Nontuberculous Mycobacteria (NTM)

What Is NTM?

Nontuberculous mycobacteria (NTM) refers to all the species in the family of mycobacteria that may cause human disease, but do not cause tuberculosis (TB). It is estimated that 86,000 individuals are living with NTM pulmonary disease in the United States. Both here in the United States and globally, there has been an increase in people living with NTM disease. Part of this increase could be the result of more awareness of NTM infection leading to more testing. However, other factors point to increases in NTM in the environment. 

Among the NTM varieties, nearly all can cause extrapulmonary disease (meaning that the disease has spread beyond the lungs to other parts of the body). However, there are species that mainly affect the skin. M. avium and organisms within M. avium complex are the most common NTM to cause pulmonary infections in the U.S. 

Causes

Unlike tuberculosis (TB), which is spread from person to person, nontuberculous mycobacteria (NTM) infections are not considered contagious.

Although NTM bacteria can be found in water and soil, they do not affect most people. How and why people become infected with NTM is not clear. However, the vast majority of people with NTM lung disease seen at National Jewish Health are living with bronchiectasis, cystic fibrosis or COPD. 

Risk Factors

Risk factors can include being immunocompromised or having an autoimmune disorder, along with other inflammatory or congenital disorders that also lead to lung disease. Examples would include living with HIV or being on medications to suppress the immune system during a solid organ transplant or during the treatment of inflammatory bowel disease or other autoimmune disorders.  

While many individuals have an underlying lung condition that increases the risk of infection, the environment can increase risk as well. Recent environmental studies indicate that more humid environments could play a role, with NTM cases seen in Florida, Texas and Hawaii. In contrast, other mycobacteria, such as M. simiae, can be found in more arid climates found in Israel, and parts of the Unites states such as Arizona, New Mexico and Nevada.

Studies have shown that shower heads and other aerosol generating mechanisms have higher concentrations of NTM. There are data to indicate that water entering the lungs, either through swallowing or gastroesophageal reflux, is a way that mycobacteria gain access to the lungs and cause disease. However, it’s unknown if attempting to control exposures through changing showerheads, drinking UV-filtered water or changing one’s environment reduces the risk for disease.   

Types

Under the microscope, NTM and tuberculosis appear quite similar. Careful lab studies must be performed to tell them apart. Most labs are capable of distinguishing between TB and NTM. 

NTM species that usually require treatment include: 

• M. avium complex
• M. kansasii
• M. abscessus 
• M. chelonae
• M. fortuitum
• M. terrae, M. xenopi
• M. simiae
• M. szulgai
• M. malmoense 

Other NTM types predominantly involve the skin, including M. leprae, M. haemophilum and M. marinum.

The type of mycobacterium is important, but so is how often it appears when symptoms are present in a particular part of the body. For example, if a person has M. avium only isolated once from their sputum cultures but they do not have symptoms and do not have chest imaging findings of disease, treatment may be unnecessary. M. fortuitum is a very uncommon cause of lung disease and is more commonly identified as a cause of a skin infection. For all of these mycobacteria, it’s important to consult with your doctor about the significance of a positive culture and if treatment is needed.  

Infections Outside of the Lungs 

NTM most commonly affects the lungs. However, there are species that often involve the skin or other organs, such as M. leprae (the cause of leprosy) and M. ulcerans (the cause of Buruli ulcer). 

Leprosy and Buruli ulcers are extremely rare in the United States. More often, NTM infections are caused by other organisms. In the U.S., NTM infection usually occurs in the context of a traumatic injury, a procedure such as cosmetic surgery or certain cosmetic injections, or, rarely, in the context of other surgical procedures.   While overall these procedures are very safe and done with strict infection control precautions, infections with mycobacteria can occur. Additionally, people who have a weakened immune system, either due to medications they are taking or through another condition can also be at risk.

Signs and Symptoms

Like tuberculosis, nontuberculous mycobacteria  infection often affects the lungs. Therefore, NTM symptoms are similar to those produced by TB. 

Most NTM infections and resulting symptoms progress slowly. Some people may have had an infection for years before they are diagnosed. 

Symptoms may include:

• Cough
• Blood in the sputum (hemoptysis)
• Fatigue
• Fever
• Lack of appetite
• Night sweats
• Loss of energy
• Shortness of breath (dyspnea)
• Weight loss

Coughing is a common symptom and can be either “dry” or “productive” of sputum. The color of the sputum is not helpful in the diagnosis. Blood in the sputum is unusual unless there is airway irritation, due to infection, inflammation or lung disease that has progressed to include a “cavity” (a hole within the lung tissue) or severe bronchiectasis.

Loss of energy also can be described as fatigue. Some people notice they don’t have the energy to do all the activities they used to do. Some people have to take naps to get through the day.

Shortness of breath may occur, but it is not universal. It may be related to an underlying lung disease, such as emphysema, which is exacerbated by the infection.

Sometimes, people will have no symptoms, and the NTM infection is discovered when chest imaging is ordered for other reasons. When this occurs, doctors will often recommend a careful evaluation to look for other conditions that are associated with NTM lung disease. Doctors may help patients manage these associate conditions first before starting antibiotics.  

Symptoms of NTM Outside of the Lungs

Symptoms of an extrapulmonary NTM typically occur within 2–4 weeks of exposure. However, some cases have developed 2–4 months or longer after exposure. The time to before symptoms develop can depend on the part of the body involved and the nature of the exposure. Keep in mind that these symptoms could be due to many different causes, and it’s always important to have a full exam for any new/progressive symptoms.  

Symptoms if NTM infection outside of the lungs may include:

• Single or multiple localized skin lesions at the site where bacteria entered. The lesions may appear as a “bump.” They may be crusted or wart-like in appearance, and are initially not painful. Over weeks or months, they may spread up the affected limb.
• Swelling and eventual pain in the affected area. For example if a person had an injection in their knee, they may start to have knee swelling and pain.  
• Swelling of the lymph nodes

Diagnosis

An NTM diagnosis can be difficult to establish. It is important for your doctor to determine if the infection is TB or NTM, because the treatment is different. If it is NTM, the specific species of NTM is also important. Because these organisms are abundant in the environment, specialists require more than one positive sputum sample. For NTM outside of the lungs (called extrapulmonary NTM), one culture may be sufficient depending on the location of the sample, how it was collected and other symptoms of disease. 

In addition, it is critical for the doctor to determine whether the NTM infection requires treatment. Some people harbor the germs and remain unaffected. They may need to be observed without treatment. Others develop symptoms consistent with progressive illness. A complete medical history and physical examination by a health care provider (often a pulmonary doctor) is often necessary, and your diagnosis may involve the following tests, depending on the type of NTM.

Imaging Tests

CT scan of the chest: A CT or CAT scan is a shortened name for computerized tomography. During a CT scan of the chest, detailed pictures are taken of cross sections or slices of the thoracic structures in your body. Thoracic structures include your lungs, heart and the bones around these areas. Sometimes intravenous contrast is administered to better see the blood vessels in the lung. For extrapulmonary NTM, other imaging may be needed, including an MRI or PET/CT.  

Lab Tests

Sputum cultures: If pulmonary NTM is suspected, an analysis of several sputum cultures is often necessary and must be done at specialized labs. Sputum is the sticky fluid produced in the lungs that is sometimes coughed up. One positive test does not always mean NTM disease is present. 

Other cultures: If extrapulmonary disease is a possibility, then specific cultures from the area of the body that is involved are ideal, as well as pathology specimens. Pathology examinations can help determine whether the mycobacterium found in a culture is responsible for the symptoms.  

Diagnostic Procedures

Bronchoscopy: A bronchoscopy allows the doctor to look inside the airways in the lungs for signs of pulmonary NTM. The bronchoscopy can be recorded to look at later. Your doctor also may do a lavage, which involves putting a small amount of fluid into the airways. The fluid is then pulled out with cells from the airways of your lungs. A biopsy of the airway also may be done, where a small amount of the tissue is taken from the lining of the lung. The cells and tissue can be studied closely to help determine your diagnosis and the best treatment for you.

Diagnosis of NTM Skin Infections

Compared to bacterial skin infections, mycobacterial skin infections are very rare. Providers who are unfamiliar with these rare infections may not think of mycobacteria as a possible cause, leading to delays in diagnosis. Routine bacterial cultures will not detect these infections. Special mycobacterial cultures are required. They are held to incubate for several weeks, as these organisms typically grow very slowly (days to weeks) in culture. In contrast, most other bacterial infections grow within several hours to a couple of days in culture. Talk to your doctor if you are concerned about an NTM skin infection. 

Treatment

Some of the important goals of NTM treatment are improvement in symptoms, including the return of physical function and, ideally, a sustained cure. There are many factors that can impact how a person responds to treatment, including: 

• the type of mycobacterium identified
• the medications available to treat the disease
•  the ability of the patient to remain on a particular treatment regimen 

If sputum cultures become negative and remain negative after treatment, this is considered a microbiologic cure. Doctors also follow clinical symptoms and watch for a resolution of fevers, night sweats, cough, etc. Finally, doctors examine imaging (CT scans of the chest) while patients are being treated, monitoring the improvement in nodes, the closure of cavities and decreases in inflammation.  

For patients with extrapulmonary disease, determining a cure is much more difficult, as performing follow-up cultures may not be feasible or practical. In these scenarios, doctors will use other tests such as markers of inflammation (CRP, ESR), in addition to follow-up imaging to look for improvement in symptoms to guide decisions about when treatment is considered complete and a person is considered cured.

Medications

Most NTM are naturally resistant to common antibiotics. The treatment regimens recommended vary greatly depending on the species. Some of medications used to treat NTM happen to treat tuberculosis (TB) as well. To overcome drug resistance, people with NTM may need to take several different antibiotics at the same time. Typically, the regimen includes three antibiotics. Because these medications may have side effects, close monitoring is important. 

Treatment may be necessary for as long as two years. The goal of pulmonary disease treatment is to achieve “negative” sputum cultures and maintain that result for 12 months before stopping. Other important goals are to improve symptoms and allow for the recovery of physical function and the return to usual activities. Sometimes treatment is ongoing, depending on the severity of the disease.  

The most common organisms involved in human infection are M. avium complex, M. kansasii 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 complex, M. chelonae and M. abscessus can be more challenging to treat, and often three to five medications may be needed. 

Procedures

Depending on how localized the disease is, surgery also may be helpful. Infrequently, rapidly progressing or deeply invasive NTM disease may also result in surgery. Surgery should always be accompanied by antimicrobial therapy.

Clinical Trials

Clinical trials help determine new treatment options for diseases and conditions. Patients with NTM have access to clinical trials and should speak with their physician to determine what trials might work best for them.