GNOST I IC D

C I I TE GNOST I IC D

GNOST Updates in Nontuberculous Mycobacteria (NTM): I IC NIC D I C Best Practices for Diagnosis,C Management andI TPersonalizedEI

C Treatment Selection I I TE INIC S C Y S M M O TO GNICST IIN IC D C S NOS Y S G T M M I IC TO D SC YI I S IOG MTE O M D T OG DI C IT I INIC E C n Chronic cough n Weight loss IOG D n Fatigue n Shortness n Fever/chills of breath S n S n Night sweats Hemoptysis INIC Y n Nodular or cavitary opacities on chest radiograph or MTO M C n High resolutation computed tomography showing IO multifocal bronchiectasisTE withO multiple small nodules O C G NIOS Y TGE TO I IGC IOG n Positive culture results from at least two separate expectoratedS C D DY YS IO sputum samples of the same species M TE O M C G TO Y n Positive culture results of at least one bronchial wash or lavage

n Transbronchial biopsy or other lung biopsy with mycobacterialC GNOShistopathologicT features and positive culture for NTM or biopsyIT EI I showingIC mycobacterial histopathologic features and one or more n Nodular n CavitaryM D IOG ET EN sputum or bronchial washings that are culture positive for NTMD Bronchiectatic T T 1 IO TE O C M G NIC T E Y I E N C TM CT E EN T I T O S ITE T TION

O TIONS Treatment S Treatment Y S MO IC M M O TE IN M. avium complex O TO M. abscessus C TIONS TM E EN IO MO T Macrolide sensitive? E O T O TE T G “Functional” erm 41 gene? C Y D E YES NO C E N S M. abscessus YES NOE Y S Clofazimine IOG M. massiliense O MCavities MPresent DAILY DOMOT M. bolletti S O Moxifloxacin E D TION E T Rifampin C Ciprofloxacin EEN NO YES Ethambutol Linezolid/Tedizolid GIC Macrolide? Imipenem (IV)U Macrolide Bedaquilline Additional drug S ≥2 other drugs Cefoxitin (IV) ≥1 other drug Tigecycline (IV) OM3X/WEEKOT DAILY IV Amikacin IV Amikacin E E Linezolid/Tedizolid GIC G D U Azithromycin IO Azithromycin Add C ClofazimineT S D EEN T Rifampin Rifampin IV Amikacin E N 2+ mos MoxifloxacinTME 1-2+ mos Ethambutol Ethambutol Consider surgery TME Bedaquiline E N D E T T C T Macrolide? Macrolide EEN T E N ≥2 other drugs ≥1 other drug TME IO Treatment of MAC TEGICO inhaled Amikacin inhaled Amikacin CU G Initial Therapy S Y GIC Nodular/bronchiectatic O Consider surgery for focal disease. U Cavitary Disease S S Disease TION clarithromycin 1000 mg clarithromycin 500-1000 Macrolide tiw or azithromycin mg/day or azithromycin T T T O 500-600 mg tiw 250-500 mg/day T EI O E N Interpretation of extended clarithromycin E N T TME EthambutolTME C 25G mg/kg tiw 15 mg/kg day susceptibility results for M. abscessus Y Rifamycin rifampin 600 mg tiw rifampin 450-600 mg/day MOT O E M. abscessus M. massiliense M. abscessus Any Aminoglycoside None strep or amikacin subspecies M. abscessus* M. bolletii Clarithromycin Duration of treatment: 12 months of negative cultures 1 M susceptibility days Susceptible Susceptible Resistant ET EN T 3–5 Medical treatment T Clarithromycin D E Susceptible Resistant Resistant for refractory MAC C susceptibility day 14 EEN High-level Macrolide Amikacin Macrolide Inducible macrolide constitutive 30% additional susceptibility Liposome susceptible resistance macrolide culture O phenotype InhalationTME T NS resistance E N conversion 2 IO dysfunctional functional erm(41) 23S ribosomal RNA SuspensionT Genetic implication erm(41) gene gene point mutation T Risk of increased respiratory adverse GIC U Macrolide reactions. Please refer to new CLSI MIC anti-mycobacterial immunomodulatory immunomodulatory cutpoints.4 S Effect Management strategies for common side effects of inhaled amikacin. MO *15-20% of M. abscessus will have a dysfunctional 3 O O TE erm(41) gene (c28 sequevar) * Side Effects: ManagementS Strategy OtotoxicityT IOFollowN audiograms T T Dysphonia Discontinue use of drug for a brief E EN period of time and then reintroduce TM Coughing Bronchodilator D E *Based on expertMO opinion for the monitoring NC O TE EE and management of side effects.

n Provide patient education n Detect side effects early n Manage side effects E GIC D n U C Optimize nutrition,S physical fitness, overall EEN well-being and caregiver relationships

T T GIC Surgical Treatment of E EN U TM S Pulmonary NTM Disease Indications to consider surgery n Massive hemoptysis n Cavitary lesions n Failure of medical therapy n Focal severe bronchiectasis n Intolerance to medical therapy n Focal disease with M. abscessus infection T T n Macrolide resistant MAC infection E N TME

1 Am J Respir Crit Care Med Vol 175. pp 367–416, 2007. | 2 Am J Respir Crit Care Med 2017; 195(6): 814–823. 3 Thorax 2017;72(Suppl 2):ii1 | 4 CLSI: M62: 2018 National Jewish

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