• Journal of Microbiology and Biotechnology
• /
• 제31권12호
• /
• pp.1632-1642
• /
• 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
• /
• 제78권3호
• /
• pp.168-174
• /
• 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
• /
• 제86권3호
• /
• pp.234-244
• /
• 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.

• 보험의학회지
• /
• 제28권1_2호
• /
• pp.15-18
• /
• 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
• /
• 제58권3호
• /
• pp.243-247
• /
• 2005

연구배경 : 한국에서 결핵환자의 유병률은 지속적으로 감소하고 있으나 약제에 대한 내성은 치료 실패의 중요한 요인이다. 국가적인 조사가 시행되지 않는 현 시점에서 지속적인 내성률 조사가 더욱 필요하다. 이에 저자들은 최근 4년간 서울 소재 한 대학병원에서 조사된 결핵균의 내성률 및 관련된 위험인자를 조사하였다. 대상 및 방법 : 1999년 3월부터 2003년 3월까지 한양대학교 의료원에서 치료 받은 결핵환자 중 결핵 배양 및 감수성 검사를 시행한 239명을 대상으로 하였다. 결 과 : 239명 중 한가지 이상의 약제에 내성을 보인 경우는 25명(21.8%)였고, 다제 내성 결핵은 30명(12.6%)이었다. INH, RFP, EMB, SM, PZA의 내성률은 각각 18.4%, 13.8%, 11.7%, 6.7%, 8.4%였다. 과거 결핵 치료력이 있는 환자는 90명이었으며 이들 중 약제 내성률은 36.7%, 다제 내성률은 25.6%였다. 약제 내성을 보인 환자의 63.5%는 과거 치료력이 있었으며 약제 감수성군의 과거 치료력은 30.5%였다. 결 론 : 서울에 소재한 한 대학병원에서 조사된 결핵 내성률은 21.8%, 다제 내성 결핵의 비율은 12.6%였다. 과거 결핵 치료력이 있는 경우에 약제 내성률이 높았다.

• Tuberculosis and Respiratory Diseases
• /
• 제78권1호
• /
• pp.27-30
• /
• 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.

• 대한임상검사과학회지
• /
• 제54권2호
• /
• pp.125-132
• /
• 2022

다제내성결핵과 광범위내성결핵은 결핵 치료의 문제가 되고 있으며 발생빈도 역시 증가하고 있다. 본 연구는 2010년 1월부터 2019년 12월까지 녹십자의료재단 의뢰된 환자를 대상으로 Löwenstein-Jensen 고체배지와 pyrazinamide for pyrazinamidase를 이용하여 약물감수성시험(DST)을 시행하여 내성으로 전환되는 항결핵제 패턴과 평균 추적 기간을 분석하였다. 항결핵제 중 1개 이상의 항결핵제 내성을 보인 증례들에서 초기 의뢰 시 INH 항결핵제에 내성인 경우가 55명(33.1%)으로 가장 높은 비율로 나타났으며, 내성으로 전환된 항결핵제는 EMB 17명(26.6%), RFP 14명(21.9%), QUI 14명(21.9%), PZA 12명(10.9%) 순으로 조사되었다. 10개의 항결핵제에 모두 감수성인 증례들에서는 INH 항결핵제에 대한 내성 전환은 43명(7.2%)으로 가장 빈도가 높았으며, 평균 추적 기간은435.6일로 조사되었으며, 내성으로 전환되는 항결핵제의 내성전환율은 INH 43명(7.2%), RFP 23명(3.9%), SM 11명(1.9%), QUI 4명(0.7%), AMK 3명(0.5%), EMB 3명(0.5%)이었다. 이에 본 연구는 항결핵제에 대한 감수성에서 내성으로의 전환은 특히 다제내성결핵과 광범위 내성결핵의 전환되는 환자에게 매우 중요한 자료가 될 것으로 보이며, 결핵 치료에서 환자 치료에 도움이 될 것으로 사료된다.

• 대한임상검사과학회지
• /
• 제53권2호
• /
• pp.137-142
• /
• 2021

본 연구는 결핵환자의 초기 치료에서 모든 항결핵제에 감수성을 보이는 경우, 치료 과정 중 항결핵제에 대한 내성 전환을 조사하였다. 2010년 1월부터 2019년 12월까지 111개 의료기관에서 녹십자의료재단에 항결핵제감수성 검사를 의뢰한 760건의 환자를 대상으로 하였다. 항결핵제에 모두 감수성인 594명중 추적 기간에 감수성에서 내성으로 전환되는 56명을 분석한 결과 INH, RIF, SM, QUI 순으로 단독 내성 전환율이 가장 높게 나타났으며, INH, RIF에 동시에 복합 내성을 보인 경우는 56명중 17명(30.4%)으로 높은 내성 전환율을 보이고 있다. 전환 시기는 INH 항결핵제는 최소 98일부터 1,862일, 평균 435.6일이며, RIF 항결핵제는 최소 108일부터 1,673일, 평균 457.7일로 분석되었다. 이에 본 연구는 결핵 초기 치료 후 모든 항결핵제에 감수성을 보였다면 3개월이 지난 시점에서 반드시 항결핵제 감수성 검사를 통해 내성 전환 및 다제내성결핵을 확인해야만 한다고 사료되며, 국민보건향상과 국민건겅증진을 위한 국가결핵관리 사업에 도움이 되었으면 한다.

• Annals of Laboratory Medicine
• /
• 제38권6호
• /
• pp.563-568
• /
• 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
• /
• 대한임상약리학회 2006년도 제15차 추계학술대회
• /
• pp.93-93
• /
• 2006