• Korean Journal of Clinical Laboratory Science
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• v.53 no.2
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• pp.137-142
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• 2021

This study investigated the patterns of acquiring anti-mycobacterial resistance in individuals who were susceptible to all anti-mycobacterial drugs in their initial treatment. From 2010 to 2019, anti-mycobacterial drug susceptibility tests were conducted on patients who were referred to the Green Cross Laboratories. The test results of 594 anti-mycobacterial drug sensitivity tests were collected at 111 medical institutions. The first test results had 594 cases in which all anti-mycobacterial drugs were susceptible. Isoniazid (INH), rifampin (RIF), streptomycin (SM), and quinolone (QUI) showed the highest single-resistant conversion rates. Out of 56 patients, 17 patients (30.4%) showed a high conversion rate of resistance to both INH and RIF. The tracking period was analyzed from a minimum of 98 days to 1,862 days, and an average of 435.6 days for INH, and a minimum of 108 days to 1,673 days, with an average of 457.7 days for RIF. In the case of tuberculosis patients who are susceptible to all anti-mycobacterial drugs, it is considered that the conversion to resistant and multi-drug resistant tuberculosis (MDR-TB) must be confirmed through an anti-mycobacterial susceptibility test after 3 months. It is hoped that this study will help the national tuberculosis management project to improve public health.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.2
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• pp.125-132
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• 2022

The prevalence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) are increasing. We analyzed the patterns of drug resistance and tracking period days of acquiring anti-mycobacterial resistance. From January 2010 to December 2019, drug susceptibility tests (DST) were performed by the absolute concentration method using the Löwenstein-Jensen solid medium and pyrazinamidase activity test (to assess pyrazinamide resistance) in samples from patients who were referred to the Green Cross Laboratories in Yongin. Among the cases that showed resistance to one or more anti-tuberculosis drugs, 55 patients (33.1%) were resistant to isoniazid (INH) at the time of initial referral, and the rates for the development of resistant anti-tuberculosis drugs were ethambutol (EMB) (26.6%), rifampicin (RFP) (21.9%), quinolones (QUI) (21.9%) and pyrazinamide (PZA) (10.9%), in that order. In the cases sensitive to all 10 anti-tuberculosis drugs initially, the development of resistance to INH was the most frequent, seen in 43 patients (7.2%). The average follow-up period was 435.6 days, and the resistance development was observed in the order of INH (7.2%), RFP (3.9%), SM (1.9%), QUI (0.7%), amikacin (AMK) (0.5%), and EMB (0.5%). The conversion of susceptible strains to resistant strains is an important warning sign for the patient, especially in cases of conversion to MDR or XDR. This information would be helpful for improving patient care during TB treatment.

• Tuberculosis and Respiratory Diseases
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• v.64 no.2
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• pp.87-94
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• 2008

Background: Surveillance of TB drug resistance (DR) is essential for providing information on the magnitude and trends in resistance, for developing treatment guidelines and for monitoring the effect of interventions. Up to now national surveys of drug resistance of M. tuberculosis have been conducted four times since 1994 among patients registered at health centers. The purpose of this study is to estimate the prevalence of primary drug resistance among new cases identified in private sector, and to compare it with the previous national drug resistance surveys. Methods: The study collected results of drug susceptibility testing (DST) performed at the Korean Institute of Tuberculosis by the request of private sector from January 2003 to December 2005, and then finally selected new cases for the analysis from the database of Korean TB Surveillance (KTBS) by matching patients' name and social identification numbers. Results: Of the 5,132 new patients included in the study, 689 (13.4%) patients were found to have drug resistance at least one drug, 530 patients (10.3%) were isoniazid resistant, 195 patients (3.8%) were multi-drug resistant (MDR), and 21 patients (0.4%) were extensively drug resistant (XDR). The rate of drug resistance tended to decrease annually but it was not statistically significant. When compared with previous national DR surveys in 2003 and in 2004 respectively, they were not significantly different. Conclusion: The prevalence of DR among new cases managed in the private sector did not show significant difference from that of new patients registered in the public sector in the same year.

• Tuberculosis and Respiratory Diseases
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• v.55 no.2
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• pp.154-164
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• 2003

Background : Until the early 1990's in Korea, treatment outcomes of patients with pulmonary tuberculosis in the private sector were reported to be inferior to those of the public health center under the National Tuberculosis Programme. The purpose of this study was to analyze the clinical characteristics and the treatment efficacy of the patients with pulmonary tuberculosis recently diagnosed at a private general hospital. Materials and Methods : The study included all pulmonary tuberculosis patients diagnosed at Samsung Medical Center and notified to the public health center from August 2000 to January 2001. Results : Of the 232 patients included in the study during a 6-month period, 188 were (81.0%) initial treatment cases and 44 (19.0%) were re-treatment cases. Eighty-three (35.8%) patients had smear-positive sputa, and 27 (11.6%) had smear-negative, culture-positive sputa. Initial sputum examinations were not performed in 47 (20.3%) patients. A six-month, short-course treatment using isoniazid, rifampin, ethambutol and pyrazinamide was prescribed for 31.4% of the patients under the initial treatment. The success rate (cured plus treatment completed) of the initial treatment for the smear-positive patients was 69.1%. Eleven (13.3%) of the 83 patients with smear-positive pulmonary tuberculosis discontinued their treatment without notice. Conclusions : To improve the treatment efficacy and decrease the default rates of the patients with pulmonary tuberculosis in the private sector, further efforts are required in line with the Korean Academy of Tuberculosis and Respiratory Disease Treatment Guidelines and in the implementation of an appropriate model of public-private mix for tuberculosis control in Korea.

• 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.60 no.4
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• pp.404-411
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• 2006

Purpose : Multidrug-resistant tuberculosis (MDR-TB) is an emerging threat to human beings. However, there is little data on the current status of MDR-TB in Korea. This study investigated the current status of MDR-TB in Korea using a survey of all the data from drug susceptibility tests (DST) performed across the country over the last three years. Method : The DST results between Jan. 2000 and Dec. 2002 from 7 laboratories, which were in charge of all antituberculous DSTs across the country as of March 2002, were collected and analyzed to determine the actual number of drug-resistant or MDR-TB patients, annual trend, degree and pattern of resistance against anti-TB drugs, etc. Results : Six laboratories used the absolute concentration method for DST and one used the proportional method. 59, 940 tests had been performed over the 3 year study period. The number of DST performed annually was 18,071, 19,950, and 21,919 in 2000-2002, respectively. The number of resistant tuberculosis patients (resistant against at least one anti-TB drug) had increased by 16.9% from 6,338 in 2000 to 7,409 in 2002. The rate of resistant tuberculosis among all DST results was 35.1% in 2000, 34.5% in 2001, and 33.8% in 2002. The number of MDR-TB patients (resistant against at least both isoniazid and rifampin) showed an increasing trend (14.5%) from 3,708 in 2000 to 4,245 in 2002. Conclusion : Approximately 4,000 MDR-TB cases are newly identified by DST annually and the number is showing an increasing trend. This study suggests that in order to cope with the current MDR-TB situation, the DST methods will need to be standardized and more aggressive measures will be required.

• Clinical and Experimental Pediatrics
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• v.52 no.1
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• pp.61-67
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• 2009

Purpose : The rate of drug-resistant tuberculosis (DR-TB) in children is an indicator of the effectiveness of TB control programs in the community. This study aimed to assess the prevalence of DR-TB in children and evaluate TB management. Methods : Between January 1999 and July 2007, drug susceptibility tests for anti-TB drugs were employed for patients aged less than 19 years with culture-positive TB. Results : A total of 607 cases (16.6%) were resistant to at least one anti-TB drug as follows: isoniazid (INH; 13.8%), rifampin (8.9%), pyrazinamide (4.2%), streptomycin (3.7%), ethambutol (EMB; 5.9%), and para-aminosalicylic acid (PAS; 1.9%). Multidrug-resistant (MDR) TB was found in 276 cases (7.6%); extensive drug resistant (XDR) TB, in 5 cases (0.2%). The rate of resistance to at least one anti-TB drug in children aged >15 years (16.1%) was significantly lower than that in children aged <15 years (20.5%) (P=0.016). The rate of resistance to at least one anti-TB drug and multidrug-resistance in this survey decreased significantly (P<0.001) as compared to the previous survey (1987-1995). The rate of resistance to INH, EMB, and PAS also significantly decreased (P<0.05). Conclusion : The rate of DR-TB in children in Korea has decreased over time; however, it remains higher than that in other countries. MDR-TB and XDR-TB are the emerging problems in Korean children. Therefore, the selection of effective drugs through drug susceptibility tests and evaluating risk factors of resistant TB is essential to successful therapy and a decreased incidence of DR-TB.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.405-412
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• 1994

Background: In Korea, the prevalence of tuberculosis and hepatitis is high, and combined therapy with rifampicin and pyrazinamide is used in tuberculosis, so drug induced hepatitis is not only problem of tuberculosis therapy but also cause of treatment failure. However most of recent reports on drug induced hepatitis during antituberculosis medication have dealt with its pathogenesis and have stressed the biochemical, and histopathological aspects of the disorder, whereas this study was designed primarily to provide information on the clinical features. Method: The subjects of study were 1414 patients treated with antituberculosis drugs on the department of chest medicine at National Medical Center during the 5-year 6-month period from January 1, 1988, to June 30, 1993. Retrospective analysis of clinical features for the 29 patients who developed drug induced hepatitis was done. Results: 1) The incidence of antituberculosis drug induced hepatitis was 2.1%. 2) Male to fema1e ratio of antituberculosis drug induced hepatitis was 2:1, but case rates among males and females were not significantly different. 3) Rates of drug induced hepatitis according to age distribution shows the most common incidence between 35 to 49 year old age group, but rates among groups of age were not significant1y different. 4) Drug induced hepatitis was most common in the case of moderate advanced pulmonary tuberculosis(rate is 2.78%), but rates among types of tuberculosis were not significant1y different. 5) 18 cases(62%) of antituberculosis drug induced hepatitis patients had no signs or symptoms. In remaining cases, they were nausea, vomiting, jaundice, hepatomegaly, icteric sclera, right upper quadrant tenderness in order. 6) 22 cases(76%) of antituberculosis drug induced hepatitis cases had occured within the first month. 7) The duration of abnormal liver function was $28{\pm}5$(Mean${\pm}$SD), ranged from 5 days to 180 days. 8) One case of antituberculosis drug induced hepatitis died. 9) The levels of abnormal GOT ranged from 64 to 1055U/L and GPT from 68 to 931U/L. Conclusion: There are no dicided predisposing factors of antituberculosis drug induced hepatitis, so it should be done biochemical monitoring as well as close monitoring for overt signs or symptoms of hepatitis to avoid the development of irreversible hepatic reaction, especially at the treatment of the first month.

• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.693-700
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• 1996

Background : Antituberculous therapy is set a short-term therpy used isoniazid(INH), rifampin(RFP), ethambutol(EMB), pyrazinamide(PZA) from 1970s' and treatment rate has been very improved. But drug interruption or irregular medication due to side effects and resistance of drug are serious problem to retreatment cases, specially. Ofloxasine(OFX), developed from Quinolone at 1980's is effective not only other respiratory infectious disease but also pulmonary tube rculosis. And this is useful drug instead of injection agents for retreatment patients who have side effects to other drugs, lived far distance from medical clinics. So, we will evaluate theffectiveness as four oral drugs involving OFX. Method : A retrospective study was made through the regular follow up of smear positive cases,who treated by four drug, namely, prothionamide (PTA) cycloserine(CS), OFX, paraminosalicylic acid(pAS). Results: 1) Out of 66case with positive sputum AFB smear, 42(64%)cases achieved the negative conversion. 2) Considering the negative conversion in all group, 34 case (52%) of sputum conversion occured within first 6 months, on the extent of diease was minimal, moderate, far advanced pulmonary tuberculosis, sputum AFB smear negative response to treatment was 100%, 78%, 46% respectively. 3) The roentgenological improvement occured in 38(58%), extent of diease was minimal, moderately, far advanced pulmonary tuberculosis, Roentgenological improvement to retreatment was 75%, 64%, 46%. 4) When the drnation of patients illness was less than 1 year, 1 to 3 years, 3 10 5 years and more than 5 years, sputum AFB smear negative response to retreatment was 100%, 88%, 80%, 52 %. 5) On side effects, major problems are gastrointestinal troubles, mild liver function abnormality, psychotic problemes, and skin problem(urticaria, itching sensation). Conclusion : The duration & extents of patients illness was shorter & minimal, sputum AFB smear negative response rate was better. Radiologic response is better as shorter duration and minimal extent of diease. But, as diease is longer duration & far advanced, sputum negative conversion & Roentgenological improvement is poor and limited. The adverse reaction was mainly observed gastrointestinal troubles(indigestion, abdominal pain, nausea, vomiting, diarrhea) and are well controled by symptomatic management in most patients, as regard to tolerance to the secondary drugs.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.251-263
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• 1997

Background : The emergence of multidrug-resistant strains of Mycobacterium tuberculosis presents a significant challange to the treatment and control of tuberculosis, and there is an urgent need to understand the mechanisms by which strains acquire multidrug resistance. Recent advances in molecular methods for the detection of M. tuberculosis genetic targets have approached the sensitivity of culture. Furthermore the prospect of determining resistance in mycobacteria at the nucleic acid level particulary to first-line drugs like rifampin, isoniazid has provided a glimps of the next generation of sensitivity test for M. tuberculosis. Previous studies in RMP resistant M. tuberculosis have shown that mutation in $\beta$subunit of RNA polymerase is main mechanism of resistance. Method : In this study, rpoB gene for the $\beta$subunit of RNA polymerase from M. tuberculosis of 42 cultured samples (32 were RMP resistant and 10 were sensitive cases) were isolated and characterised the mutations. Direct sequencing data were compared with the results of INNO-LiPA Line Probe Assay (LiPA, Innogenetics, Belgium), commercial RMP resistance detecting kit using reverse hybridization method. Results : All of the RMP resistant samples were revealed the presence of mutation by LiPA. In 22 samples (68.8%) out of 32 RMP resistant cases, the mutation types were confirmed by the positive signal at one of 4 mutation bands in the strip. The most frequent type was R5 (S531L) which were 17 cases (77.3%). Results of direct sequencing were identified the exact characteristics of 8 mutations which were not confirmed by LiPA. S522W type point mutation and 9 base pair deletion at codon 513~515 were new identified mutations for the first time. Conclusion : Mutations in rpoB gene is the main mechanism of RMP resistance in M. tuberculosis and LiPA is a very useful diagnostic tool for the early diagnosis of RMP resistance in M. tuberculosis.