• Tuberculosis and Respiratory Diseases
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• v.65 no.3
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• pp.177-182
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• 2008

Background: Isoniazid (INH, H) is a key drug of the standard first-line regimen for the treatment of tuberculosis (TB), yet some reports have suggested that treatment efficacy was maintained even though INH was omitted from the treatment regimen. Methods: One hundred forty C57BL/6 mice were infected with the H37Rv strain of M. tuberculosis with using a Glas-Col aerosol generation device, and this resulted in depositing about 100 bacilli in the lung. Four weeks after infection, anti-TB treatment was initiated with varying regimens for 4-8 weeks; Group 1: no treatment (control), Group 2 (4HREZ): 4 weeks of INH, rifampicin (R), pyrazinamide (Z) and ethambutol (E), Group 3: 1HREZ/3REZ, Group 4: 4REZ, Group 5: 4HREZ/4HRE, Group 6: 1HREZ/3REZ/4RE, and Group 7: 4REZ/4RE. The lungs and spleens were harvested at several time points until 28 weeks after infection, and the colony-forming unit (CFU) counts were determined. Results: The CFU counts increased steadily after infection in the control group. In the 4-week treatment groups (Group 2-4), even though the culture was negative at treatment completion, the bacilli grew again at the 12-week and 20-week time points after completion of treatment. In the 8-week treatment groups (Groups 5-7), the bacilli did not grow in the lung at 4 weeks after treatment initiation and thereafter. In the spleens of Group 7 in which INH was omitted from the treatment regimen, the culture was negative at 4-weeks after treatment initiation and thereafter. However, in Groups 5 and 6 in which INH was taken continuously or intermittently, the bacilli grew in the spleen at some time points after completion of treatment. Conclusion: TThe exclusion of INH from the standard first-line regimen did not affect the treatment outcome in a murine model of TB in the early stage of disease. Further studies using a murine model of chronic TB are necessary to clarify the role of INH in the standard first-line regimen for treating TB.

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

• Pediatric Infection and Vaccine
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• v.7 no.2
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• pp.240-244
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• 2000

Rifampin is a bactericidal antibiotic used primarily in the treatment of tuberculosis. The adverse effects of rifampin, though few, include dermatologic, gastrointestinal, and hepatic manifestations. Occasionally it produces a flu-like syndrome, interstitial nephritis, hemolytic anemia, and thrombocytopenia. These manifestations usually appear in patients who take the drug intermittently. We experienced a 13 year-old girl who developed thrombocytopenia during rifampin administration of daily dosage, therefore we report a brief review with the related literatures.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.166-166
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• 1993

만성 신부전환자에서 isoniazid(INH)의 약동학적 변화여부를 검토하고 특히 N-acetylation 대사능의 억제 여부를 평가함으로써 만성신부전환자에서 적정 INH 항결핵 요법율 위한 기본자료를 제공코자 하였다. 본 연구는 pararell group 디자인에 의한 일차 연구와 sequential 디자인에 의한 2차연구로 진행하였다. 일차 연구는 37명의 정상 성인군과 14명의 만성신부전 환자군을 대상으로 INH 400 mg 경구 투여 후 INH 및 AcINH의 약동학적 성상을 비교하였다. 이차연구는 만성신부전 환자에서 신이식에 따른 INH의 acetylation 대사능의 변화를 관찰코자 1차연구에 참여하고 성공적인 신이식을 받은 환자 10명을 대상으로 INH 및 AcINH의 약동학적 검토를 재시행하였으며, 이러한 연구 방법을 통하여 만성 신부전 환자에서 Acetylation 대사능의 변화를 검토하였다.

• Proceedings of the KIEE Conference
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• 2003.07d
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• pp.2809-2811
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• 2003

Biochip-based diagnostic technology is an effective, time- and money-saving way of identifying Rifampin and Isoniazid resistant tuberculosis strains. In this paper, we suggest the optical system which is designed with the simple structure and has an appropriate specification for biochip analyzer including a CCD camera system. It consists of two parts with the same structure but opposite direction. each part is made by one lens, achromatic doublet and meniscus. We changed the working distance of the optical system and observed its characteristics.

• Tuberculosis and Respiratory Diseases
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• v.60 no.1
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• pp.38-43
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• 2006

Background : Even though two-month rifampicin (RMP, R) and pyrazinamide (PZA, P) treatment has some advantages over isoniazid (INH, H) treatment for latent tuberculosis infection (LTBI), it was withdrawn from the list of treatment regimens for LTBI because of reported cases of severe hepatotoxicity. The purpose of this study was to estimate the frequency of hepatotoxicity of RMP and PZA treatment excluding INH in a Korean population. Method : TIn order to recruit patients who were prescribed RMP and PZA excluding INH, 256 INH-resistant tuberculosis patients were investigated through retrospective medical record analysis. A standard four-drug regimen was changed to a RMP/PZA-containing regimen excluding INH in 64 patients (RZ+ group). In the same study period, 146 patients who were prescribed an INH/RMP/PZA-containing standard regimen were randomly selected as a control (HRZ+ group). Clinical characteristics including liver diseases and the frequency of drug-induced hepatitis were compared between the RZ+ and HRZ+ groups. Result : The mean age of patients in the RZ+ group was 50.2 (${\pm}16.2$) and the male-to-female ratio was 36:28. The frequency of underlying liver diseases was 10.9% (7/64), which was not significantly different from that of the HRZ+ group (4.1%, 6/146). Even though the treatment duration of RZ+ ($5.5{\pm}4.8months$) was longer that than that of HRZ+ ($2.7{\pm}2.3months$), the frequency of toxic hepatitis was not significantly different between RZ+ and HRZ+ groups, 3.5% (2/57) and 7.1% (10/140), respectively. Conclusion : Hepatotoxicity was mild and occurred in a minor proportion of patients in a Korean population prescribed an RMP/PZA-containing regimen. A future prospective study including more patients is needed.

• Tuberculosis and Respiratory Diseases
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• v.56 no.3
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• pp.261-268
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• 2004

Background : The resurgence of tuberculosis and outbreaks of multidrug resistant (MDR) tuberculosis have increased the emphasis for the development of new susceptibility testing of the Mycobacterium tuberculosis for the effective treatment and control of the disease. Conventional drug susceptibility testings, such as those using egg-based or agar-based media have some limits, such as the time required and difficulties in determining critical inhibitory concentrations, but these are still being used in many diagnostic laboratories because of no better lternatives, considering cost and accuracy. To overcome these limits, a rapid and simple method for new susceptibility testing, using live and dead assays, was applied for a bacterial cell viability assay to distinguish dead from live bacterial cells based on two-color fluorescence. Materials and Methods Strains : Forty strains were used in this study, 20 susceptible to all antituberculosis drugs and the other 20 resistant to the four first line antituberculosis drugs isoniazid, rifampicin, streptomycin and ethambutol. Antibiotics : The four antibiotics were dissolved in 7H9 broth to make the following solutions: $0.1{\mu}g\;isoniazid(INH)/m{\ell}$, $0.4{\mu}g\;rifampicin(RMP)/m{\ell}$, $4.0{\mu}g\;streptomycin(SM)/m{\ell}$ and $4.0{\mu}g\;ethambutol(EMB)/m{\ell}$. Results : Live and dead Mycobacterium tuberculosis cells fluoresced green and red with the acridin (Syto 9) and propidium treatments, respectively. These results are very well accorded with conventional drug susceptibility testing by proportional method on Lowensen-Jensen media (L-J) containing 4 drugs (INH, RMP, EMB and SM), showing a 93.7 % accordance rate in susceptible strains and 95% in resistant strains. Conclusion : The results of the drug susceptibility testing using the live and dead bacterial cell assay showed high accordance rates compared with the conventional proportion method on L-J. This finding suggests that the live and dead bacterial cell assay can be used as an alternative to conventional drug susceptibility testing for M. tuberculosis strains.

• Pediatric Infection and Vaccine
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• v.18 no.1
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• pp.91-96
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• 2011

Bacille Calmette-Gu$\acute{e}$rin (BCG) vaccine is a live attenuated vaccine derived from Mycobacterium bovis. Frequent complications after BCG vaccination are localized ulcer formation and regional lymphadenitis, but there could be rarely severe systemic reactions to BCG vaccine such as osteomyelitis and disseminated BCG infection. Although disseminated BCG infection can be complicated in infants with underlying immunodeficiency after BCG vaccination, it is very unlikely to develop in immunocompetent infants or children. We report a 13-month-old infant who presented with fever, skin nodules, and multiple enlarged lymph nodes 5 months following BCG vaccination. She was diagnosed with disseminated BCG infection by PCRconfirmed M. bovis BCG infection at ${\geq}$2 anatomical sites beyond the region of vaccination. The patient showed no obvious evidence of immunodeficiency as judged on the basis of previous disease history, plasma immunoglobulin levels, B and T lymphocytes counts in peripheral blood, DHR (dihydrorhodamine 123 fluorescence) test and HIV test. She started antituberculous treatment with isoniazid and rifampin, and now, apparently her symptoms have been improved.

• Clinical and Experimental Pediatrics
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• v.45 no.4
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• pp.454-458
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• 2002

Purpose : Bacillus Calmette-$Gu\acute{e}rin$(BCG) lymphadenitis is one of the most common complications of BCG vaccination. The involved lymph nodes usually subside spontaneously, but they may become enlarged and form an abscess. Treatment of these infants is controversial. The Pan American Health Organization recommends local isoniazid or rifampicin instillation for patients with suppurative BCG lymphadenitis. Methods : The study group comprised 37 patients who presented with BCG lymphadenitis over the last three years. BCG lymphadenitis was diagnosed if the affected patient developed an ipsilateral axillary or supraclavicular lymphadenitis, with no other identifiable cause for the lymphadenitis. We used rifampicin instillation therapy for patients with suppurative BCG lymphadenitis. Results : Lymphadenitis regressed spontaneously in three patients. Thirty four patients showed a progression to abscess formation. Among 34 patients with suppurative lymphadenitis, drainage developed spontaneously during the follow-up period in nine patients before therapy. Twenty five patients received needle aspiration and local rifampicin instillation therapy. Reaspiration was performed in seven patients. One of these patients still has large lymph nodes after the second attempt. Conclusion : Needle aspiration and local rifampicin instillation therapy into the node is a safe and effective form of treatment for suppurative BCG lymphadenitis.

• Tuberculosis and Respiratory Diseases
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• v.66 no.3
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• pp.198-204
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• 2009

Background: First-line drugs, if sensitive, are the most potent drugs in the treatment of multidrug-resistant tuberculosis (MDR-TB). This study examined the frequency and risk factors associated with acquired drug resistance to first-line drugs during a standardized treatment using first-line drugs in patients with MDR-TB. Methods: This study included patients who were diagnosed with MDR-TB at the National Masan Tuberculosis Hospital between January 2004 and May 2008, treated with standardized first-line drugs, and for whom the preand post-treatment results of the drug susceptibility test were available. Their medical records were reviewed retrospectively. Results: Of 41 MDR-TB patients, 14 (34.1%) acquired additional resistance to ethambutol (EMB) or pyrazinamide (PZA). Of 11 patients initially resistant to isoniazid (INH) and rifampicin (RFP), 3 (27.3%) acquired additional resistance to both EMB and PZA, and 3 (27.3%) to PZA. Of 18 patients initially resistant to INH, RFP and EMB, 6 (33.3%) acquired additional resistance to PZA. Of 6 patients initially resistant to INH, RFP and PZA, 2 (33.3%) acquired additional resistance to EMB. Ten of the 41 MDR-TB patients (24.4%) changed from resistant to susceptible. No statistically significant risk factors associated with acquired resistance could be found. Conclusion: First-line drugs should be used cautiously in the treatment of MDR-TB in Korea considering the potential acquisition of drug resistance.