

• Tuberculosis and Respiratory Diseases
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• v.81 no.1
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• pp.6-12
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• 2018

The role of the treatment for latent tuberculosis infection (LTBI) has been underscored in the intermediate tuberculosis (TB) burden countries like South Korea. LTBI treatment is recommended only for patients at risk for progression to active TB-those with frequent exposure to active TB cases, and those with clinical risk factors (e.g., immunocompromised patients). Recently revised National Institute for Health and Care Excellence (NICE) guideline recommended that close contacts of individuals with active pulmonary or laryngeal TB, aged between 18 and 65 years, should undergo LTBI treatment. Various regimens for LTBI treatment were recommended in NICE, World Health Organization (WHO), and Centers for Disease Control and Prevention guidelines, and superiority of one recommended regimen over another was not yet established. Traditional 6 to 9 months of isoniazid (6H or 9H) regimen has an advantage of the most abundant evidence for clinical efficacy-60%-90% of estimated protective effect. However, 6H or 9H regimen is related with hepatotoxicity and low compliance. Four months of rifampin regimen is characterized by less hepatotoxicity and better compliance than 9H, but has few evidence of clinical efficacy. Three months of isoniazid plus rifampin was proved equivalence with 6H or 9H regimen in terms of efficacy and safety, which was recommended in NICE and WHO guidelines. The clinical efficacy of isoniazid plus rifapentine once-weekly regimen for 3 months was demonstrated recently, which is not yet introduced into South Korea.

• Tuberculosis and Respiratory Diseases
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• v.78 no.2
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• pp.125-127
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• 2015

We report a case of agranulocytosis caused by ethambutol in a 79-year-old man with pulmonary tuberculosis. He was referred for fever and skin rash developed on 21th day after antituberculosis drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide) intake. Complete blood count at the time of diagnosis of pulmonary tuberculosis was normal. On the seventh admission day, agranulocytosis was developed with absolute neutrophil count of $70/{\mu}L$. We discontinued all antituberculosis drugs, and then treated with granulocyte colony-stimulating factor. Three days later, the number of white blood cell returned to normal. We administered isoniazid, pyrazinamide, and ethambutol in order with an interval. However, fever and skin rash developed again when adding ethambutol, so we discontinued ethambutol. After these symptoms disappeared, we added rifampicin and ethambutol in order with an interval. However after administering ethambutol, neutropenia developed, so we discontinued ethambutol again. He was cured with isoniazid, rifampicin, and pyrazinamide for 9 months.

• Annals of Laboratory Medicine
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• v.38 no.6
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• pp.569-577
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• 2018

Background: The increasing prevalence of drug-resistant tuberculosis (TB) infection represents a global public health emergency. We evaluated the usefulness of a newly developed multiplexed, bead-based bioassay (Quantamatrix Multiplexed Assay Platform [QMAP], QuantaMatrix, Seoul, Korea) to rapidly identify the Mycobacterium tuberculosis complex (MTBC) and detect rifampicin (RIF) and isoniazid (INH) resistance-associated mutations. Methods: A total of 200 clinical isolates from respiratory samples were used. Phenotypic anti-TB drug susceptibility testing (DST) results were compared with those of the QMAP system, reverse blot hybridization (REBA) MTB-MDR assay, and gene sequencing analysis. Results: Compared with the phenotypic DST results, the sensitivity and specificity of the QMAP system were 96.4% (106/110; 95% confidence interval [CI] 0.9072-0.9888) and 80.0% (72/90; 95% CI 0.7052-0.8705), respectively, for RIF resistance and 75.0% (108/144; 95% CI 0.6731-0.8139) and 96.4% (54/56; 95% CI 0.8718-0.9972), respectively, for INH resistance. The agreement rates between the QMAP system and REBA MTB-MDR assay for RIF and INH resistance detection were 97.6% (121/124; 95% CI 0.9282-0.9949) and 99.1% (109/110; 95% CI 0.9453-1.0000), respectively. Comparison between the QMAP system and gene sequencing analysis showed an overall agreement of 100% for RIF resistance (110/110; 95% CI 0.9711-1.0000) and INH resistance (124/124; 95% CI 0.9743-1.0000). Conclusions: The QMAP system may serve as a useful screening method for identifying and accurately discriminating MTBC from non-tuberculous mycobacteria, as well as determining RIF- and INH-resistant MTB strains.