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Nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing in incidence globally and challenging to manage. The 2020 multisociety treatment guideline and the 2022 consensus recommendations provide comprehensive evidence-based guides to manage pulmonary diseases caused by the most common NTM. However, with >190 different NTM species that may require different multidrug regimens for treatment, the breadth and complexity of NTM-PD remain daunting for both patients and clinicians. In this narrative review, we aim to distill this broad, complex field into principles applicable to most NTM species and highlight important nuances, specifically elaborating on the presentation, diagnosis, principles of patient-centered care, principles of pathogen-directed therapy, and prospects of NTM-PD., Competing Interests: Potential conflicts of interest . S. H. K. reports consulting with AN2 Therapeutics, Insmed, and Paratek Pharmaceuticals; investigator work with Insmed; and speaker work with AN2 Therapeutics, Insmed, and Paratek Pharmaceuticals. J. D. M. reports consulting with Intuitive Surgical. D. E. G. reports advisory board work with Insmed and consulting with AN2 Therapeutics, Insmed, and Paratek Pharmaceuticals. C. L. D. reports grant support from AN2 Therapeutics, Bugworks, Insmed, Juvabis, and Paratek Pharmaceuticals; advisory board work with AN2 Therapeutics, AstraZeneca, Cepheid, Hyfe, Insmed, MannKind, Matinas Biopharma, NobHill, Spero Therapeutics, and Zambon; consulting with Genentech and Pfizer; and data monitoring committee work with Otsuka Pharmaceutical and the Gates Foundation. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Adverse events are frequent in nontuberculous mycobacteria pulmonary disease treatment, but evidence to support their management is scarce. An expert panel survey on management of adverse events shows consistent opinions on management of hepatoxicity, ocular toxicity, ototoxicity, tinnitus, and gastrointestinal upset. These opinions can provide assistance in individual patient management decisions., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Societyof America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: We report the largest clinical experience using tigecycline-containing regimens for salvage treatment of patients with Mycobacterium abscessus and Mycobacterium chelonae., Patients and Methods: Data were collected from 52 patients on emergency/compassionate use (n = 38) or two open-label studies (n = 7 patients each). Based on information that was available, 46 (88.5%) of the subjects received antibiotic therapy prior to treatment with tigecycline. Treatment groups were evaluated based on length of tigecycline therapy (<1 and ≥1 month). ClinicalTrials.gov identifiers: Study 205, NCT00600600 and Study 310, NCT00205816., Results: The most commonly used concomitant antimicrobials were macrolides, amikacin and linezolid. Pulmonary disease was the most common presentation (36/52; 69.2%), and 58.3% of these patients had underlying cystic fibrosis. The majority were M. abscessus complex (n = 30) or M. chelonae/abscessus (n = 4). With therapy ≥1 month (mean, 255.0 ± 265.7 days), 10/15 patients (66.7%) with cystic fibrosis and 16/26 (61.5%) overall were considered improved. Skin/soft-tissue/bone infections were the most common extrapulmonary infections. With therapy ≥1 month (mean, 143 ± 123 days), 9/12 patients (75.0%) were considered improved. Nine of the 16 cases reported as failures regardless of site of infection occurred in patients who stopped treatment due to adverse events. There were eight deaths; none was related to tigecycline., Conclusions: Tigecycline given for ≥1 month as part of a multidrug regimen resulted in improvement in >60% of patients with M. abscessus and M. chelonae infections, including those with underlying cystic fibrosis, despite failure of prior antibiotic therapy. Adverse events were reported in >90% of cases, the most common being nausea and vomiting., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

We initiated a prospective trial of an intermittent clarithromycin-containing regimen for the treatment of patients with Mycobacterium kansasii lung disease. Eighteen patients (10 men and 8 women) with M. kansasii lung disease received a regimen consisting of 500-1000 mg of clarithromycin, 25 mg/kg ethambutol, and 600 mg of rifampin 3 times per week. The primary treatment end point was a 12-month period during which sputum cultures were sterile while the patient was receiving therapy. Four male patients were lost to follow-up, but all of the remaining patients successfully completed therapy without significant drug-related adverse events. The mean time (+/- standard deviation [SD]) to sputum conversion was 1.0+/-0.9 months, and the mean duration (+/-SD) of therapy was 13.4+/-0.9 months. No patient who successfully completed therapy had relapsed after a mean (+/-SD) of 46+/-8.0 months. Clarithromycin- and rifampin-containing regimens offer the possibility of effective short-course and intermittent treatment of M. kansasii lung disease.

The genomic DNA patterns (genotypes) of 55 episodes of late positive sputum isolates, collected after >or=4 consecutive months of negative sputum cultures, in prospective macrolide treatment trials of Mycobacterium avium complex (MAC) lung disease were assessed by pulsed-field gel electrophoresis (PFGE). Having >or=2 cultures positive for MAC after completion of therapy was documented 23 times; of 20 episodes studied by PFGE, 17 (85%) represented new genotypes (i.e., new infections), and 87% occurred in patients with nodular bronchiectasis. With >or=2 positive cultures after therapy was stopped prematurely, 6 (86%) of 7 episodes were relapses. Single positive cultures after completion of therapy occurred 16 times; only 1 (6%) was predictive of a subsequent relapse. No late isolates were macrolide resistant. Thus, relapses of MAC lung disease with these macrolide regimens are unusual, and most infections after completing therapy resulted from new strains in patients with nodular bronchiectasis.