Mycobacterium avium-intracellulare infection

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Mycobacterium avium-intracellulare infection
Other namesMycobacterium avium complex infection
Lady windermere syndrome ct.JPG
CT scan of patient with right middle lobe aspiration and Mycobacterium avium infection consistent with Lady Windermere syndrome
Specialty Infectious disease   OOjs UI icon edit-ltr-progressive.svg

Mycobacterium avium-intracellulare infection (MAI) is an atypical mycobacterial infection, i.e. one with nontuberculous mycobacteria or NTM, caused by Mycobacterium avium complex ("MAC"), which is made of two mycobacteria species, M. avium and M. intracellulare. [1] This infection causes respiratory illness in birds, pigs, and humans, especially in immunocompromised people. In the later stages of AIDS it can be very severe. It usually first presents as a persistent cough. It is typically treated with a series of three antibiotics for a period of at least six months.

Nontuberculous mycobacteria (NTM), also known as environmental mycobacteria, atypical mycobacteria and mycobacteria other than tuberculosis (MOTT), are mycobacteria which do not cause tuberculosis or leprosy. NTM do cause pulmonary diseases that resemble tuberculosis. Mycobacteriosis is any of these illnesses, usually meant to exclude tuberculosis. They occur in many animals, including humans.

Mycobacterium avium complex is a group of mycobacteria comprising Mycobacterium intracellulare and Mycobacterium avium that are commonly grouped together because they infect humans together; this group, in turn, is part of the group of nontuberculous mycobacteria. These bacteria cause disease in humans called Mycobacterium avium-intracellulare infection or Mycobacterium avium complex infection.

Infection invasion of a host by disease-causing organisms

Infection is the invasion of an organism's body tissues by disease-causing agents, their multiplication, and the reaction of host tissues to the infectious agents and the toxins they produce. Infectious disease, also known as transmissible disease or communicable disease, is illness resulting from an infection.


M. avium, M. intracellulare, and M. chimaera are each saprotrophic organisms present in soil and water; entry into hosts is usually via the gastrointestinal tract, but also can be via the lungs.

Organism Any individual living physical entity

In biology, an organism is any individual entity that propagates the properties of life. It is a synonym for "life form".

Gastrointestinal tract organ system within humans and other animals pertaining the stomach and intestines

The gastrointestinal tract is an organ system within humans and other animals which takes in food, digests it to extract and absorb energy and nutrients, and expels the remaining waste as feces. The mouth, esophagus, stomach and intestines are part of the gastrointestinal tract. Gastrointestinal is an adjective meaning of or pertaining to the stomach and intestines. A tract is a collection of related anatomic structures or a series of connected body organs.

Lung Essential respiration organ in many air-breathing animals

The lungs are the primary organs of the respiratory system in humans and many other animals including a few fish and some snails. In mammals and most other vertebrates, two lungs are located near the backbone on either side of the heart. Their function in the respiratory system is to extract oxygen from the atmosphere and transfer it into the bloodstream, and to release carbon dioxide from the bloodstream into the atmosphere, in a process of gas exchange. Respiration is driven by different muscular systems in different species. Mammals, reptiles and birds use their different muscles to support and foster breathing. In early tetrapods, air was driven into the lungs by the pharyngeal muscles via buccal pumping, a mechanism still seen in amphibians. In humans, the main muscle of respiration that drives breathing is the diaphragm. The lungs also provide airflow that makes vocal sounds including human speech possible.

MAC infections can cause fevers, diarrhea, malabsorption, as well as loss of appetite and weight loss, and can disseminate to the bone marrow. MAI is typically resistant to standard mycobacterial therapies.

Fever common medical sign characterized by elevated body temperature

Fever, also known as pyrexia and febrile response, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using values between 37.5 and 38.3 °C. The increase in set point triggers increased muscle contractions and causes a feeling of cold. This results in greater heat production and efforts to conserve heat. When the set point temperature returns to normal, a person feels hot, becomes flushed, and may begin to sweat. Rarely a fever may trigger a febrile seizure. This is more common in young children. Fevers do not typically go higher than 41 to 42 °C.

Diarrhea Loose or liquid bowel movements

Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin with loss of the normal stretchiness of the skin and irritable behaviour. This can progress to decreased urination, loss of skin color, a fast heart rate, and a decrease in responsiveness as it becomes more severe. Loose but non-watery stools in babies who are exclusively breastfed, however, are normal.

Malabsorption human disease

Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety of anaemias.

Signs and symptoms

Symptoms are similar to tuberculosis (TB), and include fever, fatigue, and weight loss. Pulmonary involvement is similar to TB, while diarrhea and abdominal pain are associated with gastrointestinal involvement.

Tuberculosis Infectious disease caused by the bacterium Mycobacterium tuberculosis

Tuberculosis (TB) is an infectious disease usually caused by Mycobacterium tuberculosis (MTB) bacteria. Tuberculosis generally affects the lungs, but can also affect other parts of the body. Most infections do not have symptoms, in which case it is known as latent tuberculosis. About 10% of latent infections progress to active disease which, if left untreated, kills about half of those affected. The classic symptoms of active TB are a chronic cough with blood-containing mucus, fever, night sweats, and weight loss. It was historically called "consumption" due to the weight loss. Infection of other organs can cause a wide range of symptoms.


M. avium and M. haemophilum infections in children form a distinct clinical entity, not associated with abnormalities of the immune system. M. avium typically causes unilateral swelling of one of the lymph nodes of the neck. This node is firm at the beginning, but a collarstud abscess' is formed eventually, which is a characteristic blue-purple in colour with multiple discharging sinuses. The treatment of choice is surgical excision of the affected lymph nodes, [2] with antibiotic treatment (usually clarithromycin and rifabutin for 18 to 24 months) reserved for those patients who cannot have surgery.

Clarithromycin chemical compound

Clarithromycin, sold under the brand name Biaxin among others, is an antibiotic used to treat various bacterial infections. This includes strep throat, pneumonia, skin infections, H. pylori infection, and Lyme disease, among others. Clarithromycin can be taken by mouth as a pill or liquid.

Rifabutin chemical compound

Rifabutin (Rfb) is an antibiotic used to treat tuberculosis and prevent and treat Mycobacterium avium complex. It is typically only used in those who cannot tolerate rifampin such as people with HIV/AIDS on antiretrovirals. For active tuberculosis it is used with other antimycobacterial medications. For latent tuberculosis it may be used by itself when the exposure was with drug-resistant TB.


MAC bacteria are common in the environment and cause infection when inhaled or swallowed. Recently, M. avium has been found to deposit and grow in bathroom shower heads from which it may be easily aerosolized and inhaled. [3]


Mycobacterium avium complex (MAC), also called Mycobacterium avium-intracellulare complex, is a microbial complex of three Mycobacterium species (i.e. M. avium, M. intracellulare, and M. chimaera. [4] It causes Mycobacterium avium-intracellulare infection. [5] [6] Some sources also include Mycobacterium avium subspecies paratuberculosis (MAP). [7]

Risk factors

MAI is common in immunocompromised individuals, including senior citizens and those with HIV/AIDS or cystic fibrosis. Bronchiectasis, the bronchial condition which causes pathological enlargement of the bronchial tubes, is commonly found with MAI infection. Whether the bronchiectasis leads to the MAC infection or is the result of it is not always known. [8]

The Mycobacterium avium complex (MAC) includes common atypical bacteria, i.e. nontuberculous mycobacteria (NTM), found in the environment which can infect people with HIV and low CD4 cell count (below 100/microliter); mode of infection is usually inhalation or ingestion.

MAC causes disseminated disease in up to 40% of people with human immunodeficiency virus (HIV) in the United States, producing fever, sweats, weight loss, and anemia. [9] [10] [11] Disseminated MAC (DMAC) characteristically affects people with advanced HIV disease and peripheral CD4+ T-lymphocyte counts less than 50 cells/uL. Effective prevention and therapy of MAC has the potential to contribute substantially to improved quality of life and duration of survival for HIV-infected persons. [12]


Mycobacterium avium complex is the most commonly found form of non-tuberculous mycobacteria. [13]

Immunodeficiency is not a requirement for MAI. [14]

Mycobacterium avium complex (MAC) usually affects patients with abnormal lungs or bronchi. However, Jerome Reich and Richard Johnson describe a series of six patients with MAC infection of the right middle lobe or lingula who did not have any predisposing lung disorders. [15] [16]

The right middle lobe and lingula of the lungs are served by bronchi that are oriented downward when a person is in the upright position. As a result, these areas of the lung may be more dependent upon vigorous voluntary expectoration (cough) for clearance of bacteria and secretions.

Since the six patients in their retrospective case series were older females, Reich and Johnson proposed that patients without a vigorous cough may develop right middle lobe or left lingular infection with MAC. They proposed this syndrome be named Lady Windermere syndrome, after the character Lady Windermere in Oscar Wilde's play Lady Windermere's Fan. However, little research has confirmed this speculative cause. [17]


Diagnosis can be achieved through blood cultures or cultures of other bodily fluids such as sputum. Bone marrow culture can often yield an earlier diagnosis but is usually avoided as an initial diagnostic step because of its invasiveness.

Many people will have anemia and neutropenia if the bone marrow is involved. MAC bacteria should always be considered in a person with HIV infection presenting with diarrhea.

The diagnosis requires consistent symptoms with two additional signs:

Disseminated MAC is most readily diagnosed by one positive blood culture. Blood cultures should be performed in patients with symptoms, signs, or laboratory abnormalities compatible with mycobacterium infection. Blood cultures are not routinely recommended for asymptomatic persons, even for those who have CD4+ T-lymphocyte counts less than 100 cells/uL. [12]

HIV infection

MAC in patients with HIV disease is theorized to represent recent acquisition rather than latent infection reactivating (which is the case in many other opportunistic infections in immunocompromised patients).

The risk of MAC is inversely related to the patient's CD4 count and increases significantly when the CD4 count decreases below 50 cells/mm³. Other risk factors for acquisition of MAC infection include using an indoor swimming pool, consumption of raw or partially cooked fish or shellfish, bronchoscopy and treatment with granulocyte stimulating factor.

Disseminated disease was previously the common presentation prior to the advent of highly active antiretroviral therapy (HAART). Today, in regions where HAART is the standard of care, localized disease presentation is more likely. This generally includes a focal lymphadenopathy/lymphadenitis.


People with AIDS are given macrolide antibiotics such as azithromycin for prophylactic treatment. [18]

People with HIV infection and less than 50 CD4+ T-lymphocytes/uL should be administered prophylaxis against MAC. Prophylaxis should be continued for the patient's lifetime unless multiple drug therapy for MAC becomes necessary because of the development of MAC disease. [12]

Clinicians must weigh the potential benefits of MAC prophylaxis against the potential for toxicities and drug interactions, the cost, the potential to produce resistance in a community with a high rate of tuberculosis, and the possibility that the addition of another drug to the medical regimen may adversely affect patients' compliance with treatment. Because of these concerns, therefore, in some situations rifabutin prophylaxis should not be administered. [12]

Before prophylaxis is administered, patients should be assessed to ensure that they do not have the active disease due to MAC, M. tuberculosis, or any other mycobacterial species. This assessment may include a chest radiograph and tuberculin skin test. [12]

Rifabutin, by mouth daily, is recommended for the people's lifetime unless disseminated MAC develops, which would then require multiple drug therapy. Although other drugs, such as azithromycin and clarithromycin, have laboratory and clinical activity against MAC, none has been shown in a prospective, controlled trial to be effective and safe for prophylaxis. Thus, in the absence of data, no other regimen can be recommended at this time. The 300-mg dose of rifabutin has been well tolerated. Adverse effects included neutropenia, thrombocytopenia, rash, and gastrointestinal disturbances. [12]


Postinfection treatment involves a combination of antituberculosis antibiotics, including rifampicin, rifabutin, ciprofloxacin, amikacin, ethambutol, streptomycin, clarithromycin or azithromycin.

NTM infections are usually treated with a three-drug regimen of either clarithromycin or azithromycin, plus rifampicin and ethambutol. Treatment typically lasts at least 12 months.

Although studies have not yet identified an optimal regimen or confirmed that any therapeutic regimen produces sustained clinical benefit for patients with disseminated MAC, the Task Force concluded that the available information indicated the need for treatment of disseminated MAC. The Public Health Service, therefore, recommends that regimens be based on the following principles: [12]

Clinical manifestations of disseminated MAC—such as fever, weight loss, and night sweats—should be monitored several times during the initial weeks of therapy. The microbiologic response, as assessed by blood culture every 4 weeks during initial therapy, can also be helpful in interpreting the efficacy of a therapeutic regimen. Most patients who ultimately respond show substantial clinical improvement in the first 4–6 weeks of therapy. Elimination of the organism from blood cultures may take somewhat longer, often requiring 4–12 weeks. [12]

HIV-infected children

HIV-infected children less than 12 years of age also develop disseminated MAC. Some age adjustment is necessary when clinicians interpret CD4+ T-lymphocyte counts in children less than 2 years of age. Diagnosis, therapy, and prophylaxis should follow recommendations similar to those for adolescents and adults. [12]

Society and culture


"Lady Windermere syndrome" is one term to describe infection in the lungs due to MAC. [15] It is named after a character in Oscar Wilde's play Lady Windermere's Fan . [19]

In recent years, some have described the eponym as inappropriate, [20] and some have noted that it would have been unlikely that Lady Windermere had the condition to which her name was assigned. [21]

The more commonly used term is nontuberculous mycobacteria (NTM) infection, or non-tuberculous mycobacterial infection (NMI). There is no evidence that a person's reluctance to spit has any causal role in NTM infection, the chief reason for the term having been applied to older women presenting with the condition. [22]

Lady Windermere syndrome is a type of mycobacterial lung infection. [23]

Literary reference

The original Chest article proposing the existence and pathophysiology of the Lady Windermere syndrome suggested the character Lady Windermere in Oscar Wilde's Victorian-era play Lady Windermere's Fan is a good example of the fastidious behavior believed to cause the syndrome. The article states:

We offer the term, Lady Windermere's Syndrome, from the Victorian-era play, Lady Windermere's Fan, to convey the fastidious behavior hypothesized: "How do you do, Lord Darlington. No, I can't shake hands with you. My hands are all wet with the roses."

Victorian women presumably believed "ladies don't spit," and consequently might have been predisposed to develop lung infection.

Shortly after the Lady Windermere syndrome was proposed, a librarian wrote a letter to the editor of Chest [24] challenging the use of Lady Windermere as the eponymous ancestor of the proposed syndrome. In the play, Lady Windermere is a vivacious young woman, married only two years, who never coughs or displays any other signs of illness. While her avoidance of shaking hands might be interpreted as "fastidiousness", two alternative explanations may be just as probable:

1) Lady Windermere actually is in the midst of arranging flowers and consequently cannot properly greet her guest:
[LADY WINDERMERE is at table R., arranging roses in a blue bowl.] [25]
2) Lady Windermere wishes to discourage the flirtatious advances of her would-be suitor Lord Darlington and cites her wet hands as an excuse to keep him from touching her:
LADY WINDERMERE. Lord Darlington, you annoyed me last night at the Foreign Office. I am afraid you are going to annoy me again. . . .
LORD DARLINGTON. [Takes chair and goes across L.C.] I am quite miserable, Lady Windermere. You must tell me what I did. [Sits down at table L.]
LADY WINDERMERE. Well, you kept paying me elaborate compliments the whole evening.] [25]

The scholars highlight the literary malapropism, [26] but some in the medical community have adopted the term regardless, and peer-reviewed medical journals still sometimes mention the Lady Windermere syndrome, although it is increasingly viewed as a limiting and sexist term for a serious bacterial infection. [27] [28]

See also

Related Research Articles

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