Nontuberculous Mycobacteria (NTM)

📋 Key Information Summary

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Nontuberculous mycobacteria (NTM) are environmental organisms found in soil and water; over 190 species identified, but only a minority cause clinically significant pulmonary disease in humans.
The ATS/IDSA 2020 diagnostic criteria require clinical, radiological, AND microbiological evidence — a positive culture alone is insufficient for diagnosis.
Mycobacterium avium complex (MAC) is the most common NTM species causing pulmonary disease in Australia, followed by M. abscessus complex and M. kansasii.
Two major radiological phenotypes exist: nodular bronchiectatic (fibrocavitary) and upper-lobe cavitary disease — the phenotype guides treatment intensity and duration.
MAC pulmonary disease is treated with a macrolide-based triple regimen: clarithromycin (or azithromycin) + rifampicin + ethambutol for a minimum of 12 months after sputum culture conversion.
Macrolide monotherapy must be avoided in MAC to prevent acquired macrolide resistance, which dramatically worsens outcomes.
Inhaled amikacin (Arikayce® liposomal) is PBS-listed (Authority Required) as add-on therapy for refractory MAC pulmonary disease in adults.
M. abscessus pulmonary disease requires multidrug IV and oral therapy guided by species-level identification (M. abscessus subsp. abscessus vs massiliense vs bolletii) and susceptibility testing; macrolide susceptibility is critical.
Surgical resection should be considered in localised NTM pulmonary disease (especially M. abscessus) that is refractory to medical therapy and in select MAC cavitary disease.
Drug toxicity monitoring is essential: audiometry and vestibular assessment for amikacin, liver function for macrolides and rifampicin, visual acuity and colour vision for ethambutol, and renal function for aminoglycosides.
Aboriginal and Torres Strait Islander Australians in remote communities may have higher exposure to environmental NTM; rheumatic heart disease-related bronchiectasis increases susceptibility to NTM infection.
Recurrence rates after treatment completion are 20–50%; long-term sputum surveillance (at least 12 months post-treatment) is recommended.

Introduction & Australian Epidemiology

Nontuberculous mycobacteria (NTM) are ubiquitous environmental organisms found in natural and engineered water systems, soil, and aerosols. Unlike Mycobacterium tuberculosis, NTM are not transmitted person-to-person. Over 190 species have been identified, but relatively few cause clinically significant pulmonary disease. The most clinically relevant species in the Australian context are Mycobacterium avium complex (MAC), Mycobacterium abscessus complex, and Mycobacterium kansasii.

The incidence and prevalence of NTM pulmonary disease are increasing worldwide, including in Australia. Data from the NTM project and laboratory notifications suggest that NTM isolation rates in Australia have risen over the past two decades. Contributing factors include an ageing population, increasing prevalence of structural lung disease (particularly bronchiectasis), improved laboratory detection methods, and greater clinical awareness.

Australian Epidemiology

MAC accounts for approximately 50–70% of NTM pulmonary isolates across major Australian centres.
M. abscessus complex is the second most common pulmonary NTM and is the most challenging to treat due to intrinsic multidrug resistance.
M. kansasii is less common in Australia than in parts of North America and Europe but remains an important cause of cavitary pulmonary disease.
NTM disease is more common in patients with pre-existing bronchiectasis (including post-infectious bronchiectasis), chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and immunosuppression.
Hot-tub lung and hypersensitivity pneumonitis-like presentations from MAC in household water systems are increasingly recognised.
Age-standardised NTM notification rates are highest in patients aged >60 years, with a female predominance (particularly for nodular bronchiectatic MAC disease).
Aboriginal and Torres Strait Islander Australians may be disproportionately affected due to higher prevalence of bronchiectasis (often post-rheumatic fever), remote living conditions, and limited access to specialist respiratory services.

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Clinical significance of NTM isolation: Isolation of NTM from a respiratory specimen does not equate to disease. Many NTM isolates represent environmental contamination or colonisation. All patients must be assessed against formal diagnostic criteria (ATS/IDSA 2020) before initiating treatment.

Diagnosis & Species

ATS/IDSA 2020 Diagnostic Criteria

Diagnosis of NTM pulmonary disease requires the integration of clinical, radiological, and microbiological criteria. A positive NTM culture alone is insufficient for diagnosis.

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ATS/IDSA 2020 criteria require all three elements:
1. Clinical: Pulmonary symptoms (cough, sputum, fatigue, dyspnoea, haemoptysis) ± constitutional symptoms, OR radiological abnormalities.
2. Radiological: CT chest showing nodular or cavitary opacities, bronchiectasis with tree-in-bud nodules, or consolidation — not attributable to another cause.
3. Microbiological: ≥2 positive sputum cultures from separate specimens, OR ≥1 positive bronchoscopic wash/lavage culture, OR biopsy with histopathological features of mycobacterial disease with positive culture.

Microbiological Criterion	Requirement	Notes
Sputum (expectorated or induced)	≥2 positive cultures from separate specimens	At least 1 specimen should be an early-morning sample
Bronchoscopic wash or BAL	≥1 positive culture	Useful when sputum is non-productive or results are equivocal
Lung biopsy	Positive culture + compatible histopathology (granulomatous inflammation or AFB)	Reserved for diagnostic uncertainty

Key NTM Species in Australia

Species / Complex	Clinical Significance	Typical Radiological Pattern	Culture Characteristics
*MAC (M. avium* complex)**	Most common NTM pathogen; two phenotypes — nodular bronchiectatic (NB) and fibrocavitary (FC)	NB: right middle lobe/lingula tree-in-bud nodules with bronchiectasis FC: upper lobe cavitation with fibrosis	Slow-growing; pigmented or non-pigmented colonies on LJ/MGIT; requires 2–6 weeks incubation
M. abscessus complex	Most treatment-resistant NTM; subdivided into subsp. abscessus, massiliense, bolletii	Bronchiectasis with nodules; cavitary disease in severe cases	Rapid-growing (visible within 7 days); scotochromogenic; species-level ID essential
*M. kansasii*	Second most common cause of NTM cavitary disease; typically responds well to treatment	Upper lobe cavitation mimicking TB; mass-like opacities	Slow-growing; photochromogenic (yellow pigment on light exposure); requires ≤14 days for visible growth on liquid media
*M. xenopi*	Thermophilic; associated with hot-water systems; causes cavitary disease in COPD patients	Upper lobe cavities; often indistinguishable from TB	Slow-growing; optimal growth at 42°C; pale yellow pigment

Culture Confirmation & Susceptibility Testing

Specimen collection: At least two early-morning sputum specimens on separate days. If the patient cannot expectorate, consider sputum induction (hypertonic saline) or bronchoscopy with BAL.
Laboratory processing: Specimens should be decontaminated (N-acetyl-L-cysteine–sodium hydroxide [NALC-NaOH]) and inoculated onto both liquid (MGIT/BACTEC) and solid (Middlebrook 7H11 or Löwenstein-Jensen) media. Extended incubation (≥8 weeks for slow growers) is required.
Species identification: Essential for guiding treatment. Matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry is increasingly available in Australian laboratories. Molecular methods (16S rRNA gene sequencing, rpoB gene sequencing, hsp65 PCR-restriction enzyme analysis) provide definitive species-level identification.
Susceptibility testing: Performed at reference laboratories (e.g., Victorian Infectious Diseases Reference Laboratory [VIDRL], Queensland Mycobacterial Reference Laboratory).
- MAC: Clarithromycin (critical — determines macrolide resistance status), amikacin, ethambutol, rifampicin, moxifloxacin, linezolid.
- M. abscessus complex: Clarithromycin (including 14-day extended incubation to detect erm(41)-inducible resistance in subsp. abscessus), amikacin, cefoxitin, imipenem, tigecycline, linezolid, clofazimine, bedaquiline.
- M. kansasii: Rifampicin (critical — rifampicin-susceptible M. kansasii responds well to standard TB-like regimen), isoniazid, ethambutol.
Quality assurance: All NTM-positive cultures should be confirmed at a mycobacterial reference laboratory. Rapid-growing species require species-level identification (subspecies for M. abscessus complex) before treatment initiation.

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Critical distinction: Always differentiate M. kansasii from M. tuberculosis. M. kansasii can cause cavitary pulmonary disease indistinguishable from TB on imaging. Species-level confirmation is mandatory before initiating NTM-directed therapy. Failure to treat M. tuberculosis promptly has public health implications.

MAC Pulmonary Disease — Treatment

Treatment of MAC pulmonary disease is guided by the radiological phenotype (nodular bronchiectatic vs fibrocavitary) and the presence of macrolide resistance. Macrolide-based combination therapy is the cornerstone of treatment, but regimen intensity and duration vary.

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Never use macrolide monotherapy for MAC pulmonary disease. Monotherapy rapidly selects for macrolide-resistant mutants via the erm(41) gene, leading to treatment failure and significantly worse outcomes. All macrolide-containing regimens must include at least ethambutol + rifampicin.

Nodular Bronchiectatic (NB) MAC Disease

The most common phenotype, particularly in older women with focal bronchiectasis (typically right middle lobe and lingula).

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Clarithromycin

Klacid® · Macrolide antibiotic

Adult dose 500 mg PO BD (preferred macrolide in NB phenotype)

Paediatric dose 7.5 mg/kg PO BD (max 500 mg BD)

Renal adjustment Reduce dose if eGFR <30 mL/min: 250 mg BD or 250 mg OD

Key interactions CYP3A4 inhibitor — check interactions with statins, warfarin, digoxin, carbamazepine

PBS status ✔ PBS General Benefit

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Azithromycin

Zithromax® · Azalide (macrolide alternative)

Adult dose 250–500 mg PO daily (alternative to clarithromycin)

Paediatric dose 5 mg/kg PO daily (max 250 mg)

Renal adjustment No adjustment required

Advantages Once-daily dosing; better tolerated GI; fewer CYP interactions

PBS status ✔ PBS General Benefit

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Rifampicin

Rifadin® · Rifamycin

Adult dose 450 mg PO daily (<50 kg) or 600 mg PO daily (≥50 kg); three-times-weekly option: 600 mg TDSW

Paediatric dose 10–20 mg/kg PO daily (max 600 mg)

Renal adjustment No adjustment required

Key interactions Potent CYP inducer — reduces efficacy of oral contraceptives, warfarin, antiretrovirals, tacrolimus. Orange discolouration of body fluids.

PBS status ✔ PBS General Benefit

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Ethambutol

Myambutol® · Ethambutol hydrochloride

Adult dose 15 mg/kg PO daily (all three-times-weekly regimens: 25 mg/kg TDSW)

Paediatric dose 15 mg/kg PO daily (use with caution — visual assessment difficult in young children)

Renal adjustment eGFR 10–50: dose every 24–48 h; eGFR <10: dose every 48 h or avoid

Toxicity Optic neuritis — baseline and monthly visual acuity + red-green colour discrimination. Avoid in children too young for serial visual assessment.

PBS status ✔ PBS General Benefit

Recommended Regimens — Nodular Bronchiectatic Disease

Standard regimen (three-times-weekly):

Clarithromycin 1000 mg PO three times per week (or azithromycin 500 mg PO three times per week) PLUS
Rifampicin 600 mg PO three times per week PLUS
Ethambutol 25 mg/kg PO three times per week
Duration: Continue for a minimum of 12 months after sputum culture conversion (negative cultures from at least two separate specimens).

Daily regimen (alternative for more severe NB disease):

Clarithromycin 500 mg PO BD (or azithromycin 250 mg PO daily) PLUS
Rifampicin 450–600 mg PO daily PLUS
Ethambutol 15 mg/kg PO daily

Fibrocavitary (FC) MAC Disease

Fibrocavitary disease carries a worse prognosis than NB disease and requires more aggressive treatment. Consider addition of an injectable aminoglycoside in the intensive phase.

Clarithromycin 500–1000 mg PO daily PLUS
Rifampicin 450–600 mg PO daily PLUS
Ethambutol 15 mg/kg PO daily PLUS
Amikacin 10–15 mg/kg IV/IM daily (or three times per week) during the initial 2–3 months, pending clinical and microbiological response.
Consider substituting IV amikacin with inhaled amikacin (liposomal) once IV induction is complete.

Inhaled Amikacin (Liposomal)

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Amikacin liposomal inhalation

Arikayce® · Liposomal aminoglycoside for inhalation

Adult dose 590 mg inhaled once daily via Lamira™ nebuliser system

Indication Add-on therapy for adults with refractory MAC pulmonary disease (≥6 months of guideline-based therapy with persistently positive sputum cultures)

Key adverse effects Dysphonia, cough, haemoptysis, bronchospasm, ototoxicity (less than IV amikacin but still requires monitoring)

Monitoring Baseline and 3-monthly audiometry; serum amikacin trough levels if concerns; respiratory function tests

PBS status ✔ PBS Authority Required — Refractory MAC pulmonary disease with persistently positive cultures after ≥6 months of guideline-based therapy

Macrolide-Resistant MAC

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Macrolide-resistant MAC (MIC >16 µg/mL for clarithromycin) has cure rates <50%. Refer to a mycobacterial specialist centre. Regimen should include amikacin + ethambutol + rifampicin + a fluoroquinolone (moxifloxacin 400 mg PO daily). Consider linezolid 600 mg PO daily. Surgical evaluation for localised disease is strongly recommended.

Duration of Therapy

Treatment should continue for a minimum of 12 months after the first negative sputum culture. In practice, this means a total treatment duration of 15–24 months for most patients. Patients with fibrocavitary disease or macrolide-resistant MAC may require extended treatment (≥24 months). The decision to stop treatment should be based on achieving sustained sputum culture conversion (≥3 consecutive negative cultures over ≥3 months), resolution of symptoms, and radiological improvement or stability.

M. kansasii Pulmonary Disease

M. kansasii is generally more responsive to therapy than MAC. Rifampicin-susceptible M. kansasii is treated with a TB-like regimen:

Rifampicin 600 mg PO daily PLUS
Isoniazid 300 mg PO daily PLUS
Ethambutol 15 mg/kg PO daily
Duration: Continue for 12 months after sputum culture conversion (minimum total duration 12 months).
Supplement with pyridoxine 25 mg PO daily to prevent isoniazid-related neuropathy.

Rifampicin-resistant M. kansasii should be treated in consultation with a mycobacterial specialist, considering moxifloxacin + ethambutol + isoniazid (if susceptible) + sulfamethoxazole-trimethoprim.

M. abscessus Complex — Management

Mycobacterium abscessus complex is the most treatment-resistant NTM species encountered in clinical practice. It comprises three subspecies — M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii — each with distinct macrolide resistance profiles that critically influence treatment outcomes.

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Species-level identification is mandatory. M. abscessus subsp. abscessus harbours a functional erm(41) gene that confers inducible macrolide resistance (initially susceptible, becomes resistant after 14 days of incubation). M. abscessus subsp. massiliense has a non-functional erm(41) and remains macrolide-susceptible, making macrolide-based therapy much more effective.

Treatment Principles

Multidrug IV induction therapy (typically ≥2–4 weeks, often extended to 2–3 months) followed by long-term oral/inhaled continuation therapy.
Regimen selection is guided by subspecies identification, macrolide susceptibility, and drug susceptibility testing (DST) results.
Treatment duration: minimum 12 months after sputum culture conversion, but many patients require ≥18–24 months total.
Outcomes are poor: culture conversion rates are approximately 30–50% overall; better with subsp. massiliense.
Early referral to a specialist mycobacterial centre is strongly recommended.

Standard Multidrug Regimen

Intensive Phase (IV)

Induction Therapy (2–3 months)

Amikacin IV + Cefoxitin IV + (clarithromycin or azithromycin if macrolide-susceptible)

Setting: Inpatient initiation; may complete IV at home via Hospital in the Home (HITH)

Continuation Phase

Oral/Inhaled Maintenance (≥12–18 months)

Clarithromycin (or azithromycin) + oral clofazimine ± inhaled amikacin + (linezolid, tigecycline, or imipenem per DST)

Setting: Outpatient with close monitoring

Key Agents

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Amikacin (IV)

Amikacin Sulfate · Aminoglycoside

Adult dose 10–15 mg/kg IV daily (target peak 25–30 µg/mL, trough <1 µg/mL); extended-interval dosing 15–20 mg/kg OD may be used

Renal adjustment eGFR <50: extend interval to every 48 h; eGFR <10: avoid if possible. TDM essential.

Toxicity Nephrotoxicity, ototoxicity (cochlear + vestibular), neuromuscular blockade (rare)

Monitoring Serum levels (peak + trough) with each dose change; baseline + monthly audiometry; weekly creatinine/eGFR

PBS status ✔ PBS General Benefit (IV formulation)

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Cefoxitin

Mefoxin® · Cephamycin (2nd generation)

Adult dose 2 g IV every 6–8 h (up to 12 g/day in severe disease)

Renal adjustment eGFR 30–50: 1–2 g every 8–12 h; eGFR <10: 1 g every 24–48 h

Key adverse effects Hypersensitivity; Clostridioides difficile infection; neutropenia with prolonged use; phlebitis

PBS status ✔ PBS General Benefit

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Tigecycline

Tygacil® · Glycylcycline

Adult dose 50 mg IV every 12 h (loading dose 100 mg, then 50 mg every 12 h)

Renal adjustment No adjustment required

Key adverse effects Nausea/vomiting (common); photosensitivity; avoid in pregnancy (Category D); FDA boxed warning for increased all-cause mortality in certain infections

Role Second-line agent; used in combination when standard agents cannot be tolerated or are resistant. Per DST guidance.

PBS status ✔ PBS Authority Required

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Imipenem-cilastatin

Primaxin® · Carbapenem

Adult dose 1 g IV every 6–8 h (often combined with cefoxitin for synergistic activity against M. abscessus)

Renal adjustment eGFR 30–50: 500–750 mg every 8 h; eGFR <30: 500 mg every 12 h

Key adverse effects Seizures (dose-related — avoid in patients with seizure history if possible); nausea; C. difficile infection

PBS status ✔ PBS Authority Required

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Linezolid

Zyvox® · Oxazolidinone

Adult dose 600 mg PO/IV daily (used as an oral agent in the continuation phase)

Renal adjustment No adjustment required (metabolites accumulate — monitor for lactic acidosis in renal impairment)

Key adverse effects Myelosuppression (thrombocytopenia, anaemia), peripheral neuropathy, optic neuritis, serotonin syndrome (with SSRIs)

Monitoring FBC fortnightly for first 2 months, then monthly; visual acuity at baseline and 3-monthly

PBS status ✔ PBS Authority Required

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Clofazimine

Lamprene® · Riminophenazine

Adult dose 100 mg PO daily (or 100 mg three times per week during long-term therapy)

Renal adjustment No adjustment required

Key adverse effects Skin discolouration (pink-brown to blackish); GI upset; QT prolongation (monitor ECG); dry skin

Access Special Access Scheme (SAS) or hospital pharmacy; not routinely PBS-listed for NTM

PBS status Not PBS-listed for NTM indication — Access via SAS Category B

Surgical Resection

Surgical resection should be considered in the following circumstances:

Localised disease (e.g., single lobe or segment) refractory to ≥6 months of appropriate medical therapy.
Persistent cavitary disease with ongoing positive sputum cultures despite optimised multidrug therapy.
Massive haemoptysis requiring intervention.
In combination with medical therapy — pre- and post-operative antimicrobial coverage reduces recurrence.
Surgery should be performed by a thoracic surgeon experienced in NTM disease at a specialist centre, with adequate pulmonary reserve assessment (formal lung function testing with split-function studies).

ℹ️

Peri-operative antimicrobial strategy: Continue the established NTM regimen through the peri-operative period (ideally ≥4 weeks pre-operatively and ≥4–6 weeks post-operatively). Change IV agents to oral equivalents when feasible. Inhaled amikacin may be resumed post-operatively once the patient can use the nebuliser device.

Emerging Therapies for M. abscessus

Bedaquiline: Case reports and small series suggest activity against M. abscessus in vitro; compassionate use in refractory disease. Accessed via Special Access Scheme.
Omadacycline: Tetracycline-class agent with in vitro activity against M. abscessus; clinical data limited.
Phage therapy: Experimental; individualised bacteriophage cocktails have shown promise in case reports; available through compassionate use pathways at select international centres.

Monitoring & Follow-up

Monitoring during NTM treatment encompasses three domains: (1) microbiological response — sputum culture conversion; (2) drug toxicity surveillance; and (3) clinical and radiological assessment. The duration and frequency of monitoring are long-term given the extended treatment courses required.

Sputum Culture Conversion

Baseline

Collect ≥2 sputum specimens for AFB culture and susceptibility testing before starting treatment. Establish baseline species identification and DST profile.

Monthly (first 6 months)

Monthly sputum collection (early morning) for AFB smear and culture. Cultures are assessed for conversion to negative.

Every 2 months (6–12 months)

If culture conversion achieved, continue two-monthly sputum cultures to confirm sustained conversion.

Every 3 months (12–24 months)

During the culture-negative continuation phase, continue three-monthly cultures. Treatment continues for ≥12 months after the first negative culture.

Post-treatment surveillance

Sputum cultures every 3 months for the first 12 months after treatment cessation, then every 6 months for ≥2 years to detect recurrence.

Drug Toxicity Monitoring

Agent	Toxicity	Monitoring Parameter	Frequency
Ethambutol	Optic neuritis (dose- and duration-related)	Visual acuity + red-green colour discrimination (Ishihara plates)	Baseline; monthly for first 6 months; then every 3 months
Clarithromycin / Azithromycin	GI intolerance, QT prolongation, hepatotoxicity	LFTs, ECG (if risk factors for QT prolongation)	Baseline; 1 month; then every 3 months
Rifampicin	Hepatotoxicity, GI intolerance, orange discolouration, drug interactions	LFTs (ALT, ALP, bilirubin); INR if on warfarin	Baseline; 2 weeks; 1 month; then every 3 months
Amikacin (IV)	Nephrotoxicity, ototoxicity (cochlear + vestibular)	Serum creatinine/eGFR; trough levels; audiometry; vestibular function	Trough levels with every dose; creatinine twice weekly during IV; audiometry baseline + monthly
Amikacin (inhaled)	Dysphonia, cough, bronchospasm, potential ototoxicity	Audiometry; respiratory symptoms; spirometry	Baseline; 3-monthly audiometry; spirometry at 3 months
Linezolid	Myelosuppression, peripheral neuropathy, optic neuritis, lactic acidosis	FBC; visual acuity; peripheral nerve function	FBC fortnightly ×2 months, then monthly; visual acuity 3-monthly
Tigecycline	Nausea/vomiting, photosensitivity, coagulopathy	LFTs; coagulation studies; clinical tolerance	Baseline; weekly during IV therapy
Clofazimine	Skin discolouration, GI upset, QT prolongation	ECG (QTc); clinical assessment of skin changes; GI symptoms	Baseline ECG; 1 month; then every 3 months

Treatment Duration Criteria

Minimum treatment duration: 12 months after the first negative sputum culture (from ≥2 separate specimens).
Culture conversion definition: Three consecutive negative cultures collected over ≥3 months, with no subsequent positive cultures during treatment.
Extended treatment indications: Fibrocavitary disease, macrolide-resistant MAC, M. abscessus disease, immunosuppressed patients — these groups may require ≥24 months of total therapy.
Treatment failure considerations: Persistently positive cultures after ≥6 months of appropriate therapy, clinical/radiological deterioration despite adherence, or emergence of new drug resistance. Consider regimen modification, surgical evaluation, or transition to suppressive therapy.

Recurrence Surveillance

Recurrence rates after completing treatment are significant (20–50% depending on species and phenotype). Long-term surveillance is essential:

Sputum cultures every 3 months for the first 12 months post-treatment, then every 6 months for ≥2 years.
CT chest at 6 and 12 months post-treatment, then annually for ≥2 years.
Patients should be counselled to present early if new or worsening respiratory symptoms develop.
Reinfection is common (particularly with MAC from the same environmental source) and must be differentiated from relapse by genotyping (if available) or comparison with pre-treatment isolate susceptibility profiles.

⚠️

Immunosuppressed patients: Patients receiving biologics (anti-TNF agents), corticosteroids, or other immunosuppressants are at higher risk of NTM acquisition and recurrence. NTM screening should be considered before initiating immunosuppressive therapy in patients with risk factors (bronchiectasis, prior NTM exposure).

Special Populations

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Pregnancy

Ethambutol Generally considered safe in pregnancy; category A (TGA). Continue if already on treatment.

Rifampicin Category C. Can be used when benefits outweigh risks; monitor for neonatal bleeding (vitamin K supplementation).

Clarithromycin / Azithromycin Clarithromycin: Category B3 (avoid if possible — teratogenic in animal studies). Azithromycin: Category B1 (preferred macrolide in pregnancy).

Amikacin Category D — ototoxicity risk to foetus. Avoid in pregnancy unless life-threatening NTM disease.

Linezolid Category C — teratogenic in animal studies. Avoid in pregnancy.

Strategy: For stable NTM disease, consider deferring treatment until after delivery if clinically safe. If treatment is essential, use ethambutol + rifampicin + azithromycin (substituting for clarithromycin). Avoid aminoglycosides. Multidisciplinary planning with respiratory medicine, obstetrics, and infectious diseases is essential.

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Paediatrics

MAC treatment Clarithromycin 7.5 mg/kg BD + ethambutol 15 mg/kg daily + rifampicin 10–20 mg/kg daily. Three-times-weekly regimens may be used for NB disease in older children.

Ethambutol caution Visual toxicity monitoring difficult in young children. Use with careful risk-benefit assessment; the ATS/IDSA 2020 statement permits use in children when indicated, with appropriate monitoring.

M. abscessus in CF Common in paediatric CF patients. Multidrug IV regimens should be weight-adjusted. Inhaled amikacin (non-liposomal, off-label) may be considered for continuation therapy. Refer to CF/NTM specialist centre.

Notes: NTM lymphadenitis (typically MAC or M. scrofulaceum) in children is managed primarily by surgical excision; antibiotics are reserved for incomplete excision or recurrence. Cervicofacial NTM lymphadenitis is self-limiting in many cases but surgical excision is preferred over incision and drainage.

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Elderly

Polypharmacy Rifampicin and clarithromycin have extensive drug interactions (CYP3A4, CYP2C9). Conduct thorough medication review before initiating NTM therapy.

Aminoglycosides Increased nephro- and ototoxicity risk. Baseline audiometry and renal function essential. Prefer inhaled over IV amikacin in elderly patients when feasible.

Ethambutol Optic neuritis risk may be higher in elderly. Monitor visual function closely. Reduce dose for renal impairment.

Notes: Elderly patients with nodular bronchiectatic MAC may be asymptomatic or minimally symptomatic. Treatment decisions should incorporate patient goals of care, comorbidities, and life expectancy. Observation with serial cultures may be appropriate in frail elderly patients with mild, indolent disease.

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Renal Impairment

Amikacin Significant nephrotoxicity risk. eGFR <30: use with extreme caution or avoid. TDM mandatory with every dose.

Ethambutol Excreted renally. Dose reduction required for eGFR <50. Extended dosing interval for eGFR <10.

Clarithromycin Reduce dose for eGFR <30. Azithromycin may be preferred (no renal adjustment needed).

Linezolid Metabolites accumulate in renal impairment — monitor for lactic acidosis and myelosuppression.

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Hepatic Impairment

Rifampicin Hepatotoxicity — avoid in severe hepatic impairment (Child-Pugh C). Monitor LFTs regularly.

Clarithromycin Hepatic metabolism — dose reduction may be needed; monitor LFTs. Azithromycin (biliary excretion) may be preferred.

General NTM treatment regimens are hepatotoxic. Baseline LFTs, fortnightly for first 2 months, then monthly. Stop and seek specialist advice if ALT >5× ULN or symptomatic hepatotoxicity.

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Immunocompromised

HIV/ART MAC prophylaxis (azithromycin 1200 mg weekly) when CD4 <50 cells/µL. ART initiation before or concurrent with MAC treatment. Drug interactions between rifamycins and antiretrovirals require expert guidance.

Biologics/immunosuppressants Anti-TNF agents increase NTM risk. Screen for NTM before initiating biologics in patients with bronchiectasis or risk factors. Consider holding immunosuppression during NTM treatment.

Transplant recipients NTM can cause disseminated disease. Immunosuppression minimisation is essential. Drug interactions between calcineurin inhibitors and rifampicin/clarithromycin require close TDM.

Cystic fibrosis High prevalence of M. abscessus in CF. May preclude lung transplant listing in some centres if sputum-positive. Refer early to NTM specialist and CF/transplant team.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

Environmental Exposure

Aboriginal and Torres Strait Islander Australians living in remote and tropical communities may have increased environmental exposure to NTM through soil and water contact. Warm, humid climates and proximity to natural water sources create conditions favourable for NTM proliferation.

Bronchiectasis Burden

The prevalence of bronchiectasis is significantly higher in Aboriginal and Torres Strait Islander populations, particularly in children and young adults, often secondary to early-life respiratory infections and rheumatic heart disease. Bronchiectasis is a major risk factor for NTM acquisition and disease.

Diagnostic Access

Access to specialist respiratory services, CT scanning, and mycobacterial reference laboratories is limited in remote communities. Telehealth respiratory consultations and portable spirometry services may help bridge this gap. Sputum specimens may require extended transport times, which can affect culture viability — liaison with the receiving laboratory is essential.

Treatment Adherence

NTM treatment regimens are prolonged (12–24+ months), complex (multiple agents), and associated with significant side effects. In remote communities, medication supply, cold-chain requirements (for some injectable agents), and regular monitoring may be challenging. Culturally safe health services and Aboriginal and Torres Strait Islander health workers can support adherence. Flexible delivery models (e.g., HITH for IV therapy, community-controlled health service partnerships) should be explored.

Drug Supply in Remote Areas

NTM treatment agents such as amikacin (IV), cefoxitin, tigecycline, linezolid, and clofazimine may not be routinely stocked in remote health facilities. Proactive supply planning through Remote Area Aboriginal Health Services (RAAHS) and hospital outreach programmes is necessary. PBS Authority applications should be initiated early.

Monitoring Challenges

Regular monitoring requirements (audiometry, visual acuity, ECG, LFTs, drug levels) are difficult to fulfil in remote settings without visiting specialist services. Fly-in/fly-out (FIFO) respiratory outreach clinics, tele-otology for audiometry, and point-of-care laboratory testing can support monitoring. Creative solutions for visual acuity assessment (e.g., validated smartphone-based Ishihara testing) may improve accessibility.

Coexistent Tuberculosis

NTM and TB can coexist, particularly in communities with high TB burden. Differential diagnosis is essential to avoid misdiagnosis and delayed treatment of either condition. Cross-referral with state/territory TB services is important. Ensure TB is excluded (with appropriate cultures and molecular testing) before attributing disease solely to NTM.

Cultural Safety

Respiratory illness carries significant stigma in some Aboriginal and Torres Strait Islander communities. Health education should be delivered in culturally appropriate language and context. Involving Aboriginal and Torres Strait Islander health workers in treatment planning, patient education, and follow-up improves trust and engagement. Acknowledgement of the social determinants of health — housing, water quality, nutrition, and access to healthcare — is essential when discussing NTM prevention and management.

📚 References

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