• Tuberculosis and Respiratory Diseases
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• v.67 no.4
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• pp.325-330
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• 2009

Background: Pulmonary tuberculosis (TB) is still common disease among the elderly patients in Korea where the overall incidence of TB is decreasing. Adverse drug reactions (ADR) associated with anti-TB drugs occurs frequently. Especially the aged tends to have more frequent ADRs than younger ones. These ADRs can cause significant morbidity, compromise therapeutic effects of drugs and even induce drug resistance. Therefore we evaluated the effect of ADRs on the first-line anti-TB drugs in elderly patients with active pulmonary TB. Methods: We retrospectively reviewed the charts and radiological findings of the patients with 65 and older who were bacteriologically confirmed as active TB and treated with standard anti-TB drugs for at least 6 months. Major ADR was defined with temporary or continuous stop of any first-line drugs intake. Results: An ADR was noted in 54% of all patients. The incidence of major ADR was 32% in all elderly patients. Dermatologic ADR (9%) was the most common among the major ADRs. GI trouble (8%), arthralgia (6%), visual change (6%), hepatotoxicity (4%), and fever (1%) were also noted. The drugs responsible for major ADR were ethambutol (62%), pyrazinamide (35%), rifampin (18%) and isoniazid (9%). Major ADRs were associated with higher ESR level at the initiation of anti-TB drugs. Conclusion: First-line anti-TB drugs in elderly patients frequently caused the major ADRs. Therefore the elderly patients receiving anti-TB drugs should be closely monitored and better tolerable therapy should be considered as part of a TB research agenda.

• 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.64 no.2
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• pp.95-101
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• 2008

Background: Drug resistant tuberculosis (TB) in patients who have not received previous TB treatment (initial drug resistance) is a serious problem for the control of TB. However, prevalence of initial drug resistance among pulmonary TB patients has not been well characterized in Korea, especially in the private sector. We assessed the prevalence of initial drug resistance and evaluated the risk factors for drug resistance in pulmonary TB patients, at a regional tertiary hospital in Cheonan. Methods: We performed a drug susceptibility test for both first and second line anti-TB drugs in all culture-confirmed pulmonary TB patients who had not received a previous TB treatment at Dankook University Hospital from September 2005 to September 2007. In addition, we evaluated the initial drug resistance pattern and clinical characteristics of patients to evaluate the risk factors for initial drug resistance. We also assessed the influence of the drug susceptibility test results on the treatment regimen. Results: Of the total 156 cases where the drug susceptibility test was performed, resistance to at least one anti-TB drug was found in 21 cases (15.6%) and multidrug resistance, where TB was resistant to at least isoniazid and rifampin, was found in one case (0.6%). Multivariate logistic regression showed no clinical characteristics were independently associated with initial drug resistance. Of the total 156 patients who underwent the drug susceptibility test, the treatment regimen was changed for 15 patients (9.6%) according to the results of the drug susceptibility test. Conclusion: Initial drug resistance is common and the drug susceptibility test is informative for pulmonary TB patients who have not received previous TB treatment.

• Tuberculosis and Respiratory Diseases
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• v.79 no.4
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• pp.282-288
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• 2016

Background: Tuberculosis (TB) is a major health problem, and accurate and rapid diagnosis of multidrug-resistant (MDR) and extended drug-resistant (XDR) TB is important for appropriate treatment. In this study, performances of solid and liquid culture methods were compared with respect to MDR- and XDR-TB isolate recovery and drug susceptibility testing. Methods: Sputum specimens from 304 patients were stained with Ziehl-Neelsen method. Mycobacterium tuberculosis (Mtb) isolates were tested for recovery on $L{\ddot{o}wenstein$-Jensen (LJ) medium and the BacT Alert 3D system. For drug susceptibility testing of Mtb, isolates were evaluated on M-KIT plates and the BacT Alert 3D system. Results: The recovery rates were 94.9% (206/217) and 98.2% (213/217) for LJ medium and the BacT Alert 3D system, respectively (kappa coefficient, 0.884). The rate of drug resistance was 13.4% for at least one or more drugs, 6.0% for MDR-TB and 2.3% for XDR-TB. M-KIT plate and BacT 3D Alert 3D system were comparable in drug susceptibility testing for isoniazid (97.7%; kappa coefficient, 0.905) and rifampin (98.6%; kappa coefficient, 0.907). Antibiotic resistance was observed using M-KIT plates for 24 of the total 29 Mtb isolates (82.8%). Conclusion: The liquid culture system showed greater reduction in the culture period, as compared with LJ medium; however, drug susceptibility testing using M-KIT plates was advantageous for simultaneous testing against multiple drug targets.

• Tuberculosis and Respiratory Diseases
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• v.57 no.2
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• pp.101-117
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• 2004

현증 결핵환자가 감소하고, 면역억제환자가 증가하고 있는 국내 추세에서 잠복결핵(latent tuberculosis)의 진단 및 치료 지침이 필요한 실정이다. 그러나 결핵의 유병률, 발생률 그리고 비씨지 접종률 등이 외국과 다른 국내의 현실에서 현증이 없는 잠복결핵의 진단 및 치료에 대한 방침은 필연적으로 외국과 다를 수 밖에 없으며, 현 시점에 국내에서 이에 대한 자료가 불충분하여 국내의 환경에 적합한 근거 중심의 지침을 설정하기는 어려운 상황이다. 그러나 결핵의 기본 병태 생리를 근거로 하여 최소한 결핵균 감염 이후 결핵 발병의 위험성이 높은 대상 환자에서는 잠복결핵 진단을 위한 검사를 시행하여 치료 여부를 결정하여야 한다. 고위험군은 사람면역결핍바이러스(human immunodeficiency virus, HIV) 감염자, 장기이식환자, 면역억제제를 장기간 사용하는 환자, 6세 이하의 소아 중 최근 전염성 결핵환자 접촉자 등을 우선적으로 고려해야 한다. 미국은 발병 위험도의 고, 중, 저에 따라 투베르쿨린 검사(tuberculin skin test, Mantoux test)의 양성기준을 달리 하여 잠복결핵을 진단하고 있으나, 국내에는 아직 이에 대한 자료가 부족하므로 발병의 위험이 높은 상기 고위험군을 대상으로 하여 PPD RT-23 2TU (Tuberculin unit)를 이용한 피부반응검사에서 10mm이상의 경결(induration)이 생성되는 경우를 양성으로 정하고 추후 연구 결과에 따라 재조정이 필요하다. 그 동안은 투베르쿨린 검사 결과 5-10 mm 사이의 경결반응을 보이는 면역억제 환자에 대하여는 개별적으로 의사의 판단에 따라 잠복결핵의 진단 및 치료 여부를 결정한다. 그러나 면역억제제를 사용하는 등 결핵 발병의 고위험군에서는 피부반응검사상 음성이라도 과거 결핵 치료력이 없이 흉부사진상 명백하게 과거에 결핵을 앓은 흉터가 남아있는 경우(석회화된 1차 결핵 소견은 제외)에는 잠복결핵의 치료를 시행한다. 상기 잠복결핵의 진단 및 검사의 적응증은 최소한 시행하여야 할 경우를 나열한 것으로 이외의 환자에 대하여는 환경 및 대상에 따라 개별화되어야 한다. 치료제로는 isoniazid (INH) 9개월 매일 치료(최소 한 6개월 이상, HIV양성 환자인 경우는 9개월), rifa-mpicin (RFP) 4개월 치료 및 INH/RFP 3개월 매일 치료를 시행할 수 있다. 상기 치료가 어려운 경우에는 RFP/pyrazinamide (PZA) 2개월 매일 치료를 고려할 수 있으나 중증 간독성의 가능성에 대한 철저한 교육 및 추적검사가 필요하다. 향후 국내 환경의 변화 및 연구결과에 따라 추후 부족한 부분에 대한 지침의 재정립이 필요하다.

• Tuberculosis and Respiratory Diseases
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• v.59 no.6
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• pp.600-605
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• 2005

Background : Primary multidrug-resistant tuberculosis is defined as Mycobacterium tuberculosis isolates that are resistant to at least isoniazid and rifampin in never-been-treated tuberculosis patients, and this malady is caused by the transmission of a resistant strain from one patient, who is infected with a resistant Mycobacterium tuberculosis strain, to another patient. The prevalence of primary multidrug-resistant tuberculosis could be a good indicator of the performance of tuberculosis control programs in recent years. We conducted a case-control study to identify the risk factors for primary multidrug-resistant tuberculosis. Methods : From January 1, 2001 to, June 30, 2003, by conducting prospective laboratory-based surveillance, we identified 29 hospitalized patients with P-MDRTB and these patients constituted a case group in this study. The controls were represented by all the patients with culture-confirmed drug susceptible tuberculosis who were admitted to National Masan Hospital during the same study period. The odds ratios for the patients with primary multidrug-resistant tuberculosis, as compared with those of the patients with drug susceptible tuberculosis, were calculated for each categorical variable with 95% confidence intervals. Results : Multivariate logistic regression showed that the presence of diabetes mellitus (odds ratio 2.68; 95% confidence interval, 1.05-6.86) was independently associated with having primary multidrug-resistant tuberculosis. Conclusion : This study has shown that diabetes mellitus might be one of the risk factors for primary multidrug-resistant tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.70 no.3
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• pp.251-256
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• 2011

The prevalence of multi-drug resistant tuberculosis (MDR-TB), which is resistant to isoniazid and rifampin, has been increasing in Korea. And the side effects of 2nd line anti-tuberculosis medications, including drug-induced hepatitis, are well known. Although prothionamide (PTH) is one of the most useful anti-TB medications and although TB medication-induced acute hepatitis is a severe complication, there are only a few published case reports about prothionamide induced hepatitis. In this case report, a 22 year old male was diagnosed with pulmonary MDR-TB and was administered 2nd line anti-TB mediations, including PTH. Afterwards, he had a spiking fever and his liver enzymes were more than 5 times greater than the upper limit of the normal range. He was then diagnosed with drug-induced hepatitis by liver biopsy. His symptoms and liver enzyme elevation were improved after stopping PTH. Accordingly, we report this case of an association between PTH and acute hepatitis.

• Tuberculosis and Respiratory Diseases
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• v.69 no.1
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• pp.43-47
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• 2010

We report a case of Mycobacterium intracellulare pulmonary infection presenting as a solitary pulmonary nodule (SPN). A 35-year-old male was admitted due to a SPN in the right upper lobe which was detected on the chest radiography being examed due to recurrent cough for 1 year. The computed tomography (CT) revealed a spiculated nodule containing air-bronchogram, which was suspicious of malignancy. We performed transbronchial biopsy and the pathology showed granulomatous inflammation with caseous necrosis. Under the presumptive diagnosis of pulmonary tuberculosis, we started anti-tuberculous medication including isoniazid, rifampin, ethambutol, and pyrazinamide. In one month, however, the sputum culture was positive for Mycobacterium intracellulare. The follow-up chest CT showed slight aggravation of the previous lesions. Under the final diagnosis of Mycobacterium intracellulare pulmonary infection presenting as a solitary pulmonary nodule, we changed the regimen to rifampin, ethambutol, and clarithromycin. The follow-up chest CT after the completion of treatment, revealed resolution of the previous lesions.

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.266-271
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• 2005

Background : Ethambutol(EMB) is one of the first-line drugs included in short-course anti-tuberculosis therapy. The point mutations in embB gene have been speculated to be associated EMB resistance. However, detection of embB mutations at these positions have been observed in both EMB-susceptible isolates; thus, it remains controversial whether these mutations are associated with EMB resistance Methods : The 36 M. tuberculosis isolates were selected from clinical isolates which tested susceptible to EMB and resistant to at least one drug. DNA extracted from the isolates was analyzed by amplifying embB gene. The PCR products were purified and directly sequenced. We reviewed the history of past drug susceptibility test results. Results : Out of 36 EMB-susceptible strains, 3 strains (8.3%) had a mutation in codon 306 or 406 of the embB gene. These three strains had at least isoniazid resistance. They grew at 1.0 mcg/ml of EMB in Lowenstein-Jensen media. The patients of the strains were continuously smear-positive for over 3 years despite taking TB therapy. One strain had been EMB-resistant in past drug susceptibility tests. Conclusion : EMB-susceptible strains containing embB mutation may be caused by decreased viability in vitro test not by itself.

• Journal of Chest Surgery
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• v.32 no.3
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• pp.287-293
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• 1999

Background: Medical treatment of multiple drug resistant(MDR) pulmonary tuberculosis has been quite unsuccessful. We analyzed our experience to identify the benefits and complications of the pulmonary resection in MDR pulmonary tuberculosis. Material and Method: A retrospective review was performed in 27 patients who unerwent pulmonary resection for MDR pulmonary tuberculosis between January 1994 and March 1998. Mean age was 40 years and the average history of diagnosis prior to surgery was 3.1 years. All had resistance to an average of 4.4 drugs, and received second line drugs selected according to the drug sensitivity test. Most patients (93%) had cavitary lesions as the main focus. Bilateral lesions were identified in 19 patients (70%), however, the main focus was recognized in one side of the lung. Eleven patients (41%) were converted to negative sputum smear and/or culture before surgery. Result: Pneumonectomy was performed in 9 patients, lobectomy in 16 and segmentectomy in 2. There was no operative mortality. Morbidity had occurred in 7 patients (26%), prolonged air leak in 3 patients, reoperation due to bleeding in 2, bronchopleural fistula in 1, and reversible neurologic defect in 1. Median follow up period was 15 months (3-45 months). Sputum negative conversion was initially achieved in 22 patients (82%), and with continuous postopertive chemotherapy negative conversion was achieved in other 4 patients (14%). Only one pneumonectized patient (4%) failed due to considerable contralateral cavity. Conclusion: For patients with localized MDR pulmonary tuberculosis and with adequate pulmonary reserve function, surgical pulmonary resection combined with appropriate pre and postoperative anti-tuberculosis chemotherapy can achieve high success rate with acceptable morbidity.