Mycobacterium Avium Complex
April  2019

A 65-year-old woman applied for life insurance. She presented to her doctor six months prior to the application. She complained of shortness of breath for the prior two years and a nagging non-productive cough for the past six months. An evaluation by a pulmonologist revealed an SpO2 of 90, a mildly reduced FVC/FEV1 of 69% of predicted, a DLCO of 65% predicted and scattered small nodules and small areas of bronchiectasis bilaterally on computed tomography of the lungs. Bronchial biopsies were benign and washings showed infection with Mycobacterium Avium Complex organisms. No treatment was prescribed. Insurance labs are negative for HIV and within normal limits. Body Mass Index on the exam was 19.

What is the significance of an infection with Mycobacterium Avium Complex and what is the anticipated prognosis?  
Mycobacterium infection can be separated into two categories: those causing tuberculosis or leprosy (i.e., Mycobacterium tuberculosis complex) and the Nontuberculous mycobacteria (NTM). NTM organisms can be further divided into rapidly growing and slow growing species (Table 1). 

Figure 1 - More Common Disease-causing Mycobacterium

Mycobacterium Tuberculosis

​Nontuberculosis Mycobacteria
Rapidly Growing
​Slow Growing
​M. tuberculosis
​M. fortuitum complex
​M. avium complex
​M. bovis
​M. chelonae
​M. terrae complex
​M. africanum
​M. abscessus
​M. ulcerans
​M. microti
​M. smegmatis
​M. xenopi
​M. canetti
​M. mucogenicum
​M. malmoense
​M. leprae

​M. simiae
​M. szulgai
​M. kansasii

​M. marinum

​M gordanae

​M. scrofulaceum
More than 200 species of Mycobacteria have been identified. This chart shows some of the more common disease-causing mycobacteria.

NTM are free living and widely present in the environment. There have been an estimated 200 species of NTM identified. 

The Mycobacterium Avium Complex (MAC) is a subset of the NTM and is made up of genetically similar organisms that are generally slower growing. People who are immune compromised (e.g., HIV infected, being treated for cancer, recipients of organ transplants) are at increased risk for NTM infection, but so are older, non-immunocompromised individuals who have some underlying lung disease. One study found NTM isolates in 13% of cystic fibrosis  (CF) patients tested at 21 treatment centers across the U.S.

MAC organisms have been identified in the plumbing/water supply of infected individuals, and NTM have been found in peat-rich potting soil. 

Population studies in the U.S. and Canada indicate that the incidence of NTM lung disease increased in the first decade of the 21st century. Details of the cause (aging of the population, more immunocompromised individuals, more awareness and testing for the infection, etc.) were not apparent from the studies.  Skin testing studies for exposure to MAC have found that about 40% of subjects are reactive with a predominance (46%) of southern states over northern states (33%). 

Infection with NTM or MAC in immunocompromised individuals is beyond the scope of this case review. However, lung disease associated with MAC occurs in a few typical settings not associated with immune suppression or CF.

Middle-aged or elderly men, often alcoholics or smokers who have underlying lung disease, appear susceptible. In addition, non-smoking women over age 50 who may or may not have underlying lung disease can present with an interstitial pattern on chest X-ray and subsequently test positive for MAC infection. There is also a condition called “hot tub lung” that is a result of hypersensitivity pneumonitis due to MAC. As the name implies, it is associated with hot tub use. Occasionally MAC infections can present as solitary pulmonary nodules. 

The diagnosis of NTM is made in a person with pulmonary symptoms who has fibrosis and cavitations or multifocal bronchiectasis with multiple small nodules on chest radiographic studies, after other causes have been excluded. Additional diagnostic criteria are either two positive sputa obtained at different times, one positive lavage or a lung biopsy positive for NTM. 

In MAC infections, treatment decisions are often made based on clinical status and radiographic findings. Patients with fibrocavitary disease may have rapid progression with destruction of lung tissue and for that reason are usually started on treatment at the time of presentation. 

Patients presenting with nodular bronchiectatic findings on imaging have a more variable course and may be followed closely rather than started on treatment. One series reported that patients with this type of presentation were initially observed without treatment 10%-25% of the time. 

Reasons for delaying treatment include the presence of co-morbidities, the prolonged course of treatment (15-18 months) with dropout rates up to 33%, side effects, the development of antimicrobial resistance and ultimate recurrence rates that approach 50%. Studies of the organisms involved in recurrence revealed that ~25% were recurrence, while ~75% were reinfections. 

Risk factors
Risk factors for progression of MAC include low BMI, increasing number of segments involved, cavitary disease, male sex, older age, hypoalbuminemia, anemia and elevated inflammation markers (ESR, CRP). A series of 265 patients with untreated nodular bronchiectatic MAC were followed for a mean of 32 months, and 48% had progression of disease requiring treatment.

Cavitations and consolidation on computed tomography increased the risk of progression. Another series of 782 patients with nodular bronchiectatic MAC, a mean age of 68.1 years and a median follow-up of 4.3 years had a 10-year mortality rate of 27.4%.

Returning to the case
The applicant was recently discovered to have MAC pulmonary disease. There are poor prognostic signs in mildly impaired pulmonary function, bronchiectasis and low BMI. It would be prudent, given the recent diagnosis, to wait for subsequent follow-up to assess the rate of progression.  

Johnson M. et al. “Nontuberculous mycobacterial pulmonary infections,” J Thorac Dis 2014;6(3):210-220.

Marras T, et al. “Variable agreement among experts regarding Mycobacterium avium complex lung disease,” Respirology 2015 20(2):348-51.

Gochi M eta l. “Retrospective study of the predictors of mortality and radiographic deterioration in 782 patients with nodular/ bronchiectatic Mycobacterium avium complex lung disease,” BMJ Open 2015;5:e008058. 

Lee G, et al., “Nodular Bronchiectatic Mycobacterium avium Complex Pulmonary Disease: Natural Course on Serial Computed Tomographic Scans,” Ann Am Thorac Soc 2013; 10(4):299-306.

Cowman, S et al., “Latent class analysis to define radiological subgroups in pulmonary nontuberculous mycobacterial disease,” BMC Pulm Med 2018;18:145.

UpToDate – Sections “Preview of nontuberculous mycobacterial infections in HIV-negative patients”, “Epidemiology of nontuberculous mycobacterial infections”, “Diagnosis on nontuberculous mycobacterial infections on the lungs in HIV-negative patients”, and “Treatment of Mycobacterium avium complex lung infection in adults” – last accessed 2/28/19.