Guideline sources The following summarized guidelines for the evaluation and management of non-tuberculous mycobacterial pulmonary disease (NTM-PD) are prepared by our editorial team based on guidelines from the Infectious Diseases Society of America (IDSA/CDC/NIH/HIVMA 2023), the Infectious Diseases Society of America (IDSA/ERS/ATS/ESCMID 2020), and the British Thoracic Society (BTS 2017). 1 2 3 Guidelines 1. Screening and diagnosis Diagnostic criteria: Use the following clinical, radiologic (both clinical and radiologic criteria required) and microbiologic criteria for the diagnosis of NTM pulmonary disease given other diagnoses are appropriately excluded: Situation Guidance https://web.pathway.md/diseases/rec0woAtEXZLxAJrf 1/8 6/30/23, 1:18 AM Non-tuberculous mycobacterial pulmonary disease Pathway Pulmonary or systemic symptoms Clinical Nodular or cavitary opacities on CXR, or a HRCT scan showing bronchiectasis with multiple small nodules Radiologic Positive culture results from at least 2 separate expectorated sputum samples Microbiologic (any) Consider obtaining repeat sputum AFB smears and cultures if the results are nondiagnostic Positive culture results from at least 1 bronchial wash or lavage Transbronchial or other lung biopsy with mycobacterial histologic features (granulomatous inflammation or AFB) and positive culture for NTM or biopsy showing mycobacterial histologic features (granulomatous inflammation or AFB) and 1 culture positive sputum or bronchial washings. 2. Diagnostic investigations Sample collection: consider collecting sputum, induced sputum, bronchial washings, BAL, or transbronchial biopsy samples to evaluate patients with suspected NTM pulmonary disease. Attempt to obtain less invasive sampling first to minimize procedural risks whenever possible. C Show 4 more Microbiological testing: use a validated rapid method to detect non-tuberculous mycobacteria in respiratory samples. B Show 6 more Susceptibility testing: follow the Clinical Laboratory Standards Institute guidelines for drug susceptibility testing and reporting. B Show 3 more Serologic testing: insufficient evidence to recommend the routine use of serological testing for the diagnosis and monitoring of patients with NTM pulmonary disease. I Interferon-gama release assay: do not obtain IGRA in the evaluation of patients with suspected NTM pulmonary disease. D Chest imaging: Obtain a CXR and CT in patients with suspected NTM pulmonary disease. B https://web.pathway.md/diseases/rec0woAtEXZLxAJrf 2/8 6/30/23, 1:18 AM Non-tuberculous mycobacterial pulmonary disease Pathway Do not obtain positron emission scanning in the evaluation of patients with suspected NTM pulmonary disease. D Skin testing: do not obtain skin testing in the evaluation of patients with suspected NTM pulmonary disease. D 3. Diagnostic procedures Lung biopsy: do not perform transbronchial biopsies routinely in patients with suspected NTM pulmonary disease. D 4. Medical management Setting of care: manage patients with NTM pulmonary disease in collaboration with a physician experienced in managing NTM pulmonary disease. B Indications for treatment: As per ATS 2020 guidelines, consider initiating treatment rather than offering watchful waiting in patients meeting the diagnostic criteria for NTM pulmonary disease, especially in the context of positive AFB sputum smears and/or cavitary lung disease. C As per BTS 2017 guidelines: Decide on initiating treatment based on the severity of NTM pulmonary disease, the risk of progressive NTM pulmonary disease, the presence of comorbidity, and the goals of treatment. B Consider obtaining a period of longitudinal assessment (symptoms, radiological change, and mycobacterial culture results) to inform NTM treatment decisions. C Antimicrobial therapy, M. avium complex: As per IDSA/ESCMID/ERS/ATS 2020 guidelines, consider initiating susceptibility-based treatment for macrolides and amikacin over empiric therapy in patients with Mycobacterium avium complex pulmonary disease. C Show 8 more As per BTS 2017 guidelines, initiate rifampicin, ethambutol, and clarithromycin or azithromycin using an intermittent (3 times weekly) or daily oral regimen in patients with clarithromycin- sensitive Mycobacterium avium complex pulmonary disease. Decide on the choice of regimen based on the severity of the disease and treatment tolerance: Situation Guidance Rifampicin 600 mg 3 times weekly, ethambutol 25 mg/kg 3 times weekly, and azithromycin 500 mg 3 times weekly or clarithromycin 1 g in 2 divided doses 3 times weekly Non-severe disease https://web.pathway.md/diseases/rec0woAtEXZLxAJrf 3/8 6/30/23, 1:18 AM Non-tuberculous mycobacterial pulmonary disease Pathway Rifampicin 600 mg daily, ethambutol 15 mg/kg daily, and azithromycin 250 mg daily or clarithromycin 500 mg BID Severe disease Consider administering IV amikacin for up to 3 months or nebulized amikacin Rifampicin 600 mg daily, ethambutol 15 mg/kg daily, and Isoniazid 300 mg (plus pyridoxine 10 mg) daily or moxifloxacin 400 mg daily Clarithromycin-resistant disease Consider administering IV amikacin for up to 3 months or nebulized amikacin. B Show 5 more Antimicrobial therapy, M. kansasii: As per IDSA/ESCMID/ERS/ATS 2020 guidelines, consider initiating susceptibility-based treatment for rifampicin over empiric therapy in patients with Mycobacterium kansasii pulmonary disease. C Show 7 more As per BTS 2017 guidelines: Initiate rifampicin, ethambutol, and isoniazid or a macrolide (clarithromycin or azithromycin) using a daily oral regimen in patients with rifampicin-sensitive Mycobacterium kansasii pulmonary disease. B Administer a 3-drug regimen guided, but not dictated by, drug susceptibility test results using a daily oral regimen in patients with rifampicin-resistant Mycobacterium kansasii pulmonary disease. B Antimicrobial therapy, M. xenopi: As per IDSA/ESCMID/ERS/ATS 2020 guidelines, insufficient evidence to recommend for or against susceptibility-based treatment in patients with Mycobacterium xenopi pulmonary disease. Show 3 more As per BTS 2017 guidelines, administer a 4-drug regimen (where tolerated) comprising rifampicin, ethambutol, and a macrolide (clarithromycin or azithromycin), with either a quinolone (ciprofloxacin or moxifloxacin) or isoniazid, in patients with Mycobacterium xenopi pulmonary disease. B Show 2 more Antimicrobial therapy, M. abscessus: As per IDSA/ESCMID/ERS/ATS 2020 guidelines, consider initiating susceptibility-based treatment for macrolides and amikacin over empiric therapy in patients with Mycobacterium abscessus pulmonary disease. C Show 4 more https://web.pathway.md/diseases/rec0woAtEXZLxAJrf 4/8 6/30/23, 1:18 AM Non-tuberculous mycobacterial pulmonary disease Pathway As per BTS 2017 guidelines, administer an initial phase antibiotic regimen (including IV and oral antibiotics) followed by a continuation phase antibiotic regimen (including inhaled and/or oral antibiotics) for the treatment of patients with Mycobacterium abscessus pulmonary disease. B Show 9 more Antimicrobial therapy (M. malmoense): initiate rifampicin, ethambutol, and a macrolide (clarithromycin or azithromycin) using a daily oral regimen in patients with Mycobacterium malmoense pulmonary disease. B Show 2 more Duration of treatment: As per ATS 2020 guidelines, consider continuing treatment for at least 12 months after culture conversion in patients with macrolide-susceptible Mycobacterium avium complex pulmonary disease. C Show 3 more As per BTS 2017 guidelines: Continue antibiotic treatment for NTM pulmonary disease (Mycobacterium avium complex, Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium malmoense, or Mycobacterium abscessus) at least 12 months after culture conversion. B Consider initiating long-term suppressive antibiotic therapy in patients with Mycobacterium abscessus pulmonary disease failed to culture-convert. C Adjuvant therapies: Do not use interferon-gamma as adjuvant therapy in patients with NTM pulmonary disease without a defined immunodeficiency affecting intrinsic interferon-gamma signaling. D Do not use Mycobacterium vaccae as adjuvant therapy in patients with NTM pulmonary disease. D 5. Surgical interventions Surgical resection: As per ATS 2020 guidelines, consider performing surgical resection as an adjuvant to medical therapy after expert consultation in selected patients with NTM pulmonary disease. C As per BTS 2017 guidelines, consider discussing the role of lung resection surgery in the management of NTM pulmonary disease at the time of diagnosis and revisit in patients developing refractory disease. C Show 4 more Lung transplantation: assess for evidence of NTM pulmonary disease in patients suitable for lung transplantation referral. B Show 3 more 6. Specific circumstances https://web.pathway.md/diseases/rec0woAtEXZLxAJrf 5/8 6/30/23, 1:18 AM Non-tuberculous mycobacterial pulmonary disease Pathway Patients with HIV (primary prophylaxis): do not administer primary prophylaxis against Mycobacterium avium complex in adult and adolescent patients immediately initiating antiretroviral therapy. D Show 5 more Patients with HIV (management of disseminated MAC disease): initiate at least 2 drugs as initial therapy to prevent or delay emergence of resistance in patients with disseminated Mycobacterium avium complex disease. Administer clarithromycin 500 mg PO BID plus ethambutol 15 mg/kg PO daily as the preferred regimen. A Administer azithromycin 500-600 mg B plus ethambutol 15 mg/kg PO daily when drug interactions or intolerance precludes the use of clarithromycin. A Show 2 more Patients with HIV (maintenance therapy): administer the same regimens for chronic maintenance therapy (secondary prophylaxis) as for treatment. Show 2 more Patients with HIV (adjuvant therapy): Consider offering NSAIDs in patients with human immunodeficiency virus experiencing moderate-to-severe symptoms attributed to immune reconstitution inflammatory syndrome. C Consider administering a short-term course (4-8 weeks) of systemic corticosteroid (equivalent to prednisone 20- 40 mg) if immune reconstitution inflammatory syndrome symptoms persist. C 7. Preventative measures Infection control: implement adequate infection control policies in both inpatient and outpatient settings to minimize risks of person-to-person transmission of Mycobacterium abscessus in patients with cystic fibrosis. B 8. Follow-up and surveillance Monitoring for medication adverse effects: monitor serum levels of aminoglycosides and creatinine in patients receiving aminoglycosides and adjust dosing according to local policies. B Show 3 more Therapeutic drug monitoring: Do not obtain therapeutic drug monitoring (other than for aminoglycosides) routinely in patients prescribed antibiotic therapy for NTM pulmonary disease. D Monitor serum levels of aminoglycosides and creatinine in patients receiving aminoglycosides and adjust dosing according to local policies. B Serial clinical assessment: obtain a detailed assessment of pulmonary and systemic symptoms at each clinical review. B Serial laboratory assessment: obtain sputum mycobacterial culture every 4-12 weeks during treatment and for 12 months after completing treatment to assess the microbiological response. https://web.pathway.md/diseases/rec0woAtEXZLxAJrf 6/8 6/30/23, 1:18 AM Non-tuberculous mycobacterial pulmonary disease Pathway B Show 2 more Serial imaging assessment: obtain CT shortly before initiating NTM treatment and at the end of NTM treatment to document the radiological response to treatment. B Clinical findings Symptoms Past medical history Chest pain Bronchiectasis Cough COPD Fatigue Immunocompromising condition Fever Mitral valve prolapse Hemoptysis Integument exam Malaise Night sweats Skin nodules Shortness of breath Microbiological findings Sputum production Weight loss sputum AFB Respiratory exam Crackles Rhonchi Squeaks Wheezing Serological findings serum anti-GPL-core IgA Imaging findings Nodular bronchiectasis Pulmonary cavity Tree-in-bud pattern References 1. Charles S Haworth, John Banks, Toby Capstick et al. British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease NTM PD . Thorax. 2017 Nov;72 Suppl 2):ii1-ii64. Open 2. Charles L Daley, Jonathan M Iaccarino, Christoph Lange et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Eur Respir J. 2020 Jul 7;56 1 2000535. Open https://web.pathway.md/diseases/rec0woAtEXZLxAJrf 7/8 6/30/23, 1:18 AM Non-tuberculous mycobacterial pulmonary disease Pathway 3. Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Department of Health and Human Services. 2023. Open 4. R Andres Floto, Kenneth N Olivier, Lisa Saiman et al. US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis. Thorax. 2016 Jan;71 Suppl 1 Suppl 1):i1 22. Open 5. Sarah A Longworth, Jennifer S Daly, AST Infectious Diseases Community of Practice. Management of infections due to nontuberculous mycobacteria in solid organ transplant recipients-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33 9):e13588. 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