Non-tuberculous mycobacterial infection

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Non-tuberculous mycobacteria live in water, soil and engineered environments, so recovery from a non-sterile site has variable meaning. The central diagnostic task is attribution: does this species, recovered with this burden and repetition, explain the patient's radiology and symptoms better than bronchiectasis, bacterial exacerbation, aspergillosis, malignancy or tuberculosis?

The infectious-disease scope extends beyond lung. Advanced untreated HIV may present with fever, weight loss, cytopenia and disseminated MAC; rapidly growing mycobacteria can infect injections, wounds and devices; M marinum follows aquarium or water exposure. These syndromes use different specimens, source-control decisions and regimens from pulmonary MAC.

Treatment is deliberately specialist because multiple drugs must remain active together while toxicity is monitored over months. A culture-conversion date, macrolide and amikacin susceptibility, renal and hepatic function, vision, hearing, ECG and interaction review are operational parts of the regimen. Observation is equally active when chosen: it needs an owner, interval and objective threshold to reconsider treatment.

Key points

An acid-fast smear is not a species result. Use M tuberculosis molecular testing and culture before relaxing infection control or applying an NTM label.
For pulmonary disease, combine symptoms, characteristic CT and reproducible microbiology; one low-burden sputum isolate can be contamination or transient carriage.
Two separate sputum cultures growing the same species strengthen pulmonary causality; one positive bronchoscopic sample or compatible biopsy can satisfy the microbiological component in the right syndrome.
Species and subspecies change both pathogenicity and treatment: MAC, M kansasii, M xenopi, M malmoense and M abscessus cannot share one generic regimen.
NTM can also cause disseminated MAC in advanced HIV, catheter or surgical-site infection, skin and soft-tissue disease after procedures, and M marinum infection after aquatic exposure.
Do not give macrolide monotherapy for active MAC disease or before excluding NTM in someone considered for long-term bronchiectasis macrolide prophylaxis; resistance can remove the pivotal drug.
Stable non-cavitary pulmonary disease may be observed with defined culture, symptom and imaging triggers, whereas smear positivity, cavities, systemic illness or objective progression favours treatment.
Pulmonary MAC therapy usually continues for at least 12 months after culture conversion; disseminated MAC duration also depends on clinical response, ART success and immune recovery.
Routine person-to-person spread is unusual, but cystic-fibrosis services use additional cross-infection policies and healthcare-associated clusters may require infection-prevention investigation.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Environmental acquisition

Water, soil and aerosols repeatedly expose airways and skin to NTM; ordinary clinical disease usually reflects environmental acquisition rather than routine person-to-person spread.

Damaged pulmonary clearance

Bronchiectasis, COPD, cystic fibrosis, prior TB and fibrotic lung disease retain organisms and permit chronic airway and parenchymal infection.

Cellular immune failure

Advanced HIV and selected cytokine-pathway defects weaken macrophage control, allowing MAC and other species to disseminate through blood and reticuloendothelial organs.

Procedure and device inoculation

Injections, surgery, contaminated products, water exposure and foreign material can introduce rapidly growing mycobacteria into skin, soft tissue or device biofilm.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Macrophage persistence
NTM resist intracellular killing and survive within macrophages, producing granulomatous inflammation when host clearance or local anatomy is impaired.
2
Airway structural cycle
Chronic infection drives neutrophilic inflammation, mucus retention and bronchial damage, which further reduces clearance and permits greater organism burden.
3
Cavitary destruction
Progressive parenchymal inflammation and necrosis form cavities with high microbial burden, haemoptysis risk and declining gas-exchange reserve.
4
Bloodstream dissemination
Profound cellular immune deficiency permits organisms to spread through blood to marrow, liver, spleen, lymph nodes, skin and other organs.
5
Foreign-body biofilm
Rapidly growing species adhere to catheters and implanted material, where biofilm lowers antibiotic effectiveness until the source is removed or exchanged.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Nodular bronchiectatic pulmonary disease

Chronic sputum, cough, fatigue and recurrent exacerbations accompany multifocal bronchiectasis, small nodules and tree-in-bud change, often with slow progression.

Fibrocavitary pulmonary diseaseRed flag

Upper-lobe cavities, pleural thickening, haemoptysis and weight loss resemble tuberculosis or chronic fungal disease and usually justify faster specialist assessment.

Disseminated MAC in advanced HIVRed flag

Persistent fever, night sweats, weight loss, anaemia or pancytopenia, lymphadenopathy, hepatosplenomegaly and raised alkaline phosphatase suggest bloodstream and reticuloendothelial infection.

Rapidly growing mycobacterial focusRed flag

Indolent draining nodules, wound inflammation, catheter infection or postoperative collections after injection, surgery or cosmetic procedure may yield M abscessus, M chelonae or M fortuitum complex.

Aquatic skin infection

A slowly ascending nodular skin or tendon-sheath process after aquarium, fish or water exposure suggests M marinum and requires deep tissue rather than a surface swab.

Low-significance isolate

A single poorly collected sputum culture without compatible symptoms or CT has little weight; species such as M gordonae are often less pathogenic than M kansasii.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Serial sputum smear and mycobacterial cultureFirst step
Why
Demonstrate reproducible pulmonary isolation and quantify organism burden before treatment.
Interpretation and limitations
Collect at least two good-quality samples on different days and request species-level identification. Smear positivity indicates burden but cannot distinguish tuberculosis from NTM.
02
M tuberculosis molecular exclusion
Why
Resolve the immediate infection-control and public-health branch when acid-fast bacilli or cavitation is present.
Interpretation and limitations
A negative respiratory NAAT lowers probability but does not always exclude paucibacillary TB; integrate epidemiology, sample quality and culture with the TB service.
03
High-resolution CT chest
Why
Define nodular bronchiectatic, fibrocavitary, consolidative or disseminated pulmonary patterns and measure progression.
Interpretation and limitations
The appearances support but do not prove NTM. Compare earlier scans and investigate a focal obstructing mass, fungal cavity or embolic pattern separately.
04
Species, subspecies and resistance testing
Why
Identify clinically meaningful macrolide, amikacin and inducible-resistance information for regimen design.
Interpretation and limitations
Reference-laboratory methods and breakpoints are organism specific. M abscessus subspecies and erm-mediated inducible resistance can change whether a macrolide is counted as active.
05
Mycobacterial blood culture and HIV assessment
Why
Investigate disseminated MAC and define the immune state that controls treatment duration.
Interpretation and limitations
Use dedicated blood-culture methods when disseminated disease is suspected. Confirm ART, viral load and CD4 count; ordinary sputum criteria do not diagnose bloodstream MAC.
06
Deep tissue, device or sterile-fluid culture
Why
Diagnose cutaneous, surgical, catheter, bone or other focal NTM and preserve susceptibility yield.
Interpretation and limitations
Send fresh tissue or aspirate for mycobacterial culture and separate histology; tell the laboratory the suspected NTM because incubation temperature and processing may differ.
07
Baseline toxicity and interaction profile
Why
Determine whether a prolonged multidrug regimen can be delivered safely.
Interpretation and limitations
Record weight, FBC, renal and liver tests, visual acuity and colour discrimination, audiology, ECG for QT-active combinations, pregnancy and every interacting medicine.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Pulmonary tuberculosis

Cavities, weight loss and acid-fast smears overlap; M tuberculosis molecular testing, culture identification and epidemiology determine infection-control and statutory action.

Bronchiectasis exacerbation

Ordinary bacteria can cause acute sputum and symptom change despite stable NTM burden, so routine cultures and trajectory remain important.

Chronic pulmonary aspergillosis

Fungal colonisation or invasive cavity disease can coexist with NTM; pleural thickening, fungal markers and imaging progression guide parallel investigation.

Malignancy or inflammatory disease

A focal enlarging lesion, nodes or constitutional decline may require tissue because cancer, sarcoidosis and vasculitis can mimic or accompany NTM.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Acid-fast resultExclude the transmissible diagnosis firstFirst stepA respiratory smear or culture reports acid-fast mycobacteria before species is known.

1Review TB epidemiology, symptoms and imaging and maintain the local airborne pathway when pulmonary TB remains plausible.
2DefinitiveRequest rapid M tuberculosis complex testing and retain cultures for definitive species and susceptibility rather than assuming the smear is TB or NTM.
3Communicate the provisional uncertainty to the patient and infection-prevention team and assign ownership of every pending result.

02Pulmonary attributionSeparate disease from environmental recoveryAn NTM is isolated from sputum, lavage or lung tissue.

1Match species and repeated microbiology to symptoms, high-resolution CT and competing diagnoses in an NTM-experienced multidisciplinary review.
2If disease is mild and non-progressive, optimise airway clearance, nutrition, reflux or aspiration and structural-lung care with scheduled cultures and reassessment.
3Move toward treatment for cavities, smear positivity, significant symptoms, repeated high-burden cultures or objective radiological or functional decline, after shared discussion of benefit and toxicity.

03Pulmonary MAC treatmentProtect the macrolide with companion drugsMacrolide-susceptible MAC pulmonary disease is progressive or sufficiently burdensome to treat.

1For non-severe smear-negative non-cavitary disease, an expert service may select three-times-weekly rifampicin, ethambutol and macrolide therapy.
2For smear-positive, cavitary or severe disease, use daily rifampicin, ethambutol and azithromycin or clarithromycin and consider early intravenous or nebulised amikacin.
3Obtain serial cultures, define conversion with the service and continue treatment for at least 12 months beyond conversion while monitoring organ toxicity and interactions.

04Disseminated MACCombine antimycobacterial therapy with immune recoveryAdvanced HIV or another profound cellular immune defect accompanies systemic MAC disease.

1Obtain dedicated blood and site cultures, macrolide susceptibility and complete HIV staging while excluding active tuberculosis before any rifamycin monotherapy exposure.
2Use a macrolide plus ethambutol with rifabutin or rifampicin through an HIV-mycobacterial team, selecting the rifamycin around antiretroviral interactions and burden.
3Start or optimise effective ART and treat for at least 12 months; BHIVA discontinuation requires clinical improvement, culture conversion, suppressed viral load and CD4 above 100 cells/mm3 for at least 6 months.

05Focal or device diseaseGet deep material and control the sourceNTM involves skin, a wound, line, injected material, bone or another local compartment.

1Obtain deep aspirate or tissue for species and susceptibility and investigate procedure, water or product exposures that could link additional cases.
2Remove infected foreign material or drain collections when feasible because biofilm and devitalised tissue can defeat otherwise active drugs.
3Build a species-specific combination with mycobacterial expertise; M abscessus and other rapidly growing species require inducible-resistance interpretation and must not inherit a pulmonary-MAC regimen.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Core multidrug treatment for smear-positive, cavitary or otherwise severe macrolide-susceptible pulmonary MAC disease.

Daily triple regimen for severe macrolide-susceptible pulmonary MAC

Give rifampicin 600 mg daily, ethambutol 15 mg/kg daily and azithromycin 250 mg daily or clarithromycin 500 mg twice daily.

Never omit active companions or use macrolide monotherapy. Check rifampicin induction, clarithromycin CYP3A4 interactions, QTc, liver tests, renal-adjusted ethambutol exposure and baseline and serial visual function; azithromycin is often simpler with rifamycins.

BTS option for non-severe, smear-negative, non-cavitary pulmonary MAC under an experienced service.

Intermittent triple regimen for selected non-severe pulmonary MAC

Give rifampicin 600 mg, ethambutol 25 mg/kg and azithromycin 500 mg or clarithromycin 1 g in two divided doses three times weekly.

Do not use intermittent therapy for cavitary, smear-positive, severe or poorly characterised disease, or extrapolate it to disseminated MAC. Apply the same visual, hepatic, QT and interaction monitoring and confirm culture response.

Adds early activity for severe, cavitary or smear-positive MAC and selected resistant or M abscessus regimens.

Amikacin for severe pulmonary disease

When indicated, give intravenous amikacin 15 mg/kg three times weekly with concentration-guided adjustment; BTS also describes specialist nebulised amikacin 500 mg twice daily.

Measure renal function, baseline and serial hearing, vestibular symptoms and correctly timed concentrations; reduce or stop for toxicity. Nebulised injectable amikacin is unlicensed for NTM, can cause bronchospasm and requires an expert device and infection-control plan.

Treats bloodstream and reticuloendothelial MAC while effective antiretroviral therapy restores cellular immunity.

Combination treatment for disseminated MAC in HIV

Give clarithromycin 500 mg twice daily or azithromycin 500 mg daily plus ethambutol 15 mg/kg daily; add rifabutin, commonly 300 mg daily, or rifampicin with specialist adjustment for antiretroviral interactions.

Avoid macrolide monotherapy. Reconcile rifamycin and macrolide interactions with ART, anticoagulants and transplant medicines; monitor vision, liver, blood counts, QT and immune-reconstitution inflammation, and exclude active TB before rifamycin exposure.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Chronic respiratory failure

Expanding cavities, bronchiectasis and recurrent infection progressively reduce ventilatory reserve, exercise capacity and quality of life.

Major haemoptysis

Inflamed bronchial vessels around cavities or severely damaged airways can bleed enough to threaten gas exchange and airway protection.

Disseminated organ disease

Bloodstream infection in advanced immune deficiency causes marrow suppression, lymphadenopathy, hepatosplenomegaly and progressive multi-organ functional decline.

Persistent device or wound infection

Retained foreign material and unrecognised contaminated sources promote relapse, sinus formation and spread across procedure-linked cases.

Drug toxicity and resistance

Months of interacting therapy can injure liver, kidney, vision, hearing and marrow, while incomplete active combinations select resistance that sharply narrows future options.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

During pulmonary observation, record cough, sputum, haemoptysis, weight, exercise tolerance, lung function, culture burden and imaging change at a predefined interval.
During treatment, obtain sputum cultures every 4 to 12 weeks as agreed, record the service-defined culture-conversion date and continue post-treatment surveillance for relapse or reinfection.
Check renal, hepatic and haematological tests according to the exact regimen and sooner after acute illness, dose change or an interacting prescription.
Repeat visual acuity and colour assessment with ethambutol, audiology and vestibular review with aminoglycosides, and ECG when multiple QT-active drugs or electrolyte risks coexist.
For disseminated MAC, follow symptoms, blood-culture clearance, viral load, CD4 recovery, ART adherence and immune-reconstitution features; do not stop solely because fever resolves.
For device or wound disease, document removal or drainage, culture the deep site and investigate shared procedure, water or product exposures through infection prevention when indicated.
Recheck every new medicine for rifamycin induction, clarithromycin inhibition, nephrotoxicity and QT effects throughout the prolonged course.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

The first fork is TB

A respiratory acid-fast result changes isolation before it changes treatment; species confirmation protects contacts and prevents months of the wrong regimen.

Criteria do not compel therapy

Meeting pulmonary diagnostic criteria establishes disease attribution, but severity, trajectory, expected success, toxicity and the patient's goals still determine whether to treat now.

Conversion needs a date

Serial negative cultures, not one isolated negative sample, establish culture conversion and anchor the additional twelve-month pulmonary treatment period.

NTM is more than lung

Advanced HIV, devices, wounds and aquatic exposure create syndromes whose specimens, source control and drug combinations differ fundamentally from pulmonary MAC.

A macrolide can spend resistance

Unprotected macrolide exposure in active MAC can select resistance that markedly reduces the chance of successful future treatment.

Reinfection is not relapse

A later positive culture may represent a new strain or species; retain species and molecular information before declaring the original regimen a failure.

11Common pitfallsFrequent interpretation and management errors.

01
Ending TB precautions as soon as an acid-fast smear is called 'likely NTM'.
02
Treating one incidental sputum isolate without compatible symptoms and CT.
03
Giving long-term macrolide monotherapy for bronchiectasis before excluding active NTM.
04
Applying a pulmonary MAC regimen to M abscessus, a wound infection or disseminated HIV-associated MAC without specialist redesign.
05
Using intermittent MAC therapy for cavitary or smear-positive disease.
06
Failing to define culture conversion or continuing an unowned observation plan indefinitely.
07
Missing vision, hearing, renal, hepatic, QT and interaction monitoring during a prolonged combination.