eMedicine Specialties > Infectious Diseases > Mycobacterial Infections

Mycobacterium Avium-Intracellulare

Author: Janak Koirala, MD, MPH, FACP, FIDSA, Associate Professor, Department of Internal Medicine, Division of Infectious Diseases, Southern Illinois University School of Medicine
Contributor Information and Disclosures

Updated: Jan 12, 2010

Introduction

Background

Mycobacterium avium complex (MAC) consists of two species— M avium and M intracellulare. Because these species are difficult to differentiate, they are also collectively referred to as Mycobacterium avium-intracellulare (MAI) .

MAC causes disseminated infection in immunocompromised hosts, but only a minority of immunocompetent hosts with MAC infection develop MAC lung disease. Patients with underlying lung disease or immunosuppression may develop progressive MAC lung disease. M avium is the isolate in more than 95% of patients with AIDS who develop MAC infections; M intracellulare is responsible for 40% of such infections in immunocompetent patients. MAC is the most common cause of infection by nontuberculous mycobacteria (NTM) in patients with AIDS.

MAC is ubiquitous in distribution. It has been isolated from freshwater and saltwater worldwide. The common environmental sources of MAC include aerosolized water, piped hot water systems (including household and hospital water supplies), bathrooms,1 house dust, soil, birds, farm animals, and cigarette components such as tobacco, filters, and paper.

Pathophysiology

MAC is transmitted via inhalation through the respiratory tract and ingestion via the GI tract.

MAC can invade and translocate across the mucosal epithelium. The bacteria subsequently infect the resting macrophages in the lamina propria and spread in the submucosal tissue; they are then carried to the local lymph nodes by lymphatics. In immunocompromised hosts, such as patients with AIDS, they are subsequently spread hematogenously to the liver, spleen, bone marrow, and other sites.

Patients with MAC infection who have AIDS and/or lymphomas usually develop disseminated MAC (DMAC) infection when their CD4 count falls 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 is 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 MAC infection in these patients. It can also 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 has also been associated with the pulmonary infection and bronchiectasis in elderly women without a 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 is suitable for growth of the organisms.2 This particular type of infection is also referred to as Lady Windermere syndrome (see image below).

CT thorax of a 77-year-old woman who presented wi...

CT thorax of a 77-year-old woman who presented with chronic cough and sputum production, without a history of underlying pre-existing lung disease. Sputum culture grew Mycobacterium avium complex. The diagnosis was Lady Windermere syndrome.

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CT thorax of a 77-year-old woman who presented wi...

CT thorax of a 77-year-old woman who presented with chronic cough and sputum production, without a history of underlying pre-existing lung disease. Sputum culture grew Mycobacterium avium complex. The diagnosis was Lady Windermere syndrome.


MAC has been also associated with a hypersensitivity pneumonitislike reaction (known as hot-tub lung) in patients exposed to aerosolized MAC.3,4 Hot-tub lung is thought to be caused by a pulmonary response to infectious aerosols of MAC found in water. However, the roles of other organic and inorganic cofactors present in the aerosols and host predispositions have not been established.

Although some studies have reported an association between Mycobacterium avium paratuberculosis and Crohn disease, a clear causation has not been established, and the pathophysiology remains largely unexplored.5

Frequency

United States

NTM infections 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 .

A recent 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.6

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 but has since declined because of the subsequent use of highly active antiretroviral therapy (HAART). Prior to the widespread use of combination antiretroviral therapy, 30% of patients infected with HIV developed DMAC infection. In a 1996 study, only 2% of patients receiving HAART, including a protease inhibitor, developed DMAC infection.

International

M avium is prevalent worldwide. A surveillance study estimated that, in France from 2001-2003, the incidence of NTM pulmonary infections in patients without HIV infection was 0.72-0.74 per 100,000 inhabitants.7 In 2004, a similar study in New Zealand showed an incidence of NTM disease estimated at 1.92 per 100,000 population.8 Most of these infections were caused by MAC in both countries. MAC infection has also been reported from other parts of the world, including Australia, Japan, Tanzania, and Zambia, among others.

Mortality/Morbidity

MAC may be isolated from the sputum of immunocompetent patients without any evidence of lung disease. Transient MAC colonization was reported in up to 11% of patients with tuberculosis in the 1950s. Repeated isolation of MAC from sputum, even in the absence of obvious lung disease, may signify an underlying slow progression of lung disease.

  • 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.9 Life expectancy is now longer with the wider use of effective antiretroviral therapy. The most common complication of DMAC infection is anemia that may require transfusion. 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.
  • The clinical course of pulmonary MAC infection in patients without HIV infection is usually indolent. Approximately 50% of patients in one study were alive 5 years after diagnosis. Patients with extensive parenchymal involvement may die of progressive respiratory failure, but the associated mortality rate is low in patients with milder disease.
  • In children, MAC lymphadenitis generally has a benign course. It may resolve spontaneously or may rupture and form a sinus tract in untreated cases.

Race

  • MAC infection has no racial predilection.

Sex

  • Han and Tarrand (2005) 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.10 The female-to-male ratio of MAC pulmonary infection was found to be 3:2 in Oregon.6

Age

  • 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).

Clinical

History

M avium complex (MAC) infection usually presents in 1 of 3 forms: (1) pulmonary MAC infection in immunocompetent hosts, (2) disseminated MAC (DMAC) infection in individuals with advanced AIDS, or (3) MAC lymphadenitis in children.

  • Pulmonary MAC infection in immunocompetent hosts generally manifests as cough, sputum production, weight loss, fever, lethargy, and night sweats. The onset of symptoms is insidious. Symptoms may be present for weeks to months. Many patients have only a chronic cough with purulent sputum production. Hemoptysis is rare in MAC infection. Less commonly, MAC has been associated with hot-tub lung, a type of hypersensitivity pneumonitislike lung disease due to exposure to MAC in hot tubs.
  • Patients with advanced AIDS (generally with CD4 counts <50 cells/µL) and DMAC infection commonly present with fever of unknown origin (FUO). They usually also have sweating, weight loss, fatigue, diarrhea, shortness of breath, and right upper quadrant abdominal pain. In addition, other reported MAC infection manifestations in patients with AIDS have included mastitis, pyomyositis, cutaneous abscess, brain abscess, and GI mycobacteriosis. Immune reconstitution syndrome associated with MAC has been reported in patients with underlying MAC infection presenting shortly after the introduction of HAART.
  • MAC lymphadenitis is predominantly a disease of children aged 1-4 years, primarily involving unilateral cervical lymph nodes. It usually involves submandibular and submaxillary lymph nodes, although preauricular, postauricular, and submental nodes may also be affected. Rarely, infection of the axillary, epitrochlear, or inguinal lymph nodes may develop following direct cutaneous inoculation. The lymph nodes usually enlarge insidiously but may enlarge more rapidly in younger children. Generally, they resolve spontaneously. The lymph nodes may also caseate and rupture through the skin, forming a sinus tract with chronic discharge.
  • Less commonly, patients may present with skin and soft-tissue infections, osteomyelitis, peritonitis (in patients with cirrhosis), bursitis, septic arthritis, and tenosynovitis.

Physical

Physical findings in MAC infection depend on the form of infection and the patient.

  • In immunocompetent patients with pulmonary MAC infection, generally lung crackles, rhonchi, or both can be heard on auscultation. Additionally, depending on the type of lung lesion and severity of infection, patients with pulmonary MAC infection may have tachypnea, dullness on chest percussion, or bronchial breath sounds.
  • DMAC infection in patients with AIDS can cause generalized wasting, skin pallor, tender hepatosplenomegaly, and lymphadenopathy.
  • Lymphadenitis in children can cause unilateral enlargement of submandibular, preauricular, parotid, and/or postauricular lymph nodes. They are usually multiple and rubbery to firm and may appear to be fixed to the deeper structures. They may become matted together as the disease progresses. The overlying skin may appear shiny, thin, and erythematous or violaceous. Sinus tracts may be present in advanced cases.
  • Patients with synovitis may present with pain and swelling of a joint or features of bursitis or tenosynovitis.

Causes

MAC infections are caused by M avium and M intracellulare, which belong to the Runyon group 3 mycobacteria. M avium is further divided into various subspecies based on molecular, biochemical, and growth characteristics. Mycobacterium avium avium is the only important subspecies associated with human infection, whereas M avium paratuberculosis has been associated with Crohn disease . Although M avium paratuberculosis is a well-known cause of paratuberculosis (Johne Disease) in cattle, its role in the etiology of Crohn disease in humans remains to be proven.

Some of the known predisposing factors for MAC infections include the following:

  • Pulmonary MAC infection is associated with chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), chronic bronchitis, bronchiectasis, cystic fibrosis, mitral valve prolapse, skeletal abnormalities (eg, pectus excavatum, mild scoliosis, straight back), and lung cancer.
  • MAC infection in patients with AIDS or lymphoreticular malignancies is associated with a CD4+ lymphocyte count of under 50 cells/µL.
  • Deficiency of IFN-gamma and TNF-alpha production and absence or defects of IFN-gamma receptors are also 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.11
  • Lady Windermere syndrome is believed to be associated with suppression of cough in otherwise healthy, thin, elderly women.
  • Other possible risk factors include gastroesophageal reflux disease (GERD), acid suppression, and aspiration or microaspiration.12

More on Mycobacterium Avium-Intracellulare

Overview: Mycobacterium Avium-Intracellulare
Differential Diagnoses & Workup: Mycobacterium Avium-Intracellulare
Treatment & Medication: Mycobacterium Avium-Intracellulare
Follow-up: Mycobacterium Avium-Intracellulare
Multimedia: Mycobacterium Avium-Intracellulare
References
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References

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Further Reading

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Keywords

Mycobacterium avium complex, MAC, M avium complex , Mycobacterium avium-intracellulare, M avium-intracellulare, Mycobacterium avium, M avium, Mycobacterium intracellulare, M intracellulare, MAI, Lady Windermere syndrome, MAC lung disease, disseminated MAC, DMAC, disseminated M avium complex, MAC bacteremia, MAC infection, MAC lymphadenitis, hot-tub lung, MAC mastitis, MAC pyomyositis, Mycobacterium avium avium, M avium avium, Mycobacterium avium paratuberculosis, M avium paratuberculosis

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Contributor Information and Disclosures

Author

Janak Koirala, MD, MPH, FACP, FIDSA, Associate Professor, Department of Internal Medicine, Division of Infectious Diseases, Southern Illinois University School of Medicine
Janak Koirala, MD, MPH, FACP, FIDSA is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians-American Society of Internal Medicine, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, International Society for Infectious Diseases, and International Society of Travel Medicine
Disclosure: Nothing to disclose.

Medical Editor

Klaus-Dieter Lessnau, MD, FCCP, Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital
Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Artificial Internal Organs, American Thoracic Society, Physicians for Social Responsibility, and Society of Critical Care Medicine
Disclosure: sepracor Ownership interest None

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Aaron Glatt, MD, Professor of Clinical Medicine, New York Medical College; President and CEO, Former Chief Medical Officer, Departments of Medicine and Infectious Diseases, New Island Hospital
Aaron Glatt, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Infectious Diseases Society of America, International AIDS Society, and Society for Healthcare Epidemiology of America
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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