• Clinical Pain
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• v.18 no.2
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• pp.102-106
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• 2019

Tuberculosis in the foot progresses gradually; thus, diagnosis is usually delayed, and early treatment is rarely provided. If osteomyelitis occurs due to delayed diagnosis and treatment, surgical treatment should be considered. We report the case of a 46-year-old man with osteomyelitis of the calcaneus who was diagnosed with multidrug-resistant pulmonary tuberculosis and he was treated with anti-tuberculosis drugs. Bilateral adrenal masses, abscess of both testes and a small wound in the left plantar heel were observed. Both adrenal masses and abscess were regarded as paradoxical reaction of anti-tuberculosis treatment. After 1 month, he developed a pain in the left plantar heel that was compatible with calcaneal osteomyelitis in radiological features. He underwent right orchiectomy for right scrotal abscess aggravation and surgical treatment for left calcaneal osteomyelitis. Mycobacterium tuberculosis was confirmed by polymerase chain reaction. The patient was immobilized by cast for 8 weeks and the heel pain gradually improved.

• Annals of Laboratory Medicine
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• v.38 no.6
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• pp.563-568
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• 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.

• Tuberculosis and Respiratory Diseases
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• v.68 no.3
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• pp.146-154
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• 2010

Background: The increasing incidence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) has become a serious worldwide problem. However, there is insufficient data regarding the current status of MDR-TB and XDR-TB in Korea. This study examined the recent status of MDR- and XDR-TB using the data from 7 laboratories, in which almost all drug susceptibility tests (DST) for Mycobacterium tuberculosis were performed. Methods: The patients' identification data and DST results were collected from all 7 laboratories from 2001 to 2006 and the number of patients with MDR-TB and XDR-TB were calculated. Results: The number of DSTs was 140,638 for 6 years with an increasing incidence each year (p<0.001). The number of DST with MDR results was 18,510 and personal identifying information was obtained in 16,640 (89.9%) tests. The number of MDR-TB patients from 2001 to 2006 was 2,329, 2,496, 2,374, 2,300, 2,354, and 2,178, respectively, when counting the duplications in a year as one patient. The number of MDR-TB patients when counting the duplications in 6 years as one patient was 2,281, 1,977, 1,620, 1,446, 1,512, and 1,373, respectively. When the same method was adopted, the number of XDR-TB patients was 191, 238, 282, 260, 272, and 264, respectively, and 189, 150, 130, 90, 122, and 110 patients, respectively. Conclusion: Despite the national efforts to control TB, there are still a large number of MDR- and XDR-TB patients in Korea.

• Tuberculosis and Respiratory Diseases
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• v.78 no.3
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• pp.253-257
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• 2015

Background: Tuberculosis (TB) is the leading cause of mortality among human immunodeficiency virus (HIV) patients and the majority of them occur in developing countries. The aims of the present study were to determine the frequency of HIV/TB co-infection and other probable associated factors. Methods: This 10 year retrospective study was conducted on 824 HIV patients in the south-west of Iran. HIV infection was diagnosed by the enzyme linked immunosorbent assay and confirmed by Western blot. TB diagnosis was based on consistency of the clinical manifestations, chest X-ray, and microscopic examination. Drug susceptibility testing was done by the proportional method on $L{\ddot{o}}wenstein$-Jensen media. Results: Of 824 HIV patients, 59 (7.2%) were identified as TB co-infected and the majority (86.4%) of them were male. Of the overall TB infected patients, 6 cases (10.2%) showed multidrug-resistant with the mean CD4+ lymphocyte count of $163{\pm}166cells/mm^3$. The main clinical forms of TB were pulmonary (73%). There was a significant (p<0.05) correlation between TB infection and CD4+ lymphocyte counts ${\leq}200cells/mm^3$, gender, prison history, addiction history, and highly active anti-retroviral therapy. Conclusion: We reported novel information on frequency of HIV/TB co-infection and multidrug resistant-TB outcome among co-infected patients that could facilitate better management of such infections on a global scale.

• 대한예방의학회:학술대회논문집
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• 2004.10a
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• pp.35.2-35.2
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• 2004

• Journal of the Korea Academia-Industrial cooperation Society
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• v.12 no.11
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• pp.5012-5018
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• 2011

According to the nationwide survey of tuberculosis from 1965 to 1995, the incidence and drug resistance rate of tuberculosis have been decreased in Korea, but the prevalence of multidrug resistance of Mycobacterium tuberculosis is still a serious problem. The purpose of this study is to investigate the drug resistance rate and pattern of tuberculosis in Daejeon from 2001 to 2008. Of the total 581cases where the drug susceptibility test was performed, resistance to at least one anti-TB drug was found in 104 cases(17.9%) of these, 68(11.7%) were resistant to at least INH and 41(7.1%) were resistant to at least RFP. Single-drug resistance was found for isolates from 37(6.4%) ; 18(3.1%) of these were resistant to INH and 5(0.9%) to RFP. Multidrug resistance, where TB was resistant to at least isoniazid and refampin, was found in 35 cases(6.0%). and Factors associated with MDR-TB included age under 40-60.The drug-resistance rate of pulmonary TB, especially MDR-TB, is higher in the initial treated patients at a private referral hospital than in those in the pubulic sector. Initial drug resistance is common and the drug susceptibility test is informative for pulmonary TB patients who have not received previous TB treatment. The need for an improved control program, coupled with early diagnosis of MDR-TB, to reduce the spread and development of resistance. Multidrug resistance rate is still problem in korea. Efforts to decrease multidrug resistance rate either independently or in cooperation with the pubulic sector will be needed.

• Tuberculosis and Respiratory Diseases
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• v.78 no.2
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• pp.78-84
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• 2015

Background: Reports of therapeutic drug monitoring (TDM) for second-line medications to treat multidrug-resistant tuberculosis (MDR-TB) remain limited. Methods: A retrospective cohort from the Virginia state tuberculosis (TB) registry, 2009-2014, was analyzed for TDM usage in MDR-TB. Drug concentrations, measured at time of estimated peak ($C_{max}$), were compared to expected ranges. Results: Of 10 patients with MDR-TB, 8 (80%) had TDM for at least one drug (maximum 6 drugs). Second-line drugs tested were cycloserine in seven patients (mean $C_{2hr}$, $16.6{\pm}10.2{\mu}g/mL$; 4 [57%] below expected range); moxifloxacin in five (mean $C_{2hr}$, $3.2{\pm}1.5{\mu}g/mL$; 1 [20%] below); capreomycin in five (mean $C_{2hr}$, $21.5{\pm}14.0{\mu}g/mL$; 3 [60%] below); para-aminosalicylic acid in five (mean $C_{6hr}$, $65.0{\pm}29.1{\mu}g/mL$; all within or above); linezolid in three (mean $C_{2hr}$, $11.4{\pm}4.1{\mu}g/mL$, 1 [33%] below); amikacin in two (mean $C_{2hr}$, $35.3{\pm}3.7{\mu}g/mL$; 1 [50%] below); ethionamide in one ($C_{2hr}$, $1.49{\mu}g/mL$, within expected). Two patients died: a 38-year-old woman with human immunodeficiency virus/acquired immune deficiency syndrome and TB meningitis without TDM, and a 76-year-old man with fluoroquinolone-resistant (pre-extensively drug-resistant) pulmonary TB and low linezolid and capreomycin concentrations. Conclusion: Individual pharmacokinetic variability was common. A more standardized approach to TDM for MDR-TB may limit over-testing and maximize therapeutic gain.

• Tuberculosis and Respiratory Diseases
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• v.71 no.2
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• pp.120-125
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• 2011

Background: Although the prevalence of pulmonary tuberculosis has progressively decreased all over the world, drug-resistant tuberculosis is major obstacle in treating tuberculosis. This study was performed to examine the current prevalence and risk factors of drug resistant tuberculosis in a single tertiary hospital in Busan, Korea. Methods: We enrolled 367 patients with active pulmonary tuberculosis on a retrospective basis who had undergone mycobacterium culture and drug sensitivity tests between January 2005 and December 2009. We analyzed all clinical and radiographic parameters to find predictors related to drug resistant tuberculosis. Results: At least one incident of drug resistance was found in 75 (20.4%) patients. Isoniazid (18.8%) was the most frequent resistant drug, followed by rifampin (10.9%), ethambutol (7.1%), streptomycin (4.9%), and fluoroquinolone (2.7%). Resistance to second-line drugs was found in 37 (10.1%) patients. Multidrug resistance and extensively drug resistance was evident in 39 (10.6%) and 4 (1.1%) patients, respectively. Using multiple logistic regression analysis, history of previous treatment including relapse (odd ratio [OR], 11.3; 95% confidence interval [CI], 4.92~26.08; p<0.01), treatment failure (OR, 24.1; 95% CI, 5.65~102.79; p<0.01) and an age of below 46 years-old (OR, 3.8; 95% CI, 1.62~8.65; p<0.01) were found to be independent predictors of multidrug resistant tuberculosis. Conclusion: We found that the prevalence of drug resistant tuberculosis was considerably high. A careful consideration for possible drug resistant tuberculosis is warranted in patients with a history of previous treatment or for younger patients.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1143-1153
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• 1998

Background : Recent outbreaks of pulmonary disease due to drug-resistant strains of Mycobacterium Tuberculosis have resulted in significant morbidity and mortality in patients worldwide. We reviewed our experience to evaluate the effects of pulmonary resection on the management of multidrug-resistant tuberculosis. Method : A retrospective review was performed of 41 patients undergoing pulmonary resection for multidrug-resistant tuberculosis between January 1993 and December 1997. We divided these into 3 groups according to the radiologic findings : (1) patients who have reasonably localized lesion (Localized Lesion Group ; LLG) (2) patients who have cavitary lesions after pulmonary resection on chest roentgenogram (Remained Cavity Group : RCG) (3) patients who have Remained infiltrative lesions postoperatively (Remained infiltrative group : RIG). We evaluated the negative conversion rate after resection and overall response rate of the groups. Then they were compared with the results of the chemotherapy on the multi drug-resistant tuberculosis which has been outcome by Goble et al. Goble et al reported that negative conversion rate was 65% and overall response rate, 56% over a mean period of 5.1 months. Results : Seventy five point six percent were men and 24.4% women with a median age of 31 years (range, 16 to 60 years). Although the patients were treated preoperatively with multidrug regimens in an effort to reduce the mycobacterial burden, 22 of 41 were still sputum culture positive at the time of surgery. 20 of 22 patients(90.9%, p<0.01) responded which is defined as negative sputum cultures within 2 months postoperative. Of 26 patients with the sufficient follow up data, 19 have Remained sputum culture negative for a mean duration of 25.7 months (73.1%, p<0.05). The bulk of the disease was manifest in one lung, but lesser amounts of contralateral disease were demonstrated in 15, consisted of 8 in RIG and 7 in RCG, of 41. 12 of 12 patients (100%, p<0.01) who were sputum positive at the time of surgery in LLG converted successfully. 14 of 15 patients (93.3%, p<0.05) with the follow up have completed treatment and not relapsed for a mean period of 25. 7 months. The mean length of postoperative drug therapy of LLG was 12.2 months. In RIG, postoperative negative conversion rate was 83.3% which was not significant statistically. There was a statistical significance in overall response rate (100%, p<0.05) of RIG for a mean period of 24.4 months with a mean length of postoperative chemotherapy, 11.8 months. In RCG a statistically lower overall response rate (14.3%, p<0.01) has been revealed for a mean duration of follow up, 24.2 months. A negative conversion rate of RCG was 75% which was not significant statistically. Conclusion : Surgery plays an important role in the management of patients with multidrug-resistant Mycobacterium tuberculosis infection. Aggressive pulmonary resection should be performed for resistant Mycobacterium tuberculosis infection to avoid treatment failure or relapse. Especially all cavitary lesions on preoperative chest roentgenogram should be resected completely. If all of them could not be resected perfectly, you should not open the thorax.

• Tuberculosis and Respiratory Diseases
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• v.60 no.2
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• pp.180-186
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• 2006

Background : Para-aminosalicylic acid(PAS) is a 2nd-line drug that can cause severe adverse reactions leading to poor patient compliance. This study evaluated the relapse rate according to the discontinuance of PAS at a certain point after bacteriological conversion during the course of chemotherapy for multidrug-resistant tuberculosis(MDR-TB). Methods : 42 out of 452 MDR-TB patients were enrolled in this study. All subjects were receiving chemotherapy including PAS at National Masan TB Hospital between Jan. 1, 2000 and Dec. 31, 2001. The relapse rate was evaluated after the discontinuance of PAS from their initial regimen as a result of the severe adverse reactions at a certain point after the bacteriological conversion during the course of chemotherapy for MDR-TB. Results : The male to female ratio was 2.5:1, and the mean age was 47.2 years old. The average number of past histories, used drugs and resistant drugs was 1.2, 3.9 and 4.3. The mean number of sensitive drugs included in the inirial regimen was 3.9. The mean time for bacteriological conversion and discontinuance of the PAS was 2.3 months after initiating treatment and 6 months after bacteriological conversion, respectively. There was no relapse after discontinuing PAS during a mean follow up period of 31.6 months. Conclusion : PAS may be discontinued in the cases of serious gastrointestinal problems approximately 6 months after bacteriological conversion without concern about relapse.