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

Updated: Oct 17, 2019
Author: Janak Koirala, MD, MPH, FACP; Chief Editor: Michael Stuart Bronze, MD 

Overview

Background

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 are also 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 Mycobacterium avium complex (MAC), diagnostic testing includes acid-fast bacillus (AFB) staining and culture of sputum specimens. If disseminated MAC (DMAC) infection is suspected, culture specimens should also 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, are also used as additional agents. MAC lymphadenitis in children is treated with surgical excision of the affected lymph nodes. (See Treatment.)

Pathophysiology

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 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 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 is also 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 has been also 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.

Etiology

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 is also 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 is also a risk factor for MAC infection.

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.[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]

No risk factors for primary cutaneous MAI infection or cervical adenitis are known.

Epidemiology

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

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 .

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 may also 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 elderly individuals (>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 has also 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).

Prognosis

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 is usually 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. AIDS patients with MAC infection should be instructed on how to recognize anemia, which can complicate MAC infection in these patients and may require transfusion.

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

 

Presentation

History

Mycobacterium avium complex (MAC) infection usually presents in 1 of 3 forms:

  • Pulmonary MAC infection in immunocompetent hosts

  • Disseminated MAC (DMAC) infection in individuals with advanced AIDS

  • 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 pneumonitis-like lung disease due to exposure to MAC in hot tubs.

Patients with advanced AIDS (generally with CD4 counts < 50 cells/µL) who have DMAC infection commonly present with fever of unknown origin (FUO). Usual signs and symptoms are as follows:

  • Sweating

  • Weight loss

  • Fatigue

  • Diarrhea

  • Shortness of breath

  • 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. These cases develop shortly after the patient initiates HAART.

MAC lymphadenitis is predominantly a disease of children aged 1-4 years, primarily involving unilateral cervical lymph nodes. Submandibular and submaxillary lymph nodes are the usual sites, but 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. The lymphadenitis generally resolves spontaneously, but the lymph nodes may also caseate and rupture through the skin, forming a sinus tract with chronic discharge.

Less commonly, MAC may produce any of the following:

  • Skin and soft-tissue infections

  • Osteomyelitis

  • Peritonitis (in patients with cirrhosis)

  • Bursitis

  • Septic arthritis

  • Tenosynovitis

Any history of the introduction of a foreign object (eg, needle, splinter) should be sought if cutaneous MAC infection is suspected.

Physical Examination

Physical findings in MAC infection depend on the form of infection and the patient. In immunocompetent patients with pulmonary MAC infection, lung crackles, rhonchi, or both can generally 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. Involved nodes are usually multiple and rubbery to firm and may appear to be fixed to 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.

Complications

Patients with MAC lymphadenitis may develop sinus tract with drainage.

Patients with cavitary MAC lesions may develop secondary bacterial or fungal infection.

Patients with HIV/AIDS may develop immune reconstitution inflammatory syndrome (IRIS) after initiation of antiretroviral and anti-MAC therapies. This may mimic worsening of symptoms and paradoxical enlargement of infected lymph nodes.

 

DDx

Diagnostic Considerations

Cutaneous infection, a rare manifestation of Mycobacterium avium complex (MAC) infection, should be considered in patients with antibiotic-resistant cellulitis, in those with nonhealing nodules and ulcers, and in patients who are immunosuppressed with evidence of disseminated MAC infection. Primary cutaneous infection is rare, but it does not necessarily mandate a workup for immunosuppression. Of note, isoniazid is a first-line agent in the treatment of M tuberculosis, but it is ineffective for DMAC infection.

Perrin reported a patient with AIDS and a cutaneous MAC infection that mimicked histoid leprosy.[23]

Other problems to be considered in the differential diagnosis of MAC infection include the following:

  • Mumps

  • Parotid tumor

  • HIV wasting

  • Lung cancer

  • Lymphoma

  • Mycobacterium scrofulaceum infection

  • Other nontuberculous mycobacterial infections

Differential Diagnoses

 

Workup

Approach Considerations

In patients who may have pulmonary infection with Mycobacterium avium complex (MAC), diagnostic testing includes acid-fast bacillus (AFB) staining and culture of sputum specimens. If disseminated MAC (DMAC) infection is suspected, culture specimens should also include blood and urine. Stool cultures can be collected if diarrhea is present. Cutaneous lesions should be cultured.

Imaging studies of the chest should be performed to assess pulmonary involvement.

In patients with DMAC, a complete blood count (CBC) often shows anemia and occasionally pancytopenia due to bone marrow suppression secondary to the infection, although either leukocytosis or leukopenia may be present. Hypogammaglobulinemia may be found. On liver function studies, patients with DMAC usually have elevated transaminase and alkaline phosphatase levels.

An enzyme immunoassay (EIA) kit used in Japan has been used to detect serum IgA antibody to MAC-specific glycopeptidolipid core antigen. This could be useful for serodiagnosis of MAC pulmonary infection. Sensitivity and specificity of this EIA kit were reported as 84% and 100%, respectively.[24] Other serological tests are also currently under investigation.

If pulmonary or disseminated MAC infection is suspected, an HIV test should be performed.

Diagnosis of MAC lymphadenitis in children generally involves lymph node biopsy or complete excision of lymph nodes. Skin testing (MAC tuberculin test) contributes very little in establishing diagnosis.

The American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) have issued guidelines for the diagnosis, treatment, and prevention of nontuberculous mycobacterial pulmonary infection.[25]

ATS/IDSA Diagnostic Guidelines

ATS/IDSA guidelines for NTM mycobacterial lung disease

The ATS/IDSA guidelines include clinical/radiographic and bacteriologic criteria to establish a diagnosis of nontuberculous mycobacterial lung disease.[25]

Clinical and radiographic criteria are as follows (both criteria required):

  • Pulmonary symptoms, nodular or cavitary opacities on chest radiography, or a high-resolution CT scan that shows multifocal bronchiectasis with multiple small nodules
  • Appropriate exclusion of other diseases (eg, carcinoma, tuberculosis)

Bacteriologic criteria are as follows (at least one required):

  • At least 2 culture-positive sputum samples
  • At least one culture-positive bronchial washing or lavage
  • Biopsy with histopathologic features consistent with mycobacterial infections (eg, granulomatous inflammation or positive AFB stain) and positive culture result (sputum, endobronchial, or biopsy specimen)

Other considerations are as follows:

  • When NTM are recovered in regions where they are unusual pathogens or they are typically environmental contaminants, an expert consultation should be obtained.
  • If patients suspected of having NTM lung disease do not meet the diagnostic criteria, they should be monitored until the diagnosis is firmly established or excluded.
  • Treatment decisions for NTM infection should be based on potential risks and benefits of therapy for the individual patient.

ATS/IDSA suggested criteria for diagnosis of hot-tub lung

The ATS/IDSA guidelines recommend basing the diagnosis of hot-tub lung (hypersensitivity pneumonitis-like lung disease) on a compatible clinical picture, including hot-tub exposure, microbiological data, radiographic findings, and histopathology. In the absence of histopathology, evidence for hot-tub lung needs to include the following:

  • Subacute onset of respiratory symptoms
  • Hot-tub exposure
  • Characteristic radiologic changes (ground-glass opacities, centrilobular nodules, air trapping on expiratory CT scans)
  • Isolation of MAC from sputum, bronchoalveolar lavage (BAL), lung tissue, and hot-tub water

Acid-Fast Bacillus Stains and Cultures

At least 3 sputum specimens, preferably early-morning samples taken on different days, should be collected for AFB staining and culture. Sputum AFB stains are positive for MAC in most patients with pulmonary MAC infection. Mycobacterial cultures grow MAC in about 1-4 weeks, depending on the culture technique and bacterial burden.

If patient is unable to produce sputum, sputum induction may be helpful in obtaining respiratory tract sample. Procedures such as bronchoscopy with bronchoalveolar lavage (BAL) with or without biopsy may be necessary to obtain appropriate respiratory specimen.

Interpretation of sputum AFB stain and culture may be difficult, as MAC can colonize the respiratory tract without causing clinical infection. See the American Thoracic Society (ATS)/Infectious Disease Society of America (IDSA) guidelines for clinical interpretation of culture results.

The species-specific molecular probes are used for rapid identification of mycobacterial species grown in culture (eg, Mycobacterium tuberculosis, M kansasii, MAC). Various nucleic acid amplification techniques (eg, polymerase chain reaction [PCR], ligase chain reaction, transcription-mediated amplification) are also used for this purpose, as well as for direct detection of mycobacteria in the sputum. However, these assays need further refinement to improve their sensitivity to detect mycobacteria directly in patient's specimens.

Mycobacterial susceptibility testing for various antimycobacterial agents is available in specialized laboratories. Because studies have shown poor correlations between in vitro susceptibility results and clinical outcome, the ATS/IDSA guidelines recommend routine antibiotic susceptibility testing for clarithromycin only. The guidelines also recommend susceptibility testing in patients who have previously received macrolide therapy, who relapse or fail to respond after 6 months of treatment, who develop bacteremia on macrolide prophylaxis, and who develop persistent bacteremia after 3 months of treatment with macrolide-based therapy. Based on the experience at the author's institution, susceptibility tests are reliable if performed selectively at highly experienced laboratories that specialize in mycobacteriology.

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.

Blood cultures

Blood cultures in appropriate mycobacterial culture media should be performed for suspected disseminated MAC (DMAC) infection. This should be performed routinely in patients with advanced AIDS and persistent undiagnosed febrile illness. Over 90% of patients with DMAC infection have positive blood culture results and do not require invasive methods for diagnosis. Blood cultures generally take 1-2 weeks to turn positive. Early in the course of infection, bacteremia may be low-level or intermittent, possibly causing false-negative blood culture results. Later in the course of infection, blood cultures results are invariably positive.

Chest Radiography and Computed Tomography

Chest radiography is indicated to assess pulmonary involvement if disseminated disease is suspected. One series found that 8 of 11 cases of DMAC infection with cutaneous involvement had positive results on chest radiographs.

Chest radiography generally reveals MAC pulmonary lesions. However, in cases with limited lung infection, CT scanning of the chest and even high-resolution CT (HRCT) scanning are needed to reveal the lung lesions. HRCT scanning has been shown to be more sensitive than chest radiography for revealing pulmonary abnormalities associated with MAC infection.

Patients with pulmonary MAC infection with underlying lung disease often have cavities revealed by imaging studies. Typically, these patients have fibrocavitary changes and nodules that involve the upper lung zones.

Chest radiograph in a 67-year-old man who smokes a Chest radiograph in a 67-year-old man who smokes and has a history of chronic obstructive pulmonary disease (COPD) and Mycobacterium avium complex (MAC) infection.

Elderly women without underlying lung disease but with MAC pulmonary infection develop a fibronodular bronchiectasis that often involves the lingula and right middle lobe. A strong association between MAC infection and bronchiectasis with circumscribed nodules has been shown in these patients. Surveys of patients with fibronodular bronchiectasis have documented MAC infection in 25-50% of patients.

Other radiological changes include atelectasis, consolidation, tree-in-bud appearance, and ground-glass opacities.

Thoracic CT scan in a 72-year-old woman who presen Thoracic CT scan in a 72-year-old woman who presented with chronic cough and sputum production, without a history of an underlying pre-existing lung disease. Sputum culture grew Mycobacterium avium complex (MAC). The diagnosis was Lady Windermere syndrome.

In patients with AIDS and DMAC infection, CT scan of the abdomen reveals retroperitoneal or periaortic lymphadenopathy and hepatosplenomegaly.

Hypersensitivity pneumonitis-like changes characterized by ground-glass attenuation, centrilobular nodules, and air trapping on expiratory images are seen on CT scans in patients with hot-tub lung, which is a type of hypersensitivity pneumonitis-like syndrome described in patients exposed to aerosolized MAC.

Biopsy

Bronchoscopy and transbronchial biopsy may be needed to diagnose pulmonary MAC infection. Alternatively, a CT-guided needle biopsy, video-assisted thoracoscopic (VAT) biopsy, or open lung biopsy may be performed, depending on the size and location of the lesion.

If blood cultures fail to grow MAC in patients with AIDS, procedures that may be helpful to establish diagnosis of DMAC infection include lymph node biopsy, bone marrow biopsy, and liver biopsy. These procedures are also helpful to exclude other causes of lymphadenopathy, anemia, or pancytopenia. Liver biopsy is rarely necessary to establish a diagnosis of MAC infection.

Diagnosis of MAC lymphadenitis is based on a high level of clinical suspicion and biopsy or complete excision of involved nodes with histological and microbiological confirmation. Fine-needle aspiration of lymph nodes has been used to obtain tissue for diagnosis when complete excision is not feasible (eg, for inaccessible nodes, such as those that overlie the facial nerve).

Results of acid-fast staining of tissue or pus are usually negative because of the small number of bacilli present. The culture result may take a few weeks to become positive. Nucleic acid amplification methods can provide a more rapid diagnosis.

Biopsy should be performed in patients with cutaneous lesions. Tissue samples may be obtained for histopathologic evidence of mycobacterial infection, and staining with Ziehl-Neelsen stain may reveal acid-fast bacilli.

Histologic Findings

Histologic findings of MAC infection include necrotizing and nonnecrotizing granulomas and positive AFB smear results. Numbers of AFB are usually higher in MAC infection than in M tuberculosis infection. Patients with HIV/AIDS have evidence of DMAC infection in multiple organs, but granuloma formation is less common. DMAC infection in patients with AIDS typically demonstrates the presence of sheets of macrophages laden with AFB.

Histologic findings of lymph node biopsies in children infected with MAC in a reported series generally showed bright eosinophilic serpiginous necrosis with nuclear debris scattered throughout the necrotic foci. Most of these cases also had Langhans-type giant cells, but infiltration by plasma cells and neutrophils was not consistently observed.

Patients with hypersensitivity pneumonitis secondary to MAC infection show multiple well-formed nonnecrotizing granulomas positive for AFB.

 

Treatment

Approach Considerations

Mycobacterium avium complex (MAC) is intrinsically resistant to many antibiotics and antituberculosis drugs but is fairly susceptible to the following agents:

  • Macrolides (eg, clarithromycin, azithromycin)

  • Rifamycins (eg, rifampin, rifabutin)

  • Ethambutol

  • Clofazimine

  • Fluoroquinolones (eg, ciprofloxacin, levofloxacin, moxifloxacin)

  • Aminoglycosides (eg, amikacin, streptomycin)

  • Inhaled amikacin liposome suspension

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, are also used as additional agents.[26]

In 2007, aerosolized amikacin was found to be an effective adjunctive therapy in a small case series.[27] The FDA approved amikacin liposome inhalation suspension in 2018 for MAC infections as part of a combination antibacterial drug regimen in adults who do not achieve negative sputum culture results after a minimum of 6 consecutive months of a multidrug background regimen therapy. The prescribing information for amikacin liposome inhalation cautions that, since only limited clinical safety and effectiveness data are available, it should be reserved for adults who have limited or no alternate treatment options. The drug gained accelerated approval based on the CONVERT clinical trial (n=336). Patients were randomized 2:1 to receive once-daily amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) or GBT alone. Culture conversion was achieved in 29% of the ALIS-GBT group compared with 8.9% of the GBT group (P< 0.001).[28]

Fluoroquinolones (levofloxacin, moxifloxacin) and clofazimine should be used as second-line agents against MAC because of the poor outcome associated with them compared with macrolide-containing regimens. Linezolid and ketolides also demonstrate good in vitro activity against MAC and other mycobacteria, although clinical data to support their use are lacking.

MAC lymphadenitis in children is treated with surgical excision of the affected lymph nodes. Antibiotics are generally not required but may be beneficial in patients with extensive lymphadenitis or with a poor response to surgical therapy.

Clinical trials have failed to show any significant clinical benefit for antimycobacterial drugs used to treat Crohn disease secondary to M aviumparatuberculosis.[29]

Pulmonary MAC infection in patients with lung disease may require surgical excision of focal pulmonary nodules. Lobectomy has also been recommended for more extensive lung infection in patients who have not responded to antibiotics in the past. This, however, does not occur as often now that more potent antibiotics are available.

The American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) have issued guidelines for the diagnosis, treatment, and prevention of nontuberculous mycobacterial pulmonary infection.[25] Since these guidelines were published, recent antibiotic advances have been reviewed.[30]

Pulmonary MAC Infection in Immunocompetent Patients

In immunocompetent patients with MAC lung disease, treatment decisions should be based on any underlying comorbid conditions, severity of lung disease, risk of progression, and goals of treatment.[31, 10] Patients should be informed about the need for long-term treatment with a multiple-drug regimen, along with the potential risks and benefits of treatment. If the decision is to withhold treatment, the patients should be monitored long-term for any progression in clinical symptoms, radiographic changes, and microbiological evaluations. A Korean study found radiographic progression of fibronodular lung disease in over 97% of untreated patients observed for at least 4 years.[32] A study from Japan found that negative prognostic factors for MAC-specific and all-cause mortality included fibrocavitary with or without nodular/bronchiectatic lung disease, BMI less than 18.5 kg/m2, and anemia.[33]

Treatment of MAC infection in immunocompetent patients involves the combination of a newer macrolide (azithromycin or clarithromycin), ethambutol, and rifabutin. Treatment should be continued for 12 months after sputum culture results for MAC turn negative.

ATS/IDSA guidelines recommend that most patients with nodular or bronchiectatic disease can be treated with a thrice-weekly regimen of clarithromycin 1000 mg or azithromycin 500 mg, rifampin 600 mg, and ethambutol 25 mg/kg. Therapy should be continued for at least one year after culture results revert to negative.[25] Intermittent treatment with three-times-per-week regimens in patients with noncavitary nodular bronchiectatic MAC lung disease has been shown to yield fewer adverse effects and improved compliance.[34]

Lam et al verified comparable results between daily and thrice-weekly therapy in patients with noncavitary lung disease, but found that patients with cavitary lung disease had worse outcomes with thrice-weekly therapy.[35] Therefore, patients with fibrocavitary lung disease or severe nodular or bronchiectatic disease should receive a daily regimen of clarithromycin (500-1000 mg) or azithromycin (250-500 mg), rifampin (600 mg) or rifabutin (150–300 mg), and ethambutol (15 mg/kg).

In addition, the ATS/IDSA guidelines suggest the addition of amikacin or streptomycin thrice-weekly early in the course of treatment (initial 2-3 months) in patients with severe and extensive fibrocavitary lung disease.[25] Streptomycin has been used successfully in combination with macrolides for the first 6-12 weeks of treatment in patients with cavitary lung disease. In situations when rifamycins fail or cannot be taken, clofazimine has also been used with good outcome.[36]

A randomized controlled study showed comparable efficacy and tolerance when either clarithromycin or ciprofloxacin was given to patients with pulmonary MAC infection as a third drug in regimens containing rifampin and ethambutol.[37] Based on these results, it is suggested that fluoroquinolones can be used as a substitute for macrolides.

A macrolide-containing regimen has been shown to carry a cure rate of about 56%, including the dropouts and relapses in the analysis. Macrolides carry high rates of intolerance. Clarithromycin, a cytochrome P-450 inhibitor, interacts with many drugs metabolized in the liver. Similarly, rifamycins are known to induce hepatic enzymes and can alter metabolism of many drugs taken concomitantly.

In 2017, British guidelines suggested nebulized amikacin as an alternative to intravenous amikacin when long-term treatment with an aminoglycoside is required and intravenous or intramuscular injections are impractical or contraindicated.[31] An inhalational form of amikacin liposome was approved by the FDA in 2018 for patients with refractory MAC lung disease defined as failure to achieve negative sputum MAC culture results after 6 months of standard anti-MAC therapy.

A clinical study failed to verify the benefit of inhaled interferon (IFN)-gamma in patients with pulmonary MAC infection.[35] However, patients with a defect in the IFN-gamma pathways may show a better response if IFN-gamma is given in addition to the antimicrobials.

Disseminated MAC Infection in Patients with AIDS

A combination of a newer macrolide antibiotic (eg, clarithromycin, azithromycin) with ethambutol and rifabutin is probably the most active regimen. Efficacies of clarithromycin and azithromycin in DMAC infection have been demonstrated in clinical studies, but monotherapy should be avoided, as it can lead to resistance. Ethambutol appears to be the best second choice to combine with a macrolide. Rifabutin should be used as a third agent.

A study comparing clarithromycin and ethambutol (dual therapy) with clarithromycin, ethambutol, and rifabutin (triple therapy) showed improved microbiological clearance and survival in the triple-therapy arm. Published data suggest 50%-60% microbiological clearance rates for both macrolides when used in combination with ethambutol and rifabutin.

Current guidelines recommend a combination of clarithromycin (500 mg twice daily) and ethambutol (15 mg/kg daily) with or without rifabutin (300 mg daily). Azithromycin (500-600 mg daily) can be substituted for clarithromycin. The addition of rifabutin has been recommended, especially in patients with advanced immunosuppression (CD4+ count < 50 cells/µL), with high mycobacterial loads (>100 colony-forming units/mL of blood), or in the absence of effective antiretroviral therapy.

Based on experience in patients without HIV infection, the guidelines suggest the use of amikacin or streptomycin as third or fourth drugs in these patients.[38]

The guidelines recommend continuing treatment for at least 12 months and until symptoms completely resolve and cellular immunity is reconstituted (sustained CD4 counts >100 cells/µL for 6 months).[38]

Drug interactions are a major problem with rifabutin and clarithromycin (see Medication). Higher doses of rifabutin (≥450 mg/day) are associated with higher rates of uveitis. The usual dose of rifabutin (300 mg/day) should be reduced by half (150 mg/day) if the patient is also receiving protease inhibitors. Higher doses of clarithromycin (1000 mg bid) are associated with higher mortality rates.[38] Clofazimine use in patients with DMAC infection has been associated with a worse outcome.[39]

Fever should improve within 2-4 weeks of therapy initiation. If patients remain febrile for a longer duration than expected, repeat blood cultures in 4-8 weeks, and assess susceptibilities to antimicrobial agents. If the isolate is susceptible to a macrolide and the infection is not responding to therapy, consider adding other agents such as streptomycin or amikacin.

If the MAC strain is resistant to macrolides, the macrolide can be replaced with a fluoroquinolone. Although macrolide-fluoroquinolone combinations have been used to treat MAC infections in past, studies have suggested antagonism between the two classes of antibiotics in infections with some strains of MAC and higher rates of macrolide resistance among patients receiving the combination.[26]

Although patients with MAC infection who are concomitantly receiving antiretroviral therapy may develop immune reconstitution inflammatory syndrome (IRIS), antiretroviral therapy should be started concomitantly or soon after initiating antimycobacterial treatment. If the patient is already receiving antiretroviral therapy and there is a potential drug interaction, the ART regimen should be modified as needed.[38] The ART therapy reduces the risk of other opportunistic infections.

Patients with IRIS are generally treated by infectious disease specialists with nonsteroidal anti-inflammatory drugs (NSAIDS) and, if necessary, with a short course (4-8 weeks) of systemic steroids such as prednisone.[38]

Addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) has been reported to be helpful in the treatment DMAC infection in patients with HIV/AIDS in whom traditional antimycobacterial therapy failed.[40]

Chemoprophylaxis

Antimycobacterial prophylaxis is recommended in HIV-infected patients with a CD4+ T-lymphocyte count under 50 cells/µL if they are not on ART or remain viremic despite taking ART. However, anti-MAC prophylaxis is not indicated in patients who are initiating ART, and it can be discontinued if the viremia is fully suppressed on ART.[38]

The drug of choice is either clarithromycin 500 mg twice daily or azithromycin 1200 mg/wk. In a study that compared clarithromycin prophylaxis with placebo, the incidence of MAC bacteremia was 5.6% in the clarithromycin group and 15.5% in the placebo group. Clarithromycin also conferred an improved survival rate. More than half of the patients in the clarithromycin group who developed bacteremia were infected with clarithromycin-resistant isolates.[41]

Rifabutin 300 mg/d is an alternative to macrolides for MAC prophylaxis. However, rifabutin-associated drug interactions and complications (eg, uveitis) complicate the use of this agent. Patients should be monitored closely for side effects.

If the HIV viral load is suppressed on ART or the patient's CD4 count rises to more than 100 cells/µL for a sustained period (>6 months), MAC prophylaxis can be discontinued.[38]

MAC Lymphadenitis

MAC lymphadenitis in children is treated with surgical excision of the affected lymph nodes, resulting in a cure rate that exceeds 90%. Antibiotics are generally not required but may be beneficial in patients with extensive lymphadenitis or with a poor response to surgical therapy. However, MAC lymphadenitis in immunocompromised patients, including patients with HIV infection/AIDS, generally responds to 6-12 months of antimycobacterial therapy and does not require surgery.[26]

A randomized Dutch study found no significant difference in healing time with antibiotic therapy versus a conservative wait-and-see approach in children with advanced nontuberculous mycobacterial cervicofacial lymphadenitis. The study included 50 children (age range, 14–114 mo) whose lymphadenitis was predominantly due to M avium or M hemophilum. The median time of resolution in the group receiving rifabutin and clarithromycin was 36 weeks, compared with 40 weeks for the wait-and-see group.[42]

Hot-Tub Lung

The role of antimycobacterials and corticosteroids in the treatment of hypersensitivity pneumonitis-like lung disease (hot-tub lung) due to MAC infection remains controversial. Removing environmental sources and avoiding exposure to infected aerosols are the best preventive measures.[2] Patients with severe lung disease or respiratory failure should be treated with prednisone tapered over 4-8 weeks. Immunocompromised patients and those with bronchiectasis also benefit from a short course (3-6 months) of anti-MAC treatment.[25]

Consultations and Long-Term Monitoring

An infectious disease specialist should be consulted for MAC infections in patients with AIDS. In addition, a general surgeon for lymph node biopsy, a gastroenterologist for liver biopsy, and a hematologist-oncologist for bone marrow biopsy may be needed.

Consultants for patients with lung disease who develop pulmonary MAC infection include an infectious diseases specialist and a pulmonologist. Occasionally, if surgical resection or biopsy of lungs is desired, a cardiothoracic surgeon may be needed.

Consultants for lymphadenitis in children include a pediatric infectious diseases specialist. A general surgeon or an ear, nose, and throat (ENT) specialist may be needed for lymph node resection.

Monitoring

Carefully monitor patients with AIDS for adverse effects of medications, especially for hepatotoxicity and uveitis. They may also require blood transfusions if anemia is significant. Patients should also be monitored for immune reconstitution inflammatory syndrome (IRIS).[38]

Carefully monitor patients with lung disease who develop pulmonary MAC infection for improvement in symptoms and for adverse effects of medications.

After completion of treatment, patients should be monitored clinically and, if needed, radiologically for relapse of the infection. Patients in whom MAC infection is suspected based on a single culture result or radiographic findings but who do not meet diagnostic criteria for MAC disease, and consequently do not undergo treatment, require close long-term follow-up for clinical and radiographic monitoring.

 

Guidelines

Guidelines for Diagnosis, Treatment, and Prevention of NTM Infections, Including MAC Infection

Official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases[25]

Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America[38]

British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD)[31]

British Thoracic Society Guidelines for the Workup and Treatment of Nontuberculous Mycobacterial Pulmonary Disease

Workup

Sputum, induced sputum, bronchial washings, bronchoalveolar lavage, or transbronchial biopsy samples can be used to evaluate individuals suspected of having nontuberculous mycobacterial (NTM) pulmonary disease.

Whenever possible, less invasive sampling should be attempted first to minimize procedural risks.

Respiratory samples should be processed within 24 hours of collection (or refrigerated at 4°C if delays are anticipated).

Oropharyngeal swab culture or serology testing should not be used to diagnose NTM pulmonary infection.

If sputum cultures are negative but clinical suspicion of NTM infection is high, consider performing CT-directed bronchial washings to obtain targeted samples.

If individuals undergoing diagnostic evaluation for NTM infection are taking antibiotics that may impair NTM growth (eg, aminoglycosides, macrolides, tetracyclines, cotrimoxazole, linezolid), consider discontinuing these antibiotics 2 weeks before collecting samples.

A validated rapid method should be used to detect NTM in respiratory samples.

All respiratory samples should be stained using auramine-phenol after liquefaction and concentration and then examined by microscopy.

Respiratory tract samples should be cultured (following decontamination) on solid and liquid media in a ISO15189-accredited clinical laboratory for 8 weeks, extending to 12 weeks if necessary.

Routine use of non–culture-based detection methods is not recommended at the present time.

All NTM isolates from respiratory samples should be identified to at least species level using validated molecular or mass spectrometry techniques.

Isolates of M abscessus should be subspeciated using appropriate molecular techniques.

If person-to-person transmission of M abscessus is suspected, isolates should be typed, preferably using whole genome sequencing.

Drug susceptibility testing and reporting

Drug susceptibility testing and reporting should follow the Clinical Laboratory Standards Institute (CLSI) guidelines.

For M avium complex (MAC), clarithromycin and amikacin susceptibility testing should be performed on an isolate taken before initiation of treatment and on subsequent isolates if the patient fails to respond to treatment or recultures MAC after culture conversion.

Macrolide-resistant MAC isolates should be tested against a wider panel of antibiotics to guide, but not dictate, treatment regimens.

For M kansasii, rifampicin susceptibility testing should be performed on an isolate prior to initiation of treatment and on subsequent isolates if the patient fails to respond to treatment or recultures M kansasii after culture conversion.

Rifampicin-resistant M kansasii isolates should be tested against a wider panel of antibiotics to guide, but not dictate, treatment regimens.

Susceptibility testing for M abscessus should include at least clarithromycin, cefoxitin, and amikacin (and preferably also tigecycline, imipenem, minocycline, doxycycline, moxifloxacin, linezolid, co-trimoxazole, and clofazimine if a validated method is available) to guide, but not dictate, treatment regimens.

A minimum of 2 sputum samples collected on separate days should be sent for mycobacterial culture when investigating an individual suspected of having NTM pulmonary disease.

Individuals suspected of having NTM pulmonary disease whose sputum samples are consistently culture-negative for mycobacteria should have CT-directed bronchial washings sent for mycobacterial culture.

Individuals suspected of having NTM pulmonary disease who are unable to expectorate sputum should have CT-directed bronchial washings sent for mycobacterial culture.

Transbronchial biopsies should not be performed routinely in individuals suspected of having NTM pulmonary disease.

Treatment

Clarithromycin-sensitive MAC pulmonary disease should be treated with rifampicin, ethambutol, and clarithromycin or azithromycin using an intermittent (3 times per week) or daily oral regimen. The choice of regimen should be based on the severity of disease and treatment tolerance.

An intermittent (3 times per week) oral antibiotic regimen should not be used in individuals with severe MAC pulmonary disease or in individuals with a history of treatment failure.

An injectable aminoglycoside (amikacin or streptomycin) should be considered in individuals with severe MAC pulmonary disease.

Clarithromycin-resistant MAC pulmonary disease should be treated with rifampicin, ethambutol, and isoniazid or a quinolone, and consider an injectable aminoglycoside (amikacin or streptomycin).

Nebulized amikacin may be considered in place of an injectable aminoglycoside when intravenous/intramuscular administration is impractical or contraindicated or when longer-term treatment with an aminoglycoside is required for the treatment of MAC pulmonary disease.

Macrolide monotherapy or macrolide/quinolone dual therapy regimens should not be used for the treatment of MAC pulmonary disease.

Antibiotic treatment for MAC pulmonary disease should continue for a minimum of 12 months after culture conversion.[31]

 

Medication

Medication Summary

The drugs used most often for treatment of Mycobacterium avium complex (MAC) infection include a macrolide (eg, clarithromycin, azithromycin), ethambutol, and a rifamycin (eg, rifabutin, rifampin).

Clarithromycin or azithromycin in combination with ethambutol and rifabutin are the first-choice drugs. Combination therapy is important for enhancing efficacy and preventing resistance.

Alternatively, clofazimine, streptomycin, amikacin, or a fluoroquinolone may be used as a substitute for one of the first-line agents. Streptomycin has been shown to be useful in cavitary lung disease. Amikacin is used for refractory cases.

Clofazimine should be avoided in patients with disseminated MAC (DMAC) infection because of worse outcomes compared with other regimens. The combination of a macrolide with a fluoroquinolone should be avoided, as they show antagonism in infections with some strains of MAC, and their combination has been associated with the development of resistance.

The duration of treatment is not established. In general, patients with MAC pulmonary infection should be treated for a minimum of 1 year or until 12 months after sputum stains are negative for MAC. The rate of relapse is high, especially if the treatment duration is too short. Long-term treatment, however, is harder to tolerate and increases the likelihood of adverse effects.

Macrolides are likely to interact with drugs metabolized in the liver.

Ethambutol may cause optic neuritis and blindness, especially in patients with coexisting renal dysfunction.

Rifampin and rifabutin may decrease the effectiveness of contraceptives and other drugs metabolized in the liver. Advise patients of this potential effect. Rifabutin is also known to cause uveitis, for which patients need regular eye examinations.

Failing to offer prophylaxis to patients with HIV with a CD4+ lymphocyte count of below 50 cells/µL may lead to development of DMAC infection.

Antibiotics

Class Summary

Empiric antimicrobial therapy must be comprehensive.

Clarithromycin (Biaxin, Biaxin XL)

Clarithromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl transfer RNA (tRNA) from ribosomes, arresting RNA-dependent protein synthesis.

Azithromycin (Zithromax, Zmax)

Azithromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, arresting RNA-dependent protein synthesis.

Ethambutol (Myambutol)

Ethambutol impairs cell metabolism by inhibiting synthesis of 1 or more metabolites, which in turn causes cell death. No cross-resistance has been demonstrated. Mycobacterial resistance is frequent with previous therapy. Use in these patients in combination with second-line drugs that have not been administered previously.

Rifabutin (Mycobutin)

Rifabutin is an ansamycin antibiotic derived from rifamycin S. It inhibits DNA-dependent RNA polymerase, preventing chain initiation, in susceptible bacterial strains. If GI upset occurs, administer dose twice daily with food.

Rifampin (Rifadin)

Useful in combination with other drugs, rifampin inhibits bacterial DNA-dependent RNA polymerase.

Ciprofloxacin (Cipro)

Ciprofloxacin is a fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth, by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. It is used in combination with other agents in the treatment of MAC.

Levofloxacin (Levaquin)

Levofloxacin is a fluorinated quinolone that inhibits bacterial DNA gyrase and topoisomerase IV.

Moxifloxacin (Avelox)

This agent inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.

Amikacin

Amikacin irreversibly binds to the 30S subunit of bacterial ribosomes, blocks the recognition step in protein synthesis, and causes growth inhibition. Use the patient's ideal body weight (IBW) for dosage calculation.

Streptomycin

Streptomycin acts by binding to the 30S ribosomal subunit and interferes with translational proofreading, which result in an inhibition of protein synthesis. It is used in combination with other drugs in the treatment of MAC.

Clofazimine (Lamprene)

Clofazimine is a lipophilic rhimophenazine dye that inhibits template function of DNA by binding to it. It is weakly bactericidal and has anti-inflammatory effects. This agent was originally developed to treat tuberculosis. Although its mechanism of action is unclear, it seems to exert its main effect upon neutrophils and monocytes in a variety of ways (eg, stimulating phagocytosis and release of lysosomal enzymes).

Clofazimine is absorbed orally, accumulates in tissues, and has half-life >70 d. In addition to daily dose, loading dose of 300 mg once a month (under supervision) is given in leprosy control programs. This approach maintains optimal amount of drug in body tissue, even if the patient occasionally misses daily dose.

This agent was discontinued from the United States market in 2005, but is now available as orphan product.

Amikacin liposome inhalation (Arikayce)

Bactericidal aminoglycoside enters bacterial cell by disrupting overall cell wall architecture. It is indicated for Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen in adults who do not achieve negative sputum culture results after a minimum of 6 consecutive months of a multidrug background regimen therapy.

 

Questions & Answers

Overview

Which species cause mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI])?

What is mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI])?

How frequently does mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) lung disease occur in immunocompetent patients?

What are common environmental sources of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI])?

What tests are performed in the workup of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI])?

What are the treatment options for mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI])?

How is mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) transmitted?

Which patients are at risk of developing a disseminated mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What is the most important risk factor for mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection in HIV negative patients?

What is the role of tumor necrosis factor (TNF)–alpha and interferon (IFN)–gamma in the pathogenesis of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI])?

What is the role of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection in the pathogenesis of Lady Windermere syndrome?

What is the role of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection in the pathogenesis of hypersensitivity pneumonitis (hot-tub lung)?

What is the role of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection in the pathogenesis of cutaneous diseases?

What causes mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infections?

What are the risk factors for pulmonary mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What is the prevalence of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection among immunocompromised individuals?

What is the role of IFN-gamma and TNF-alpha production in the etiology of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

How are M avium and M intracellulare differentiated in mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What are possible risk factors for mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What is the prevalence of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infections in the US?

What is the global prevalence of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infections?

How does the prevalence of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection vary by sex?

How does the prevalence of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection vary by age?

What is the life expectancy for HIV-positive patients with mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infections?

What are the most common complications of disseminated mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infections?

What is the clinical course of pulmonary mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What is the prognosis of more extensive mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) disease?

What is the clinical course of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) lymphadenitis in children?

What are negative prognostic factors for mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What instructions should be provided to patients with mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

Presentation

What are the possible presentations of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What are less common symptoms of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What should be the focus of history in suspected mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What are the physical findings characteristic of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

DDX

When should cutaneous mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection be considered?

Which conditions should be included in the differential diagnoses of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What are the differential diagnoses for Mycobacterium Avium Complex (MAC) (Mycobacterium Avium-Intracellulare [MAI])?

Workup

What testing is included in the workup of suspected mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What are the ATS/IDSA diagnostic guidelines for nontuberculous mycobacterial (NTM) lung disease?

What are ATS/IDSA diagnostic guidelines for hot-tub lung (hypersensitivity pneumonitis-like lung disease)?

What is the role of acid-fast bacillus stains in the diagnosis of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What is the role for blood cultures in the diagnosis of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What is the role of imaging in the diagnosis of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What is the role of biopsy in the diagnosis of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What are the histologic findings characteristic of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

Treatment

What medications are used in the treatment of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What are treatment options for mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

How are pulmonary Mycobacterium avium complex (MAC) (Mycobacterium avium-intracellulare [MAI]) infections treated in immunocompetent patients?

What is the most effective treatment regimen for pulmonary mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What is the efficacy of fluoroquinolones in the treatment of pulmonary mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

Which combination therapies are used in the treatment of disseminated mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection in patients with AIDS?

What are the treatment guidelines for mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection in patients with AIDS?

How should disseminated mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection in patients with AIDS be treated if unresponsive to initial therapy?

When do guidelines recommend withholding antiretroviral therapy during the treatment of disseminated mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection in patients with AIDS?

What is the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the treatment of disseminated mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection in patients with AIDS?

What is the role of chemoprophylaxis in the treatment of disseminated mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection in patients with AIDS?

What are the treatment options for mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) lymphadenitis?

What is the role of antimycobacterials and corticosteroids in the treatment of hypersensitivity pneumonitis-like lung disease (hot-tub lung) due to mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

Which specialist consultations are needed for the treatment of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What is included in long-term monitoring of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

Guidelines

What are the British Thoracic Society (BTS) guidelines for the workup of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What are the British Thoracic Society (BTS) guidelines for drug susceptibility testing in the evaluation of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What are the British Thoracic Society (BTS) treatment guidelines for mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

Medications

Which medications are used for the treatment of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What medication should be avoided in patients with disseminated mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What is the duration of treatment for mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

What should be considered when selecting medications for the treatment of mycobacterium avium complex (MAC) (mycobacterium avium-intracellulare [MAI]) infection?

Which medications in the drug class Antibiotics are used in the treatment of Mycobacterium Avium Complex (MAC) (Mycobacterium Avium-Intracellulare [MAI])?