What is Mycobacterium avium intracellulare (MAI)?

What is Mycobacterium avium Intracellulare (MAI)?

Mycobacterium avium complex (MAC), also called MAI, comprises two distinct mycobacterial species—M. avium and M. intracellulare—that are ubiquitous environmental organisms found in water, soil, and various animals, causing both pulmonary and disseminated disease primarily in immunocompromised patients. 1

Organism Classification and Epidemiology

MAC organisms are nontuberculous mycobacteria (NTM) that cannot be differentiated using traditional physical and biochemical tests, though DNA probes can distinguish between the two species. 1 M. avium is the predominant pathogen in disseminated disease (particularly in HIV/AIDS patients), while M. intracellulare more commonly causes respiratory infections in immunocompetent individuals. 1, 2

Environmental Sources and Transmission

• MAC is acquired from environmental reservoirs, not from person-to-person or animal-to-human transmission. 1
• The organisms are recovered from fresh water, sea water, soil, dairy products, and animals including chickens, pigs, dogs, cats, and insects. 1
• Water systems are the primary reservoir: MAC colonizes natural water sources, indoor water systems, pools, hot tubs, and recirculating hot-water systems. 1, 3
• Transmission occurs through inhalation or ingestion of contaminated aerosols, with the gastrointestinal tract considered the most common site of colonization and dissemination. 1, 4

Clinical Disease Patterns

MAC causes distinctly different disease presentations depending on the patient's immune status:

Disseminated Disease (Primarily HIV/AIDS Patients)

Disseminated MAC occurs almost exclusively in severely immunocompromised patients with CD4 T-cell counts below 50 cells/µL, with most cases occurring when counts fall below 10-25 cells/µL. 1 This represents 15-40% of HIV-infected patients in the United States. 1

Clinical manifestations include:

• Fever (80% of cases), night sweats (35%), and weight loss (25%). 1
• Abdominal pain, diarrhea, and hepatosplenomegaly. 1
• Severe anemia (hematocrit <25%), elevated alkaline phosphatase, and elevated lactate dehydrogenase. 1
• Persistent bacteremia with involvement of most internal organs at autopsy. 1

Diagnosis is established by positive blood cultures in patients with compatible symptoms; blood cultures are not recommended for asymptomatic persons even with low CD4 counts. 1

Pulmonary Disease (Immunocompetent and Immunocompromised)

Two distinct clinical presentations exist: 1

1. Fibrocavitary disease: Apical cavitary lung disease in males in their late 40s-50s with smoking and alcohol use history. 1

2. Nodular/bronchiectatic disease: More common in older white women with chronic bronchitis or bronchiectasis, presenting with multifocal bronchiectasis and multiple small nodules. 1, 5

Diagnostic criteria require: 4

• Pulmonary symptoms
• Nodular or cavitary opacities on chest radiograph or CT scan with multifocal bronchiectasis
• Positive cultures from two sputum specimens or one bronchoscopic specimen

Other Manifestations

Localized disease includes cervical adenitis (especially in children), pneumonitis, hepatic dysfunction, skin lesions, endophthalmitis, and abscesses. 1 Pulmonary nodules ("tuberculomas") can be indistinguishable from pulmonary neoplasms. 5

Treatment Principles

For Disseminated Disease (HIV/AIDS)

Treatment requires at least two agents and should continue for the patient's lifetime if clinical improvement occurs. 1 Every regimen should contain either azithromycin or clarithromycin plus ethambutol, with addition of one more agent: clofazimine, rifabutin, rifampin, ciprofloxacin, or amikacin. 1

Critical points:

• Macrolides should never be used as monotherapy to prevent resistance. 1
• Isoniazid and pyrazinamide have no role in MAC therapy. 1
• Rifabutin 300 mg daily is recommended for prophylaxis in patients with CD4 counts <100 cells/µL. 1

For Pulmonary Disease

The cornerstone is a three-drug macrolide-based regimen (macrolide + rifamycin + ethambutol) administered for 12 months beyond culture conversion. 1, 6, 7

Dosing strategy depends on disease severity: 1

• Intermittent three-times-weekly therapy for nodular/bronchiectatic disease or patients requiring disease suppression rather than cure
• Daily therapy with or without aminoglycoside for cavitary disease or extensive radiographic involvement

Treatment success rates are approximately 60%, with over 30% experiencing recurrence (often due to reinfection rather than relapse). 6

Important Clinical Caveats

• Drug susceptibility testing for clarithromycin and amikacin is essential, as resistance significantly worsens prognosis. 6
• Ethambutol prevents macrolide resistance development and should not be omitted. 6
• For refractory disease, amikacin liposome inhalation suspension or parenteral aminoglycosides should be added. 7
• Surgical resection achieves approximately 93% sputum conversion in eligible candidates with localized disease. 6, 5
• The prevalence is increasing globally, with rates in Korea rising from 11.4 to 56.7 per 100,000 between 2010-2021, now surpassing tuberculosis incidence. 6