Correlation between GenoType MTBDRplus Assay and Phenotypic Susceptibility Test for Prothionamide in Patients with Genotypic Isoniazid Resistance / 결핵

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.

Usefulness of flexible bronchoscopy in children with suspected pulmonary tuberculosis who have difficulty in sputum expectoration

PURPOSE: To assess the usefulness of flexible bronchoscopy in patients with suspected pulmonary tuberculosis (PTB) who have difficulty in sputum expectoration. METHODS: The subjects of this study were patients who were suspected of PTB and visited the Division of Pediatric Pulmonology at a tertiary hospital from April 2006 to March 2016. PTB suspects were determined by clinical symptoms, radiologic findings, and immunologic studies. We aimed to examine the value and safety of bronchoscopy in diagnosis and differential diagnosis of PTB in PTB-suspected patients. The diagnostic criteria for PTB were defined when Mycobacterium tuberculosis was cultured in the sputum specimen or in the bronchial washing fluid. RESULTS: A total of 19 PTB suspects were included. One patient was diagnosed with PTB by using the sputum study. However, the remaining 18 patients could not expectorate sputum or showed no evidence of Mycobacterium tuberculosis infection from the sputum study. Of the 18 patients, 15 underwent bronchoscopy. After bronchoscopy, 6 patients were diagnosed with PTB and 9 patients were diagnosed with Mycoplasma, viral, or fungal pneumonia, and tumors. For antituberculous drug resistance, there were 1 case of isoniazid (INH) resistance and 1 case of concurrent resistance to INH and prothionamide. There was no multidrug-resistant tuberculosis. None of the patients had significant complications due to bronchoscopy. CONCLUSION: Flexible bronchoscopy appears to be a definitive and safe procedure for the differential diagnosis of patients suspecting PTB in children who have difficulty expectorating sputum.

A Case of Disseminated Multidrug-Resistant Tuberculosis involving the Brain / 감염과화학요법

We report a case of a 23-year-old female immigrant from China who was diagnosed with multidrug-resistant tuberculosis affecting her lung and brain, resistant to the standard first-line therapeutics and streptomycin. She was treated with prothionamide, moxifloxacin, cycloserine, and kanamycin. However, her headache and brain lesion worsened. After the brain biopsy, the patient was confirmed with intracranial tuberculoma. Linezolid was added to intensify the treatment regimen, and steroid was added for the possibility of paradoxical response. Kanamycin was discontinued 6 months after initiation of the treatment; she was treated for 18 months with susceptible drugs and completely recovered. To our knowledge, this case is the first multidrug-resistant tuberculosis that disseminated to the brain in Korea.

Diagnosis and Treatment of Multidrug-Resistant Tuberculosis / 대한내과학회지

Despite global efforts to control tuberculosis (TB), multidrug-resistant TB (MDR-TB) is still a serious problem worldwide. The diagnosis of MDR-TB is based on mycobacterial culture followed by drug susceptibility testing, with results available in weeks to months. This requirement calls for rapid direct tests, especially genotypic tests, in which specimens are amplified directly for the detection of MDR-TB. The treatment of MDR-TB is challenging because of the high toxicity of second-line drugs and the longer treatment duration required compared to drug-susceptible TB. The selection of drugs in MDR-TB is based on the treatment history, drug susceptibility results, and TB drug resistance patterns in each region. Recent World Health Organization guidelines recommend the use of at least four second-line drugs (i.e., a newer fluoroquinolone, an injectable agent, prothionamide, and cycloserine or para-aminosalicylic acid) in addition to pyrazinamide. Kanamycin is the initial choice of an injectable drug, and newer fluoroquinolones include levofloxacin and moxifloxacin. For extensively drug-resistant TB, group 5 drugs such as linezolid and clofazimine need to be included. New drugs such as delamanid and bedaquiline have recently been approved for treating MDR-TB and other agents with novel mechanisms of action that can be given for shorter durations (6-12 months) for MDR-TB are under investigation.

Low Serum Concentrations of Moxifloxacin, Prothionamide, and Cycloserine on Sputum Conversion in Multi-Drug Resistant TB

PURPOSE: Low serum concentrations of drugs used to treat multi-drug resistant tuberculosis (MDR-TB) have occasionally been associated with treatment failure. We determined the frequencies of low serum concentrations of anti-MDR-TB drugs, and assessed the effects of these concentrations on 2-month sputum conversion. MATERIALS AND METHODS: The serum levels of moxifloxacin (MF), prothionamide (PTH), and cycloserine (CS) were determined for 89 serum samples by high-pressure liquid chromatography-tandem mass spectrometry. RESULTS: Low serum concentrations of MF, PTH, and CS below the minimal levels of the normal ranges were 83.3% (20/24), 59.2% (29/49), and 71.2% (47/66), respectively. There were no significant differences between the 2-month sputum conversion group (n=25) and the 2-month sputum non-conversion group (n=4) in median drug concentrations (microg/mL) of MF (1.46 vs. 1.60), PTH (0.91 vs. 0.70), and CS (14.90 vs. 14.90). However, a poor compliance rate was significantly greater in the 2-month sputum non-conversion group (75.0%, 3/4) than in the 2-month sputum conversion group (0%, 0/25) (p=0.001). CONCLUSION: The frequency of low serum concentrations of anti-MDR-TB drugs was substantial and might not affect the 2-month sputum conversion rate. Larger prospective studies with timely sampling are needed to investigate the role of therapeutic drug monitoring in MDR-TB.

Medical Treatment of Pulmonary Multidrug-Resistant Tuberculosis / 감염과화학요법

Treatment of multidrug-resistant tuberculosis (MDR-TB) is challenging because of the high toxicity of second-line drugs and the longer treatment duration required compared with drug-susceptible TB. The efficacy of treatment for MDR-TB is poorer than that for drug-susceptible TB. The selection of drugs in MDR-TB is based on previous treatment history, drug susceptibility results, and TB drug resistance patterns in the each region. Recent World Health Organization guidelines recommend the use of least 4 second-line drugs (a newer fluoroquinolone, an injectable agent, prothionamide, and cycloserine or para-aminosalicylic acid) in addition to pyrazinamide. The kanamycin is the initial choice of injectable durgs, and newer fluoroquinolones include levofloxacin and moxifloxacin. For MDR-TB, especially cases that are extensively drug-resistant, group 5 drugs such as linezolid, clofazimine, and amoxicillin/clavulanate need to be included. New agents with novel mechanisms of action that can be given for shorter durations (9-12 months) for MDR-TB are under investigation.

A Case of Prothionamide Induced Hepatitis on Patient with Multi-Drug Resistant Pulmonary Tuberculosis / 결핵및호흡기질환

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.

Comparison of Anti-mycobacterial Drug Susceptibility Test Results by Institutes and Methods / 대한임상미생물학회지

BACKGROUND: The purposes of the current study were to evaluate the concordant rates of anti-mycobacterial drug susceptibility test (DST) results in different solid media performed in different institutes, and to determine reliable susceptible testing methods. METHODS: One hundred and twenty two Mycobacterium tuberculosis strains were isolated from patients in A Hospital in 2005. DSTs were performed by the absolute concentration method using L?wenstein Jensen medium in both A Hospital (method A-1) and B Institute (method B-1) and by the proportion method using Middlebrook 7H10 agar in B Institute (method B-2). Nine drugs were used including isoniazid and rifampin. Sensitivity and specificity of each method were estimated by using the acceptable standard of 90% for isoniazid and rifampin and 80% for other drugs. The therapeutic outcomes of quinolone-administered patients were evaluated according to ofloxacin susceptibility results. RESULTS: Method B-1 showed sensitivity and specificity levels over the acceptable standard levels for all drugs. Method B-2 showed specificity lower than the acceptable levels for rifampin and cycloserine. Method A-1 showed specificity lower than the acceptable levels for isoniazid, streptomycin, p-aminosalicylic acid, and ofloxacin and sensitivity lower than the acceptable levels for prothionamide and cycloserine. The concordance rates of therapeutic outcomes with method B-1, method B-2, and method A-1 were 77%, 74%, and 65%, respectively. CONCLUSION: The drug susceptibility results for some drugs were discordant between the testing laboratories and media, requiring an urgent application of quality control programs to raise the reliability of anti-mycobacterial DST.

The survey for clinical course of intractable pulmonary tuberculosis / 대한내과학회지

BACKGROUND: Although various standard anti-tuberculosis chemotherapy regimens were suggested by World Health Organization in pulmonary tuberculosis, as yet, treatment regimen has not been established in intractable pulmonary tuberculosis. Also those surveys for intractable pulmonary tuberculosis were few. Therefore, the purpose of this study is to investigate the clinical course of radiological finding and pulmonary function pattern in intractable pulmonary tuberculosis, to assess the factors that affect the fate and so to make some suggestions for the management of intractable pulmonary tuberculosis. METHODS: This study population was composed of 40 patients with culture-proven pulmonary tuberculosis hospitalized. Although all 40 patients were received regular standard anti-tuberculosis chemotherapy which was individualized on the basis of susceptibility results, all patients were chronic excretors of mycobacterium tuberculosis bacilli (chronics), whose sputum cultures tested positive at both 11 and 12 months after admission. RESULTS: The rate of male and female was about 6:1 and mean age was 47.8+/-14.6 years old. Resistance to most of anti-tuberculosis drugs was observed and especially high degree resistance of isoniazid (95%), rifampicin (92.5%), ethambutol (87.5%), prothionamide and ofloxacin was found. Irrespective of the type of anti-tuberculosis chemotherapy and use of sensitive drug, clinical course was not significantly changed. On the pulmonary function test, most represented restrictive (57.5%) or combined pattern (27.5%) and had no significant interval change. Also arterial blood gas analysis finding was not changed. On chest X-ray findings, 80% had cavitary lesions, 87.5% showed far advanced stage and most (85%) had no significant interval change. However, 15% has changed to aggravation state, which had high frequency in patient with more than 3 susceptible drugs and significant decrease of FEV1 and FEV1/FVC on pulmonary function test findings that did not affect the mortality. The mortality rate was 30%, the average interval from diagnosis to death was 30.6+/-20.3 months and the fate was not associated with radiological findings, arterial blood gas analysis findings and pulmonary function test findings but only body weight at diagnosis of intractable pulmonary tuberculosis. CONCLUSIONS: The clinical course of intractable pulmonary tuberculosis that had no specific treatment did not depend on radiological findings and pulmonary function test findings but nutrition state at diagnosis. Therefore, in addition to anti-tuberculosis treatment, intractable pulmonary tuberculosis patient is recommended to be received aggressive conservative treatment that focuses on nutrition balance. Also it is probably essential to prevent the spread of intractable pulmonary tuberculosis to healthy person.

An Analysis of Antituberculosis Drug Susceptibility Test Results in Kyung Hee Medical Center During Recent Four years / 대한임상미생물학회지

BACKGROUND: Tuberculosis is still one of the most seriously threatening infections in Korea, because of multidrug resistant tuberculosis. Results of antituberculosis drug susceptibility test can provide clinicians very important informations for selection of proper regimens for treatment. METHODS: In this study the results of antituberculosis drug susceptibility test of 298 cases at Kyunghee Medical Center from 2000 to 2003 were retrospectively analysed to evaluate the trend of antituberculosis drug susceptibility. The procedure of drug susceptibility test was based on the absolute concentration method using Lowenstein-Jensen solid media. RESULTS: The resistance rate of Mycobacterium tuberculosis to one or more drugs was increased from 29.3% in 2000 to 48.2% in 2003, and the rates of multiple resistance to two or more drugs increased from 13.3% in 2000 to 20.5% in 2003. The increase in resistance rate to individual drug during study period were 20.0% to 24.1% in isoniazid, 9.3% to 19.3% in rifampicin, 5.3% to 15.7% in ethambutol, 4.0% to 10.8% in para-aminosalicylic acid, 2.7% to 6.0% in kanamycin, 1.3% to 7.2% in ethionamide, 1.3% to 6.0% in capreomycin, 1.3% to 7.2% in prothionamide, 0.0% to 12.1% in ofloxacin, 6.7%to 3.6% in streptomycin, 6.7% to 7.2% in cycloserine, 10.7% to 8.4% in pyrazinamide, respectively. CONCLUSIONS: The resistance rate of M. tuberculosis has been increased with years and multidrug resistant M. tuberculosis was commonly encountered in the specimens from the patients visited Kyunghee Medical center.

Pharmacokinetics of ofloxacin in Patients with Multidrug-Resistant Tuberculosis / 결핵

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 frequentl y co-prescribed to those patients. In this study, the PK disposition of ofloxacin, a fluoroquinolone, was evaluated in patients with MDR-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

Clinical Effects of Prothinoamide, Cycloserine, Para-Aminosalicylic Acid, Ofloxasine in Retreatment of Pulmonary Tuberculosis / 결핵

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 drags involving OFX. METHOD: A retrospective study was made through the regular follow up of smear positive cases,who treated by four drag, 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 advavanced 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 duration of patients 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 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.

Clinical Effects of Prothinoamide, Cycloserine, Para-Aminosalicylic Acid, Ofloxasine in Retreatment of Pulmonary Tuberculosis / 결핵

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 drags involving OFX. METHOD: A retrospective study was made through the regular follow up of smear positive cases,who treated by four drag, 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 advavanced 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 duration of patients 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 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.

The Fate of Intractable Tuberculosis Cases Under National Tuberculosis Programme / 결핵

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.

A Clinical Effect of Ofloxacin, Prothionamide, Cycloserine Streptomycin (Kanamycin or Tuberactinomycin) in Retreatment of Pulmonary Tuberculosis / 결핵

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.

Treatment of paucibacillary leprosy with a regimen containing rifampicin, dapsone and prothionamide.

Ninety paucibacillary leprosy patients having indeterminate (I), tuberculoid (TT) and borderline tuberculoid (BT) type of leprosy with bacterial index (BI) of less than two on the Ridley scale were treated with rifampicin (RFM) 600 mg once a month, dapsone (DDS) 100 mg daily and prothionamide (PTH) 250 mg daily. Treatment was stopped at the end of six months. The patients tolerated the drugs fairly well and in only two patients the drugs had to be stopped (in one due to jaundice and in the other due to gastric intolerance). About 6% of patients had early reactions which subsided with additional steroid therapy. The inactivity rate was 60% at six months and this improved to 96% at 12 months. No cases of late reactions and relapses were encountered in the limited follow-up period of six months; and a longer follow-up is necessary for ascertaining the relapse rates. The preliminary results however suggest that the addition of prothionamide to the standard WHO paucibacillary regimen is well-tolerated with increased inactivity rate and fewer instances of late reactions.

A clinical effect of retreatment by prothionamide, cycloserine, para-aminosalicylic acid, streptomycin(kanamycin or tuberactinomyc-in) on pulmonary tuberculosis / 결핵

No abstract available.