With the emergence of drug resistant tuberculosis, it is very urgent to find novel anti-tuberculosis drugs, especially novel anti-drug-resistant tuberculosis drugs. Because of the slow growth and the need to work in a biosafty environment of Mycobacterium tuberculosis, the development of evaluation of drug effect is severely impeded. In order to solve these issues, non-pathogenic fast-growing Mycobacterium smegmatis is introduced as test organism. The inhA is one of a target of isoniazid (INH) overexpression or mutation of this gene in Mycobacterium tuberculosis conferring resistant to INH. A recombinant plasmid bearing inhA was constructed and electroporated into Mycobacterium smegmatis, using shuttle expression vector pMV261. Transformants were induced to express a protein of inhA, identified by SDS-PAGE. Results show that Mycobacterium smegmatis containing inhA plasmids exhibited 100-fold or greater increased resistance to INH, but it conferred no increased resistance to others first-line anti-tuberculosis drugs. Resazurin microtiter assay plate testing of Mycobacterium smegmatis susceptibility to drugs is a rapid, simple, and inexpensive method and could decrease color background of drugs by detecting fluorescence. It will be benefit for high-throughout screening of drugs of anti-isoniazid-resistant Mycobacteria.
Anti-Bacterial Agents ; pharmacology ; Antibiotics, Antitubercular ; pharmacology ; Antitubercular Agents ; pharmacology ; Bacterial Proteins ; genetics ; metabolism ; Drug Resistance, Bacterial ; Electroporation ; Ethambutol ; pharmacology ; Isoniazid ; pharmacology ; Microbial Sensitivity Tests ; Mycobacterium smegmatis ; drug effects ; genetics ; metabolism ; Oxidoreductases ; genetics ; metabolism ; Plasmids ; Rifampin ; pharmacology ; Streptomycin ; pharmacology

Tuberculosis infection remains an important cause of mortality. The clinical and radiological manifestations can be non-specific and resemble many other conditions, including malignancies. This could lead to diagnostic delay. We report the case of a 48-year-old woman with tuberculosis presenting with a right upper lobe mass manifesting as metastatic lung cancer. She also had liver cirrhosis secondary to chronic hepatitis B infection. She developed hepatitis two weeks into her tuberculosis treatment. Our case highlights the importance of considering tuberculosis in patients suspected to have underlying malignancy and to be aware of the potential adverse effects of treatment.
Lung Neoplasm ; Neoplasms ; Antitubercular Agents

Paradoxical response refers to the enlargement of old lesions or unexpected appearance of new lesions after initial improvement following treatment with antitubercular agents. Various types of paradoxical responses have been reported in the world, but they are rarely reported in Korean children. We report the case of a 17-year-old boy who was diagnosed with tuberculous pleurisy and was treated appropriately. Although the tuberculous pleurisy initially responded to medication with resolution of the pleural fluid, a new pulmonary lesion subsequently developed 3 weeks after the initiation of treatment that eventually cleared with continuation of the original drug regimen.
Adolescent ; Antitubercular Agents ; Child ; Humans ; Tuberculosis, Pleural

BACKGROUND: A paradoxical response is defined as the radiological and clinical worsening of a previous lesion or the development of new lesion after initial improvement during theprocess of antituberculous treatment. The related factors for the development of a paradoxical response in patients with tuberculous pleurisy are not certain. METHODS: We selected patients with tuberculous pleurisy who had been treated for more than 4 months. The changes onthe serial chest X-ray findings before and after treatment were reviewed. Paradoxical responses were regarded as any worsening or development of new lesion at least 2 weeks after the initiation of treatment. The baseline clinical characteristics and laboratory findings of the peripheral blood and pleural fluid were compared between the patients with a paradoxical response and the patients without a paradoxical response. RESULTS: Paradoxical responses appeared in sixteen patients (21%) among the 77 patients.It took a mean of 38.6 days after the treatment and the time to resolve the paradoxical response was a mean of 32.1 days. For the patients with a paradoxical response, the median age was younger (30.5 years vs 39.0 years, respectively) and the lymphocytic percentage of white blood cells in the pleural fluid was higher (82.1% vs 69.6%, respectively) than for the patients without a paradoxical response. CONCLUSION: The development of a paradoxical response during the treatment of patients with tuberculous pleurisy was not rare and this was related with the age of the patients and the percentage of lymphocytic white blood cells in the pleural fluid.
Antitubercular Agents ; Humans ; Leukocytes ; Thorax ; Tuberculosis, Pleural

Antitubercular Agents/therapeutic use* ; Axilla ; Humans

BACKGROUND/AIMS: To determine the incidence and clinical characteristics of tuberculosis (TB) medication-associated Clostridium difficile infection. METHODS: This multicenter study included patients from eight tertiary hospitals enrolled from 2008 to 2013. A retrospective analysis was conducted to identify the clinical features of C. difficile infection in patients who received TB medication. RESULTS: C. difficile infection developed in 54 of the 19,080 patients prescribed TB medication, representing a total incidence of infection of 2.83 cases per 1,000 adults. Fifty-one of the 54 patients (94.4%) were treated with rifampin. The patients were usually treated with oral metronidazole, which produced improvement in 47 of the 54 patients (87%). Twenty-three patients clinically improved with continuous rifampin therapy for C. difficile infection. There were no significant differences in improvement between patients treated continuously (n=21) and patients in whom treatment was discontinued (n=26). CONCLUSIONS: The incidence of C. difficile infection after TB medication was not low considering the relatively low TB medication dosage compared to other antibiotics. It may not be always necessary to discontinue TB medication. Instead, decisions concerning discontinuation of TB medication should be based on TB status.
Adult ; Aged ; Aged, 80 and over ; Anti-Infective Agents/therapeutic use ; Antibiotics, Antitubercular/*adverse effects ; *Clostridium difficile ; Enterocolitis, Pseudomembranous/chemically induced/drug therapy/*epidemiology ; Female ; Humans ; Incidence ; Male ; Metronidazole/therapeutic use ; Middle Aged ; Retrospective Studies ; Rifampin/*adverse effects ; Treatment Outcome ; Tuberculosis/*drug therapy

Antitubercular Agents ; standards ; Child ; Humans ; Tuberculosis ; drug therapy ; prevention & control

Pyrazinamide (PZA) is one of the most important drugs for the treatment of Mycobacterium tuberculosis infection. However, the increasing frequency of PZA-resistant strains limits its effectiveness. In Korea, most PZA-resistant strains also exhibit both isoniazid and rifampin resistance making it essential to identify these resistant strains accurately and rapidly for effective treatment of mycobacterial infection. In this study, the characteristics and frequency of mutations of the pncA gene encoding pyrazinamidase were investigated in PZA-resistant clinical isolates from Korea. Automated DNA sequencing was used to evaluate the usefulness of DNA-based detection of PZA resistance. Among 95 PZA-resistant clinical isolates, 92 (97%) exhibited mutations potentially affecting either the production or the activity of the enzyme. Mutations were found throughout the pncA gene including the upstream region. Single nucleotide replacement appeared to be the major mutational event (69/92), although multiple substitutions as well as insertion and deletion of nucleotides were also identified. The high frequency of pncA mutations observed in this study supports the usefulness of DNA-based detection of PZA-resistant M. tuberculosis. Having verified the scattered and diverse mutational characteristics of the pncA gene, automated DNA sequencing seems to be the best strategy for rapid detection of PZA-resistant M. tuberculosis.
Amidohydrolases/*genetics ; Antitubercular Agents/*pharmacology ; Drug Resistance, Bacterial ; *Mutation ; Mycobacterium tuberculosis/*drug effects/genetics ; Pyrazinamide/*pharmacology

Anti-tuberculosis drugs can produce levels of hepatotoxicity ranging from mild elevation of aminotransferase to severe acute hepatitis. A few cases of drug-induced autoimmune hepatitis or the drug reaction with eosinophilia and systemic symptom (DRESS) syndrome by anti-tuberculosis medications have been reported. However, concomitant occurrence of these two disorders has not been reported. Here, we present a case of severe acute hepatitis with DRESS syndrome and autoimmune hepatitis resulting from primary standard anti-tuberculosis drugs. Both conditions were successfully treated with a systemic steroid regimen.
Antitubercular Agents ; Drug Hypersensitivity Syndrome ; Eosinophilia* ; Ethambutol* ; Hepatitis ; Hepatitis, Autoimmune* ; Isoniazid*

Adult ; Antitubercular Agents ; adverse effects ; Humans ; Isoniazid ; adverse effects ; Male ; Pulmonary Fibrosis ; chemically induced ; diagnosis