• Tuberculosis and Respiratory Diseases
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• v.63 no.2
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• pp.128-138
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• 2007

Backgrounds: Mutations of katG and inhA (ORF and promoter) are known to be related to isoniazid (INH) resistance of Mycobacterium tuberculosis. Because reports on these mutations in Korean isolates are limited (i.e. only the frequency of katG codon 463 was evaluated.), we tried to know the kinds of mutations of two genes and their frequencies in INH resistant Korean M. tuberculosis strains. Methods: PCR was performed to amplify katG (2,223 bp), inhA ORF (-77~897, 975 bp), and inhA promoter (-168~80, 248 bp) from 29 multidrug resistant M. tuberculosis (MDR-TB) DNAs prepared by bead beater-phenol method. Their sequences were determined and analyzed by ABI PRISM 3730 XL Analyzer and MegAlign package program, respectively. Results: All of the isolates had more than one mutation in katG or inhA gene. Twenty seven (93%) of 29 tested strains had katG mutations, which suggests that katG is a critical gene determining INH resistance of M. tuberculosis. Amino acid substitutions, such as Arg463Leu and Ser315Thr, due to point mutations of the katG were the most frequent (62.1% and 55.2%) mutations. In addition, deletion of the katG gene was frequently observed (17.2%). Analyzed Korean MDR-TB isolates also had variable inhA mutations. Point mutation of inhA promoter region, such as -15 ($C{\rightarrow}T$) was frequently found. Substitution of amino acid (Lsy8Asn) due to point mutation ($AAA{\rightarrow}AAC$) of inhA ORF was found in 1 isolate. Interestingly, 14 point mutated types that were not previously reported were newly found. While four types resulted in amino acid change, the others were silent mutations. Conclusions: Although it is not clear that the relationship of these newly found mutations with INH resistance, they show marked diversity in Korean MDR-TB strains. It also suggests their feasibility as a molecular target to supplement determining the INH resistance of clinical isolates because of the possible existence of low-level INH resistant strains.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.831-837
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• 1995

Background: We conducted a study to determine the factors associated with, patterns of, and proportion of cases of pulmonary tuberculosis with multiple drug-resistance at Kosin medical center in Pusan. Methods: We abstracted data from 141 patients, who had active pulmonary tuberculosis and report forms of drug susceptibility between 1986 and 1994, and related the previous treatment history, the extent of lung involvement and the presence of cavities on chest X-ray films to the drug resistance. Results: Overall, 59(41.8%) of the 141 cases of tuberculosis were resistant to at least one drug and 29(20.9%) of the 139 cases were resistant to isoniazid(INH) and rifampin(RIF). Among the 63 patients with previous tuberculosis therapy, 40(63.5%) had isolates that were drug-resistant and 24(38.1%) were multi-drug resistant. Among the 78 without previous therapy, 19(24.4%) had isolates that were drug-resistant and 5(7.5%) were multi-drug resistant. For all 141, resistance to INH was most common(39.0%) followed by RIF(21.6%), ethambutol(EMB, 16.3%), $\rho$- aminosalicylic acid(10.8%), streptomycin(SM, 8.7%), and pyrazinamide(PZA, 8.0%). INH, RIF and PZA resistances were independently associated with a history of previous tuberculosis therapy (odds ratio; 3.3, 7.2 and 10.8 respectively), and RIF and SM resistance were significantly high according to the extent of lung involvement on the chest films(odds ratio; 2.9 and 2.8 respectively). Conclusions: We conclude, (1) that all persons in whom pulmonary tuberculosis is diagnosed should initially receive at least four-drug therapy(INH, RIF, PZA, and EMB or SM), (2) that susceptibility testing be done in all culture-positive patient, and (3) that those with a history of previous tuberculosis therapy or those who have advanced pulmonary tuberculosis need very careful clinical and microbiological follow-up.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.470-478
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• 1997

Background : Phagocytosis is probably the first step for mycobacteria to be virulent in host because virulent strains are more readily phagocytosed by macrophage than attenuated strains. According to the traditional concept, multi-drug resistant strains have been regarded as less virulent. However, this concept has been challenged, since recent studies(reported) showed that the degree of virulence and drug-resistance is not related. The purpose of this study is to evaluate whether the phagocytic activity of M.tuberculosis by peripheral blood mononuclear cells(PBMC) is different according to drug-resistance or host factor. To evaluate this, we estimated the difference of phagocytic activity of drug-resistant and drug-sensitive M.tuberculosis and also estimated the phagocytic activity of PBMC from intractable tuberculosis patients and healthy controls. Methods : PBMC from ten intractable tuberculosis patients and twelve healthy control, and three different strains of heat-killed M.tuberculosis, ie, ADS(all drug sensitive), MDR(multi-drug resistant), and ADR(all drug resistant) were used. After incubation of various strains of M.tuberculosis with PBMC, the phagocytic activity was evaluated by estimating proportion of PBMC which have phagocytosed M.tuberculosis. Results : Drug-resistant strains of M.tuberculosis were phagocytosed easily than drug sensitive strains(Percentage of PBMC phagocytosed M.tuberculosis in healthy control : ADS : $32.3{\pm}2.9%$, ADR : $49.6{\pm}3.4%$, p = 0.0022, Percentage of PBMC phagocytosed M.tuberculosis in intractable tuberculosis patients : ADS : $34.9{\pm}3.6%$, ADR : $50.7{\pm}4.5%$, p = 0.0069). However, there was no difference in phagocytic activity of PBMC from healthy control and intractable tuberculosis patients. Conclusion : Drug-resistant strains of M.tuberculosis were phagocytosed easily than drug sensitive strains and host factors does not seems to influence the phagocytosis of M.tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.49 no.6
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• pp.774-779
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• 2000

Pseudomembranous colitis, although uncommon, is an important complication of antibiotics that is related to a variety of deleterious effects on the gastrointestinal tract. Rifampicin is one of the 1st line agents in the treatment of tuberculosis and a large number of patients are exposed to its potential adverse effects. We report upon a patient that had diarrhea due to pseudomembranous colitis after receiving antitubeculous medication, and which was probably caused by rifampicin. A 77-year-old man was admitted with diarrhea of three weeks duration. One month previously, he suffered from left pleuritic chest pain and left pleural effusion was noticed at chest X-ray. One week prior to the onset of diarrhea, he was started on empirically isoniazid, rifampicin, ethambutol and pyrazynamide as antituberculous medication. On admission, he complained of diarrhea, left pleuritic chest pain, dyspnea and sputum. On physical examination, breathing sound was decreased in the left lower lung field and bowel sound increased. Pleural biopsy revealed chronic granulomatous inflammation, which was compatible with tuberculosis, Sigmoidoscopy showed whitish to yellowish pseudomembrane with intervening normal mucosa, and his stool was positive for C.difficle toxin. He was diagnosed as pseudomembranous colitis and treated with oral metronidazole and vancomycin. The diarrhea did not recur after reinstitution of the anti-tuberculous medication without rifampicin inpatients with severe diarrhea receiving anti-tuberculous medication, rifampicin induced pseudomembranous colitis should be excluded.

• Tuberculosis and Respiratory Diseases
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• v.51 no.5
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• pp.416-425
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• 2001

Background : The incidence of drug-resistant tuberculosis has recently decreased in Korea. However, it is still one of the major obstacles in treating pulmonary tuberculosis. This study was performed to determine the prevalence and clinical characteristics associated with drug-resistance in pulmonary tuberculosis at the tertiary referral hospital in Pusan, Korea. Methods : The medical records of 138 patients, who had been diagnosed as active pulmonary tuberculosis were retrospectively reviewed, and results of drug susceptibility from May 1997 to June 2000. The relationships among those with a history of previous tuberculosis treatment, the extent of lung involvement, the presence of cavities on the initial chest X-ray films and patterns of drug resistance were analyzed. Results : The total number of patients who had drug resistance to at least one drug was 55(39.9%). Among them 34(24.6%) had resistance to isoniazid(INH) and rifampin(RFP). There was drug resistance in 20(22%) of 91 patients without previous tuberculosis therapy, and among them 9(9.9%) were multi-drug resistant. Thirty-two(74.5%) out of 47 patients with previous therapy were drug-resistant and 25(53.2%) were multidrug resistant. For all 138 patients, resistance to INH was the most common(34.1%), followed by RFP(26.1%) and ethambutol(EMB)(14.5%). Drug resistance to INH, RFP, PZA and streptomycin(SM) were independently associated with a history of previous treatment(odds ratio; 9.43, 9.09, 8.93 and 21.6 respectively, p<0.01). The extent of lung involvement on the chest films was significantly associated with the drug resistance to INH and RFP(odds ratio; 2.12 and 2.40 respectively, p<0.01). The prevalence of drug resistance to RFP, INH and RFP was significantly more common in patients with a cavitary lesion on the chest films by multivariate analysis(odds ratio; 4.17 and 4.81 respectively, p<0.05). Conclusion : This study revealed that patients with a prior treatment history for pulmonary tuberculosis, and the presence of a cavitary lesion on chest films had a higher prevalence of anti-tuberculosis drug resistance. A very careful clinical and microbiological examination is needed for patients with such characteristics.