• Journal of Microbiology and Biotechnology
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• v.31 no.12
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• pp.1632-1642
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• 2021

Tuberculosis is a highly contagious disease caused by Mycobacterium tuberculosis. It affects about 10 million people each year and is still one of the leading causes of death worldwide. About 2 to 3 billion people (equivalent to 1 in 3 people in the world) are infected with latent tuberculosis. Moreover, as the number of multidrug-resistant, extensively drug-resistant, and totally drug-resistant strains of M. tuberculosis continues to increase, there is an urgent need to develop new anti-tuberculosis drugs that are different from existing drugs to combat antibiotic-resistant M. tuberculosis. Against this background, we aimed to develop new anti-tuberculosis drugs using probiotics. Here, we report the anti-tuberculosis effect of Pediococcus acidilactici PMC202 isolated from young radish kimchi, a traditional Korean fermented food. Under coculture conditions, PMC202 inhibited the growth of M. tuberculosis. In addition, PMC202 inhibited the growth of drug-sensitive and -resistant M. tuberculosis- infected macrophages at a concentration that did not show cytotoxicity and showed a synergistic effect with isoniazid. In a 2-week, repeated oral administration toxicity study using mice, PMC202 did not cause weight change or specific clinical symptoms. Furthermore, the results of 16S rRNA-based metagenomics analysis confirmed that dysbiosis was not induced in bronchoalveolar lavage fluid after oral administration of PMC202. The anti-tuberculosis effect of PMC202 was found to be related to the reduction of nitric oxide. Our findings indicate that PMC202 could be used as an anti-tuberculosis drug candidate with the potential to replace current chemical-based drugs. However, more extensive toxicity, mechanism of action, and animal efficacy studies with clinical trials are needed.

• Tuberculosis and Respiratory Diseases
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• v.78 no.3
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• pp.168-174
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• 2015

Drug-resistant tuberculosis (TB) is still a major threat worldwide. However, recent scientific advances in diagnostic and therapeutic tools have improved the management of drug-resistant TB. The development of rapid molecular testing methods allows for the early detection of drug resistance and prompt initiation of an appropriate treatment. In addition, there has been growing supportive evidence for shorter treatment regimens in multidrug-resistant TB; and for the first time in over 50 years, new anti-TB drugs have been developed. The World Health Organization has recently revised their guidelines, primarily based on evidence from a meta-analysis of individual patient data (n=9,153) derived from 32 observational studies, and outlined the recommended combination and correct use of available anti-TB drugs. This review summarizes the updated guidelines with a focus on the medical management of drug-resistant TB.

• 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.

• 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.58 no.3
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• pp.243-247
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• 2005

Background : The prevalence of tuberculosis is slowly decreasing in Korea. However, the drug-resistance of pulmonary tuberculosis is a major risk factor of treatment failure. Moreover, the National Surveillance System has recently been discontinued. Therefore, a continuous survey is necessary for the exact detection of the rate of drug resistance. We studied the recent 4-year drug resistance rate of tuberculosis at a single University hospital in Seoul. Materials and Methods : The study included 239 pulmonary tuberculosis patients performed with a tuberculosis culture and a drug-sensitivity test at Hanyang University Medical Center from March 1999 to March 2003. Results : Of the 239 patients included in the study during the 4-year period, 52 patients showed resistance to one or more anti-tuberculosis drug (21.8%). The rate of multi-drug resistance was 12.6%. The resistance rates to isoniazid, rifampin, ethambutol, streptomycin and pyrazinamide were 18.4%, 13.8%, 11.7%, 6.7% and 8.4%, respectively. Ninety patients had a history of previous anti-tuberculosis treatment, and the rates of the overall drug resistance and multi-drug resistance of these patients were 36.7% and 25.6%, respectively. The patients with drug-resistance showed a higher rate of a previous tuberculosis treatment history (63.5%) than the drug-sensitive group patients (30.5%). Conclusion : The rate of drug resistant tuberculosis is 21.8%, and multi-drug resistant tuberculosis is 12.6%. The rate of drug resistance is higher in those previously treated for tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.78 no.1
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• pp.27-30
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• 2015

The drug reaction with eosinophilia and systemic symptom (DRESS) syndrome is a severe adverse drug-induced reaction which includes a severe skin eruption, fever, hematologic abnormalities (eosinophilia or atypical lymphocytes) and internal organ involvement. The most frequently reported drug was anticonvulsants. The diagnosis of DRESS syndrome is challenging because the pattern of cutaneous eruption and the types of organs involved are various. The treatments for DRESS syndrome are culprit drug withdrawal and corticosteroids. Here we report a 71-year-old man with skin eruption with eosinophilia and hepatic and renal involvement that appeared 4 weeks after he had taken anti-tuberculosis drugs (isoniazid, ethambutol, rifampicin, and pyrazinamide), and resolved after stopping anti-tuberculosis drugs and the administration of systemic corticosteroids. DRESS recurred after re-challenging isoniazid, we identified isoniazid was causative drug.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.2
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• pp.125-132
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• 2022

The prevalence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) are increasing. We analyzed the patterns of drug resistance and tracking period days of acquiring anti-mycobacterial resistance. From January 2010 to December 2019, drug susceptibility tests (DST) were performed by the absolute concentration method using the Löwenstein-Jensen solid medium and pyrazinamidase activity test (to assess pyrazinamide resistance) in samples from patients who were referred to the Green Cross Laboratories in Yongin. Among the cases that showed resistance to one or more anti-tuberculosis drugs, 55 patients (33.1%) were resistant to isoniazid (INH) at the time of initial referral, and the rates for the development of resistant anti-tuberculosis drugs were ethambutol (EMB) (26.6%), rifampicin (RFP) (21.9%), quinolones (QUI) (21.9%) and pyrazinamide (PZA) (10.9%), in that order. In the cases sensitive to all 10 anti-tuberculosis drugs initially, the development of resistance to INH was the most frequent, seen in 43 patients (7.2%). The average follow-up period was 435.6 days, and the resistance development was observed in the order of INH (7.2%), RFP (3.9%), SM (1.9%), QUI (0.7%), amikacin (AMK) (0.5%), and EMB (0.5%). The conversion of susceptible strains to resistant strains is an important warning sign for the patient, especially in cases of conversion to MDR or XDR. This information would be helpful for improving patient care during TB treatment.

• Korean Journal of Clinical Laboratory Science
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• v.53 no.2
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• pp.137-142
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• 2021

This study investigated the patterns of acquiring anti-mycobacterial resistance in individuals who were susceptible to all anti-mycobacterial drugs in their initial treatment. From 2010 to 2019, anti-mycobacterial drug susceptibility tests were conducted on patients who were referred to the Green Cross Laboratories. The test results of 594 anti-mycobacterial drug sensitivity tests were collected at 111 medical institutions. The first test results had 594 cases in which all anti-mycobacterial drugs were susceptible. Isoniazid (INH), rifampin (RIF), streptomycin (SM), and quinolone (QUI) showed the highest single-resistant conversion rates. Out of 56 patients, 17 patients (30.4%) showed a high conversion rate of resistance to both INH and RIF. The tracking period was analyzed from a minimum of 98 days to 1,862 days, and an average of 435.6 days for INH, and a minimum of 108 days to 1,673 days, with an average of 457.7 days for RIF. In the case of tuberculosis patients who are susceptible to all anti-mycobacterial drugs, it is considered that the conversion to resistant and multi-drug resistant tuberculosis (MDR-TB) must be confirmed through an anti-mycobacterial susceptibility test after 3 months. It is hoped that this study will help the national tuberculosis management project to improve public health.

• 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.

• 대한임상약리학회:학술대회논문집
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• 2006.11a
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• pp.93-93
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• 2006