NTM Pulmonary Disease Guidelines

NTM Epidemiology - Relevant Species in UK

M. avium complex: 45%

M. malmoense: 22%

M. abscessus: 14%

M. xenopi: 5%

M. kansasii: 4%

M. chelonae: 2.6%

M. simiae: 1.8%

M. fortuitum: 1.8%

                    Possible Causes for Increasing Prevalence:
                    Enhanced awareness and improved detection
Reduced incidence of TB
Exposure: showers, reduced hot water temperatures, and soil
Antibiotic exposure creates a favourable niche
Impaired host immunity: ageing, lung disease, drugs
Person-to-person transmission

                

Definition of NTM-Pulmonary Disease

To determine the clinical relevance of NTM-positive cultures, it is essential to distinguish transient or persistent colonisation from infection. Use of the ATS/IDSA 2007 definition of NTM-PD is recommended:

Clinical Criteria (both required)

Pulmonary symptoms, nodular or cavitary opacities on chest radiograph, or a high-resolution CT scan that shows multifocal bronchiectasis with multiple small nodules
Appropriate exclusion of other diagnoses

Microbiological Criteria (one of following)

Positive cultures results from at least two separate expectorated sputum samples
Positive culture result from at least one bronchial wash or lavage
Transbronchial or other lung biopsy with mycobacterial histopathological features and positive culture for NTM

Microbiological Sampling for NTM-PD

Sample types: Sputum, induced sputum, bronchial washings, bronchoalveolar lavage or transbronchial biopsy samples can be used
Less invasive first: Whenever possible, less invasive sampling should be attempted first to minimise procedural risks
Minimum samples: A minimum of two sputum samples collected on separate days should be sent for mycobacterial culture
CT-directed sampling: For consistently culture-negative sputum samples, CT-directed bronchial washings should be sent for mycobacterial culture
Sputum induction: Should be considered for individuals unable to spontaneously expectorate sputum

                    Mycobacterial Culture
                    All respiratory samples should be stained using auramine-phenol after liquefaction and concentration
Respiratory tract samples should be cultured on solid and liquid media in an ISO15189 accredited clinical laboratory for 8 weeks extending to 12 weeks if necessary

                

Treatment Regimens

MAC-Pulmonary Disease

Condition	Treatment	Duration
Non-severe MAC-PD (AFB smear negative, no radiological evidence of lung cavitation or severe infection, mild-to-moderate symptoms)	Rifampicin 600mg 3×/week + Ethambutol 25mg/kg 3×/week + Azithromycin 500mg 3×/week or Clarithromycin 1g 2×/week	Minimum 12 months after culture conversion
Severe MAC-PD (AFB smear positive, radiological evidence of lung cavitation/severe infection, severe symptoms)	Rifampicin 600mg daily + Ethambutol 15mg/kg daily + Azithromycin 250mg daily or Clarithromycin 500mg 2×daily + Consider IV amikacin	Minimum 12 months after culture conversion
Clarithromycin-resistant MAC	Rifampicin 600mg daily + Ethambutol 15mg/kg daily + Isoniazid 300mg + pyridoxine 10mg daily or moxifloxacin 400mg daily + Consider IV amikacin	Minimum 12 months after culture conversion

M. kansasii-Pulmonary Disease

Condition	Treatment	Duration
Rifampicin-sensitive M. kansasii	Rifampicin 600mg daily + Ethambutol 15mg/kg daily + Isoniazid 300mg with pyridoxine 10mg daily or Azithromycin 250mg daily or clarithromycin 500mg 2×daily	Minimum 12 months after culture conversion

M. malmoense & M. xenopi

Similar treatment regimens to MAC with rifampicin, ethambutol, and clarithromycin/azithromycin. For severe disease, consider addition of IV amikacin and moxifloxacin/isoniazid.

M. abscessus

Complex multi-drug regimen requiring specialist management:

Initial phase (≥1 month): IV amikacin + IV tigecycline ± IV imipenem + oral clarithromycin
Continuation phase: Nebulised amikacin + 2-4 oral antibiotics guided by susceptibility
Duration of IV therapy: 3-6 months may be most appropriate for those who can tolerate it

Treatment Monitoring & Assessment

Microbiological Response

Sputum samples for culture every 4-12 weeks during treatment
For 12 months after completing treatment
CT-directed bronchial wash if doubt about persisting infection

Radiological Response

CT scan before starting treatment
CT scan at end of treatment
Document radiological response

Clinical Response

Detailed assessment of pulmonary and systemic symptoms
Record at each clinical review
Monitor treatment tolerance

Drug Monitoring

Therapeutic drug monitoring not routine except for aminoglycosides
Monitor serum levels and creatinine for aminoglycosides
Consider in cases of malabsorption or drug interactions

Role of Thoracic Surgery & Lung Transplantation

Thoracic Surgery

Should be considered at time of diagnosis and revisited in individuals who develop refractory disease
May be indicated for individuals with localised areas of severe disease
Should only be performed following expert multidisciplinary assessment
Patients should be established on antibiotic treatment prior to surgery
Continue treatment for 12 months after culture conversion

Lung Transplantation

Individuals being considered should be assessed for evidence of NTM-pulmonary disease
Potential candidates should be treated whenever possible prior to listing
High post-operative risk of developing invasive and disseminated NTM disease
Progressive NTM-pulmonary disease despite optimal antibiotic therapy likely contraindication to listing

Decision to Treat

The decision should be influenced by:

Severity of NTM-pulmonary disease
Risk of progressive NTM-pulmonary disease
Presence of comorbidity
Goals of treatment
Views of the affected individual on potential risks and benefits

Note: Individuals may require a period of longitudinal assessment (symptoms, radiological change and mycobacterial culture results) to inform NTM treatment decisions.