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Understanding Nontuberculous Mycobacteria

Dr. Michelle Frank

|

February 6, 2023
CoughPro is not a medical product. It is a wellness app intended only for users to obtain a better understanding of their cough. It is not intended to diagnose, monitor, or treat any illness.

We at Hyfe, Inc., are a company devoted to working on tools to better understand the importance of cough. It is Hyfe’s intention in the future to seek regulatory approval for medical products that analyze cough in order that they may be used to diagnose, monitor, and facilitate better treatment of respiratory illnesses.

Nontuberculous Mycobacteria

When considering the bacteria Mycobacterium, you may immediately associate it with tuberculosis. However, there are other species of this genus of bacteria, over 150 variants, which are capable of causing lung infection1. Nontuberculous mycobacteria (NTM) plays a role in an increasing number of lung infections2, surpassing the disease burden of tuberculosis.

While lung infections are the most common, NTM can also result in infection anywhere in the body. This article will explore the type of bacteria NTM are and how such infections can be diagnosed and treated.

What Is Nontuberculous Mycobacteria?

Mycobacteria are aerobic bacteria, which means they thrive in oxygen-rich environments. They can move and are positively identified through a test called alcoholic acid-fast staining. Soil and water are the biggest reservoirs of nontuberculous mycobacteria. This means that NTM can be transmitted through household plumbing, marshes, peat-rich soil, and aerosol spread of contaminated water3.

Tuberculosis spreads through exposure to contaminated droplets, usually from someone else who has the disease. However, there are no convincing studies to indicate that humans are a likely source of NTM infections. As mentioned, aerosolization of contaminated droplets from water or soil is the most likely method of transfer. This transmission can also occur through household appliances that draw from contaminated sources, such as heaters and showers4.

Some of the most common bacteria species which cause NTM infection are:

  • Mycobacterium avium complex (MAC)
  • Mycobacterium abscessus
  • Mycobacterium kansasii

The reason these groups of bacteria are classified as nontuberculous bacteria is that they come from the same family but don't cause classic tuberculosis. While lung infections can be serious with NTM, especially among those who are immunodeficient (such as on immunosuppressants or with an immunocompromising condition), there are differences in their disease process which warrant a different classification for their infections.

Who Is at an Increased Risk of NTM Infection?

Among those who have efficient immune systems, inhaling NTM bacteria may not cause any symptoms.

Some people are at a higher risk of developing serious NTM infections. Two factors these factors are the strength of your immune defenses and the mycobacterial load present.

One of the most susceptible groups is those who have had previous lung disease. Cystic fibrosis, chronic obstructive pulmonary disease (COPD), bronchiectasis, lung cancer, and those with prior history of tuberculosis come within this high-risk group5.

Another high-risk category is those who have acquired immunodeficiency, such as following HIV infection6. Additionally, those who have blood cell malignancies (various blood cancers) are at risk of developing serious NTM infections.

Patients who have undergone solid organ transplantation, especially lung transplantation, often are observed to develop serious lung infections with NTM, with an increased risk of mortality, particularly among those who have had their lungs transplanted7.

Some cases can receive prophylactic measures to prevent severe illness and curb NTM disease progression. However, due to the risks, it is vital to watch out for the early signs of disease. 

What Are the Symptoms of NTM?

Lung infections with nontuberculous mycobacteria present similarly to viral and bacterial infections that cause pneumonia. Some of the characteristic signs that can imply NTM lung disease include:

  • Relentless cough along with sputum/mucus production
  • Fever
  • Unintentional weight loss
  • Loss of energy
  • Difficulty breathing 
  • Swollen lymph nodes

Chest pain can also be common, especially since it becomes difficult to breathe as lung function deteriorates. Sometimes even after treatment chest pain can linger for a few months until complete recovery.

Because of the disease process of NTM, and since it is mostly observed among immunodeficient individuals, it results in a chronic cough with sputum production. Severe damage to respiratory pathways can also result in hemoptysis, which is coughing up blood8. Therefore, particularly when immunocompromised patients present with a chronic cough, checking for underlying NTM is important9.

How Can Nontuberculous Mycobacteria Be Diagnosed?

There are no specific symptoms that specifically indicate an exact diagnosis for nontuberculous mycobacteria. However, if you have a chronic cough, fever, or swollen lymph nodes, and fall under a high-risk category, it is best to get a check up for NTM.

Initially, your doctor will conduct a thorough examination and ask you for relevant medical history to understand whether you could have an infection with nontuberculous mycobacteria. They will also investigate possible exposure to contaminated water or soil. Next is a physical examination of your lungs to distinguish underlying lung infections. You can read about all the possible tests the doctor may conduct here.

Some of the early lab investigations include a chest X-ray and a collection of your sputum. Sputum may contain bacteria, so it will be stained with an acid-fast reagent to give a preliminary diagnosis of any possible mycobacterial infectious agents. It will also be cultured.

Findings from a chest X-ray can show nodular opacities and areas of fibrosis. NTM also presents with areas of bronchiectasis. 9.3% of patients with bronchiectasis have an NTM infection, making it crucial to consider as a possible diagnosis10

Further Testing

However, such findings on X-rays are not specific to NTM. This is why further radiography with CT scans can help to confirm a diagnosis. While it may still not be specific, studies have indicated that A.I. technology is helping to make a more precise diagnosis by studying NTM-specific CT scan images11.

Additionally, gene sequencing and amplification methods, such as the polymerase chain reaction (PCR) technique, confirm a diagnosis. Once your doctor suspects it's NTM, they use this often because different NTM species require different drugs for treatment.

Ultimately, the definitive diagnosis of NTM will come from the lab test that cultures the bacteria from the sputum.

How Is NTM Treated?

Nontuberculous mycobacteria infections are treated with a multi-drug regime because of the chances of bacterial resistance. Different species of NTM will have different drug combinations in the treatment regimes.

Macrolide antibiotics, such as clarithromycin or azithromycin, are the mainstay for the management of NTM12. These often go along with rifamycin and ethambutol. This drug combination is given in a thrice-a-week dose, rather than daily13. You continue this multiple-drug regime for 12–18 months.

During treatment, regular sputum cultures are conducted to check if the antibiotics are helping reduce bacterial load. When 12 months of cultures come back negative, you will usually stop the antibiotic treatment.

Surgery may sometimes be required to manage NTM. For cases where there's resistance to antibiotics, more localized lesions may benefit from surgical removal14. Surgery can also prove useful when complicated cases, such as those presenting with massive hemoptysis (vomiting blood), show up.

Additionally, patients of NTM also undergo lung rehabilitation during the course of their treatment. This can include methods to clear the airways of mucus collection. Physical therapy and postural drainage (taking certain body positions to help fluid drain from various parts of the lungs) can be conducted.

Patients who have HIV are recommended to receive prophylaxis for possible mycobacterium avium complex infections. When levels of T-helper cells (part of the immune system) fall below 75–100 cells per microliter, patients are given azithromycin prophylaxis15. This treatment is continued until the level of T-helper cells increase.

To prevent the worsening of lung condition, immunizations against the flu and other possible causes of superinfection should be considered. Patients are recommended to quit habits such as smoking and to limit exposure to such irritants within their environments.

Conclusion

Currently, the cases of nontuberculous mycobacterial infections are higher than those of tuberculosis. A lot of this rise is due to the asymptomatic spread of the NTM bacteria. NTM can result in severe lung disease, especially among those who are immunocompromised. Since symptoms are non-specific, such as a chronic cough, fever, weight loss, and swelling of the lymph nodes, specific diagnostic tests are crucial to confirm a diagnosis. NTM is treated with a multi-drug regime including macrolide, rifamycin, and ethambutol. Supportive care such as lung rehabilitation and immunizations can also help the outcomes of NTM.

  1. Greif, G., Coitinho, C., van Ingen, J., & Robello, C. (2020). Species Distribution and Isolation Frequency of Nontuberculous Mycobacteria, Uruguay. Emerging infectious diseases, 26(5), 1014–1018. https://doi.org/10.3201/eid2605.191631[]
  2. Ratnatunga, C. N., Lutzky, V. P., Kupz, A., Doolan, D. L., Reid, D. W., Field, M., Bell, S. C., Thomson, R. M., & Miles, J. J. (2020). The Rise of Non-Tuberculosis Mycobacterial Lung Disease. Frontiers in Immunology, 11. https://doi.org/10.3389/fimmu.2020.00303[]
  3. Falkinham J. O., 3rd (2013). Ecology of nontuberculous mycobacteria--where do human infections come from?. Seminars in respiratory and critical care medicine, 34(1), 95–102. https://doi.org/10.1055/s-0033-1333568[]
  4. Falkinham, J. O., 3rd, Iseman, M. D., de Haas, P., & van Soolingen, D. (2008). Mycobacterium avium in a shower linked to pulmonary disease. Journal of water and health, 6(2), 209–213. https://doi.org/10.2166/wh.2008.032[]
  5. Ratnatunga, C. N., Lutzky, V. P., Kupz, A., Doolan, D. L., Reid, D. W., Field, M., Bell, S. C., Thomson, R. M., & Miles, J. J. (2020). The Rise of Nontuberculous Mycobacterial Lung Disease. Frontiers in immunology, 11, 303. https://doi.org/10.3389/fimmu.2020.00303[]
  6. Lapinel, N. C., et al.(2019). Prevalence of non-tuberculous mycobacteria in HIV-infected patients admitted to hospital with pneumonia. The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease, 23(4), 491–497. https://doi.org/10.5588/ijtld.18.0336[]
  7. Huang, H. C., et al.(2011). Non-tuberculous mycobacterium infection after lung transplantation is associated with increased mortality. The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation, 30(7), 790–798. https://doi.org/10.1016/j.healun.2011.02.007[]
  8. Minomo, S., Kobayashi, T., Katayama, K., Ryuge, M., Kagawa, T., Tsuyuguchi, K., Matsui, H., & Suzuki, K. (2021). Risk factors for hemoptysis in Mycobacterium avium complex lung disease. Respiratory investigation, 59(2), 218–222. https://doi.org/10.1016/j.resinv.2020.09.007[]
  9. Finegold I. (2008). Nontuberculous mycobacterial infection in the differential diagnosis of chronic cough. Allergy and asthma proceedings, 29(3), 343–344. https://doi.org/10.2500/aap.2008.29.3124[]
  10. Chu, H., Zhao, L., Xiao, H., Zhang, Z., Zhang, J., Gui, T., Gong, S., Xu, L., & Sun, X. (2014). Prevalence of nontuberculous mycobacteria in patients with bronchiectasis: a meta-analysis. Archives of medical science: AMS, 10(4), 661–668. https://doi.org/10.5114/aoms.2014.44857[]
  11. Wang, L., Ding, W., Mo, Y., Shi, D., Zhang, S., Zhong, L., Wang, K., Wang, J., Huang, C., Zhang, S., Ye, Z., Shen, J., & Xing, Z. (2021). Distinguishing nontuberculous mycobacteria from Mycobacterium tuberculosis lung disease from CT images using a deep learning framework. European journal of nuclear medicine and molecular imaging, 48(13), 4293–4306. https://doi.org/10.1007/s00259-021-05432-x[]
  12. Egelund, E. F., Fennelly, K. P., & Peloquin, C. A. (2015). Medications and monitoring in nontuberculous mycobacteria infections. Clinics in chest medicine, 36(1), 55–66. https://doi.org/10.1016/j.ccm.2014.11.001[]
  13. Ryu, Y. J., Koh, W. J., & Daley, C. L. (2016). Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease: Clinicians' Perspectives. Tuberculosis and respiratory diseases, 79(2), 74–84. https://doi.org/10.4046/trd.2016.79.2.74[]
  14. Mitchell J. D. (2015). Surgical approach to pulmonary nontuberculous mycobacterial infections. Clinics in chest medicine, 36(1), 117–122. https://doi.org/10.1016/j.ccm.2014.11.004[]
  15. Phillips, P., Chan, K., Hogg, R., Bessuille, E., Black, W., Talbot, J., O'Shaughnessy, M., & Montaner, J. (2002). Azithromycin prophylaxis for Mycobacterium avium complex during the era of highly active antiretroviral therapy: evaluation of a provincial program. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 34(3), 371–378. https://doi.org/10.1086/324743[]

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