Non-Tuberculous Mycobacteria (NTM)

Definition

Non-tuberculous mycobacteria (NTM) are environmental mycobacteria — a large family of organisms living in soil, natural water and domestic plumbing, quite separate from the organism that causes tuberculosis. Breathing them in is common and almost always harmless. NTM lung disease develops only where the lung’s structure or defences are altered, and is defined by the combination of symptoms, characteristic imaging and repeated isolation of the same organism — not by a single positive culture. Mycobacterium avium complex (MAC) is the commonest cause. NTM is not passed from person to person.

Pathophysiology

Establishing infection

NTM are inhaled as fine aerosol droplets from water and soil. In a susceptible airway they evade mucociliary clearance and resist destruction by alveolar macrophages, surviving intracellularly and establishing chronic, low-grade infection rather than the acute pneumonia typical of most bacteria.

The granulomatous response

Once established, NTM provoke a granulomatous inflammatory response similar to tuberculosis, producing nodules, tree-in-bud change, progressive bronchiectasis and, in more aggressive disease, cavitation. Because the organism divides slowly, tissue damage accumulates over months to years rather than days — which is precisely why NTM is so often mistaken for a gradual decline in the underlying lung condition rather than a distinct new infection.

The vicious cycle

NTM both requires and worsens airway damage. Bronchiectasis impairs clearance, allowing NTM to establish; NTM inflammation destroys more airway wall, worsening the bronchiectasis; and the resulting increase in retained secretions favours further colonisation. Breaking that cycle — with clearance as much as antibiotics — is the therapeutic principle.

Co-morbidities

NTM disease rarely occurs in a structurally normal lung. It is closely linked to bronchiectasis, COPD and emphysema, cystic fibrosis and previous tuberculosis, each of which both predisposes to NTM and is worsened by it. Gastro-oesophageal reflux with silent aspiration is a recognised contributor, particularly in nodular–bronchiectatic disease. Immunosuppression — long-term corticosteroids, biologic therapy, particularly tumour necrosis factor inhibitors — raises risk substantially. A distinctive body morphotype is well described: patients with NTM lung disease are more likely to be tall and slender with low body mass index, scoliosis, pectus excavatum and mitral valve prolapse, with associated immune differences, suggesting a constitutional predisposition rather than chance.¹

Prevalence

NTM lung disease is becoming more common worldwide, particularly among older adults and people with pre-existing bronchiectasis or COPD, reflecting both a genuine rise in incidence and more sensitive detection. Prevalence varies markedly by region and climate, with warmer, humid areas reporting higher rates because the organisms thrive in warm soil and water. Among people with bronchiectasis, NTM can be isolated from sputum in a significant minority, though only some of those represent true disease requiring treatment rather than transient or incidental carriage.

Causes and risk factors

NTM disease is not acquired from another person but from environmental reservoirs entering an already-vulnerable airway. Showerheads, taps, hot-water systems, rainwater tanks, spa pools, humidifiers and potting mix are all established sources, and the organisms form biofilm within domestic plumbing that resists standard disinfection.²

• Structural lung disease — bronchiectasis, COPD, cystic fibrosis, prior tuberculosis, prior chest surgery.
• Reflux and aspiration, particularly in nodular–bronchiectatic disease.
• Immunosuppression — corticosteroids, biologics, transplantation, HIV.
• Low body mass index and the associated body morphotype.
• Age — incidence rises steadily beyond 60.
• Environmental exposure to aerosolised water and to soil or potting mix.

Mycobacterium avium complex

The two disease patterns

MAC is the most common cause of NTM lung disease and follows one of two patterns. Nodular–bronchiectatic disease is the more common: small nodules and bronchiectasis, classically in the middle lobe and lingula, seen most often in slighter-built older women — a picture historically called Lady Windermere syndrome. Fibrocavitary disease is more aggressive, with upper-lobe cavities, more typical of people with pre-existing COPD or emphysema, and progresses considerably faster if untreated.

Other species

M. abscessus is far harder to treat, with extensive intrinsic drug resistance, and is of particular concern in cystic fibrosis where it can affect transplant candidacy. M. kansasii behaves more like tuberculosis and responds better to treatment. Species identification is therefore not academic — it determines the regimen, the duration and the prognosis.

Reducing your exposure

Everyday exposure cannot be eliminated, but the load can be reduced: run hot taps and showerheads for a minute before use, keep hot-water systems at a high temperature, clean and thoroughly dry nebuliser equipment after every use, avoid prolonged breathing of aerosolised water in enclosed spaces such as spa pools, and wear a mask and gloves when handling potting mix or garden soil.

Symptoms

An insidious presentation

NTM lung disease is slow and easy to miss. Common features are a persistent cough, increased sputum, fatigue, low-grade fevers or night sweats, and gradual weight loss. Because these overlap entirely with the underlying lung condition, NTM is usually found when someone is simply not doing as well as expected.

The clue that should prompt testing

Unexplained decline — more sputum, more fatigue, falling weight, more frequent exacerbations — in someone with bronchiectasis or COPD whose treatment has not changed. The threshold for sending mycobacterial cultures should be low, because the alternative is months of attributing decline to the underlying disease.

Warning signs

Diagnosis

Why diagnosis matters

Diagnosis distinguishes true NTM disease, which warrants a long and demanding course of treatment, from harmless carriage, which does not. Getting it wrong in either direction is costly: unnecessary treatment exposes patients to months of toxic antibiotics, while missed disease allows progressive, irreversible lung destruction.

How is it diagnosed?

Diagnosis requires all three of the following, per international guidelines: compatible symptoms; characteristic imaging; and microbiological confirmation — the same species grown from at least two separate sputum samples, or from a single bronchoscopic or biopsy specimen.³ Meeting the criteria does not automatically mean treatment is required; that is a separate decision.

Radiology

CT is the imaging test of choice. Nodular–bronchiectatic disease shows bronchiectasis with clustered small nodules and tree-in-bud change, characteristically in the middle lobe and lingula. Fibrocavitary disease shows upper-lobe cavities with surrounding consolidation and pleural thickening. Serial imaging tracks progression and is often what tips the balance towards treating.

Microbiology

Mycobacterial culture requires specific media and takes several weeks, and must be requested explicitly — a routine sputum culture will not detect NTM. Species identification and drug susceptibility testing follow, and both matter: macrolide susceptibility in MAC and M. abscessus is the single strongest predictor of treatment success.

Investigations for related conditions

Assessment covers the underlying structural disease with CT and lung function, reflux and swallowing, nutritional state and body mass index, immune function where disease is unusually aggressive or disseminated, and CFTR testing in adults with otherwise unexplained bronchiectasis and NTM.

Management

Management and goals

The goals are to decide correctly whether to treat, to achieve sustained culture conversion where treatment is given, to preserve lung function and weight, and to manage the underlying condition that allowed the infection in the first place. Not treating is a legitimate and often correct decision.

Watchful waiting

Many patients with nodular–bronchiectatic MAC and mild symptoms are monitored rather than treated, with serial imaging, weight and cultures. Given that treatment involves three antibiotics for well over a year with substantial toxicity, the decision to start is made jointly with the patient and is revisited rather than assumed.

Antibiotic therapy

When treatment is indicated it is a multi-drug regimen, typically three agents, continued for at least 12 months beyond culture conversion — usually 15 to 18 months in total. Monotherapy must be avoided absolutely, as it rapidly generates macrolide resistance and forfeits the most important drug in the regimen.

Airway clearance and the underlying disease

Regular airway clearance and optimised treatment of the underlying bronchiectasis or COPD are core components rather than adjuncts. In many patients clearance and nutrition do more for symptoms than the antibiotics do.

Nutrition

Low body mass index is both a risk factor and a consequence, and weight loss during treatment predicts poorer outcomes. Dietetic input, energy- and protein-dense intake and monitored weight are part of the treatment plan.

Cystic fibrosis and special groups

NTM in cystic fibrosis requires specific management, including screening, infection-control precautions to prevent person-to-person transmission of M. abscessus between people with CF, and consideration of transplant candidacy — set out in joint US and European consensus recommendations.⁴

Surgery and identifying deterioration

Surgical resection is considered for localised, refractory or cavitary disease in fit patients. Failure to convert cultures by six months, radiological progression, continued weight loss or new haemoptysis all indicate the need to reassess the regimen, check adherence and susceptibility, and consider surgical referral.

Medications

Medications for NTM lung disease

For macrolide-susceptible MAC, the standard regimen is a macrolide — azithromycin or clarithromycin — with ethambutol and a rifamycin, given daily in cavitary or severe disease and three times weekly in milder nodular–bronchiectatic disease. Macrolide-containing regimens for nodular–bronchiectatic MAC achieve culture conversion in the majority of patients, with intermittent therapy well tolerated.⁵ An injectable aminoglycoside is added in extensive or cavitary disease.

Refractory disease

Amikacin liposome inhalation suspension added to guideline-based therapy achieved significantly higher culture conversion by month six than guideline therapy alone in treatment-refractory MAC lung disease, and is now an established option in that setting.⁶

Correct use of medications

The regimen is long, the tablet burden is heavy and side effects are common — gastrointestinal upset, hepatotoxicity, ethambutol-related optic neuritis requiring baseline and periodic vision and colour testing, aminoglycoside ototoxicity and nephrotoxicity requiring audiometry and renal monitoring, and extensive rifamycin drug interactions. Monotherapy is never acceptable, and a patient who stops two of three drugs because of side effects should stop all three and be reviewed rather than continue on one.

Multi-system manifestations

Disseminated disease

In profound immunosuppression, particularly advanced HIV, NTM can disseminate to blood, bone marrow, liver and spleen, causing fever, weight loss, anaemia and hepatosplenomegaly. This is a different clinical entity from NTM lung disease and is managed accordingly.

Lymphadenitis

Cervical lymphadenitis in young children, usually caused by MAC, presenting as a painless enlarging neck node that may discharge. Surgical excision is generally preferred to prolonged antibiotics.

Skin, soft tissue and bone

Rapidly growing mycobacteria including M. abscessus, M. fortuitum and M. marinum cause post-surgical, post-injection, tattoo-associated and aquarium-associated infections, and occasionally osteomyelitis. These are frequently missed because routine wound cultures do not detect them.

Systemic effects of chronic infection

Weight loss, sarcopenia, fatigue and reduced exercise capacity are prominent and often more disabling than the respiratory symptoms themselves — and are the part of the illness most responsive to physiotherapy and dietetics.

Treatment-related multi-system toxicity

Not a manifestation of the infection but a genuine multi-system burden: ocular toxicity from ethambutol, vestibular and cochlear toxicity from aminoglycosides, hepatotoxicity, gastrointestinal intolerance and the psychological toll of a multi-year treatment course.

Living with NTM lung disease

A long treatment course

Eighteen months of three antibiotics, with side effects, monitoring appointments and slow progress, is genuinely hard. Patients need to know at the outset how long it will be and what the milestones are, or adherence fails around month four when they feel better but the cultures are still positive.

Daily airway clearance

Clearance continues throughout treatment and usually indefinitely afterwards, since the underlying bronchiectasis persists. A routine that fits the day, timed around bronchodilators, is what gets done.

Nutrition and weight

Maintaining weight is a treatment goal, not a lifestyle matter. Low body mass index predicts progression and poorer conversion, and appetite is suppressed by both the infection and the antibiotics. Regular weighing and early dietetic input are worthwhile.

Reducing environmental exposure

The showerhead, hot water system, nebuliser hygiene and potting-mix precautions described above. These are practical and worth doing, though it should be said honestly that exposure reduction has not been shown to prevent recurrence.

Exercise and staying active

Fatigue and weight loss push people towards rest, which accelerates deconditioning and sarcopenia. Regular exercise maintains capacity, aids sputum clearance and supports appetite.

Mood and support

A chronic infection with a slow course, an arduous treatment and an uncertain outcome carries a real psychological burden, compounded by the isolation of having a condition few people have heard of. Anxiety and low mood are common and worth asking about.

Prognosis

The outlook varies considerably with the disease pattern, the species and the underlying lung condition. Many people with nodular–bronchiectatic MAC remain stable for years without treatment, and a majority of those treated achieve culture conversion — though recurrence, from either relapse or reinfection, occurs in a substantial minority. Fibrocavitary disease progresses faster and carries a worse prognosis, as does M. abscessus infection, where cure rates are considerably lower. Progression is predicted by cavitation, low body mass index, hypoalbuminaemia, older age, and the presence of systemic symptoms — which is why weight and nutrition are monitored as closely as cultures.⁷

Infection prevention and control

NTM were long assumed to be acquired only from the environment, and for most people that remains true. Whole-genome sequencing changed the picture for M. abscessus specifically: dense clusters of near-identical isolates were found across cystic fibrosis centres and between countries, a pattern that environmental acquisition alone does not explain.⁸ The inference is indirect person-to-person transmission — via contaminated surfaces, equipment and airborne droplet nuclei — rather than direct contact.

The UK Cystic Fibrosis Trust convened a working group on this specific question, and its recommendations remain the clearest statement of the resulting practice.⁹

In cystic fibrosis services

• Surveillance culture for mycobacteria at least annually, and whenever there is unexplained clinical or radiological decline — NTM is found by looking for it, since a routine sputum culture will not report it.⁴
• Segregation of patients with M. abscessus, in line with the wider rule that people with CF are not brought into contact with one another — the same principle applied to Pseudomonas aeruginosa and, most strictly of all, to Burkholderia cepacia complex.
• Aerosol-generating procedures — nebulisation, airway clearance with productive coughing, spirometry and sputum induction — are the highest-risk activities. They should be performed in a single room, ideally with negative pressure or dedicated ventilation, with an appropriate room rest period before the space is reused.
• FFP3/P2 respiratory protection for staff during aerosol-generating procedures in a patient known to be infected.
• Terminal cleaning of the room and full decontamination or single-use handling of all equipment afterwards.

Environmental exposure, and what to tell patients

NTM are ubiquitous in soil and in water systems, including domestic plumbing, showerheads, hot tubs and garden hoses, where they persist in biofilm and tolerate chlorination. Complete avoidance is neither possible nor a reasonable goal, and advice framed that way causes anxiety without reducing risk. Sensible, proportionate measures — letting a shower run before entering a rarely used bathroom, avoiding spa pools, using gloves and damp compost when gardening — are the reasonable limit of what can be said.

Role of the physiotherapist

In a disease driven by impaired clearance and worsened by retained secretions, physiotherapy is a core treatment rather than an adjunct. Regular airway clearance reduces sputum burden and symptoms and supports the antibiotic regimen, following the same principles as in bronchiectasis — individualised technique selection, adequate time, humidification and hydration, and regular review of technique rather than one-off instruction.¹⁰ Long-term airway clearance in bronchiectasis improves sputum clearance and health-related quality of life,¹¹ and NTM patients frequently need more of it, not less, during treatment.

Exercise training is the second pillar. In non-cystic-fibrosis bronchiectasis, exercise training improves exercise capacity and quality of life and reduces exacerbation frequency, with benefits persisting after the programme ends.¹² Given that sarcopenia, low body mass index and fatigue dominate the functional picture in NTM, resistance training alongside aerobic work is particularly important, and is delivered in coordination with dietetic input since exercise without adequate protein intake will not build muscle.

Physiotherapists also contribute practical education that is genuinely specific to this condition — nebuliser cleaning and drying, showerhead and water-system precautions, potting-mix handling — and, because they see these patients repeatedly across a long treatment course, are often the first to notice the weight loss, rising sputum volume or falling exercise tolerance that signals progression or treatment failure.

Part 1 · References

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2. Falkinham JO 3rd. Environmental sources of nontuberculous mycobacteria. Clin Chest Med 2015;36(1):35–41.
3. Daley CL, Iaccarino JM, Lange C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Clin Infect Dis 2020;71(4):e1–e36.
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8. Bryant JM, Grogono DM, Rodriguez-Rincon D, et al. Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium. Science 2016;354(6313):751–757.
9. UK Cystic Fibrosis Trust Mycobacterium abscessus Infection Control Working Group. Mycobacterium abscessus: recommendations for infection prevention and control. Bromley: Cystic Fibrosis Trust; November 2017.
10. Hill AT, Sullivan AL, Chalmers JD, et al. British Thoracic Society guideline for bronchiectasis in adults. Thorax 2019;74(Suppl 1):1–69.
11. Muñoz G, de Gracia J, Buxó M, Alvarez A, Vendrell M. Long-term benefits of airway clearance in bronchiectasis: a randomised placebo-controlled trial. Eur Respir J 2018;51(1):1701926.
12. Lee AL, Hill CJ, Cecins N, et al. The short and long term effects of exercise training in people with non-cystic fibrosis bronchiectasis: a randomised controlled trial. Respir Res 2014;15:44.

References are numbered in citation order (Vancouver/BMJ style) and were current at the time of writing. Guidelines are living documents — verify against the latest version before clinical use.