• Journal of Yeungnam Medical Science
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• v.37 no.4
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• pp.277-285
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• 2020

Tuberculosis (TB) is still a major health problem worldwide. Especially, multidrug-resistant TB (MDR-TB), which is defined as TB that shows resistance to both isoniazid and rifampicin, is a barrier in the treatment of TB. Globally, approximately 3.4% of new TB patients and 20% of the patients with a history of previous treatment for TB were diagnosed with MDR-TB. The treatment of MDR-TB requires medications for a long duration (up to 20-24 months) with less effective and toxic second-line drugs and has unfavorable outcomes. However, treatment outcomes are expected to improve due to the introduction of a new agent (bedaquiline), repurposed drugs (linezolid, clofazimine, and cycloserine), and technological advancement in rapid drug sensitivity testing. The World Health Organization (WHO) released a rapid communication in 2018, followed by consolidated guidelines for the treatment of MDR-TB in 2019 based on clinical trials and an individual patient data meta-analysis. In these guidelines, the WHO suggested reclassification of second-line anti-TB drugs and recommended oral treatment regimens that included the new and repurposed agents. The aims of this article are to review the treatment strategies of MDR-TB based on the 2019 WHO guidelines regarding the management of MDR-TB and the diagnostic techniques for detecting resistance, including phenotypic and molecular drug sensitivity tests.

• 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.86 no.3
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• pp.234-244
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• 2023

Background: Effective treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis (FQr-MDR-TB) is difficult because of the limited number of available core anti-TB drugs and high rates of resistance to anti-TB drugs other than FQs. However, few studies have examined anti-TB drugs that are effective in treating patients with FQr-MDR-TB in a real-world setting. Methods: The impact of anti-TB drug use on treatment outcomes in patients with pulmonary FQr-MDR-TB was retrospectively evaluated using a nationwide integrated TB database (Korean Tuberculosis and Post-Tuberculosis). Data from 2011 to 2017 were included. Results: The study population consisted of 1,082 patients with FQr-MDR-TB. The overall treatment outcomes were as follows: treatment success (69.7%), death (13.7%), lost to follow-up or not evaluated (12.8%), and treatment failure (3.9%). On a propensity-score-matched multivariate logistic regression analysis, the use of bedaquiline (BDQ), linezolid (LZD), levofloxacin (LFX), cycloserine (CS), ethambutol (EMB), pyrazinamide, kanamycin (KM), prothionamide (PTO), and para-aminosalicylic acid against susceptible strains increased the treatment success rate (vs. unfavorable outcomes). The use of LFX, CS, EMB, and PTO against susceptible strains decreased the mortality (vs. treatment success). Conclusion: A therapeutic regimen guided by drug-susceptibility testing can improve the treatment of patients with pulmonary FQr-MDR-TB. In addition to core anti-TB drugs, such as BDQ and LZD, treatment of susceptible strains with later-generation FQs and KM may be beneficial for FQr-MDR-TB patients with limited treatment options.

• Tuberculosis and Respiratory Diseases
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• v.80 no.4
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• pp.336-343
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• 2017

Despite progress made in tuberculosis control worldwide, the disease burden and treatment outcome of multidrug-resistant tuberculosis (MDR-TB) patients have remained virtually unchanged. In 2016, the World Health Organization released new guidelines for the management of MDR-TB. The guidelines are intended to improve detection rate and treatment outcome for MDR-TB through novel, rapid molecular testing and shorter treatment regimens. Key changes include the introduction of a new, shorter MDR-TB treatment regimen, a new classification of medicines and updated recommendations for the conventional MDR-TB regimen. This paper will review these key changes and discuss the potential issues with regard to the implementation of these guidelines in South Korea.

• 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.

• 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.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.84 no.1
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• pp.74-83
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• 2021

Background: This study compared the treatment outcomes of patients with multidrug-resistant tuberculosis (MDR-TB) before and after the implementation of public-private mix (PPM). Factors affecting treatment success were also investigated. Methods: Data from culture-confirmed pulmonary MDR-TB patients who commenced MDR-TB treatment at Pusan National University Hospital between January 2003 and December 2017 were retrospectively reviewed. Patients were divided into two groups in terms of PPM status: pre-PPM period, patients who commenced MDR-TB treatment between 2003 and 2010; and post-PPM period, patients treated between 2011 and 2017. Results: A total of 176 patients were included (64 and 112 in the pre- and post-PPM periods, respectively). 36.9% of the patients were resistant to a fluoroquinolone or a second-line injectable drug, or both. The overall treatment success rate was 72.7%. The success rate of post-PPM patients was higher than that of pre-PPM patients (79.5% vs. 60.9%, p=0.008). Also, loss to follow-up was lower in the post-PPM period (5.4% vs. 15.6%, p=0.023). In multivariate regression analysis, age ≥65 years, body mass index ≤18.5 kg/m², previous TB treatment, bilateral lung involvement, and extensively drug-resistant (XDR)- or pre-XDR-TB were associated with poorer treatment outcomes. However, the use of bedaquiline or delamanid for ≥1 month increased the treatment success. Conclusion: The treatment success rate in MDR-TB patients was higher in the post-PPM period than in the pre-PPM period, particularly because of the low rate of loss to follow-up. To ensure comprehensive patient-centered PPM in South Korea, investment and other support must be adequate.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.12 no.11
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• pp.5012-5018
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• 2011

According to the nationwide survey of tuberculosis from 1965 to 1995, the incidence and drug resistance rate of tuberculosis have been decreased in Korea, but the prevalence of multidrug resistance of Mycobacterium tuberculosis is still a serious problem. The purpose of this study is to investigate the drug resistance rate and pattern of tuberculosis in Daejeon from 2001 to 2008. Of the total 581cases where the drug susceptibility test was performed, resistance to at least one anti-TB drug was found in 104 cases(17.9%) of these, 68(11.7%) were resistant to at least INH and 41(7.1%) were resistant to at least RFP. Single-drug resistance was found for isolates from 37(6.4%) ; 18(3.1%) of these were resistant to INH and 5(0.9%) to RFP. Multidrug resistance, where TB was resistant to at least isoniazid and refampin, was found in 35 cases(6.0%). and Factors associated with MDR-TB included age under 40-60.The drug-resistance rate of pulmonary TB, especially MDR-TB, is higher in the initial treated patients at a private referral hospital than in those in the pubulic sector. Initial drug resistance is common and the drug susceptibility test is informative for pulmonary TB patients who have not received previous TB treatment. The need for an improved control program, coupled with early diagnosis of MDR-TB, to reduce the spread and development of resistance. Multidrug resistance rate is still problem in korea. Efforts to decrease multidrug resistance rate either independently or in cooperation with the pubulic sector will be needed.

• Tuberculosis and Respiratory Diseases
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• v.76 no.5
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• pp.245-248
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• 2014

Miliary tuberculosis (TB) is a rare extrapulmonary form of TB, and there have been only two reports of miliary TB associated with infection with multidrug-resistant (MDR)-TB pathogen in an immunocompetent host. A 32-year-old woman was referred to our hospital because of abnormal findings on chest X-ray. The patient was diagnosed with MDR-TB by a line probe assay and was administered proper antituberculous drugs. After eight weeks, a solid-media drug sensitivity test revealed that the pathogen was resistant to ethambutol and streptomycin in addition to isoniazid and rifampicin. The patient was then treated with effective antituberculous drugs without delay after diagnosis of MDR-TB. To the best of our knowledge, this is the first case of miliary TB caused by MDR-TB pathogen in Korea.