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1 J KMA Special Issue Won Jung Koh, MD O Jung Kwon, MD Division of Pulmonary and Critical Care Medicine, Department of Medicine, Sungkyunkwan University School of Medicine E mail : wjkoh@smc.samsung.co.kr ojkwon@smc.samsung.co.kr J Korean Med Assoc 2006; 49(9): Abstract As the prevalence of tuberculosis declines, the proportion of mycobacterial lung disease due to nontuberculous mycobacteria (NTM) is increasing worldwide. In Korea, M. avium complex and M. abscessus account for most of the pathogens encountered, whilst M. kansasii is a relatively uncommon cause of NTM pulmonary diseases. NTM pulmonary disease is highly complex in terms of its clinical presentation and management. Because its clinical features are indistinguishable from those of pulmonary tuberculosis and NTMs are ubiquitous in the environment, the isolation and identification of causative organisms are mandatory for diagnosis, and some specific diagnostic criteria have been proposed. The treatment of NTM pulmonary disease depends on the infecting species, but decisions concerning the institution of treatment are far from being easy. It requires the use of multiple drugs for 18 to 24 months. Thus, the treatment is expensive, often has significant side effects, and is frequently not curative. Therefore, clinicians should be confident that there is a sufficient clinical evidence to warrant prolonged, multidrug treatment regimens. In all situations, outcomes can be best optimized only when the clinicians, radiologists, and laboratories work cooperatively. The purpose of this article is to review the common presentations, diagnosis and treatment of the NTM that most commonly cause lung disease in Korea. Keywords : Atypical mycobacteria; Mycobacterium avium complex; Lung diseases 806

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3 Koh WJ Kwon OJ Criteria for the diagnosis of nontuberculous mycobacterial lung disease in non immunocompromised patients (1, 3) Clinical criteria 1. Compatible symptoms and signs 2. Reasonable exclusion of other disease Radiographic criteria 1. Plain chest radiography Infiltrates with or without nodules (persistent 2 months, or progression) Cavitation Nodules alone (multiple) 2. High resolution computed tomography (HRCT) Multiple small nodules Multifocal bronchiectasis with or without small lung nodules Bacteriologic criteria 1. If three sputum/bronchial wash results are available from the previous 12 months: Three positive cultures with negative AFB smear results, or Two positive cultures and one positive AFB smear 2. If only one bronchial wash is available: Positive culture with a 2+, 3+, or 4+ AFB smear, or 2+, 3+, or 4+ growth on solid media 3. If sputum/ bronchial wash evaluations are nondiagnostic or another disease cannot be excluded: Transbronchial or lung biopsy yielding NTM, or Biopsy showing mycobacterial histopathologic features (granulomatous inflammation or AFB smear) and one or more sputa or bronchial washing procedures positive for NTM, even in low numbers AFB: acid fast bacilli, NTM: nontuberculous mycobacteria 808

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5 Koh WJ Kwon OJ M. intracellulare pulmonary disease of the upper lobe cavitary form in a 56 year old man. Chest radiograph shows cavitary consolidation in the right upper lobe. 810

M. intracellulare pulmonary disease of the nodular bronchiectatic form in a 67 year old woman. Chest radiograph shows a multifocal patchy distribution of small nodular clusters in both lungs.

6 M. intracellulare pulmonary disease of the nodular bronchiectatic form in a 67 year old woman. Chest radiograph shows a multifocal patchy distribution of small nodular clusters in both lungs. Transaxial lung window CT images (2.5mm section thickness, 70mA) show small centrilobular nodules and bronchiectasis in the both lungs, especially in the right middle lobe and in the lingular division of the left upper lobe. 811

7 Koh WJ Kwon OJ Treatment protocol for nontuberculous mycobacterial lung diseases (1, 3) Organism Doses Drug Duration Surgery M. avium complex Clarithromycin 500 mg b.i.d. Rifampin 600 mg (450mg, body weight 50kg) Ethambutol 25mg/ kg for 2 mo, then 15mg/kg Streptomycin (dosing based on age, body weight, renal function) considered for severe/advanced Until culture negative for 1 yr based on monthly sputum cultures Consider resection for localized disease if isolate becomes macrolide resistance disease M. abscessus Clarithromycin 500 mg b.i.d. and Amikacin 15 mg/kg and Cefoxitin 200 mg/kg (max 12 g/d) or Imipenem 750 mg t.i.d. Oral antibiotics for prolonged duration along with parenteral antibiotics for initial Consider resection for localized disease 4 wk for symptomatic and progressive disease M. kansasii Isoniazid 300 mg Rifampin 600 mg (450 mg, body weight 50 kg) Ethambutol 25mg/kg for 2 mo, then 15mg/kg 18 mo (culture negative at least 1 yr) Not routinely indicated b.i.d., twice daily; t.i.d., three times daily. 812

M. abscessus pulmonary disease in a 60 year old woman. Chest radiograph shows multifocal patchy areas of small nodular clusters in both lungs. Transaxial lung window CT images (2.

8 M. abscessus pulmonary disease in a 60 year old woman. Chest radiograph shows multifocal patchy areas of small nodular clusters in both lungs. Transaxial lung window CT images (2.5mm section thickness, 70 ma) show bronchiectasis and small centrilobular nodules or tree in bud opacities in the both lungs, especially in the right middle lobe. Also note bronchiolitis of small centrilobular nodules and tree in bud opacities in both lower lobes. 813

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10 1. American Thoracic Society. Diagnosis and treatment of disease caused by nontuberculous mycobacteria. Am J Respir Crit Care Med 1997; 156: S British Thoracic Society. Management of opportunist mycobacterial infections: Joint Tuberculosis Committee Guidelines Thorax 2000; 55: Korean Academy of Tuberculosis and Respiratory Diseases (KATRD). Nontuberculous mycobacterial lung disease. In: KATRD. Guideline of management of tuberculosis. Seoul: KATRD, 2005: Koh WJ, Kwon OJ, Lee KS. Diagnosis and treatment of nontuberculous mycobacterial pulmonary diseases: a Korean perspective. J Korean Med Sci 2005; 20: Koh WJ, Kwon OJ, Jeon K, Kim TS, Lee KS, Park YK, et al. Clinical significance of nontuberculous mycobacteria isolated from respiratory specimens in Korea. Chest 2006; 129: Yim JJ, Park YK, Lew WJ, Bai GH, Han SK, Shim YS. Mycobacterium kansasii pulmonary diseases in Korea. J Korean Med Sci 2005; 20: Jeon K, Koh WJ, Kwon OJ, Suh GY, Chung MP, Kim H, et al. Recovery rate of NTM from AFB smear positive sputum specimens at a medical centre in South Korea. Int J Tuberc Lung Dis 2005; 9: Field SK, Fisher D, Cowie RL. Mycobacterium avium complex pulmonary disease in patients without HIV infection. Chest 2004; 126: Jeong YJ, Lee KS, Koh WJ, Han J, Kim TS, Kwon OJ. Nontuberculous mycobacterial pulmonary infection in immunocompetent patients: comparison of thin section CT and histopathologic findings. Radiology 2004; 231: Koh WJ, Lee KS, Kwon OJ, Jeong YJ, Kwak SH, Kim TS. Bilateral bronchiectasis and bronchiolitis at thin section CT: diagnostic implications in nontuberculous mycobacterial pulmonary infection. Radiology 2005; 235: Chung MJ, Lee KS, Koh WJ, Lee JH, Kim TS, Kwon OJ, et al. Thin-section CT findings of nontuberculous mycobacterial pulmonary diseases: comparison between Mycobacterium avium intracellulare complex and Mycobacterium abscessus infection. J Korean Med Sci 2005; 20: Daley CL, Griffith DE. Pulmonary disease caused by rapidly growing mycobacteria. Clin Chest Med 2002; 23:

11 Koh WJ Kwon OJ 13. Han D, Lee KS, Koh WJ, Yi CA, Kim TS, Kwon OJ. Radiographic and CT findings of nontuberculous mycobacterial pulmonary infection caused by Mycobacterium abscessus. AJR 14. Koh WJ, Kwon OJ, Kim EJ, Lee KS, Ki CS, Kim JW. NRAMP1 gene polymorphism and susceptibility to nontuberculous mycobacterial lung diseases. Chest 2005; 128: Am J Roentgenol 2003; 181: Peer Reviewer Commentary 816

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