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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.)

Mycobacterium abscessus is an intrinsically drug-resistant, rapidly growing, nontuberculous mycobacterium; extrapulmonary infections have been reported in association with medical tourism (1). During November-December 2022, two Colorado hospitals (hospitals A and B) treated patient A, a Colorado woman aged 30-39 years, for M. abscessus meningitis. In October 2022, she had received intrathecal donor embryonic stem cell injections in Baja California, Mexico to treat multiple sclerosis and subsequently experienced headaches and fevers, consistent with meningitis. Her cerebrospinal fluid revealed neutrophilic pleocytosis and grew M. abscessus in culture at hospital A. Hospital A's physicians consulted hospital B's infectious diseases (ID) physicians to co-manage this patient (2)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Reeti Khare reports uncompensated participation on a Clinical Laboratory Standards Institute Antimycobacterial Working Group and that her laboratory does contract work for Insmed, Inc., RedHill Biopharma, Paratek Pharmaceuticals, AN2 Therapeutics, Spero Therapeutics, and MannKind Corporation. David E. Griffith reports receipt of consulting fees from Insmed, Inc., AN2 Therapeutics, and Paratek Pharmaceuticals; payments or honoraria from Insmed, Inc.; and participation on data safety monitoring boards for NOMAB: Nebulised Nitric Oxide for Mycobacterium abscessus pulmonary disease and MannKind Corporation: Clofzimine inhalation suspension for pulmonary nontuberculous mycobacterial disease. Charles L. Daley reports institutional support from AN2 Therapeutics, Bugworks, Insmed, Inc., Juvabis, Paratek Pharmaceuticals, the Cystic Fibrosis Foundation, the Food and Drug Administration, the Patient-Centered Outcomes Research Institute, and the National Institutes of Health; receipt of consulting fees from Genentech and Pfizer; participation on data safety monitoring boards for Otsuka, the Bill and Melinda Gates Foundation, and Eli Lilly; and participation on advisory boards for AN2 Therapeutics, Astrazeneca, Hyfe, Insmed, Inc., MannKind Corporation, Matinas Biopharma, Nob Hill Therapeutics, Paratek Pharmaceuticals, Spero Therapeutics, and Zambon. Minh-Vu H. Nguyen reports receipt of an honorarium from the Oregon Health and Science University (OHSU) for a presentation at Nontuberculous Mycobacteria Research Consortium (NTMRC) 2023; support for travel to IDWeek 2023 and American Thoracic Society 2023 from National Jewish Health; and support for travel to NTMRC 2023 from OHSU. No other potential conflicts of interest were disclosed.

The diagnosis of nontuberculous mycobacterial (NTM) pulmonary disease is based on three criteria: patient's symptoms, radiographic findings, and microbiologic results. The microbiologic criterion is the most complicated because it requires more than one positive sputum acid-fast bacilli culture. Clinicians are challenged to apply the diagnostic criteria in the context of variable patient symptoms, NTM pathogenicity, and host susceptibility. The decision to treat NTM pulmonary disease entails assessment of the risks and benefits of therapy and the patient's wishes and ability to receive treatment., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Mycobacterium abscessus is the second most common nontuberculous mycobacterium respiratory pathogen and shows in vitro resistance to nearly all oral antimicrobials. M abscessus treatment success is low in the presence of macrolide resistance., Research Question: Does treatment with amikacin liposome inhalation suspension (ALIS) improve culture conversion in patients with M abscessus pulmonary disease who are treatment naive or who have treatment-refractory disease?, Study Design and Methods: In an open-label protocol, patients were given ALIS (590 mg) added to background multidrug therapy for 12 months. The primary outcome was sputum culture conversion defined as three consecutive monthly sputum cultures showing negative results. The secondary end point included development of amikacin resistance., Results: Of 33 patients (36 isolates) who started ALIS with a mean age of 64 years (range, 14-81 years), 24 patients (73%) were female, 10 patients (30%) had cystic fibrosis, and nine patients (27%) had cavitary disease. Three patients (9%) could not be evaluated for the microbiologic end point because of early withdrawal. All pretreatment isolates were amikacin susceptible and only six isolates (17%) were macrolide susceptible. Eleven patients (33%) were given parenteral antibiotics. Twelve patients (40%) received clofazimine with or without azithromycin as companion therapy. Fifteen patients (50%) with evaluable longitudinal microbiologic data demonstrated culture conversion, and 10 patients (67%) sustained conversion through month 12. Six of the 33 patients (18%) demonstrated mutational amikacin resistance. All were patients using clofazimine or clofazimine plus azithromycin as companion medication(s). Few serious adverse events occurred for ALIS users; however, reduction of dosing to three times weekly was common (52%)., Interpretation: In a cohort of patients primarily with macrolide-resistant M abscessus, one-half of the patients using ALIS showed sputum culture conversion to negative findings. The emergence of mutational amikacin resistance was not uncommon and occurred with the use of clofazimine monotherapy., Trial Registry: ClinicalTrials.gov; No.: NCT03038178; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: D. E. G. received support as a consultant from Insmed, Inc., AN2 Therapeutics, and Paratek Pharmaceuticals and received research support from Insmed, Inc. J. V. P. received support as part of advisory boards for Insmed, Inc., AN2 Therapeutics, and Paratek Pharmaceuticals and received research support from Insmed, Inc., AN2 Therapeutics, Paratek Pharmaceuticals, Electromed, Inc., Hillrom, and Zambon. R. J. W. received research support from Insmed, Inc. K. L. W. received support as a consultant from Insmed, Inc., AN2 Therapeutics, Paratek Pharmaceuticals, RedHill Biopharma, Renovion, Inc., and Spero Therapeutics and received research support from Insmed, Inc., AN2 Therapeutics, Paratek Pharmaceuticals, RedHill Biopharma, and Renovion, Inc. None declared (S. A. R. S., B. A. B.-E., A. E. B., P. E. S., C. F., L. S.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Mycobacterium abscessus infections have been reported as adverse events related to medical tourism. We report M. abscessus meningitis in a patient who traveled from Colorado, USA, to Mexico to receive intrathecal stem cell injections as treatment for multiple sclerosis. We also review the management of this challenging central nervous system infection.

The 2020 clinical practice guideline for the treatment of non-tuberculous mycobacterial pulmonary disease (NTM-PD) by the American Thoracic Society, European Respiratory Society, European Society of Clinical Microbiology and Infectious Diseases, and Infectious Diseases Society of America; and the 2017 management guideline by the British Thoracic Society covered pulmonary diseases in adults caused by Mycobacterium avium complex, Mycobacterium kansasii, Mycobacterium xenopi, and Mycobacterium abscessus. In order to provide evidence-based recommendations for the treatment of less common non-tuberculous mycobacterial (NTM) species in adult patients without cystic fibrosis or HIV infection, our expert panel group performed systematic literature searches to provide management guidance for pulmonary diseases caused by seven additional organisms: Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium genavense, Mycobacterium gordonae, Mycobacterium malmoense, Mycobacterium simiae, and Mycobacterium szulgai. Treatment recommendations were developed by a structured consensus process. The evidence from the scientific literature published in English for treatment recommendations for pulmonary diseases caused by other NTM species was of very low quality, with the exception of M malmoense, and based on the evaluation of case reports and case series. For M malmoense, results from two randomised controlled trials and three retrospective cohort studies provided a better evidence base for treatment recommendations, although the evidence was still of low quality., Competing Interests: Declaration of interests CLD reports grants and personal fees from Insmed, Paratek, and Spero; personal fees from AN2 and Matinas, and grants from BugWorks; outside the submitted work. DEB reports grants and personal fees from Insmed. CL is supported by the German Center for Infection Research (DZIF) and reports personal fees from Chiesi, Gilead, Janssen, Novartis, Oxfordimmunotec, and Insmed outside the submitted work. TKM reports grants and personal fees from Insmed; and personal fees from Astra Zeneca, RedHill Biopharma, Novartis, and Spero; outside the submitted work. KNO is supported by the intramural research program of the NHLBI, NIH and reports grants from Beyond Air outside the submitted work. KW reports grants and personal fees from Insmed; and personal fees from Paratek, Red Hill Biopharma, Horizon, and Spero; outside the submitted work. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Mycobacterium abscessus is the second most common nontuberculous mycobacterial lung disease pathogen and comprises three subspecies: abscessus, massiliense, and bolletii. Subspecies identification is critical for disease management, as subspecies abscessus and bolletii have an inducible macrolide resistance gene [erm(41)] that results in clinical macrolide resistance. In contrast, subspecies massiliense does not have an active erm(41) gene and is therefore susceptible in vitro and clinically to macrolide-containing regimens. M abscessus is also vulnerable to acquired mutational macrolide resistance. Macrolide resistance has such a profoundly negative impact on M abscessus treatment response that preserving macrolide susceptibility with adequate companion drugs for macrolides is among the highest treatment priorities. After the macrolides, amikacin is regarded as the next most important drug for M abscessus treatment, although data validating that assertion are lacking. The considerations for preventing acquired macrolide resistance also apply to amikacin. Recent guidelines suggest that treatment should be guided by in vitro susceptibilities but, aside from macrolides and amikacin, no other antibiotics have a validated minimum inhibitory concentration for M abscessus. Currently, phase therapy (intensive and continuation) is recommended for M abscessus. This approach is successful with macrolide-susceptible M abscessus but not with macrolide-resistant M abscessus, in which even more aggressive therapy is not predictably successful. Newer drugs have become available, with encouraging in vitro activity against M abscessus, but in vivo validation of their superiority to current agents is not yet available. In the absence of unequivocally effective regimens, we offer suggestions for managing this treatment-refractory organism., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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.)

The US Food and Drug Administration convened a workshop to discuss clinical trial design challenges and considerations related to the treatment of nontuberculous mycobacterial pulmonary disease, to include topics such as clinical trial end points, duration, and populations. The clinicians participating in the meeting provide here their interpretation of the discussion, which included US Food and Drug Administration and industry representatives. The treatment of nontuberculous mycobacterial pulmonary disease typically includes multiple antibiotics for a prolonged period and can be difficult to tolerate; there is a great need for new treatment options. Most individuals have a microbiologic response to therapy, but data correlating decreasing bacillary load with patient-reported outcomes or measured functional improvement are lacking. Accordingly, trial designs for new therapeutic agents should incorporate both microbiologic and clinical outcome measures and select appropriate study candidates with capacity for measurable change of such outcome measures. The need for shorter study designs, early primary end points, and placebo control arms was highlighted during the workshop., (Copyright © 2020 American College of Chest Physicians. All rights reserved.)

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is an emerging opportunistic infection, but basic epidemiological data are lacking in most regions. We have investigated epidemiology and diagnostic and treatment practices in five EU countries (United Kingdom, Spain, Italy, France, Germany; EU5) and Japan., Study Design: and methods: Annual prevalence in each country was established using a 2-round Delphi method in combination with a regional prevalence-estimation model that incorporated data obtained from a blinded physician screening survey (3154 physicians) and a real-world NTM-PD treating-physician/patient-chart observational study (619 physicians - 1429 patient charts)., Results: The annual prevalence of NTM-PD was estimated at 6.2/100,000 in the EU5 and 24.9/100,000 in Japan. Overall prevalence between the EU5 was comparable, while differences in regional prevalence were found to be pronounced in France and The United Kingdom. Regional differences were also found in Japan, with the majority of cases in Chubu and Kanto regions., Conclusion: This new methodology for obtaining often missing regional-level epidemiological data reveals dramatic variations in NTM-PD annual prevalence and helps pinpoint areas that may merit special preventative and treatment focus., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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.)

Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a challenging infection which is becoming increasingly prevalent, particularly in the elderly, for reasons which are unknown. While underlying lung disease is a well-established risk factor for NTM-PD, it may also occur in apparently healthy individuals. No single common genetic or immunological defect has been identified in this group, and it is likely that multiple pathways contribute towards host susceptibility to NTM-PD which further interact with environmental and microbiological factors leading to the development of disease.The diagnosis of NTM-PD relies on the integration of clinical, radiological and microbiological results. The clinical course of NTM-PD is heterogeneous, with some patients remaining stable without the need for treatment and others developing refractory disease associated with considerable mortality and morbidity. Treatment regimens are based on the identity of the isolated species, drug sensitivity testing (for some agents) and the severity of disease. Multiple antibiotics are typically required for prolonged periods of time and treatment is frequently poorly tolerated. Surgery may be beneficial in selected cases. In some circumstances cure may not be attainable and there is a pressing need for better regimens to treat refractory and drug-resistant NTM-PD.This review summarises current knowledge on the epidemiology, aetiology and diagnosis of NTM-PD and discusses the treatment of two of the most clinically significant species, the M. avium and M. abscessus complexes, with a focus on refractory disease and novel therapies., Competing Interests: Conflict of interest: S. Cowman has nothing to disclose. Conflict of interest: J. van Ingen has nothing to disclose. Conflict of interest: D.E. Griffith reports grants, personal fees for consultancy and non-financial support from Insmed Inc., outside the submitted work. Conflict of interest: M.R. Loebinger reports personal fees for advisory board work and lecturing from Insmed, personal fees for advisory board work from Savara, outside the submitted work., (Copyright ©ERS 2019.)

Nontuberculous mycobacterial (NTM) lung infections are increasingly recognized as a cause of chronic pulmonary disease. This article focuses on the most common NTM species known to cause human lung disease and the treatment options currently available. The diagnosis of NTM lung disease is also discussed, emphasizing the necessity for treating clinicians to have sufficient familiarity of the mycobacteria laboratory to provide optimal patient management., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background/aims: The nontuberculous mycobacterial lung disease (NTM), caused by Mycobacterium avium complex (MAC) is an increasing health problem in the USA and worldwide. The NTM disease is prevalent in Caucasian women with a current diagnosis or history of breast cancer (BCa), posing a significant challenge towards treatment. We hypothesize that NTM affected women with considerable therapeutic resistance may harbor pathogenic microbes other than nontuberculous mycobacterium, aiding in disease progression and therapeutic resistance., Methods: We assessed microbiome diversity in sputa from healthy women, women with nontuberculous mycobacterial lung disease (NTM) and women with both nontuberculous mycobacterial lung disease and breast cancer (NTM-BCa). First, we collected sputa and isolated DNA from sputa of these healthy women and women with NTM and NTM-BCa. We also isolated DNA from sera derived extracellular vesicles from women with NTM-BCa. To identify diverse pathogenic microbes in various groups of subjects, we then performed 16S rDNA sequencing. Data analysis was performed utilizing the analytical pipelines at the Center for Metagenomic and Microbiome Research (CMMR), Baylor College of Medicine., Results: A large community of resident microbes, including bacteria, virus, Archeas and Fungi live in the human body are being increasingly recognized as the key components of human health and disease. We identified a diverse microbiome community in the sputa and the extracellular vesicles dominated by Streptococcus, Haemophillus, Veillonella, Neisseria, Prevotella, Fusobacterium, Bacteroides, Allistipes, Faecalibacterium and Staphylococcus in women with nontuberculous mycobacterial lung disease as well as women with both nontuberculous mycobacterial lung disease and breast cancer. Some of these genera, including Fusobacterium, Bacteroides, and Allistipes have estrobolome activity and associated with breast and other neoplasms., Conclusion: This work confirms the presence of a distinct pathogenic microbiome other than nontuberculous mycobacteria in the sputa and the circulating extracellular vesicles of these patients. This information could be useful for better therapeutic design to treat the NTM patients., Competing Interests: The authors have no competing interests., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

Nontuberculous mycobacterial lung disease (NTM), including Mycobacterium avium complex (MAC), is a growing health problem in North America and worldwide. Little is known about the molecular alterations occurring in the tissue microenvironment during NTM pathogenesis. Utilizing next generation sequencing, we sequenced sputum and matched lymphocyte DNA in 15 MAC patients for a panel of 19 genes known to harbor cancer susceptibility associated mutations. Thirteen of 15 NTM subjects had a diagnosis of breast cancer (BCa) before or after NTM infection. Thirty three percent (4/12) of these NTM-BCa cases exhibited at least 3 somatic mutations in sputa compared to matched lymphocytes. Twenty four somatic mutations were detected with at least one mutation in ATM, ERBB2, BARD1, BRCA1, BRCA2, AR, TP53, PALB2, CASP8, BRIP1, NBN and TGFB1 genes. All four NTM-BCa patients harboring somatic mutations also exhibited 15 germ line BRCA1 and BRCA2 mutations. The two NTM subjects without BCa exhibited twenty somatic mutations spanning BRCA1, BRCA1, BARD1, BRIP1, CHEK2, ERBB2, TP53, ATM, PALB2, TGFB1 and 3 germ line mutations in BRCA1 and BRCA2 genes. A single copy loss of STK11 and AR gene was noted in NTM-BCa subjects. Periodic screening of sputa may aid to develop risk assessment biomarkers for neoplastic diseases in NTM patients.

Background: Non-cystic fibrosis bronchiectasis ("bronchiectasis") is a chronic inflammatory lung disease often associated with nontuberculous mycobacteria (NTM) infection. Very little data exist to guide bronchiectasis management decisions. We sought to describe patterns of inhaled corticosteroid (ICS) and antibiotic therapy in the United States., Methods: We invited 2,000 patients through NTM Info & Research (NTMir) to complete an anonymous electronic survey. We separately queried baseline clinical and laboratory data from the US Bronchiectasis and NTM Research Registry (BRR)., Results: Among 511 NTMir survey responders with bronchiectasis, whose median age was 67 years, 85 (17%) reported asthma and 99 (19%) reported COPD. History of ICS use was reported by 282 (55%), 171 (61%) of whom were treated 1 year or longer, and 150 (53%) were currently taking ICSs. Fewer reported ever taking azithromycin for non-NTM bronchiectasis (203 responders [40%]) or inhaled tobramycin (78 responders [15%]). The median age of 1,912 BRR patients was 69 years; 528 (28%) had asthma and 360 (19%) had COPD. Among 740 patients (42%) without NTM, 314 were taking ICSs at baseline. Among patients without NTM who were taking ICSs, only 178 (57%) had a concurrent diagnosis of COPD or asthma that could explain ICS use. Fewer were taking suppressive macrolides (96 patients [13%]), and of the 70 patients (10%) taking inhaled suppressive antibiotics, 48 (68%) had chronic Pseudomonas aeruginosa infection., Conclusions: ICS use was common in two national samples of patients with bronchiectasis, with relatively few patients taking suppressive antibiotic therapies. Further research is needed to clarify the safety and effectiveness of these therapies in patients with bronchiectasis., (Copyright © 2017 American College of Chest Physicians. All rights reserved.)

Rationale: Lengthy, multidrug, toxic, and low-efficacy regimens limit management of pulmonary nontuberculous mycobacterial disease., Objectives: In this phase II study, we investigated the efficacy and safety of liposomal amikacin for inhalation (LAI) in treatment-refractory pulmonary nontuberculous mycobacterial (Mycobacterium avium complex [MAC] or Mycobacterium abscessus) disease., Methods: During the double-blind phase, patients were randomly assigned to LAI (590 mg) or placebo once daily added to their multidrug regimen for 84 days. Both groups could receive open-label LAI for 84 additional days. The primary endpoint was change from baseline to Day 84 on a semiquantitative mycobacterial growth scale. Other endpoints included sputum conversion, 6-minute-walk distance, and adverse events., Measurements and Main Results: The modified intention-to-treat population included 89 (LAI = 44; placebo = 45) patients. The average age of the sample was 59 years; 88% were female; 92% were white; and 80 and 59 patients completed study drug dosing during the double-blind and open-label phases, respectively. The primary endpoint was not achieved (P = 0.072); however, a greater proportion of the LAI group demonstrated at least one negative sputum culture (14 [32%] of 44 vs. 4 [9%] of 45; P = 0.006) and improvement in 6-minute-walk test (+20.6 m vs. -25.0 m; P = 0.017) at Day 84. A treatment effect was seen predominantly in patients without cystic fibrosis with MAC and was sustained 1 year after LAI. Most adverse events were respiratory, and in some patients it led to drug discontinuation., Conclusions: Although the primary endpoint was not reached, LAI added to a multidrug regimen produced improvements in sputum conversion and 6-minute-walk distance versus placebo with limited systemic toxicity in patients with refractory MAC lung disease. Further research in this area is needed. Clinical trial registered with www.clinicaltrials.gov (NCT01315236).

Background: Bedaquiline is an oral antimycobacterial agent belonging to a new class of drugs called diarylquinolines. It has low equivalent minimal inhibitory concentrations for Mycobacterium tuberculosis and nontuberculous mycobacterial (NTM) lung disease, especially Mycobacterium avium complex (MAC) and Mycobacterium abscessus (Mab). Bedaquiline appears to be effective for the treatment of multidrug-resistant TB but has not been tested clinically for NTM disease., Methods: We describe a case series of off-label use of bedaquiline for treatment failure lung disease caused by MAC or Mab. Only patients whose insurance would pay for the drug were included. Fifteen adult patients were selected, but only 10 (six MAC, four Mab) could obtain bedaquiline. The 10 patients had been treated for 1 to 8 years, and all were on treatment at the start of bedaquiline therapy. Eighty percent had macrolide-resistant isolates (eight of 10). The patients were treated with the same bedaquiline dosage as that used in TB trials and received the best available companion drugs (mean, 5.0 drugs). All patients completed 6 months of therapy and remain on bedaquiline., Results: Common side effects included nausea (60%), arthralgias (40%), and anorexia and subjective fever (30%). No abnormal ECG findings were observed with a mean corrected QT interval lengthening of 2.4 milliseconds at 6 months. After 6 months of therapy, 60% of patients (six of 10) had a microbiologic response, with 50% (five of 10) having one or more negative cultures., Conclusions: This small preliminary report demonstrates potential clinical and microbiologic activity of bedaquiline in patients with advanced MAC or Mab lung disease but the findings require confirmation with larger studies.

The most common nontuberculous mycobacterial (NTM) lung pathogen, Mycobacterium avium complex (MAC), requires antibiotic treatment regimens that are long and often arduous. M kansasii is the slowly growing NTM pathogen with the most predictably successful treatment outcomes, whereas other slowly growing NTM pathogens such as M xeonpi, M szulgai, and M malmoense are less predictably responsive to antibiotic regimens. M simiae is the most difficult of the common slowly growing NTM pathogens to eradicate. Surgical intervention for slowly growing mycobacterial lung infection has proved beneficial for some patients, but the optimal candidates and timing for surgical intervention remain unknown., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Mycobacterium abscessus is a formidable and difficult-to-treat mycobacterial pathogen with multiple drug-resistance mechanisms. The most important of these mechanisms is the presence of an inducible erythromycin methylase (erm) gene, because it confers macrolide resistance. It has recently been found that "M. abscessus" can be split into three species or subspecies based on gene sequence analysis other than the 16S rRNA gene and the presence or absence of a functional erm(41) gene. Several names have been applied to these three organisms, including M. abscessus or M. abscessus subsp. abscessus, Mycobacterium massiliense or M. abscessus subsp. massiliense, and Mycobacterium bolletii or M. abscessus subsp. bolletii. No universally accepted or recognized species or subspecies designations have emerged, and no names have been universally adopted for these organisms. This uncertainty has led to inconsistencies in the medical literature and understandable confusion by clinicians about the appropriate labels for "M. abscessus" isolates. We discuss the complexities involved in mycobacterial species/subspecies identification and taxonomy and suggest possible ways to improve the present state of uncertainty surrounding the labels for "M. abscessus" clinical isolates. We also suggest necessary changes in mycobacterial laboratory processing and reporting procedures for mycobacterial isolates.

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.)

This review will utilize essential questions about nontuberculous mycobacterial (NTM) lung disease to succinctly address important new developments in the pathogenesis, diagnosis and management of NTM lung disease with a focus on practical information and "bottom line" answers. 1) What do I tell my patients who ask, “where did I get this infection” and, “should I take showers”? 2) What is the connection between bronchiectasis and the acquisition of NTM lung infection? 3) What other factors are important in the pathogenesis of NTM lung disease? 4) Why does it seem that am I seeing more new NTM lung disease patients? 5) Why is the diagnosis of NTM lung disease so complicated and does the diagnosis of NTM lung infection obligate specific treatment? 6) Unlike traditional tuberculosis, what is behind the irrelevance of most in vitro susceptibility testing reports for NTM infections? 7) Is there anything new for the management of patients with Mycobacterium avium complex lung disease? How does the radiographic appearance influence treatment? 8) Is there anything new for the management of patients with Mycobacterium abscessus lung disease? 9) What about the management of other NTM respiratory pathogens? 10) Is there a role for the use of macrolide monotherapy for non-cystic fibrosis bronchiectasis?, (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Nontuberculous mycobacterial (NTM) lung diseases present formidable obstacles to successful management, especially when compared with tuberculosis, beginning with diagnosis and extending through treatment. Factors peculiar to NTM disease such as extensive microbial resistance mechanisms and difficult to interpret, even misleading, in vitro drug susceptibility patterns are just two of the multiple and frustrating clinical management challenges. More conventional problems such as drug-drug interactions, medication side-effects, and nonadherence with therapy add further impediments to successful outcomes. In spite of these difficulties, the majority of NTM lung disease patients are still treated successfully. Because the prevalence of NTM is rising, it is increasingly necessary for clinicians to understand those unique aspects of NTM lung disease diagnosis and treatment that differ from tuberculosis and that contribute to limited treatment options., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Over the last 30 years it has become increasingly clear that nontuberculous mycobacterial (NTM) lung infections and bronchiectasis are closely related disorders. Although incontrovertible proof is lacking, there is a growing consensus of opinion that NTM lung disease characterized by nodules and bronchiectasis (nodular/bronchiectatic NTM lung disease) may be a consequence of preexisting bronchiectasis that predisposes to NTM infection and disease. To use published diagnostic guidelines effectively, physicians must become familiar with the disease-causing potential of individual NTM species. Essentially all NTM patients have bronchiectasis, so optimal overall patient management requires successful therapeutic strategies for both NTM infection and bronchiectasis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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 rapidly growing mycobacteria (RGM) differ from slow-growing mycobacteria such as Mycobacterium tuberculosis by virtue of their more rapid growth in culture media and their in vitro resistance to standard antituberculosis drugs. The RGM can produce numerous infections including chronic lung disease. The most common causes of pulmonary disease are Mycobacterium abscessus and Mycobacterium fortuitum. This article reviews the management of patients with lung disease caused by RGM.

Mycobacterium kansasii presents clinically in a manner most resembling tuberculosis. Diagnosis is usually not difficult; however, the significance of M kansasii isolates from some patients may be hard to determine. Usually, the presence of even one respiratory culture positive for M kansasii is sufficient to make a diagnosis, though few patients can have single respiratory culture positive for M kansasii without evidence of active disease. If not started on medication, these patients must be followed closely. Effective treatment can usually be accomplished with a rifampin-based regimen, or a rifabutin-based regimen for HIV-seropositive patients receiving antiretroviral therapy. Short course and intermittent regimens for treating M kansaii disease show promise but are not yet recommended for routine use.