• Tuberculosis and Respiratory Diseases
• /
• v.83 no.1
• /
• pp.20-30
• /
• 2020

Tuberculosis (TB) remains a threat to public health and is the leading cause of death globally. Isoniazid (INH) is an important first-line agent for the treatment of TB considering its early bactericidal activity. Resistance to INH is now the most common type of resistance. Resistance to INH reduces the probability of treatment success and increases the risk of acquiring resistance to other first-line drugs such as rifampicin (RIF), thereby increasing the risk of multidrug-resistant-TB. Studies in the 1970s and 1980s showed high success rates for INH-resistant TB cases receiving regimens comprised of first-line drugs. However, recent data have indicated that INH-resistant TB patients treated with only firs-tline drugs have poor outcomes. Fortunately, based on recent systematic meta-analyses, the World Health Organization published consolidated guidelines on drug-resistant TB in 2019. Their key recommendations are treatment with RIF-ethambutol (EMB)-pyrazinamide (PZA)-levofloxacin (LFX) for 6 months and no addition of injectable agents to the treatment regimen. The guidelines also emphasize the importance of excluding resistance to RIF before starting RIF-EMB-PZA-LFX regimen. Additionally, when the diagnosis of INH-resistant TB is confirmed long after starting the first-line TB treatment, the clinician must decide whether to start a 6-month course of RIF-EMB-PZA-LFX based on the patient's condition. However, these recommendations are based on observational studies, not randomized controlled trials, and are thus conditional and based on low certainty of the effect estimates. Therefore, further work is needed to optimize the treatment of INH-resistant TB.

• Tuberculosis and Respiratory Diseases
• /
• v.44 no.5
• /
• pp.992-1000
• /
• 1997

Background : Since up to 90% of a theophylline dose is biotransformed, probably by interaction with one or more the variants of the cytochrome P-450 drug metabolism system, anti-tuberculosis agents including drugs influencing microsomal enzyme systems, such as isoniazid and rifampicin. may be affect the elimination of theophylline. Method : The effect of combination therapy with isoniazid(INH), rifampicin(RFP), ethambutol(EMB) and pyrazinamide(PZA) on the pharmacokinetics of theophylline was evaluated by a computer program using Bayesian method. Three group were divided as follows. Group I is control, Group II is treated with INH. RFP, EMB and PZA and Group III is treated with INH, RFP and EMB. All of them were ilon-smoker who were normal in liver and renal functions, and not administered drugs affecting on the clearance of theophylline with exception of anti-tuberculous agents. Results : When it compared control with test groups, the clearance of theophylline in Group II and Group III was significantly decreased(p<0.001), and half life in Group II and Group III showed significant elevation(p<0.001). However there were no significant differences in clearance and half life between the Group II and Group III. Conclusion : These results suggest that theophylline dose may be need of readjustment in concurrent medication of anti-tuberculous agents including INH, RFP, and EMB.

• Tuberculosis and Respiratory Diseases
• /
• v.42 no.6
• /
• pp.831-837
• /
• 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
• /
• v.48 no.5
• /
• pp.730-739
• /
• 2000

Background : The aim of this study was to analyze the clinical manifestations and efficacy of treatment regimens in order to determine the adequate combination of anti-tuberculotic agents and duration of treatment for tuberculous lymphadenitis. Methods : We made a review of 373 patients with tuberculous lymphadenitis, who were admitted to four medical college hospitals in Taegu Korea from 1989 to 1998, and their diagnoses were confirmed histologically and bacteriologically. Results : The incidence of tuberculous lymphadenitis was 71.3% in women and 57.7% were between the ages of 20 and 39 years. The most common symptom was painless swelling. The most commonly involved lymph nodes were unilateral superficial cervical lymph node groups. Tuberculous lymphadenitis was accompanied with active pulmonary tuberculosis, commonly. The sensitivity of fine needle aspiration(FNA) in tuberculous lymphadenitis was 79.6%, and 92.2% of the patients had a strong positive reaction to the tuberculin skin test. The most commonly prescribed anti-tuberculotic regimen was the combination of INH, RMP, EMB, and PZA(62.6 %). Eighty percent of patient were treated for 9-12 months. There was no significantly difference in the recurrence rate of tuberculous lymphadenitis between the combinations of anti-tuberculotic agent, including INH and RMP, and between the durations of treatment, for a period of 6 months of more. Conclusion : The combination of FNA cytologic examination and tuberculin skin test may be helpful in the diagnosis of tuberculous lymphadenitis. We propose that the combination of anti-tuberculotic agents, INH, RMP, EMB, and PZA, be prescribed to patients for 6 to 9 months.

• Tuberculosis and Respiratory Diseases
• /
• v.42 no.3
• /
• pp.277-294
• /
• 1995

Background: The prevalence of tuberculosis in Korea decreased remarkably for the past 30 years, while the incidence of disease caused by mycobacteria other than tuberculosis is unknown. Korean Academy of Tuberculosis and Respiratory Diseases performed national survey to estimate the incidence of mycobacterial diseases other than tuberculosis in Korea. We analyzed the clinical data of confirmed cases for the practice of primary care physicians and pulmonary specialists. Methods: The period of study was from January 1981 to October 1994. We collected the data retrospectively by correspondence with physicians in the hospitals that referred the specimens to Korean Institute of Tuberculosis, The Korean National Tuberculosis Association for the detection of mycobacteria other than tuberculosis. In confirmed cases, we obtained the records for clinical, laboratory and radiological findings in detail using protocols. Results: 1) Mycobacterial diseases other than tuberculosis were confirmed that 1 case was in 1981, 2 cases in 1982, 4 cases in 1983, 2 cases in 1984, 5 cases in 1985, 1 case in 1986, 3 cases in 1987, 1 case in 1988, 6 cases in 1989, 9 cases in 1990, 14 cases in 1990, 10 cases in 1992, 4 cases in 1993, and 96 cases in 1994. Cases since 1990 were 133 cases(84.2%) of a total. 2) Fifty seven percent of patients were in the age group of over 60 years. The ratio of male to female patients was 2.6:1. 3) The distribution of hospitals in Korea showed that 61 cases(38.6%) were referred from Double Cross Clinic, 42 cases(26.6%) from health centers, 21 cases(13.3%) from tertiary referral hospitals, 15 cases(9.5%) from secondary referral hospitals, and 10 cases(6.3%) from primary care hospitals. The area distribution in Korea revealed that 98 cases(62%) were in Seoul, 17 cases(10.8%) in Gyeongsangbuk-do, 12 cases(7.6%) in Kyongki-do, 8 cases(5.1%) in Chungchongnam-do, each 5 cases(3.2%) in Gyeongsangnam-do and Chungchongbuk-do, 6 cases(3.8%) in other areas. 4) In the species of isolated mycobacteria other than tuberculosis, M. avium-intracellulare was found in 104 cases(65.2%), M. fortuitum in 20 cases(12.7%), M. chelonae in 15 cases(9.5%), M. gordonae in 7 cases(4.4%), M. terrae in 5 cases(3.2%), M. scrofulaceum in 3 cases(1.9%), M. kansasii and M. szulgai in each 2 cases(1.3%), and M. avium-intracellulare coexisting with M. terrae in 1 case(0.6%). 5) In pre-existing pulmonary diseases, pulmonary tuberculosis was 113 cases(71.5%), bronchiectasis 6 cases(3.8%), chronic bronchitis 10 cases(6.3%), and pulmonary fibrosis 6 cases(3.8%). The timing of diagnosis as having pulmonary tuberculosis was within 1 year in 7 cases(6.2%), 2~5 years ago in 32 cases(28.3%), 6~10 years ago in 29 cases(25.7%), 11~15 years ago in 16 cases(14.2%), 16~20 years ago in 15 cases (13.3%), and 20 years ago in 14 cases(12.4%). Duration of anti-tuberculous treatment was within 3 months in 6 cases(5.3%), 4~6 months in 17 cases(15%), 7~9 months in 16 cases(14.2%), 10~12 months in 11 cases(9.7%), 1~2 years in 21 cases(18.6%), and over 2 years in 8 cases(7.1%). The results of treatment were cure in 44 cases(27.9%) and failure in 25 cases(15.8%). 6) Associated extra-pulmonary diseases were chronic liver disease coexisting with chronic renal failure in 1 case(0.6%), diabetes mellitus in 9 cases(5.7%), cardiovascular diseases in 2 cases(1.3%), long-term therapy with steroid in 2 cases(1.3%) and chronic liver disease, chronic renal failure, colitis and pneumoconiosis in each 1 case(0.6%). 7) The clinical presentations of mycobacterial diseases other than tuberculosis were 86 cases (54.4%) of chronic pulmonary infections, 1 case(0.6%) of cervical or other site lymphadenitis, 3 cases(1.9%) of endobronchial tuberculosis, and 1 case(0.6%) of intestinal tuberculosis. 8) The symptoms of patients were cough(62%), sputum(61.4%), dyspnea(30.4%), hemoptysis or blood-tinged sputum(20.9%), weight loss(13.3%), fever(6.3%), and others(4.4%). 9) Smear negative with culture negative cases were 24 cases(15.2%) in first examination, 27 cases(17.1%) in second one, 22 cases(13.9%) in third one, and 17 cases(10.8%) in fourth one. Smear negative with culture positive cases were 59 cases(37.3%) in first examination, 36 cases (22.8%) in second one, 24 cases(15.2%) in third one, and 23 cases(14.6%) in fourth one. Smear positive with culture negative cases were 1 case(0.6%) in first examination, 4 cases(2.5%) in second one, 1 case (0.6%) in third one, and 2 cases(1.3%) in fourth one. Smear positive with culture positive cases were 48 cases(30.4%) in first examination, 34 cases(21.5%) in second one, 34 cases(21.5%) in third one, and 22 cases(13.9%) in fourth one. 10) The specimens isolated mycobacteria other than tuberculosis were sputum in 143 cases (90.5%), sputum and bronchial washing in 4 cases(2.5%), bronchial washing in 1 case(0.6%). 11) Drug resistance against all species of mycobacteria other than tuberculosis were that INH was 62%, EMB 55.7%, RMP 52.5%, PZA 34.8%, OFX 29.1%, SM 36.7%, KM 27.2%, TUM 24.1%, CS 23.4%, TH 34.2%, and PAS 44.9%. Drug resistance against M. avium-intracellulare were that INH was 62.5%, EMB 59.6%, RMP 51.9%, PZA 29.8%, OFX 33.7%, SM 30.8%, KM 20.2%, TUM 17.3%, CS 14.4%, TH 31.7%, and PAS 38.5%. Drug resistance against M. chelonae were that INH was 66.7%, EMB 66.7%, RMP 66.7%, PZA 40%, OFX 26.7%, SM 66.7%, KM 53.3%, TUM 53.3%, CS 60%, TH 53.3%, and PAS 66.7%. Drug resistance against M. fortuitum were that INH was 65%, EMB 55%, RMP 65%, PZA 50%, OFX 25%, SM 55%, KM 45%, TUM 55%, CS 65%, TH 45%, and PAS 60%. 12) The activities of disease on chest roentgenogram showed that no active disease was 7 cases(4.4%), mild 20 cases(12.7%), moderate 67 cases(42.4%), and severe 47 cases(29.8%). Cavities were found in 43 cases(27.2%) and pleurisy in 18 cases(11.4%). 13) Treatment of mycobacterial diseases other than tuberculosis was done in 129 cases(81.7%). In cases treated with the first line anti-tuberculous drugs, combination chemotherapy including INH and RMP was done in 86 cases(66.7%), INH or RMP in 30 cases(23.3%), and not including INH and RMP in 9 cases(7%). In 65 cases treated with the second line anti-tuberculous drugs, combination chemotherapy including below 2 drugs were in 2 cases(3.1%), 3 drugs in 15 cases(23.1%), 4 drugs in 20 cases(30.8%), 5 drugs in 9 cases(13.8%), and over 6 drugs in 19 cases (29.2%). The results of treatment were improvement in 36 cases(27.9%), no interval changes in 65 cases(50.4%), aggravation in 4 cases(3.1%), and death in 4 cases(3.1%). In improved 36 cases, 34 cases(94.4%) attained negative conversion of mycobacteria other than tuberculosis on cultures. The timing in attaining negative conversion on cultures was within 1 month in 2 cases(1.3%), within 3 months in 11 cases(7%), within 6 months in 14 eases(8.9%), within 1 year in 2 cases(1.3%) and over 1 year in 1 case(0.6%). Conclusion: Clinical, laboratory and radiological findings of mycobacterial diseases other than tuberculosis were summarized. This collected datas will assist in the more detection of mycobacterial diseases other than tuberculosis in Korea in near future.

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

• Tuberculosis and Respiratory Diseases
• /
• v.47 no.4
• /
• pp.442-450
• /
• 1999

Background : Isoniazid(INH) and rifampicin(RFP) are the most effective anti-tuberculosis drugs which make the short-course chemotherapy possible. Although prescribed dosages of INH and RFP in Korea are different from those recommended by American Thoracic Society, there has been few study about pharmacokinetic profiles of INH and RFP in Korean patients who receive INH, RFP, ethambutol(EMB) and pyrazinamide(PZA) simultaneously. Methods : Among the patients with active tuberculosis from Dec. 1997 to July 1998, we selected 17 patients. After an overnight fast, patients were given INH 300mg, RFP 450mg, EMB 800mg and PZA 1500mg daily. Blood samples for the measurement of plasma INH(n=15) and RFP(n=17) level were drawn each at 0, 0.5, 1, 1.5, 2, 4, 6, 8 and 12hrs, and urine was also collected. INH and RFP level in the plasma and the urine were measured by high-performance liquid chromatography(HPLC). Pharmacokinetic parameters such as peak serum concentration(Cmax), time to reach to peak serum concentration(Tmax), half-life, elimination rate constant(Ke), total body clearance(CLtot), nonrenal clearance(CLnr), and renal clearance(CLr) were calculated. Results : 1) Pharmacokinetic parameters of INH were as follows: Cmax; $7.63{\pm}3.20{\mu}g/ml$, Tmax; $0.73{\pm}0.22hr$, half-life; $2.12{\pm}0.84hrs$, Ke; $0.83{\pm}0.15hrs^{-1}$, CLtot; $17.54{\pm}8.89L/hr$, CLnr; $14.74{\pm}8.35L/hr$, CLr; $2.79{\pm}1.31L/hr$. 2) Pharmacokinetic parameters of RFP were as follows: Cmax; $8.93{\pm}3.98{\mu}g/ml$, Tmax; $1.76{\pm}1.13hrs$, half-life; $2.27{\pm}0.54hrs$, Ke; $0.32{\pm}0.08hrs^{-1}$, CLtot; $14.63{\pm}6.60L/hr$, CLr; $1.04{\pm}0.55L/hr$, CLnr; $13.59{\pm}6.21L/hr$. 3) While the correlation between body weight and Cmax of INH was not statistically significant (r=-0.514, p value>0.05), Cmax of RFP was significantly affected by body weight of the patients(r=-0.662, p value<0.01). Conclusion : In Korean patients with tuberculosis, 300mg of INH will be sufficient to reach the ideal peak blood level even in the patients over 50kg of body weight However, 450mg of RFP will not be the adequate dose in the patients who weigh over 50~60kg.

• Tuberculosis and Respiratory Diseases
• /
• v.49 no.2
• /
• pp.162-168
• /
• 2000

Background : Joint symptoms frequently occur in the course of antituberculous chemotherapy and tend to be ignored and overlooked, but in some cases, they are often very troublesome in obstructing ordinary life. Joint symptoms that develop during antituberculous chemotherapy need to be understood, but there are few materials describing them systematically. Method : This study enrolled 33 patients with tuberculosis treated with first line antituberculous agents for more than 6months. In the course of treatment, joint symptoms not associated with specific cause, such as preexisting joint disease or trauma, were investigated and compared with thæe of the asymptomatic group. We confirmed the incidence of joint symptoms and factors associated with them. Results : Nineteen of 33 patients (58%) had joint symptoms. Joint symptoms developed 1.9$\pm$1.4 months after the beginning of chemotherapy and lasted for 3.6$\pm$2.5months. In 18 of 19 symptomatic patients, multiple joints were involved: shoulder (10 patients, 53%), knee (10, 53%), finger (6, 32 %). Joint symptoms were expressed as pain (19 patiens, 100%), stiffness (7, 37%) and/or swelling (3, 16%). Fourteen patients (74%) took analgesics to relieve their symptoms and in 2 patients, antituberculous agents were discontinued because of the severity of their symptoms. The symptoms seem to be caused by agents other than pyrazinamide, but it was very difficult to identify the definite causative agent. In age, sex, underlying disease and serum uric acid level, no significant differences were noted between the two groups. Conclusions : Although joint symptoms are common during antituberculous chemotherapy, their development is difficult to predict. Because some joint symptoms can become very bothersome, the physician should pay close attention to these symptoms.

• Korean Journal of Clinical Laboratory Science
• /
• v.54 no.2
• /
• pp.125-132
• /
• 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
• /
• v.44 no.4
• /
• pp.930-934
• /
• 1997

Drug-induced thrombocytopenia and purpura have been developed by many various agents. Rifampin and Pyrazinamide have been known as bactericidal antituberculous drugs, but, the above side effects have been a problem. Especially, hematologic side effects are fatal to patients occasionally. Rifampin-induced thrombocytopenia and purpura have been well known, also, pyrazinamide-induced thrombocytopenia have been reported. A new quilonone agent, Ciprofloxacin, has been commonly used in clinics now, but it's side effects are not known well. So, we report a case of a 23-year-old female with thrombocytopenia and purpura after taking Rifampin, Pyrazinamide, and Ciprofloxacin as antituberculous agents.