• Title/Summary/Keyword: Ethambutol resistance

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Treatment of Mycobacterium avium Complex Pulmonary Disease

  • Kwon, Yong-Soo;Koh, Won-Jung;Daley, Charles L.
    • Tuberculosis and Respiratory Diseases
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    • v.82 no.1
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    • pp.15-26
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    • 2019
  • The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.

Impact of Anti-Tuberculosis Drug Use on Treatment Outcomes in Patients with Pulmonary Fluoroquinolone-Resistant Multidrug-Resistant Tuberculosis: A Nationwide Retrospective Cohort Study with Propensity Score Matching

  • Hongjo Choi;Dawoon Jeong;Young Ae Kang;Doosoo Jeon;Hee-Yeon Kang;Hee Jin Kim;Hee-Sun Kim;Jeongha Mok
    • 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.

Drug resistance of Mycobacterium tuberculosis in children (소아 결핵 환자에서의 항결핵제 내성 II)

  • Lee, Soo Jin;Ahn, Young Min;Kim, Hee Jin
    • 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.

Prevalence of Drug-resistances in Patients with Pulmonary Tuberculosis and Its Association with Clinical Characteristics at One Tertiary Referral Hospital in Pusan, Korea (부산지역 한 3차 병원으로 내원한 폐결핵 환자에서 약제 내성률과 예측인자간의 연관성)

  • Son, Choon-Hee;Yang, Doo-Kyung;Rho, Mee-Sook;Jeong, Jin-Sook;Lee, Hyuck;Lee, Ki-Nam;Choi, Pil-Jo;Lee, Soo-Keol;Chang, Kwang-Yul;Choi, Ik-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.5
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    • pp.416-425
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    • 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.

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The Current Status of Multidrug-Resistant Tuberculosis in One Tertiary Hospital in Busan, 2005~2009 (일개 부산지역 3차 병원에서 관찰한 다제내성 결핵의 실태, 2005~2009)

  • Yoon, Neul-Bom;Lee, Sung-Woo;Park, Su-Min;Jeong, Il-Hwan;Park, So-Young;Han, Song-Yee;Lee, Yu-Rim;Jung, Jin-Kyu;Kim, Joon-Mo;Kim, Su-Young;Um, Soo-Jung;Lee, Soo-Keol;Son, Choon-Hee;Hong, Young-Hee;Lee, Ki-Nam;Roh, Mee-Sook;Kim, Kyeong-Hee
    • 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.

Drug-Resistant Pulmonary Tuberculosis In Kosin Medical Center (부산지역의 한 3차 진료기관을 방문한 폐결핵 환자의 약제내성률)

  • Kim, Ji-Ho;Kim, Ji-Hong;Jang, Tae-Won;Jung, Maan-Hong
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.6
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    • pp.831-837
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    • 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.

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The Influence of Adverse Drug Reactions on First-line Anti-tuberculosis Chemotherapy in the Elderly Patients (고령에서 일차 항결핵 화학요법에 의한 약물 이상반응이 치료에 미치는 영향)

  • Jeong, Jeong Ihm;Jung, Bock Hyun;Kim, Mi Hye;Lim, Jae Min;Ha, Dong Cheon;Cho, Sung-Won;Rhui, Dae Sik
    • Tuberculosis and Respiratory Diseases
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    • v.67 no.4
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    • pp.325-330
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    • 2009
  • Background: Pulmonary tuberculosis (TB) is still common disease among the elderly patients in Korea where the overall incidence of TB is decreasing. Adverse drug reactions (ADR) associated with anti-TB drugs occurs frequently. Especially the aged tends to have more frequent ADRs than younger ones. These ADRs can cause significant morbidity, compromise therapeutic effects of drugs and even induce drug resistance. Therefore we evaluated the effect of ADRs on the first-line anti-TB drugs in elderly patients with active pulmonary TB. Methods: We retrospectively reviewed the charts and radiological findings of the patients with 65 and older who were bacteriologically confirmed as active TB and treated with standard anti-TB drugs for at least 6 months. Major ADR was defined with temporary or continuous stop of any first-line drugs intake. Results: An ADR was noted in 54% of all patients. The incidence of major ADR was 32% in all elderly patients. Dermatologic ADR (9%) was the most common among the major ADRs. GI trouble (8%), arthralgia (6%), visual change (6%), hepatotoxicity (4%), and fever (1%) were also noted. The drugs responsible for major ADR were ethambutol (62%), pyrazinamide (35%), rifampin (18%) and isoniazid (9%). Major ADRs were associated with higher ESR level at the initiation of anti-TB drugs. Conclusion: First-line anti-TB drugs in elderly patients frequently caused the major ADRs. Therefore the elderly patients receiving anti-TB drugs should be closely monitored and better tolerable therapy should be considered as part of a TB research agenda.

Treatment of Isoniazid-Resistant Pulmonary Tuberculosis (Isoniazid 내성 폐결핵의 치료실태와 치료성적)

  • Koh, Won-Jung;Kwon, O Jung;Yu, Chang-Min;Jeon, Kyeongman;Kim, Kyung Chan;Lee, Byoung-Hoon;Hwang, Jung Hye;Kang, Eun Hae;Suh, Gee Young;Chung, Man Pyo;Kim, Hojoong
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.3
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    • pp.248-260
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    • 2004
  • Background : As an effective regimen for isoniazid (INH)-resistant pulmonary tuberculosis, several treatment regimens have been recommended by many experts. In Korea, a standard regimen has not been established for INH-resistant tuberculosis, and the treatment by individual physicians has been performed on an empirical bases. The purpose of the present study was to retrospectively describe the treatment characteristics and evaluate the treatment outcomes of patients with INH-resistant tuberculosis. Materials and Methods : Sixty of 69 patients reported to have INH-resistant tuberculosis from 1994 to 2001 were retrospectively analyzed. Exclusion criteria included: death from other causes, with the exceptions of tuberculosis and incomplete treatment, including a patient's transfer-out. Results : A previous tuberculosis history was found in 28 (46.7%) patients. The sputum smear for acid-fast bacilli was positive in 44 (73.3%) patients, and 30 (50.0%) had cavitary disease. Streptomycin resistance coexisted in 25.0% of isolates. INH was to be prescribed continuously, even after INH resistance was reported, in 86.0% of patients. The treatment regimens were diverse between the patients according to drug regimen composition and treatment duration. The most frequent prescribed regimen included rifampin, ethambutol and pyrazinamide, with and without INH, for the full 12-month term of treatment. Treatment failure occurred in 13 (21.7%) patients. Cavitary disease (p=0.005) and a treatment regimen with second-line drugs, excluding rifampin (p=0.015), were associated with treatment failure. One patient experienced a relapse. Conclusions : Standardized treatment guidelines will be needed in Korea to improve the treatment efficacy for INH-resistant tuberculosis.

Clinical Effects of Prothinoamide, Cycloserine, Para-Aminosalicylic Acid, Ofloxasine in Retreatment of Pulmonary Tuberculosis (폐결핵 재치료 환자에서 Prothionamide, Cycloserine, Paraminosalicylic acid, Ofloxasine을 이용한 경구 4제 요법의 임상 효과)

  • Hong, Jae-Rak;Yoo, Min-Kyu;Jeong, Jae-Man;Kim, Young-Jun;Son, Mal-Hyeon
    • 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.

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