Nontuberculous mycobacteria

# Overview
Non-tuberculous mycobacteria (NTM) are species other than those belonging to the Mycobacterium tuberculosis complex and do not cause leprosy. NTM are generally free-living organisms that are ubiquitous in the environment. There have been more than 150 NTM species identified to-date. They can cause a wide range of infections, with pulmonary infections being the most frequent. NTM are opportunistic pathogens and are abundant in the environment such as peat-rich potting soil and drinking water in buildings and households. Risk factors associated with pulmonary NTM are included but not limited to prior infection with TB, use of glucocorticoids and other immunosuppressive drugs, some pulmonary diseases such as bronchiectasis and cystic fibrosis (CF).

# Historical Perspective
-  was first discovered by , a , in  during/following .
- In ,  mutations were first identified in the pathogenesis of .
- In , the first  was developed by  to treat/diagnose .

# Classification
- NTM is most commonly classified by the growth rate, either slowly growing or rapidly growing:
- Slow-growing mycobacteria are: Mycobacterium avium complex (includes avium and intracellulare species), M. kansasii, M. xenopi, M. simiae
- Rapid-growing mycobacteria are: M. Abscessus, M. Fortuitium, M. Chelonae

# Pathophysiology
- The pathogenesis of  is characterized by , , and .
- The  gene/Mutation in  has been associated with the development of , involving the  pathway.
- On gross pathology, , , and  are characteristic findings of .
- On microscopic histopathological analysis, , , and  are characteristic findings of .

# Clinical Features

# Differentiating nontuberculous mycobacteria from other Diseases
- NTM lung disease must be differentiated from other chronic pulmonary diseases that cause chronic cough, shortness of breath and hemoptysis such as:
- Tuverculosis
- Histoplasmosis
- Blastomyces
- Silicosis
- Pneumonia
- Granulomatosis of lung

# Epidemiology and Demographics
- The prevalence of  is approximately  per 100,000 individuals worldwide.
- In , the incidence of  was estimated to be  cases per 100,000 individuals in .

## Age
- Patients of all age groups may develop .
-  is more commonly observed among patients aged  years old.
-  is more commonly observed among .

## Gender
-  affects men and women equally.
-  are more commonly affected with  than .
- The  to  ratio is approximately  to 1.

## Race
- There is no racial predilection for .
-  usually affects individuals of the  race.
-  individuals are less likely to develop .

# Risk Factors
- Common risk factors in the development of NTM lung disease are included but not limited to prior infection with TB, use of glucocorticoids and other immunosuppressive drugs such as TNF-alpha inhibitors, some pulmonary diseases such as bronchiectasis and cystic fibrosis (CF).

# Natural History, Complications and Prognosis
- The majority of patients with  remain asymptomatic for .
- Early clinical features include , , and .
- If left untreated,  of patients with  may progress to develop , , and .
- Common complications of  include , , and .
- Prognosis is generally , and the  of patients with  is approximately .

# Diagnosis

## Diagnostic Criteria
- The diagnosis of NTM pulmonary disease is made when at least three of the following diagnostic criteria are met:
- Chest radiograph or, in the absence of cavitation, chest high-resolution computed tomography (HRCT) scan.
- Three or more sputum specimens for acid-fast bacilli (AFB) analysis.
- Exclusion of other diseases, such as tuberculosis (TB).

## Symptoms
- Symptoms of NTM may include the following:
- Chronic cough
- Fatigue
- Shortness of breath (dyspnea)
- Coughing up of blood (hemoptysis)
- Excessive mucus (sputum) production
- Fever
- Night sweats
- Loss of appetite
- Unintended weight loss.

## Physical Examination
- Patients with  usually appear .
- Physical examination may be remarkable for:

## Laboratory Findings
- There are no specific laboratory findings associated with .
- A    is diagnostic of .
- An  concentration of   is diagnostic of .
- Other laboratory findings consistent with the diagnosis of  include , , and .

## Imaging Findings
- There are two major radiological findings associated with NTM disease: Fibrocavitary and nodular bronchiectatic forms.
- High resolution computed tomography (HRCT) is the imaging modality of choice for NTM lung disease.
- On HRCT, the fibro-cavitary form of NTM is characterized by cavities with areas of increased opacity, usually located in the upper lobes, pleural thickening and volume loss by fibrosis with traction bronchiectasis are frequent. Unlike pulmonary tuberculosis, cavitation in NTM is thin-walled without lymph node calcification, no atelectasis and usually progresses more slowly.
- HRCT of nodular bronchiectatic form may demonstrate bilateral, multilobar bronchiectasis, especially in the middle and lower lung fields, with small nodules.

## Other Diagnostic Studies
-  may also be diagnosed using .
- Findings on  include , , and .

# Prophylaxis and Treatment of NTM Disease
- Treatment and prophylaxis for NTM lung disease are based on the particular pathogens involved, the severity of the disease, (whether is cavitary or nodular/bronchiectasis), assessment of risks and benefits of therapy for individual patients. Treatment requires prolonged use of a combination of multiple drugs.
- For the treatment of MAC pulmonary disease in most patients with nodular/bronchiectatic disease, a three-times-weekly regimen of clarithromycin (1,000 mg) or azithromycin (500 mg), rifampin (600 mg), and ethambutol (25 mg/kg) is recommended. For patients with cavitary MAC lung disease or severe nodular/bronchiectatic disease, a daily regimen of clarithromycin (5001,000 mg) or azithromycin (250 mg), rifampin (600 mg) or rifabutin (150300 mg), and ethambutol (15 mg/kg) with consideration of three-times-weekly amikacin or streptomycin early in therapy is recommended. Patients should be treated until culture negative on therapy for 1 year.
- Treatment of disseminated MAC disease: Therapy should include clarithromycin (1,000 mg/d) or azithromycin (250 mg/d) and ethambutol (15 mg/kg/d) with or without rifabutin (150350 mg/d). Therapy can be discontinued after the resolution of symptoms and reconstitution of cell-mediated immune function.
- Prophylaxis of disseminated MAC disease: Prophylaxis should be given to adults with acquired immunodeficiency syndrome (AIDS) with CD4+ T-lymphocyte counts less than 50 cells/l. Azithromycin 1,200 mg/week or clarithromycin 1,000 mg/day have proven efficacy. Rifabutin 300 mg/day is also effective but less well tolerated.
- Treatment of M.kansasii pulmonary disease. A regimen of daily isoniazid (300 mg/d), rifampin (600 mg/d), and ethambutol (15 mg/kg/d). Patients should be treated until culture negative on therapy for 1 year.
- Treatment of M.abscessus pulmonary disease. There are no drug regimens of proven or predictable efficacy for treatment of M.abscessus lung disease. Multidrug regimens that include clarithromycin 1,000 mg/day may cause symptomatic improvement and disease regression. Surgical resection of the localized disease combined with multidrug clarithromycin-based therapy offers the best chance for cure of this disease.
- Treatment of nonpulmonary disease caused by RGM (M.abscessus, M.chelonae, M.fortuitum). The treatment regimen for these organisms is based on in vitro susceptibilities. For M.abscessus disease, a macrolide-based regimen is frequently used. Surgical debridement may also be an important element of successful therapy.
- Treatment of NTM cervical lymphadenitis. NTM cervical lymphadenitis is due to MAC in the majority of cases and treated primarily by surgical excision, with a greater than 90% cure rate. A macrolide-based regimen should be considered for patients with extensive MAC lymphadenitis or poor response to surgical therapy.

# Surgery
- Surgical resection in conjunction with multidrug clarithromycin-based therapy is the most common approach to the treatment of localized M.abscessus lung disease.

# Prevention
- Effective measures for the primary prevention of NTM pulmonary disease include avoidance of exposure to NTM rich environments such as soil and water. Some experts believe that decreasing exposure to NTM organisms may be helpful preventive methods.