2018 Vindico Medical Education. Non-tuberculous Mycobacteria: Circumventing Difficulties in Diagnosis and Treatment

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1 Activity presentations are considered intellectual property. These slides may not be published or posted online without permission from Vindico Medical Education Please be respectful of this request so we may continue to provide you with presentation materials.

2 Faculty David E. Griffith, MD (Activity Chair) Professor of Medicine W.A. and E.B. Moncrief Distinguished Professor University of Texas Health Science Center Tyler, TX Anne E. O'Donnell, MD Professor of Medicine Chief, Division of Pulmonary, Critical Care and Sleep Medicine Georgetown University Medical Center Washington, DC Kevin Winthrop, MD, MPH Associate Professor of Infectious Diseases, Ophthalmology Professor of Public Health and Preventive Medicine (joint appointment), Division of Infectious Diseases Oregon Health & Science University Portland, Oregon Agenda Current trends and clinical manifestations Difficulties in diagnosis Complexities, variations, and challenges in the management of NTM lung disease patients NTM = nontuberculous mycobacteria.

3 Nontuberculous Mycobacteria: Current Trends and Clinical Manifestations Kevin L. Winthrop, MD, MPH Associate Professor of Infectious Diseases, Ophthalmology Professor of Public Health and Preventive Medicine Division of Infectious Diseases Oregon Health & Science University Portland, OR Nontuberculous Mycobacterium MOTT Environmental organisms Soil, lakes, rivers Municipal water systems (yes, including your tap at home) Biofilm where water flows Live with amoeba, Legionella, others MOTT = mycobacteria other than tuberculosis. Nontuberculous Mycobacterium Species and Common Sites of Infection in Immunosuppressed Hosts Pulmonary Disseminated Rapid growers M. abscessus M. chelonae M. abscessus (R) M. fortuitum (R) Slow growers MAC MAC M. kansasii M. kansasii M. xenopi M. haemophilum M. malmoense M. marinum M. genavense (R) Skin/Soft Tissue/Catheter M. abscessus M. chelonae M. fortuitum M. mucogenicum (R) MAC M. marinum M. haemophilum (R) MAC = Mycobacterium avium/mycobacterium intracellulare complex; (R) = rare. Griffith DE, et al. Am J Respir Crit Care Med. 2007;175(4):

4 NTM Disease Manifestations Henkle E, et al. Ann Am Thorac Soc. 2015;12(5): % of NTM disease is pulmonary Extrapulmonary NTM Incidence Henkel E, et al. Emerg Infect Dis. 2017;23(10): Winthrop KL, et al. Clin Infect Dis. 2012;54(11):1628, Permission to use from KL Winthrop.

5 Disseminated NTM in HIV Varley CD, et al. Emerg Infect Dis. 2017;23(3): Lung Transplant Baker AW, et al. Presented at: ID Week 2015; October 7-11, 2015; San Diego, CA. Abstract 627. M. chimaera Sommerstein R, et al. Emerg Infect Dis. 2016;22(6):

6 M. chelonae in a Cancer Patient Crude Incidence Rate per 100,000 Patient Years NTM Tuberculosis General population General population aged 50 years RA population, no anti-tnf use RA population, anti-tnf therapy exposed RA = rheumatoid arthritis; TNF = tumor necrosis factor. Winthrop KL, et al. Ann Rheum Dis 2013;72: Winthrop KL, et al. Nat Rev Rheumatol 2013;9: Environment? Host? Killer Showerheads? See Feazel LM, et al. Proc Natl Acad Sci U S A. 2009;106(38): Photo courtesy of Rebecca Prevots, PhD

7 Pulmonary NTM Most common in United States M. avium complex (MAC), M. kansasii, M. abscessus 2007 ATS/IDSA diagnostic criteria Patient with radiographic evidence of disease and pulmonary symptoms AND At least 2 sputum cultures positive, OR One BAL or tissue specimen with positive culture, OR Tissue with granulomatous histopathology in conjunction with positive culture (BAL or sputum) ATS = American Thoracic Society; IDSA = Infectious Diseases Society of America. Griffith DE, et al. Am J Respir Crit Care Med. 2007;175(4):

8 Incidence per 100,000 population Non-tuberculous Mycobacteria: Circumventing Difficulties in Diagnosis and Treatment Pulmonary MAI and M. abscessus/m. chelonae Incidence (Oregon, ) Year Henkle E, et al. Ann Am Thorac Soc. 2015;12(5): MAI M. abscessus Linear (MAI) Linear (M. abscessus) Annual Age- and Sex-specific Incidence of Pulmonary NTM Disease in Oregon, Age Group (Years) Incidence per 100,000 Males Females Henkle E, et al. Ann Am Thorac Soc. 2015;12(5): Distribution of Disease RGM = rapid-growing mycobacteria. Hoefsloot W, et al. Eur Respir J. 2013;42(6): Reproduced with permission of the ERS European Respiratory Journal Dec 2013, 42 (6) ; DOI: /

9 Two Disease Types Older male, smoker, COPD Apical cavitary or fibronodular disease More rapidly progressive Older female ( Lady Windermere ) Scoliosis, thin, pectus deformities, 1 hypomastia, mitral valve prolapse Nodular and interstitial nodular infiltrate Bronchiectasis right middle lobe/lingula Bronchiolitis ( tree and bud ) on HRCT Slowly progressive COPD = chronic obstructive pulmonary disease; HRCT = high-resolution computed tomography. 1. Iseman MD, et al. Am Rev Respir Dis. 1991;144(4): Risk Factors for Pulmonary NTM Primarily from case series level data Underlying lung architectural abnormalities Bronchiectasis, cystic fibrosis Alpha-1 antitrypsin, emphysema Prior TB or other infection GERD with micro-aspiration Exposure/transmission information lacking Gardening? Hot tubs? GERD = gastroesophageal reflux disease; TB = tuberculosis. RA is a Risk Factor for NTM NTM risk among RA is 4.1x higher (Taiwan) Yeh JJ, et al. PLoS One. 2014;9(10):e

10 Difficulties in the Diagnosis of NTM Lung Disease Anne E. O Donnell, MD Professor of Medicine Chief, Division of Pulmonary, Critical Care and Sleep Medicine Georgetown University Medical Center Washington, DC Suspecting NTM Lung Disease General clinical symptoms Pulmonary Chronic cough: productive or dry Hemoptysis: usually low grade Chest pain: relatively uncommon Constitutional symptoms Weight loss Fatigue, malaise Fever, chills, night sweats Suspecting NTM Lung Disease Supportive evidence Clinical symptoms Multiple rounds of antibiotic for bronchitis Multiple bouts of pneumonia Hemoptysis Underlying disease state COPD/emphysema Know n bronchiectasis Suggestive imaging Chest X-ray show s cavities CT scan show s cavities, bronchiectasis Right middle lobe and lingual bronchiectasis HRCT shows tree in bud nodularity/radiologist interpretation

11 NTM Lung Disease Preexisting Lung Disease Fibrocavitary disease Prior infections Sarcoidosis Bronchiectasis COPD/emphysema Males and females Smokers/former smokers Chronic lung disease Griffith DE, et al. Am J Respir Crit Care Med. 2007;175: Nodular Bronchiectasis Nonresolving infiltrates Bronchiolitis/ tree in bud Waxing and waning infiltrates and nodules Mucus plugging Female predominant Older age Low body mass index Nonsmokers Skeletal abnormalities Fibrocavitary versus Nodular Suspecting NTM Lung Disease CT scan is helpful but not diagnostic of NTM Tree in bud nodularity Right middle lobe and lingular bronchiectasis Never treat based on CT alone Sputum cultures needed Two expectorated One BAL Suggestive clinical features Griffith DE, et al. Am J Respir Crit Care Med 2007;175:

12 Radiographic Manifestations Radiographic findings are not diagnostic of NTM infection Tree in bud nodularity is not specific for NTM Multiple causes of bronchiolitis Infection/inflammatory NTM but also routine bacteria Inflammation Mucus plugging Miller WT Jr, et al. Chest. 2013;144(6): Shimon G, et al. Lung. 2015;193(5): Testing for NTM Lung Infection Sputum AFB smear and cultures At least 2 expectorated specimens OR One BAL culture How to obtain sputum Spontaneously expectorated Induced Saline nebulization/flutter-pep device Prompt processing Interfacing with the mycobacterial laboratory Griffith DE, et al. Am J Respir Crit Care Med. 2007;175(4): Testing for NTM Lung Infection Laboratory processing AFB smear Culture Rapid versus slow growing mycobacterium Identification is vital M. abscessus complex Subspeciation important M. avium complex Subspeciation useful Clinician needs to have accurate reliable results Antibiotic susceptibility testing Important for accurately pinpointing therapy AFB = Acid-Fast Bacilli. Griffith DE, et al. Am J Respir Crit Care Med. 2007;175(4):

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