Mycobacterium Avium Complex (MAC) (Mycobacterium Avium-Intracellulare [MAI])

Updated: Dec 15, 2022
  • Author: Janak Koirala, MD, MPH, FACP, FIDSA; Chief Editor: Michael Stuart Bronze, MD  more...
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Mycobacterium avium complex (MAC) infection in humans is caused by two main species: M avium and Mycobacterium intracellulare; because these species are difficult to differentiate, they also are collectively referred to as Mycobacterium avium-intracellulare (MAI). MAC is the atypical Mycobacterium most commonly associated with human disease.

MAC is primarily a pulmonary pathogen that affects individuals who are immune compromised (eg, from AIDS, hairy cell leukemia, immunosuppressive chemotherapy). In this clinical setting, MAC has been associated with osteomyelitis, tenosynovitis, synovitis, and disseminated disease involving lymph nodes, CNS, liver, spleen, and bone marrow. MAC is the most common cause of infection by nontuberculous mycobacteria (NTM) in patients with AIDS. M avium is the isolate in more than 95% of patients with AIDS who develop MAC infections.

MAC lung disease occurs rarely in immunocompetent hosts. Patients with underlying lung disease or immunosuppression may develop progressive MAC lung disease. M intracellulare is responsible for 40% of such infections in immunocompetent patients.

MAC is ubiquitous in distribution. It has been isolated from fresh water and salt water worldwide. The common environmental sources of MAC include piped plumbing systems, including household and hospital water supplies, bathrooms, hot tubs, aerosolized water, house dust, soil, birds, farm animals, and cigarette components (eg, tobacco, filters, paper). [1, 2, 3]

In patients who may have pulmonary infection with MAC, diagnostic testing includes acid-fast bacillus (AFB) staining and culture of sputum specimens. If disseminated MAC (DMAC) infection is suspected, culture specimens also should include blood and urine. (See Workup.) In areas with a high prevalence of tuberculosis (TB), most cases of MAC infection are misdiagnosed and treated as TB. [3]

In general, MAC infection is treated with 2 or 3 antimicrobials for at least 12 months. Commonly used first-line drugs include macrolides (clarithromycin or azithromycin), ethambutol, and rifamycins (rifampin, rifabutin). Aminoglycosides, such as streptomycin and amikacin, also are used as additional agents. MAC lymphadenitis in children is treated with surgical excision of the affected lymph nodes. (See Treatment.)



MAC is transmitted via inhalation into the respiratory tract and ingestion into the GI tract. It then translocates across mucosal epithelium, infects the resting macrophages in the lamina propria and spreads in the submucosal tissue. MAC is then carried to the local lymph nodes by lymphatics. In immunocompromised hosts, such as those with AIDS, the bacteria subsequently spread hematogenously to the liver, spleen, bone marrow, and other sites.

Disseminated MAC (DMAC) infection usually develops in patients with AIDS and/or lymphomas whose CD4 count has fallen below 50 cells/µL. In patients with AIDS, colonization of the GI or respiratory tract has been associated with an increased risk of developing MAC bacteremia. Approximately 60% of patients with MAC colonization in one series developed bacteremia; however, screening cultures from the respiratory or GI tract are not useful because most patients who develop bacteremia are not colonized prior to developing disseminated disease.

The most important risk factor for MAC infection in patients without HIV infection is underlying lung disease. Pulmonary disease is the most common manifestation of MAC infection in these patients. It also can cause lymphadenitis in children. MAC has surpassed Mycobacterium scrofulaceum as the most common cause of cervical adenitis in developed countries.

Both tumor necrosis factor (TNF)–alpha and interferon (IFN)–gamma play important roles in defending against mycobacterial infections. Like other mycobacteria, MAC can cause disseminated infection in multiple family members who have a deficiency of IFN-gamma receptor expression or IFN-gamma production due to genetic defects.

MAC also has been associated with pulmonary infection and bronchiectasis in elderly women without pre-existing lung disease. Pulmonary MAC infection in this population is believed to be due to voluntary cough suppression that results in stagnation of secretions, which creates an environment suitable for growth of the organisms. [4] This particular type of infection also is referred to as Lady Windermere syndrome (see the image below). A study comparing elderly women with NTM infection to a matching control group found no difference in cough reflex between the two groups; however, when a low intensity of cough stimulus was administered, the group with NTM infection did not sense the urge to cough. The authors concluded that these elderly women with NTM infection might have blunted airway afferent sensation and reduced central neural sensory processing. [5]

MAC also has been associated with a hypersensitivity pneumonitis-like reaction (known as hot-tub lung) in patients exposed to aerosolized MAC. [6, 2] Hot-tub lung is thought to be caused by a pulmonary response to infectious aerosols of MAC. However, the roles of other organic and inorganic cofactors present in the aerosols and host predispositions have not been established.

Some studies have reported an association between M aviumparatuberculosis and Crohn disease. A clear causation has not been established, however, and the pathophysiology remains largely unexplored. [7]

MAI also causes cutaneous disease. These infections occur by 3 separate mechanisms, which occur in unique patient populations with different morphologic manifestations. MAI infection may involve the skin primarily via posttraumatic inoculation, secondarily as a manifestation of disseminated Mycobacterium avium-intracellulare (DMAI) systemic disease, and by direct extension as a complication of cervical lymphadenitis.



MAC infections are caused by M avium and M intracellulare, which are acid-fast atypical mycobacteria that belong to group III in the Runyon classification of nontuberculous mycobacteria. Additional species of MAC have been identified using genetic sequencing technology. However, their role in causing human disease has not been established except for Mycobacterium chimaera, whose role also remains controversial. [8] M avium is further divided into four subspecies based on molecular, biochemical, and growth characteristics: M avium subspecies hominissuis, M avium subspecies avium, M avium subspecies paratuberculosis,and M avium subspecies ​silvaticum. [9, 10]  M aviumhominissuis is the only important subspecies associated with human infection, although M avium paratuberculosis has a possible association with Crohn disease.M avium paratuberculosis is a well-known cause of paratuberculosis (Johne Disease) in cattle, but its role in the etiology of Crohn disease in humans remains to be proven. [9]

MAC is present in soil and water. It adheres to surfaces in plumbing systems and forms biofilm, which is believed to be the most common source for human infection. [11]

Pulmonary MAC infection is associated with chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), chronic bronchitis, bronchiectasis, cystic fibrosis, and lung cancer. It also is associated with thoracic skeletal abnormalities (eg, pectus excavatum, mild scoliosis, straight back), as may occur in people with mitral valve prolapse.

MAC infection in patients with AIDS or lymphoreticular malignancies is associated with a CD4+ T-lymphocyte count of fewer than 50 cells/µL. MAC infection develops in up to half of people with AIDS. Posttransplantation immunosuppressive therapy also is a risk factor for MAC infection.

Deficiency of IFN-gamma and TNF-alpha production and absence or defects of IFN-gamma receptors also are associated with infections with MAC and other mycobacteria. Familial outbreaks have been reported in association with genetic defects related to IFN-gamma receptors. Patients in advanced stages of HIV infection/AIDS also show decreased production of IFN-gamma and dysregulation of IFN-gamma receptors. [12]

Lady Windermere syndrome is believed to be associated with suppression of cough in otherwise healthy, thin, elderly women. Further studies have shown an increased threshold for urge-to-cough sensation in this group of patients. [5]

M avium and M intracellulare can be differentiated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based on the rpoB gene. Patients with M intracellulare may have more fibrocavitary disease (26% vs 13%), more smear-positive sputum (56% vs 38%), and a less favorable microbiologic response after combination antimycobacterials. [13]

Other possible risk factors for MAC infections include gastroesophageal reflux disease (GERD), peptic acid suppression, and aspiration or microaspiration. [14]

Risk factor for primary cutaneous MAI infection includes traumatic inoculation. Cervical lymphadenitis more commonly occurs in children.



MAC is ubiquitous in the environment. It is considered an opportunistic pathogen whose source in nature is water and soil. The common environmental sources of MAC include piped plumbing systems, including household and hospital water supplies, bathrooms, hot tubs, aerosolized water, house dust, soil, birds, farm animals, and cigarette components (eg, tobacco, filters, paper). [1, 2, 3]

United States statistics

Infections with NTM began to be reported more frequently after the incidence of tuberculosis declined in the 1950s. During 1979-80, NTM represented one third of mycobacterial isolates reported to the Centers for Disease Control and Prevention (CDC), and 61% of these were MAC. MAC and Mycobacterium kansasii are two of the most predominant NTM infections in the United States .

In the United States, MAC infection is considered a nonreportable infectious disease. However, CDC surveillance data from Houston and Atlanta suggest an incidence of 1 case per 100,000 persons per year. [15] A 2009 study in Oregon estimated an annualized rate of 5.6 cases of MAC pulmonary infection per 100,000 population, with most cases (60%) affecting females. [16] One case series revealed cutaneous involvement in 6 of 30 cases of DMAC infection.

DMAC is the most common mycobacterial infection in patients with advanced AIDS. The overall prevalence of DMAC infection increased in the 1980s and early 1990s in the United States following the advent of HIV and AIDS. The highest incidence of DMAC, 37,000 cases, was measured in 1994, at the peak in the AIDS epidemic.

The incidence of DMAC has declined since the adoption of highly active antiretroviral therapy (HAART). Prior to the widespread use of combination antiretroviral therapy (ART), 30% of patients infected with HIV developed DMAC infection, whereas in a 1996 study, only 2% of patients receiving HAART including a protease inhibitor developed DMAC infection. The decrease in DMAC also may reflect the use of antimicrobial prophylaxis in HIV-infected patients.

International statistics

M avium is prevalent worldwide. A surveillance study in France from 2001-2003 estimated that the incidence of NTM pulmonary infections in patients without HIV infection was over 0.7 per 100,000 inhabitants. [17] Similarly, a population-based UK study showed an increase in the incidence of pulmonary MAC infections between 2007 and 2012, from 1.3 cases to 2.2 cases per 100,000 population. Most of these cases occurred in individuals older than 60 years. [18] In 2004, a similar study in New Zealand estimated the incidence of NTM disease at 1.92 per 100,000 population. [19] In these countries, most of the infections were caused by MAC. MAC infection also has been reported from other parts of the world, including Australia, Japan, Tanzania, and Zambia, among others. In countries with a high TB prevalence, many cases of MAC are misdiagnosed and treated as TB since most of the diagnoses are made based on positive AFB sputum results and positive findings on chest radiography. In these high-burden TB areas, 3-39% of suspected cases of TB and 12-30% of patients initially believed to have chronic TB and multiple drug–resistant TB (MDR TB) were found to have NTM infection. [3]

Race-, sex-, and age-related demographics

MAC infection has no racial predilection. Han and Tarrand found that, regardless of any underlying disease, M intracellulare is more pathogenic and tends to infect women increasingly beyond menopause. The prevalence of MAC infection in postmenopausal women was 1.86% in this study. [20] The female-to-male ratio of MAC pulmonary infection was found to be 3:2 in Oregon. [16]

Children are at risk of developing lymphadenitis secondary to MAC infection. Elderly women are at an increased risk for pulmonary MAC disease of the middle lobe, lingula, or both (also known as Lady Windermere syndrome).



Prior to the availability of newer macrolides, the life expectancy of a patient with AIDS and DMAC infection was 4 months. In a 1999 study, the median survival time was 9 months in patients treated with rifabutin, ethambutol, and clarithromycin. [21] Although HIV-infected patients with DMAC infections still have high rates of morbidity and mortality because of their advanced stage of AIDS, those receiving antiretroviral therapy and anti-MAC treatment have a relatively better prognosis.

The most common complications of DMAC infection are anemia, which may require transfusion, and weight loss.

The clinical course of pulmonary MAC infection in patients without HIV infection usually is indolent. In one study, approximately 50% of patients were alive 5 years after diagnosis. Treatment success rate in patients without HIV infection have ranged from 20-90% in various studies, with an average of 50-60% clinical success and 60-75% of sputum conversion rates.

Patients with more extensive disease have a 90% chance of recovery and a 20% chance of relapse after treatment with anti-MAC drugs. Untreated patients with significant lung disease may develop respiratory insufficiency or weight loss. Severe disability or death may result from respiratory failure.

MAC lymphadenitis in children generally has a benign course. Untreated cases may resolve spontaneously, or the affected lymph node may rupture and form a sinus tract.

Fibrocavitary pulmonary disease, BMI less than 18.5 kg/m2, and anemia are negative prognostic factors for both all-cause and MAC-specific mortality in HIV-negative patients. Therefore treatment should not be delayed in these patients with positive MAC cultures. [22]


Patient Education

Provide instructions on potential adverse effects of antimicrobial medications in patients with lung disease who develop pulmonary MAC infection, as well as patients with AIDS who are receiving antimicrobial prophylaxis. Patients with AIDS and MAC infection should be instructed on how to recognize anemia, which can complicate MAC infection and may require transfusion.

For patient education information, see the Bacterial and Viral Infections Center and Procedures Center, as well as Bronchoscopy.