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

Updated: Dec 15, 2022
  • Author: Janak Koirala, MD, MPH, FACP, FIDSA; Chief Editor: Michael Stuart Bronze, MD  more...
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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 also should 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 serologic tests also are 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]

Diagnosis of Disseminated MAC (DMAC) Infection

In an immunocompromised patient with clinical signs and symptoms, diagnosis of DMAC generally is established with blood cultures. MAC also can be isolated from body fluids and other tissue samples including lymph nodes and bone marrow. Species identification requires biochemical tests or molecular techniques such as polymerase chain reaction or whole genome sequencing, or high-performance liquid chromatography. Guidelines do not recommend a routine screening for MAC in respiratory or GI specimens. Similarly, pre-emptive treatment of MAC colonization in asymptomatic patients is not recommended. [26]  


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, microbiologic 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 a 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 above for 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) also are used for this purpose and for direct detection of mycobacteria in the sputum. However, these assays need further refinement to improve their sensitivity to detect mycobacteria directly in patient 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 culture 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.



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 also are 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.