NONTUBERCULOSIS MYCOBACTERIA DEFINITION
Nontuberculous mycobacteria (NTM) are organisms naturally found in soil and water. In some people, the organism infects the airways and lung tissue leading to disease.
NONTUBERCULOSIS MYCOBACTERIA CAUSES
Unlike tuberculosis (TB), which is spread from person to person, nontuberculous mycobacteria (NTM) infections are not considered contagious. There is no evidence that the infection can be transmitted from one person to another. How and why people become infected with NTM is not clear and the nontuberculous mycobacteria (NTM) causes are still under investigation.
Although the germs are found easily in water and soil, they do not affect most people. Doctors believe that some people who become infected have an unknown defect in their lung structure or function or in their immune systems. People who have damaged lung tissue from diseases such as emphysema, bronchiectasis, adult cystic fibrosis or previous TB infection appear to be at greater risk for developing a NTM infection. People who are immunocompromised such as those who receive strong immunosuppressant medications such as prednisone or some newer immunosuppressants such as TNF inhibitors have a greater risk of developing an NTM infection that affects all organs of the body, not only the lungs. Patients with AIDS may also develop NTM infections.
Currently there is a “hypothesis” or “theory” about acquiring NTM from a shower. In considering an apparent increase in the number of NTM lung disease cases seen over the past 25 years, it has been noted by researchers in the field, such as Dr. Pace in Boulder and Dr. Falkinham in Virginia, that NTMs may be commonly recovered from home water systems.
We speculate that in the recent past people tend to take showers rather than bathe in a tub, and when showering in a closed stall the concentration of NTMs could be higher. Additionally, to save energy, water heaters have lower temperatures now, which could allow more NTM growth in the water. These are preliminary findings and further research is required to confirm these theories.
Additionally, there are newer data to indicate that aspiration of water that we drink associated with reflux may be an additional way that mycobacteria gain access to the lungs and causes disease.
NONTUBERCULOSIS MYCOBACTERIA PATHOPHYSIOLOGY
Atypical mycobacteria are obligate aerobes that can be found in the environment in soil, water, vegetables, and even in domestic animals and dairy products. Mycobacterium avium complex (MAC) and Mycobacterium scrofulaceum are associated with lymphadenitis in immunocompetent children. All nodes in the cervical chain can be affected, but the nodes of the submandibular region appear to be the most commonly involved. Disseminated infections are usually associated with HIV infection. Host immunity seems to play a major role because a low CD4+ lymphocyte count (fewer than 100 cells/μL for adults and age-appropriate decreases in children) is associated with an increased frequency of disseminated MAC disease.
Some cytokines such as interleukin (IL)–1 alpha and IL-6 enhance extracellular growth of the organism. IL-6 also promotes intracellular growth of MAC, apparently by down-regulating membrane receptors for tumor necrosis factor (TNF)–alpha. Other cytokines, such as interferon (IFN)–gamma and IL-2, work in the other direction. IL-2 enhances lymphocyte proliferation and cytotoxic activity and upregulates production of IFN-gamma. Ongoing studies are establishing the additional roles of cytokines.
In immunocompromised patients, the intestinal tract is the primary route for MAC infection, followed by the respiratory tract as a secondary portal of entry.[15, 16] CD4+ lymphocytes but not CD8+ or gamma delta+ lymphocytes are required for host protection against MAC and dissemination through the intestinal route. Abnormal immune response to MAC colonization may cause invasion of the epithelial cells of the gastrointestinal tract, followed by disseminated disease. In one series of adult patients infected with HIV with positive respiratory or stool isolates, 75% developed mycobacteremia within a year (mean 6 mo) after the isolation. A preceding stool culture positive for isolates was present in 25-36% of the patients. Pulmonary disease in adults without acquired immunodeficiency syndrome (AIDS) may occur.
Disseminated MAC in children without HIV has been described in the literature. It is associated in some cases with IFN-gamma receptor ligand-binding deficiency, which is a recently identified autosomal recessive inherited disorder. Affected children show a severe and apparently selective susceptibility to weakly pathogenic mycobacteria (either Bacillus Calmette-Guérin or NTM. This condition has revealed the importance of IFN-gamma in the control of mycobacterial disease in humans. The importance of immune reconstitution produced by highly active antiretroviral therapy (HAART) in reducing susceptibility to MAC infection may provide clues to the critical role of the host immune defense and may establish the basis for the use of immunotherapy in disseminated MAC disease.
MAC has also been associated with the pulmonary infection and bronchiectasis in elderly women without a preexisting lung disease. Pulmonary MAC infection in this population is believed to be due to voluntary cough suppression that results in stagnation of secretions, which is suitable for growth of the organisms. This particular type of infection is also referred to as Lady Windermere syndrome.
NONTUBERCULOSIS MYCOBACTERIA SYMPTOMS
Like tuberculosis (TB), a nontuberculous mycobacteria (NTM) infection also affects the lungs. Therefore, nontuberculous mycobacteria symptoms are similar. Most NTM infections and resulting symptoms progress slowly. Symptoms may include:
- Weight loss
- Lack of appetite
- Night sweats
- Blood in the sputum (phlegm)
- Loss of energy
NONTUBERCULOSIS MYCOBACTERIA DIAGNOSIS
The diagnosis of NTMB frequently poses challenges to the clinician. As stated, NTMB are ubiquitous to the environment and may represent contamination rather than actual isolates. Additionally, NTMB may colonize the airways of individuals with structural lung abnormalities. Recovery of these organisms may represent airway colonization rather than true infection. Therefore, discovery of NTMB does not necessarily reflect disease. The diagnosis must be based on a high clinical suspicion that is compatible with symptoms and features found on x-ray.
Because of the frequent difficulty with microbiologic isolation of these organisms, the updated ATS guidelines allow for a more liberal diagnosis of NTMB based on compatible symptoms and clinical findings. However, a presumptive diagnosis based solely on clinical and x-ray findings, especially in normal, immunocompetent hosts, may not be correct and could expose individuals to prolonged courses of unnecessary, often toxic medical regimens.
The evaluation of suspected of NTMB infections should include x-ray imaging and culture from the affected site. Isolation of NTMB in culture is essential for the diagnosis of NTMB lung disease. In cases of pulmonary disease (the most common site of infection), bronchial cultures should be obtained. Patients should have at least 3 sputum specimens collected on separate days, and NTMB should be confirmed by positive results in 2 of these 3 specimens. Unfortunately, sputum cultures are often negative, and bronchoscopic washing or preferably lavage may be a useful diagnostic tool. In the right clinical setting, a single positive culture from bronchoscopic washing or lavage may be considered diagnostic. Specimens obtained from biopsy (transbronchial lung biopsy, surgical lung biopsy, or excisional biopsy from infected tissue) are also diagnostic if they produce isolation of NTMB or show granulomatous inflammation on histopathologic examination. In the right clinical setting with highly suspicious clinical and x-ray findings, tests in which cultures are negative should be repeated as isolation of NTMB is often difficult.
Although the ATS guidelines facilitate an easier diagnosis, a single positive culture may be indeterminate to provide a reliable diagnosis of NTMB. The new criteria requiring only a single positive culture may be too liberal, and a presumptive diagnosis based on clinical features and x-ray results alone may not be adequate to justify initiation of therapy. Contamination is common, especially with sputum samples. Even rinsing of the mouth with tap water can cause false positive results. Likewise, cleaning the bronchoscope or culture plates with tap water can also result in contamination and false-positive results. Therefore, a reliable diagnosis must be based on both a highly suspicious clinical picture and confident microbiologic studies. Without this, all positive cultures should be highly scrutinized, especially with less common species or in species known to be common contaminants (M gordonae, M mucogenicum, M terrae, M kansasii, Mabscessus).
As stated, the presentation of NTMB may be similar to that of active TB. Both can produce cavitary pulmonary infiltrates, extra pulmonary disease, granuloma formation, hemoptysis, and constitutional symptoms. Therefore, M tuberculosis disease must be excluded in all cases of suspected NTMB, especially with acid-fast bacillus smear positivity. Furthermore, empiric therapy for TB should be considered pending confirmation of NTMB infection. Other pulmonary granulomatous diseases such as sarcoidosis and fungal infection can resemble NTMB and should be included in the differential diagnosis.
NONTUBERCULOSIS MYCOBACTERIA TREATMENT
Most of the nontuberculousmycobactera infections are naturally resistant to many common antibiotics. It is often necessary to use some of the same medications that are used to treat tuberculosis (TB). In order to overcome drug resistance, you may need to take several different antibiotics at the same time. Because many of these medications have side effects, close monitoring is important. Furthermore, treatment may be necessary for as long as two years. Sometimes treatment is ongoing, depending on the severity of the disease.
The most common organisms involved in human infection are M. kansasii, M. avium, M. intracellulare, M. chelonae and M. abscessus. M. kansasii is easier to treat and often can be killed with only three anti-TB medications. On the other hand, organisms such as M. avium, M. chelonae and M. abscessus are among the most stubborn germs. They are more difficult to treat. Three to five medications may be needed. Depending on how localized the disease is, surgery also may be helpful.