Current Perspectives in the Diagnosis and Treatment of Nontuberculous Mycobacterial Pulmonary Disease

European Respiratory & Pulmonary Diseases, 2016;2(2):54–7 DOI: http://doi.org/10.17925/ERPD.2016.02.02.54

Abstract:

Nontuberculous mycobacteria (NTM), an extremely diverse group with a wide spectrum of virulence, appear to be rising in prevalence. This may be due to both increased awareness and improved diagnosis, among other factors. Most NTM-pulmonary disease (NTM-PD) infections are caused by the slow growing Mycobacterium avium complex (MAC) however, other species can also cause pulmonary disease including M. abscessus, M. xenopi, M. malmoense and M. kansasii. Symptoms of NTM-PD vary considerably and may include chronic cough, with or without sputum production or haemoptysis. Treatment options are limited at present and associated with significant intolerance, treatment failures and drug–drug interactions. Further prospective studies are needed to define suitable drug regimens for different NTM species and to improve knowledge of the natural history and epidemiology of NTM-PD.

Keywords: Nontuberculous mycobacteria (NTM), Mycobacterium avium complex (MAC), Mycobacterium avium, Mycobacterium intracellulare, epidemiology, diagnosis, treatment
Disclosure: Michael R Loebinger has received consultancy fees from Insmed, but this has not impacted on the article. Tobias Welte has received consultancy fees from Insmed, but this has not impacted on the article.
Acknowledgments: Medical writing assistance was provided by Catherine Amey at Touch Medical Media, London and funded by Insmed.
Received: June 09, 2016 Accepted July 25, 2016
Correspondence: Michael R Loebinger, Respiratory Medicine, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK. E: M.Loebinger@rbht.nhs.uk
Support: The publication of this article was supported by Insmed. The views and opinions expressed are those of the authors and not necessarily those of Insmed.
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit.

Nontuberculous mycobacteria (NTM) are a diverse group of bacteria with a wide spectrum of virulence.1 They are a microaerobic, non-motile organisms that have a lipid-rich, hydrophobic cell wall that is substantially thicker compared with most other bacteria.2 NTM are associated with biofilm formation, which contributes to disinfectant- and antibiotic-resistance.3–5 Many of these organisms are also resistant to high temperature and low pH.6–8 Ubiquitous in the environment, NTM are found with the greatest concentrations in water sources, both natural and treated, and in soil sources.9 There are currently over 170 species of mycobacteria and more are likely to be discovered in the future owing to improved culturing techniques and molecular technology advances.10

The majority of NTM-pulmonary disease (NTM-PD) infections are caused by the slow growing Mycobacterium avium complex (MAC) that includes Mycobacterium avium and Mycobacterium intracellulare, although other species including M. abscessus, M. xenopi, M. malmoense and M. kansasii can also cause lung disease. Not all NTM are considered pathogenic, with species such as Mycobacterium gordonae commonly isolated but not usually associated with the development of NTM-PD and a wide variability reported in the clinical relevance of species.12 Co-infection with different NTM strains or other bacteria has also been reported.9,13 NTM lung disease is characterised by clinical, microbiological and radiological criteria.1 High resolution computed tomography (CT) scanning may consist of a variety of disease patterns including nodular/bronchiectatic disease, fibrocavitary disease, solitary pulmonary nodule, disseminated disease, and hypersensitivity-like disease.1 Acquisition of NTM is believed to be from the environment; however, emerging literature, using sequencing of NTM isolates, suggest that indirect cross infection of M. abscessus is possible in patients with cystic fibrosis.14 This has led to changes in infection control standards in these patient groups.15,16

NTM are treated with antimicrobial chemotherapy, however treatment response is often poor, and side effects significant. Deciding which mycobacteria and patients to treat, and when, and the assessment of response to treatment is very difficult. The purpose of this review is to provide a succinct summary of issues surrounding the epidemiology, diagnosis and treatment of NTM-PD.

Epidemiology
In contrast to tuberculosis, NTM isolation in pulmonary specimens does not necessarily equate with active pulmonary disease, thus the incidence and prevalence of NTM pulmonary infections is difficult to characterise accurately.9 In addition, unlike tuberculosis, isolating NTM does not constitute a reportable condition in many countries. Population-based data for prevalence are available mainly from the US, Europe, New Zealand and Australia (where NTM isolation is reportable).17 These estimates are based on a mixture of microbiology laboratory reports, medical insurance returns and surveys. Annual prevalence estimates in North America and Australia range from 3.2 to 9.8 per 100,000.17 In Europe the estimates are generally lower, up to 3.3/100,000.17,18 The prevalence is significantly higher in certain regions and patient groups and period prevalence has been put at over 100/100,000 in the over 65-year-olds in the US over an 11-year period.19 The incidence of NTM disease is increasing throughout the world,11,17 with some estimates of an increase of 8.2% per year19 NTM-PD is currently more common in the US than tuberculosis.20 Improvements in awareness and diagnosis may in part underlie this rise.

In addition to the difference in prevalence, the predominant NTM species has also been reported to differ substantially by geographical region.21 To obtain information of NTM species distribution, in an NTM-Network European Trials Group (NET) collaborative study, species identification data for 20,182 patients, from 62 laboratories in 30 countries across six continents was collected.22 In total, 91 different species were isolated; M. avium complex predominated in most areas, although M. Kansaii predominated in Poland and Slovakia and M. Xenopi predominated in Hungary. MAC was most frequently isolated in Japan, Australia and South Africa.19,23–25

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Keywords: Nontuberculous mycobacteria (NTM), Mycobacterium avium complex (MAC), Mycobacterium avium, Mycobacterium intracellulare, epidemiology, diagnosis, treatment