Non-tuberculous mycobacteria (NTMs) and lung disease

Turkish Thoracic Society

16th Annual Conference

Philip Hopewell, MDCurry International Tuberculosis CenterUniversity of California, San Francisco

Non-tuberculous mycobacteria (NTMs)

At least 140 species identified Pathogenicity is highly variable Isolated from many environmental sources,

generally moist sites Can cause disease in almost any structure or tissue At least 40 reported as a cause of lung disease Distribution differs by geography Incidence/prevalence appears to be increasing Diagnosis of disease (vs. colonization) may be

difficult Response to treatment is slow and often incomplete

NTMs and lung disease

Daley CL, Griffith DE. IJTLD 2010;14

frequent

more pathogenic1

2

2

2

3

MAC

> 7 days < 7 days

NTMs gross appearance

NTMs in Izmir

MAC 13 (42%) M. Szulgai 2 (6.5%)M. abcessus 5 (16%) M. Simiae 2 (6.5%) M. Kansasii 5 (16%) M. scrofulaceum 1 (3.2%)M. fortuitum 2 (6.5%) M. not speciated 1 (3.2%)

Isolates in 31 of 77 patients thought to be causative agents of lung disease.

NTMs in Istanbul

Unidentified 43 (57%) M. fortuitum 3(8%)M. Abcessus 9 (28%) M. Szulgai 3 (8%)M. Avium complex 8 (25%) M. neonarum 1 (2%)M. Kansasii 5 (16%)M. Gordonae 6(16%) Total 75

ATS/IDSA diagnostic criteria

Clinical (both required)

1. Pulmonary symptoms, nodular or cavitary opacities on chest radiograph, or a high-resolution CTscan with multifocal bronchiectasis and multiple small nodules and2. Appropriate exclusion of other diagnoses

Microbiological

1. Positive cultures from at least two sputum samples. or2. Positive culture result from at least one bronchial wash or lavage or

Griffith DE et al AJRCCM. 2007;175

ATS/IDSA diagnostic criteria

Histological (+ microbiological)1. Transbronchial or other lung biopsy with mycobacterial histopathologic features (granulomatous inflammation or AFB) and positive culture for NTM or

2. Biopsy showing mycobacterial histopathologic features (granulomatous inflammation or AFB) and one or more sputum or bronchial washings that are culture positive for NTM

Griffith DE et al AJRCCM. 2007;175

NTMs and lung disease: Risk factors

Structural defects• Bronchiectasis• COPD• Cystic fibrosis• Previous TB• Lady Windermere syndrome (?)

Impaired systemic immunity• Inherited deficiency• Acquired deficiency: HIV, immunosupressive

therapy

MAC disease: Clinical patterns

• Bronchiectatic/cavitary disease• Middle lobe/lingular bronchiectasis (“Lady

Windermere syndrome”)• Disseminated MAC• Hypersensitivity pneumonitis (“hot tub lung”)

M. avium disease and COPD

M. avium; middle lobe/lingular bronchiectasis

M. avium progression

18 months

Disseminated MAC in HIV

MAC in HIV: lymph node biopsy

M. Avium hypersensitivity pneumonitis

Marras TK, et al. Chest. 2005; 127

MAC hot tub lung: findings

Marras TK, et al. Chest. 2005; 127

Treatment of MAC pulmonary disease Nodular/bronchiectatic (“mild”) disease:

• clarithromycin (1,000 mg) or azithromycin (500 mg),

• rifampin (600 mg), and

• ethambutol (25 mg/kg)

Fibrocavitary or severe nodular/bronchiectatic disease: • clarithromycin (500–1,000 mg) or azithromycin (250 mg), • rifampin (600 mg) or rifabutin (150–300 mg),• ethambutol (15 mg/kg) • consider three times-weekly amikacin or streptomycin early in therapy

• Patients should be treated until culture negative on therapy for 1 year.

Hypersensitivity• Macrolide and rifampin + corticosteroid (?)

three times weekly

daily

Griffith DE et al AJRCCM. 2007;175

Treatment and prevention of disseminated MAC disease in HIV

Disseminated MAC disease• clarithromycin (1,000 mg/d) or azithromycin (250

mg/d) and ethambutol (15 mg/kg/d) with or without rifabutin (150–350 mg/d) daily.

Prophylaxis (AIDS with CD4 counts less than 50)

• Azithromycin 1,200 mg/week or clarithromycin 1,000 mg/day

• Rifabutin 300 mg/day (effective, less well tolerated)

Griffith DE et al AJRCCM. 2007;175

MAC surgical treatment There are no established criteria for patient selection. There are potentially severe perioperative complications. There are few centers with extensive experience with

mycobacterial surgery. Surgical resection of limited (focal) disease in a patient

with adequate cardiopulmonary reserve to withstand partial or complete lung resection can be successful in combination with multidrug treatment regimens for treating MAC lung disease

Surgical resection of a solitary pulmonary nodule due to MAC is considered curative.

Mycobacterial lung disease surgery should be performed in centers with expertise in both medical and surgical management of mycobacterial diseases.

San Francisco General HospitalSan Francisco General Hospital