Nontuberculous mycobacteria

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Nima Nasiri, M.D.[2]

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

• [Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
• In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
• In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].

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 [disease name] is characterized by [feature1], [feature2], and [feature3].
• The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
• On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
• On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

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 [disease name] is approximately [number or range] per 100,000 individuals worldwide.
• In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].

Age

• Patients of all age groups may develop [disease name].

• [Disease name] is more commonly observed among patients aged [age range] years old.
• [Disease name] is more commonly observed among [elderly patients/young patients/children].

Gender

• [Disease name] affects men and women equally.

• [Gender 1] are more commonly affected with [disease name] than [gender 2].
• The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

Race

• There is no racial predilection for [disease name].

• [Disease name] usually affects individuals of the [race 1] race.
• [Race 2] individuals are less likely to develop [disease name].

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 [disease name] remain asymptomatic for [duration/years].
• Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
• If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
• Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
• Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with [disease name] 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 [disease name] usually appear [general appearance].
• Physical examination may be remarkable for:

• [finding 1]
• [finding 2]
• [finding 3]
• [finding 4]
• [finding 5]
• [finding 6]

Laboratory Findings

• There are no specific laboratory findings associated with [disease name].

• A [positive/negative] [test name] is diagnostic of [disease name].
• An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
• Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

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

• [Disease name] may also be diagnosed using [diagnostic study name].
• Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

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 (500–1,000 mg) or azithromycin (250 mg), rifampin (600 mg) or rifabutin (150–300 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 (150–350 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/μl. 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.