• 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.

• 대한임상약리학회:학술대회논문집
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• 2006.11a
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• pp.84-84
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• 2006

• Journal of Pharmaceutical Investigation
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• v.12 no.4
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• pp.132-144
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• 1982

The inclusion of ${\beta}-cyclodextrin$ $({\beta}-CyD)$ with prothionamide in aqueous phase was investigated by circular dichroism(CD), ultraviolet (UV) absorption, and solubility technique. The results suggested that a region of drug chromophore was located within the asymmetric center of ${\beta}-cyclodextrin$. Solubility and spectral changes were quantitatively treated to obtain stoichiometric ratio, which was found to be 1 : 1, and formation constants which were determined by solubility, CD, and UV method were 257, 367, and 389 $M^{-1}$, respectively. Also, the formation constant of the inclusion complex was determined by CD method at various pH. The result was that $K_c$ depended upon the pH of medium, and this fact also supported that thioamide moiety was accomodated in the cavity of ${\beta}-cyclodextrin$.

• Tuberculosis and Respiratory Diseases
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• v.82 no.2
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• pp.143-150
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• 2019

Background: The purpose of this study was to analyze the relationship between the gene mutation patterns by the GenoType MTBDRplus (MTBDRplus) assay and the phenotypic drug susceptibility test (pDST) results of isoniazid (INH) and prothionamide (Pto). Methods: A total of 206 patients whose MTBDRplus assay results revealed katG or inhA mutations were enrolled in the study. The pDST results were compared to mutation patterns on the MTBDRplus assay. Results: The katG and inhA mutations were identified in 68.0% and 35.0% of patients, respectively. Among the 134 isolated katG mutations, three (2.2%), 127 (94.8%) and 11 (8.2%) were phenotypically resistant to low-level INH, high-level INH, and Pto, respectively. Among the 66 isolated inhA mutations, 34 (51.5%), 18 (27.3%) and 21 (31.8%) were phenotypically resistant to low-level INH, high-level INH, and Pto, respectively. Of the 34 phenotypic Pto resistant isolates, 21 (61.8%), 11 (32.4%), and two (5.9%) had inhA, katG, and both gene mutations. Conclusion: It is noted that Pto may still be selected as one of the appropriate multidrug-resistant tuberculosis regimen, although inhA mutation is detected by the MTBDRplus assay until pDST confirms a Pto resistance. The reporting of detailed mutation patterns of the MTBDRplus assay may be important for clinical practice, rather than simply presenting resistance or susceptibility test results.

• Tuberculosis and Respiratory Diseases
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• v.39 no.2
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• pp.167-171
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• 1992

Background:In the management of patients whose primary chemotherapy has failed, very careful assessment is essential. It is important to find out as accurate a chemotherapy history as possible. Preferably it should contain the drugs which has never used before. The present report concerns the results of retreatment of pulmonary tuberculosis patients treated at National Kongju Tuberculosis Hospital. Method: A retrospective study was made through the regular follow-up of 112 smear positive cases, who were treated by four-drug regimen between July 1985 and June 1990. Four drugs were, namely prothionamide, cycloserine, para-aminosalicylic acid, and streptomycin (kanamycin or tuber-actinomycin). The duration of follow-up was over one year. Results: 1) Out of 112 cases with positive sputum AFB smear, 72 (64%) achieved the negative conversion. 2) Among the 72 patients, 85% achieved negative conversion within 3 months after treatment. 3) When the duration of patient's illness was less than 2 years, 2 to 4 years and more than 5 years, the favourable response to retreatment was 86%, 62% and 54%, respectively. 4) When the number of sensitive drugs was 4,3,2 and 1, the favourable response rate was 74%, 68%, 39% and 0%, respectively. Conclusion: The shorter the duration of patient's illness was, the larger the number of sensitive drugs was. And the larger the number of sensitive drugs was, the better the result of treatment was. Thus it is very crucial to successfully treat newly discovered patients with adequate regimens and proper case-holding.

• Tuberculosis and Respiratory Diseases
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• v.42 no.3
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• pp.295-301
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• 1995

Background: The serious problems in retreatment of pulmonary tuberculosis are a significant proportion of drug resistance. Preferably retreatment should contain the drugs which has never used before, so drug retreatment is limited in selection. A new antibacterial substance, ofloxacin(OFX) is the activity against mycobacterium tuberculosis and it has been used in the treatment of pulmonary tuberculosis. The present report concerns the result of retreatment of pulmonary tuberculosis patients containing OFX treated at National Kongju Tuberculosis Hospital. Method: A retrospective study was made through the regular follow up of 92 smear positive cases, who were treated by four drugs regimen between Mar 1991 and June 1994 at National Kongju Tuberculosis Hospital. Four drugs were, namely prothionamide, cycloserine, ofloxacin and streptomycin(kanamycin or tuberactinomycin). The duration of follow up was over one year. Results: 1) Out of 92 cases with positive sputum AFB smear, 67(73%) achieved the negative conversion. 2) Considering the negative sputum conversion in all the groups, the vast majority(85%) of sputum conversion occurred within the first 4 months. 3) The roentgenological improvement occurred in 49 percent on the whole and when the extent of disease was minimal, moderately, far advanced pulmonary tuberculosis, sputum AFB smear negative response to retreatment was 100%, 93%, 68%, respectively. 4) When the duration of patient's illness was less than 1 year, 1 to 3 years, 3 to 5 years and more than 5 years, sputum AFB smear negative response to retreatment was 87%, 76%, 65% and 55%, respectively. 5) Adverse reaction to prothionamide, with complaints of gastrointestinal troubles was common and hepatic dysfunction without jaundice was observed in 7 percent, convulsion in 1 percent, that to cycloserine occurred renal dysfunction & psycosis & convulsion, 2%, 1%, 1%, respectively. Tinnitus with KM occurred in 1% and dirrhea with OFX in 4%. Conclusion: The duration of patient's illness was shorter, sputum AFB smear negative response rate was better. Radiologic responses were not remarkable, but extent of disease by national tuberculosis association was smaller, the result of retreatment was better. Adverse reaction of the secondary antituberculosis agent was mainly observed gastrointestinal troubles, as regard to tolerance to the secondary drugs the role of the physician is of very important value and toxic effects can be overcome by the strong confidence.

• Tuberculosis and Respiratory Diseases
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• v.86 no.3
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• pp.234-244
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• 2023

Background: Effective treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis (FQr-MDR-TB) is difficult because of the limited number of available core anti-TB drugs and high rates of resistance to anti-TB drugs other than FQs. However, few studies have examined anti-TB drugs that are effective in treating patients with FQr-MDR-TB in a real-world setting. Methods: The impact of anti-TB drug use on treatment outcomes in patients with pulmonary FQr-MDR-TB was retrospectively evaluated using a nationwide integrated TB database (Korean Tuberculosis and Post-Tuberculosis). Data from 2011 to 2017 were included. Results: The study population consisted of 1,082 patients with FQr-MDR-TB. The overall treatment outcomes were as follows: treatment success (69.7%), death (13.7%), lost to follow-up or not evaluated (12.8%), and treatment failure (3.9%). On a propensity-score-matched multivariate logistic regression analysis, the use of bedaquiline (BDQ), linezolid (LZD), levofloxacin (LFX), cycloserine (CS), ethambutol (EMB), pyrazinamide, kanamycin (KM), prothionamide (PTO), and para-aminosalicylic acid against susceptible strains increased the treatment success rate (vs. unfavorable outcomes). The use of LFX, CS, EMB, and PTO against susceptible strains decreased the mortality (vs. treatment success). Conclusion: A therapeutic regimen guided by drug-susceptibility testing can improve the treatment of patients with pulmonary FQr-MDR-TB. In addition to core anti-TB drugs, such as BDQ and LZD, treatment of susceptible strains with later-generation FQs and KM may be beneficial for FQr-MDR-TB patients with limited treatment options.

• 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.52 no.2
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• pp.128-136
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• 2002

Background: There are few studies that have reported on the pharmacokinetic(PK) disposition of fluoroquinolones in patients with multi-drug resistant tuberculosis(MDR-Tb), even though fluoroquinolones are frequently co-prescribed to those patients. In this study, the PK disposition of ofloxacin, a fluoroquinolone, was evaluated in patients with MD R -Tb. Methods: Twenty patients with MDR-Tb were given 2nd line Tb drugs including ofloxacin (300mg twice a day), prothionamide, cycloserine, para-aminosalicylic acid, kanamycin, and streptomycin. The patients were grouped according to their body mass index(BMI) as an index of emaciation (group A : 18.5$\leq$BMI <23, group B : BMI < 18.5). Blood samples were serially drawn and urine samples were collected upto 24 hours after the last dose of those drugs at steady state (over 1 month). The ofloxacin concentrations were determined using HPLC (High Performance Liquid Chromatography). Results: The AUC of ofloxacin in group B was greater than that in group A ($31.4{\pm}8.9{\mu}g/ml{\cdot}h$ vs. $24.1{\pm}6.2{\mu}g/ml{\cdot}h$)(Check the symbols), (p<0.05). The total clearance(Cl/F) of ofloxacin was $0.16{\pm}0.03$ L/h/kg in group A, and $0.14{\pm}0.03$ L/h/kg in group B. The half-lives of ofloxacin in two groups were similar (group A : $5.3{\pm}0.8$ hours, group B : $5.7{\pm}0.9$ hours). In addition, the other PK parameters in two groups were also similar. Conclusions: The pharmacokinetics of ofloxacin in patients with MDR-Tb appears to be comparable with those of normal subjects, and the extent of emaciation appears to have an influence on the pharmacokinetics of ofloxaicn in chronic debilitated MDR-Tb patients.

• Tuberculosis and Respiratory Diseases
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• v.42 no.1
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• pp.11-18
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• 1995

Background: The natural history of bacillary tuberculosis was studied in India and results showed that at the end of the 5-year period, 49% of the patients were dead, 33% were cured and 18% remained sputum-positive. The aim of this survey is to observe the natural course of the patients with intractable tuberculosis disease who were incurable with all drug regimens of the national tuberculosis programme(NTP). Method: Of the patients who have been found as intractable cases in Kang-Weon Province by the supervisory medical officer during the period from January 1,1987 to December 31,1992, 179 were eligible for this study. Sputum examination was done for those who were survived until October in 1993 at the Kang-Weon provincial laboratory of KNTA. 49 out of 179 patients were transferred to the private sectors and retreated with the combination of prothionamide, cycloserine, ofloxacin, enviomycin, etc. They seemed to have been bacteriologically cured, and so they were excluded from the study. Finally 130 patients were analyzed by modified life table method to calculate the fatality rate and the survival rate during the period of 7 years. Results: 1) 80.8% of intractable cases were male and 19.2%, female. 2) More than 94% of intractable cases showed moderately or far advanced Tb findings on their X-rays at the time of registration at health centres. 3) The cumulative case-fatality rate was 19.74% at the end of 1-year period and has risen to 34.55% by the end of 4-year period(increasing by 4.9% a year on an average). The case-fatality rate has shown no appreciable rise since then until the end of 7-year period. 4) The case-survival rate was 80.26% at the end of 1-year period and has decreased to 65.45% by the end of 4-year period. And then there was no appreciable change in the survival rate until the end of 7-year observation. Conclusion: The case-survival rate of intractable cases was higher than that of untreated pulmonary tuberculosis patients and they may have risk of spreading multidrug resistant organisms. It is time we made an effort to improve case-management qualitatively.