Nontuberculous Mycobacterial Pulmonary Disease

Nontuberculous mycobacterial pulmonary disease is chronic lung infection caused by environmental mycobacteria. Mycobacterium avium complex is the commonest cause, followed by Mycobacterium abscessus, Mycobacterium kansasii and Mycobacterium xenopi. Rates are rising in many countries.

Risk groups are people with bronchiectasis, COPD, cystic fibrosis, previous tuberculosis and immunosuppression, and thin older women with nodular bronchiectasis (Lady Windermere pattern). In Africa it is often misdiagnosed as tuberculosis, and missed in patients treated for drug resistant tuberculosis who do not respond.

Pathophysiology. Organisms from water and soil are inhaled or aspirated and persist in damaged airways, where they form biofilms. The host response may be insufficient, and pathogenicity differs across species.

Chronic cough with or without sputum, fatigue, weight loss, low grade fever, night sweats, haemoptysis and dyspnoea. Two patterns exist: fibrocavitary disease in older men with COPD, with upper lobe cavities, and nodular bronchiectatic disease in older women, with right middle lobe and lingula involvement.

Massive haemoptysis, respiratory failure or severe weight loss need urgent assessment.

• Diagnosis needs all three of clinical, radiological and microbiological evidence: respiratory symptoms, nodular or cavitary opacities (or multifocal bronchiectasis with nodules) on CT, and a positive culture result from at least two separate sputum samples, or one bronchial wash or lavage, or a lung biopsy with granuloma and a positive culture.
• Species identification (molecular methods) and drug susceptibility testing: macrolides and amikacin for Mycobacterium avium complex and M abscessus, and rifampicin for M kansasii.
• CT chest: cavities, nodules, tree-in-bud, bronchiectasis and consolidation.
• Exclude tuberculosis with nucleic acid amplification and culture, HIV, immunoglobulins, cystic fibrosis genotype and aspergillosis, since mixed infections occur.
• Baseline audiometry, renal and liver function, electrocardiogram and eye examination before treatment.

Differential diagnosis.

• Pulmonary tuberculosis
• Colonisation without disease in bronchiectasis
• Chronic pulmonary aspergillosis
• Lung cancer
• Sarcoidosis
• Other causes of bronchiectasis

• Decision to treat: a patient who meets the criteria and has symptomatic or progressive disease is treated, and those with mild, stable nodular disease can be observed with repeat cultures at 3 to 6 months. Always start combination therapy, never monotherapy with a macrolide.
• Mycobacterium avium complex, nodular bronchiectatic disease: azithromycin 500 mg (or 250 mg) three times weekly, rifampicin 600 mg (450 mg under 50 kg) three times weekly and ethambutol 25 mg/kg three times weekly.
• Mycobacterium avium complex, cavitary or severe disease: daily azithromycin 250 mg, rifampicin 10 mg/kg (maximum 600 mg) and ethambutol 15 mg/kg, with intravenous or inhaled amikacin in the first 2 to 3 months, amikacin 10 to 15 mg/kg three times weekly (maximum 1 g), or for refractory disease add liposomal amikacin 590 mg inhaled once daily. Continue for 12 months after the first negative culture.
• Mycobacterium kansasii: rifampicin 10 mg/kg (maximum 600 mg), isoniazid 5 mg/kg (maximum 300 mg) with pyridoxine and ethambutol 15 mg/kg daily, for 12 months after culture conversion.
• Mycobacterium abscessus: intensive phase of intravenous amikacin 10 to 15 mg/kg daily with imipenem 1 g twice daily or cefoxitin 2 g every 6 to 8 hours (or tigecycline 50 mg twice daily) together with oral azithromycin 250 to 500 mg daily, for 4 to 12 weeks, then a continuation phase with inhaled amikacin and 2 to 3 oral drugs chosen by susceptibility (including inducible macrolide resistance), for at least 12 months after culture conversion. Treatment is complex and is made in a specialist centre.
• Safety monitoring: monthly visual acuity and colour vision (ethambutol), audiometry and vestibular symptoms, renal function and drug levels (aminoglycosides), liver function, full blood count, and QTc (macrolides).
• Airway clearance, hypertonic saline, optimisation of bronchiectasis and COPD, nutrition, and vaccination.
• Surgery (lobectomy or segmentectomy) for localised disease, cavities, or failure of drug therapy, in fit patients with adequate lung reserve.

Complications and prognosis. Progressive cavitation, bronchiectasis, haemoptysis and respiratory failure. Treatment success is about 60 to 70% for Mycobacterium avium complex and lower for M abscessus, and relapse and reinfection are common.

Monitoring. Sputum culture monthly until conversion and then every 1 to 3 months during treatment, CT at 6 to 12 months, and adverse effect monitoring throughout treatment.

Referral and escalation. Refer to a respiratory or infectious disease specialist at diagnosis, and for any M abscessus infection, macrolide resistance or intolerance.