What is Nontuberculous Mycobacteria (NTM) pulmonary disease?

What is Nontuberculous Mycobacteria (NTM) Pulmonary Disease?

NTM pulmonary disease is a chronic lung infection caused by environmental mycobacteria (excluding tuberculosis) that requires the integration of clinical symptoms, characteristic radiographic findings, and microbiologic evidence with multiple positive cultures to establish diagnosis. 1

Definition and Causative Organisms

NTM are environmental saprophytes found ubiquitously in soil, dust, and water—critically, they are not transmitted person-to-person, unlike tuberculosis. 2 The genus Mycobacterium contains numerous species, but only a small subset causes human pulmonary disease. 1

Most Common Causative Species:

• Mycobacterium avium complex (MAC): The most frequent cause, now consisting of 12 separate species including M. avium, M. intracellulare, and M. chimaera 1
• M. abscessus complex: The most common rapidly growing mycobacteria causing pulmonary disease, with subspecies abscessus, bolletii, and massiliense 1
• M. kansasii: A highly pathogenic slowly growing species 1
• M. xenopi: Another important slowly growing pathogen 1

Epidemiology and Risk Factors

The incidence and prevalence are increasing worldwide, particularly in older individuals and those with underlying bronchiectasis. 1 Rates are especially high in postmenopausal women. 1

Key Risk Factors:

• Underlying structural lung disease: Bronchiectasis and chronic obstructive pulmonary disease are the most common predisposing conditions 1
• Age: Predominantly affects individuals 50 years or older 1
• Specific morphotype: Thin body habitus, scoliosis, pectus excavatum, and mitral valve prolapse (particularly in nodular/bronchiectatic MAC disease) 1
• Cystic fibrosis: An emerging high-risk population 1

Clinical Presentation

Symptoms (Variable and Nonspecific):

• Chronic or recurring cough: Present in virtually all patients 1
• Sputum production 1
• Fatigue and malaise 1
• Dyspnea 1
• Fever 1
• Hemoptysis 1
• Chest pain and weight loss (more common with advanced disease) 1

Physical Examination Findings:

Physical findings are nonspecific and reflect underlying lung pathology: rhonchi, crackles, wheezes, and squeaks on chest auscultation. 1

Radiographic Features

Two distinct radiographic patterns exist:

1. Fibrocavitary Disease:

• Resembles tuberculosis but with thin-walled cavities with less surrounding parenchymal opacity 1
• Less bronchogenic spread but more contiguous disease spread 1
• More marked pleural involvement over affected lung areas 1
• Plain chest radiograph may be adequate for evaluation 1

2. Nodular/Bronchiectatic Disease:

• Abnormalities primarily in mid- and lower lung fields 1
• Multifocal bronchiectasis with clusters of small (≤5 mm) nodules on HRCT in up to 90% of patients 1
• High-resolution CT (HRCT) is routinely indicated to demonstrate these characteristic findings 1

Diagnostic Criteria

Diagnosis requires meeting clinical, radiographic, AND microbiologic criteria—isolation of NTM alone does not establish disease. 1

Clinical Criteria:

Pulmonary or systemic symptoms as described above 1

Radiographic Criteria:

• Nodular or cavitary opacities on chest radiograph, OR
• HRCT showing bronchiectasis with multiple small nodules 1

Microbiologic Criteria (at least one required):

1. ≥2 positive sputum cultures (same species/subspecies) 1
2. ≥1 positive bronchial wash or lavage 1
3. Transbronchial or lung biopsy with mycobacterial histologic features (granulomatous inflammation or acid-fast bacilli) AND positive culture for NTM, OR biopsy with histologic features plus ≥1 positive sputum/bronchial washing 1

Critical Diagnostic Nuances:

• Single positive sputum culture is generally indeterminate for diagnosis, especially with low organism burden 1
• Clinically significant MAC disease is unlikely with only one positive culture (2% probability) but rises to 98% with ≥2 positive cultures 1
• Species identification to the species level (and subspecies for M. abscessus) is essential for determining pathogenicity and treatment 1
• Some species (M. gordonae, M. terrae complex, M. mucogenicum, M. scrofulaceum) usually represent contamination when isolated 1
• M. kansasii is highly pathogenic—even a single positive culture in proper context may warrant treatment 1

Important Caveat:

Meeting diagnostic criteria does NOT automatically necessitate treatment. 1 A careful assessment of organism pathogenicity, risks/benefits of therapy, patient preferences, treatment goals, and ability to tolerate prolonged therapy must be conducted. 1 "Watchful waiting" may be appropriate in selected cases. 1

Treatment Principles

Treatment is complex and varies by species, extent of disease, drug susceptibility, and comorbidities. 1

General Treatment Characteristics:

• Multiple antimicrobial agents required to prevent resistance 2, 3
• Prolonged duration: Typically >12 months after sputum culture conversion 1
• Macrolides (clarithromycin/azithromycin) form the backbone of most regimens 1, 2
• Treatment outcomes are often suboptimal with frequent adverse effects 1, 3
• Expert consultation is recommended in many settings 1

Species-Specific Treatment Examples:

• M. kansasii: Daily isoniazid (300 mg), rifampin (600 mg), and ethambutol (15 mg/kg) until culture negative for 1 year 1
• MAC: Macrolide-based multidrug regimens 1
• M. abscessus: No regimens of proven efficacy; clarithromycin-based multidrug therapy may cause symptomatic improvement 1

Surgical Considerations:

In selected patients, surgical resection as adjuvant to medical therapy is suggested after expert consultation. 1 Candidates include those with:

• Failure of medical management 1
• Cavitary disease 1
• Drug-resistant isolates 1
• Complications such as hemoptysis or severe bronchiectasis 1

Surgery should be performed by a surgeon experienced in mycobacterial surgery. 1 For M. abscessus, surgical resection combined with multidrug clarithromycin-based therapy offers the best chance for cure. 1

Prognosis

The clinical course is heterogeneous: some patients remain stable without treatment while others develop refractory disease with considerable mortality and morbidity. 3 Historical mortality rates for certain species (e.g., M. xenopi) have been reported as high as 57%, possibly reflecting severe underlying pulmonary disease. 1 Complete cure may not be attainable in all cases, and clinical improvement may be a more realistic goal. 4