• Title/Summary/Keyword: Multidrug-resistant tuberculosis

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Multidrug-Resistant Tuberculosis Presenting as Miliary Tuberculosis without Immune Suppression: A Case Diagnosed Rapidly with the Genotypic Line Probe Assay Method

  • Ko, Yousang;Lee, Ho Young;Lee, Young Seok;Song, Junwhi;Kim, Mi-Yeong;Lee, Hyun-Kyung;Shin, Jeong Hwan;Choi, Seok Jin;Lee, Young-Min
    • 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.

Evaluation of the Efficacy and Safety of Linezolid by Meta-analysis for Multidrug-resistant Tuberculosis Patients (다제내성결핵 환자에서 메타분석을 통한 Linezolid의 효능 및 안전성 평가)

  • Woojin Jung;Taewook Sung;Ae Jin Kim;Jung-woo Chae;Hwi-yeol Yun
    • Korean Journal of Clinical Pharmacy
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    • v.33 no.4
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    • pp.278-289
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    • 2023
  • Background: Linezolid has been widely used in the treatment for multidrug-resistant tuberculosis. However, there are limitations to use it such as long treatment, because of related side effects, even adequate treatment period has been needed for remission of multidrug-resistant tuberculosis (MDR-TB). Method: The meta-analysis was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. To choose literatures, systematic literature reviews were conducted with databases of PubMed, Web of Science, and EMBASE. Results: Efficacy and safety of Linezolid were determined by 85% (95% CI=79~89%, p<0.05) in the sputum culture conversion and 55% (95% CI=45~64%, p<0.01) in side effects related to linezolid, respectively. In addition, I2 was estimated by 72%. In the subgroup analysis, efficacy and safety by dose and region were analyzed. In the subgroup analysis, compared with the linezolid dose in groups greater than 600 mg/day and less than 600 mg/day, this study showed 85% (95% CI 79~90%, p>0.05) in 206 patients and 82% (95% CI 73~89%, p<0.05) in 297 patients, respectively. Also, in the subgroup analysis, adverse effects caused by linezolid occurred more than 50% of treated patients. Conclusion: Therapeutic efficacy of linezolid for MDR-TB patients was confirmed regardless of the initial dose of linezolid, especially for sputum culture conversion and it was recommended that the dose of linezolid has been more effective below 600 mg/day. However, it should be necessary to closely monitored for safety issues since serious side effects possibly occurred by administration of long period treatment.

Treatment Outcomes of Patients with Multidrug-Resistant Tuberculosis: Comparison of Pre- and Post-Public-Private Mix Periods

  • Kang, Yewon;Jo, Eun-Jung;Eom, Jung Seop;Kim, Mi-Hyun;Lee, Kwangha;Kim, Ki Uk;Park, Hye-Kyung;Lee, Min Ki;Mok, Jeongha
    • 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.

Insurance risk analysis of drug-resistant tuberculosis (내성결핵의 보험의학적 위험분석)

  • Lee, Sin-Hyung
    • 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.

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Diagnosis and treatment of multidrug-resistant tuberculosis

  • Jang, Jong Geol;Chung, Jin Hong
    • 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.

Acquired Drug Resistance during Standardized Treatment with First-line Drugs in Patients with Multidrug-Resistant Tuberculosis (다제내성결핵 환자에서 표준 1차 항결핵제 치료 중 발생한 획득 내성)

  • Jeon, Doosoo;Kim, Dohyung;Kang, Hyungseok;Min, Jinhong;Sung, Nackmoon;Hwang, Soohee;Park, Seungkew
    • Tuberculosis and Respiratory Diseases
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    • v.66 no.3
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    • pp.198-204
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    • 2009
  • Background: First-line drugs, if sensitive, are the most potent drugs in the treatment of multidrug-resistant tuberculosis (MDR-TB). This study examined the frequency and risk factors associated with acquired drug resistance to first-line drugs during a standardized treatment using first-line drugs in patients with MDR-TB. Methods: This study included patients who were diagnosed with MDR-TB at the National Masan Tuberculosis Hospital between January 2004 and May 2008, treated with standardized first-line drugs, and for whom the preand post-treatment results of the drug susceptibility test were available. Their medical records were reviewed retrospectively. Results: Of 41 MDR-TB patients, 14 (34.1%) acquired additional resistance to ethambutol (EMB) or pyrazinamide (PZA). Of 11 patients initially resistant to isoniazid (INH) and rifampicin (RFP), 3 (27.3%) acquired additional resistance to both EMB and PZA, and 3 (27.3%) to PZA. Of 18 patients initially resistant to INH, RFP and EMB, 6 (33.3%) acquired additional resistance to PZA. Of 6 patients initially resistant to INH, RFP and PZA, 2 (33.3%) acquired additional resistance to EMB. Ten of the 41 MDR-TB patients (24.4%) changed from resistant to susceptible. No statistically significant risk factors associated with acquired resistance could be found. Conclusion: First-line drugs should be used cautiously in the treatment of MDR-TB in Korea considering the potential acquisition of drug resistance.

Trend of Multidrug and Extensively Drug Resistant Tuberculosis in a Tuberculosis Referral Hospital, 2001~2005 (일개 결핵병원에서 다제내성결핵과 광범위내성결핵의 추이, 2001~2005)

  • Jeon, Doosoo;Shin, Dongok;Kang, Hyungseok;Sung, Nackmoon;Kweon, Kyungsoon;Shin, Eun;Kim, Kyungsoon;Lee, Myunghee;Park, Seungkyu
    • 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.

Calcaneal Osteomyelitis Presenting as a Paradoxical Reaction during Treatment of Multidrug-Resistant Tuberculosis (다제내성 결핵의 치료 중 역설적 반응으로 나타난 종골 골수염)

  • Han, Yong Hyun;Lee, Chang Hwa;Bae, Min Joon;Hwang, Kihun
    • Clinical Pain
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    • v.18 no.2
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    • pp.102-106
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    • 2019
  • Tuberculosis in the foot progresses gradually; thus, diagnosis is usually delayed, and early treatment is rarely provided. If osteomyelitis occurs due to delayed diagnosis and treatment, surgical treatment should be considered. We report the case of a 46-year-old man with osteomyelitis of the calcaneus who was diagnosed with multidrug-resistant pulmonary tuberculosis and he was treated with anti-tuberculosis drugs. Bilateral adrenal masses, abscess of both testes and a small wound in the left plantar heel were observed. Both adrenal masses and abscess were regarded as paradoxical reaction of anti-tuberculosis treatment. After 1 month, he developed a pain in the left plantar heel that was compatible with calcaneal osteomyelitis in radiological features. He underwent right orchiectomy for right scrotal abscess aggravation and surgical treatment for left calcaneal osteomyelitis. Mycobacterium tuberculosis was confirmed by polymerase chain reaction. The patient was immobilized by cast for 8 weeks and the heel pain gradually improved.

Delamanid, Bedaquiline, and Linezolid Minimum Inhibitory Concentration Distributions and Resistance-related Gene Mutations in Multidrug-resistant and Extensively Drug-resistant Tuberculosis in Korea

  • Yang, Jeong Seong;Kim, Kyung Jong;Choi, Hongjo;Lee, Seung Heon
    • 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.