• Tuberculosis and Respiratory Diseases
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• 제81권3호
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• pp.222-227
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• 2018

Background: Rifampicin (RFP) is one of the principal first-line drugs used in combination chemotherapies against Mycobacterium tuberculosis, and its use has greatly shortened the duration of chemotherapy for the successful treatment of drug-susceptible tuberculosis. Compensatory mutations have been identified in rpoC that restore the fitness of RFP-resistant M. tuberculosis strains with mutations in rpoB. To investigate rpoC mutation patterns, we analyzed 93 clinical M. tuberculosis isolates from patients in South Korea. Methods: Drug-resistant mycobacterial isolates were cultured to determine their susceptibility to anti-tubercular agents. Mutations in rpoC were identified by sequencing and compared with the relevant wild-type DNA sequence. Results: In total, 93 M. tuberculosis clinical isolates were successfully cultured and tested for drug susceptibilities. They included 75 drug-resistant tuberculosis species, of which 66 were RFP-resistant strains. rpoC mutations were found in 24 of the 66 RFP-resistant isolates (36.4%). Fifteen different types of mutations, including single mutations (22/24, 91.7%) and multiple mutations (2/24, 8.3%), were identified, and 12 of these mutations are reported for the first time in this study. The most frequent mutation involved a substitution at codon 452 (nt 1356) resulting in amino acid change F452L. Conclusion: Fifteen different types of mutations were identified and were predominantly single-nucleotide substitutions (91.7%). Mutations were found only in dual isoniazid- and RFP-resistant isolates of M. tuberculosis. No mutations were identified in any of the drug-susceptible strains.

• Journal of Microbiology and Biotechnology
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• 제27권11호
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• pp.1932-1941
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• 2017

DFC-2, a methyl 5-[2-(dimethylamino)ethoxy]-7,12-dioxo-7,12-dihydrodinaphtho[1,2-b:2',3'-d]furan-6-carboxylate, is reported to have antitubercular effects against Mycobacterium tuberculosis. At concentrations ranging from 0.19 to $0.39{\mu}g/ml$, DFC-2 inhibited both drugusceptible and -resistant strains of M. tuberculosis. Microarray analyses were employed to gain insights into the molecular mechanisms of DFC-2's action in M. tuberculosis. The most affected functional gene category was "lipid biosynthesis," which is involved in mycolic acid synthesis. The decrease in transcription of genes related to mycolic acid synthesis was confirmed by RT-PCR. Furthermore, we found that DFC-2 triggered a reduction in mycolic acid levels, showing a similar pattern to that of mycolic acid synthesis inhibitor isoniazid. These results may explain how this compound kills mycobacteria efficiently by inhibiting mycolic acid synthesis.

• Tuberculosis and Respiratory Diseases
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• 제63권5호
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• pp.435-439
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• 2007

PZA에 의한 독성 간염은 약 2% 정도 보고되고 있으나 전격성 간염으로 진행하여 사망하는 경우는 드물게 보고되고 있다. 본 증례에서는 항결핵제에 의해 중증 독성 간염을 보였다가 회복된 후 저용량의 PZA을 재투여 하고 전격성 간염으로 진행하는 양상을 보였다. 이번 사례를 통해 저용량의 PZA를 투약시 전격성 간부전으로 진행하는 경우를 경험했고 항결핵제 투여시 면밀한 관찰이 필요하고 항결핵 약제 투여시 신중을 기울여야겠다.

• 약학회지
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• 제55권4호
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• pp.352-360
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• 2011

Standard combination chemotherapy including isoniazid, rifampin, pyrazinamide, and ethambutol is very effective against tuberculosis. But, these medicines can cause hepatotoxicity which is the main reason for treatment interruption or change in drug regimen. In order to identify risk factors associated with hepatotoxcity in Koreans and assess elevated baseline LFTs' contributions to hepatotoxicity, a retrospective case control study was performed. The medical records of 277 patients who diagnosed with tuberculosis at a community hospital from January 1st, 2007 to June 30th, 2010 were reviewed. Patients were categorized into 3 groups (non toxic group, patients without increase in LFT levels; mild to moderate hepatotoxic group and severe hepatotoxic group). And the correlation between risk factors and hepatotoxicity was analyzed by using SPSS program. The overall incidence of hepatotoxicity was 18% and 8.7% of patients developed severe toxicity. Patients in the severe toxic group had the longest treatment period among the three groups. In 75% of severe toxic group, hepatotoxicity occurred within 18.3 days after starting medication. Hypoalbuminemia (serum albumin <3 g/dl) was a significant risk factor for development of severe toxicity. Elevated baseline transaminase (except ALT), total bilirubin, and preexisting hepatitis were also risk factors which were more than twice as likely to increase risk of severe hepatotoxicity (p>0.05). In conclusion, hypoalbuminemia (serum albumin level <3 g/dl) was a significant risk factor for anti-tuberculosis druginduced severe toxicity. Therefore, before starting antituberculosis chemotherapy, serum albumin level should be assessed at baseline. In high-risk patients (hypoalbuminemia, elevated LFTs) for hepatotoxicty, liver function should be closely monitored up to at least 21 days after taking medication.

• Journal of Preventive Medicine and Public Health
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• 제16권1호
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• pp.129-134
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• 1983

The records for the tuberculosis patients who discharged from the health center during 1982 in Kangwha county were analized in order to study the characteristics and the patterns of treatments for the pulmonary tuberculosis patients with the history of previous treatment before registration and also the relationship between the previos history of treatment and the outcome at the time of discharge from the health center. The major findings are as follows. 1. Those who have a history of previous treatment were 58, 22.5% of those 258 patients who were studied. 2. There is no difference in sex however the rate of previous history of treatment was higher among middle age group (20-59) than young and old age group (under 19 or over 60). 3. The rate of previous treatment was rather higher in those lived in remote area from Eup. 4. As for the reationship with occupation, students and civil servants who easily exposured to the public relations of government's tuberculosis control program experienced lower previous treatment before registration than farmers or unemployed. 5. A total of 62.1% were previously treated less than 6 months, 29.3% between 6 and 12 months, and only 8.6% more than 12 months before registration to health center. 6. The most common used anti-tuberculosis drugs were isoniazid and ethambutol but only 13.8% used government-standardized precription and 69.0% used secondary drugs from its beginning. 7. There was no statistical difference between the previous history of treatment and the outcome at the time of discharge from the health center. However the longer the duration of treatment before registration was the lower the cure rate at health center was.

• Asian Spine Journal
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• 제12권6호
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• pp.1069-1077
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• 2018

Study Design: A case study. Purpose: To assess the chronological changes of the disease-related kyphosis after chemotherapy alone, secondly to clarify the role of growth cartilage in the healed lesion on kyphosis change, and to define the accurate prediction time in assessing residual kyphosis. Overview of Literature: None of the previous papers up to now dealt with the residual kyphosis, stability and remodeling processes of the affected segments. Methods: One hundred and one spinal tuberculosis children with various stages of disease processes, age 2 to 15 years, were the subject materials, between 1971 to 2010. They were treated with two different chemotherapy formula: before 1975, 18 months of triple chemotherapy (isoniazid [INH], para-aminosalicylic acid, streptomycin); and since 1976, 12 months triple chemotherapy (INH, rifampicin, ethambutol, or pyrazinamide). The first assessment at post-chemotherapy one year and at the final discharge time from the follow-up (36 months at minimum and 20 years at maximum) were analyzed by utilizing the images effect of the remaining growth plate cartilage on chronological changes of kyphosis after initiation of chemotherapy. Results: Complete disc destruction at the initial examination were observed in two (5.0%) out of 40 cervical spine, eight (26.7%) out of 30 dorsal spine, and six (19.4%) out of 31 lumbosacral spine. In all those cases residual kyphosis developed inevitably. In the remainders the discs were partially preserved or remained intact. Among 101 children kyphosis was maintained without change in 20 (19.8%), while kyphosis decreased in 14 children (13.7%), and increased in 67 children (66.3%) with non-recoverably damaged growth plate, respectively. Conclusions: It could tentatively be possible to predict the deformity progress or non-progress and spontaneous correction at the time of initial treatment, but it predictive accuracy was low. Therefore, assessment of the trend of kyphotic change is recommended at the end of chemotherapy. In children with progressive curve change, the deformity assessment should be continued till the maturity.

• Journal of Microbiology and Biotechnology
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• 제31권12호
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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.

• Genomics & Informatics
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• 제21권3호
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• pp.42.1-42.23
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• 2023

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Tolllike receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.

• Journal of Yeungnam Medical Science
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• 제41권2호
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• pp.113-119
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• 2024

Background: Missing isoniazid (INH) resistance during tuberculosis (TB) diagnosis can worsen the outcomes of INH-resistant TB. The BD MAX MDR-TB assay (BD MAX) facilitates the rapid detection of TB and INH and rifampin (RIF) resistance; however, data related to its performance in clinical setting remain limited. Moreover, its effect on treatment outcomes has not yet been studied. Methods: We compared the performance of BD MAX for the detection of INH/RIF resistances to that of the line probe assay (LPA) in patients with pulmonary TB (PTB), using the results of a phenotypic drug sensitivity test as a reference standard. The treatment outcomes of patients who used BD MAX were compared with those of patients who did not. Results: Of the 83 patients included in the study, the BD MAX was used for an initial PTB diagnosis in 39 patients. The sensitivity of BD MAX for detecting PTB was 79.5%. The sensitivity and specificity of BD MAX for INH resistance were both 100%, whereas these were 50.0% and 95.8%, respectively, for RIF resistance. The sensitivity and specificity of BD MAX were comparable to those of LPA. The BD MAX group had a shorter time interval from specimen request to the initiation of anti-TB drugs (2.0 days vs. 5.5 days, p=0.001). Conclusion: BD MAX showed comparable performance to conventional tests for detecting PTB and INH/RIF resistances. The implementation of BD MAX as a diagnostic tool for PTB resulted in a shorter turnaround time for the initiation of PTB treatment.

• Tuberculosis and Respiratory Diseases
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• 제44권5호
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• pp.975-991
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• 1997

배 경 : INH와 RFP에 동시내성을 보이는 다제내성 폐결핵은 적극적인 내과적 치료에도 불구하고 치료실패율이 40%에 이른다. 과거 폐결핵의 치료에 사용되었던 폐절제술이 다제내성 폐결핵의 보조적 치료수단으로 최근 다시 등장하였다. 방 법 : 1991년 1월부터 1995년 12월까지 HIV 감염이 없으면서 INH와 RFP에 동시내성을 보이는 다제내성 폐결핵 환자중 폐결핵 자체에 대한 보조적 치료로써 시행한 환자 14명을 대상으로 하여 후향적으로 의무기록과 방사선촬영소견 등을 조사하였다. 결 과 : 내과적 치료에도 불구하고 12명 (86%)의 환자에서 수술전 객담 균음전에 실패하였고 수술전 균음전이 이루어진 2명의 환자에서도 절제된 폐조직에서 실시한 결핵균 배양검사는 양성이었다. 흉부 전산화단층촬영상 양측성 병변이 10명(71%)에서 관찰되었다. 늑막폐절제술을 포함한 전폐절제술을 6명, 엽절제술 6명, 2명에서 시행하였다. 수술전 1초간 노력성 폐활량이 2L 이하였던 7명의 환자에서 수술전 폐관류스캔을 실시하였고, 절제된 폐로의 관류 중앙값 4.8%에 불과하였다. 수술과 관련한 사망은 없었으며, 1명에서 수술후 폐늑막루를 포함한 농흉이 발생하였고, 1명에서 3주이상 흉관을 통한 공기유출이 있었다. 수술후 13명(93%)의 환자에서 균음전화가 이루어졌고 중앙값 23개월간의 추적관찰기간동안 재발은 없었다. 1명(7%)의 환자는 폐절제술후에도 객담 균양성이 지속되었다. 결 론 : 과거 국내외에서 보고된 다제내성 폐결핵의 내과적 치료성적과 비교해 볼 때, 병변이 국한되어있고 적절한 폐기능을 가진 다제내성 폐결핵 환자에서 실시되는 보조적인 폐절제술은 중요한 역할을 할 것으로 기대된다.