Mycobacterium Avium Complex Infection

Mycobacterium avium complex infection is caused by a group of closely related non tuberculous mycobacteria, principally Mycobacterium avium and Mycobacterium intracellulare. They are ubiquitous in the environment (soil, water systems).

Disease occurs predominantly in two distinct populations. Immunocompromised patients with advanced HIV infection develop disseminated disease. Older patients, often with underlying structural lung disease, develop chronic pulmonary infection. Management differs substantially between these two contexts.

Pathophysiology and risk groups

Unlike Mycobacterium tuberculosis, this organism is acquired from environmental sources rather than through person to person transmission.

Disease is either localised pulmonary colonisation and infection, or haematogenous dissemination.

• Pulmonary disease occurs in a host with impaired local mucociliary clearance or structural lung damage (bronchiectasis, chronic obstructive pulmonary disease, prior tuberculosis).
• Dissemination to bone marrow, liver, spleen and other reticuloendothelial organs occurs in profound cellular immunodeficiency (CD4 count below 50 cells per microlitre in HIV infection).

Pulmonary disease presents with chronic cough, sputum production, fatigue and weight loss developing insidiously over months to years. It is often seen in an older patient with pre-existing bronchiectasis or chronic lung disease, which makes distinction from a simple exacerbation of the underlying lung condition clinically challenging.

Disseminated disease in advanced HIV infection presents with fever, night sweats, weight loss, abdominal pain and diarrhoea. Hepatosplenomegaly and cytopenias reflect bone marrow involvement. It typically occurs in patients with a CD4 count below 50 cells per microlitre who are not on effective antiretroviral therapy or prophylaxis.

Lymphadenitis, particularly cervical, is a recognised presentation in young children without HIV infection. It presents as a slowly enlarging, typically unilateral lymph node mass.

Pulmonary disease diagnosis requires compatible symptoms, radiographic abnormalities and microbiological confirmation. Radiographic abnormalities are nodular or cavitary opacities, or characteristic bronchiectasis with multifocal nodules on high resolution computed tomography. Microbiological confirmation needs at least two separate sputum samples, or a single bronchoalveolar lavage sample. A single positive specimen risks misdiagnosis from incidental environmental contamination or transient colonisation.

Disseminated disease is diagnosed through blood culture using mycobacterial specific culture media. Consider bone marrow or liver biopsy and culture where blood culture is negative but clinical suspicion remains high.

Species identification and, where relevant, drug susceptibility testing support treatment planning. Clarithromycin susceptibility is particularly relevant, given its clinical correlation with treatment response.

Pulmonary disease treatment is a three drug regimen. Give it three times weekly for nodular bronchiectatic disease, or daily for more severe cavitary disease.

Three times weekly regimen: clarithromycin 1000 mg (or azithromycin 500 mg), rifampicin 600 mg, and ethambutol 25 mg per kg. Continue for a minimum of twelve months beyond culture conversion to negative, typically giving an overall treatment duration of 18 months or longer.

Daily dosing for more severe cavitary pulmonary disease uses clarithromycin 500 to 1000 mg daily (or azithromycin 250 mg daily), rifampicin 450 to 600 mg daily, and ethambutol 15 mg per kg daily. Add an aminoglycoside (amikacin or streptomycin) for the initial months in extensive or cavitary disease.

Amikacin liposome inhalation suspension is an approved add on therapy for refractory nodular bronchiectatic disease not achieving culture conversion after six months of standard guideline based therapy.

Disseminated disease in HIV infection is treated with clarithromycin 500 mg twice daily (or azithromycin 500 to 600 mg once daily) plus ethambutol 15 mg per kg once daily. Add a third agent for more severe disease or where the CD4 count is very low: rifabutin 300 mg once daily, dose adjusted for interactions with antiretroviral therapy.

Continue for at least twelve months and until the CD4 count has risen above 100 cells per microlitre on effective antiretroviral therapy for at least six months.

Primary prophylaxis with azithromycin 1200 mg once weekly is indicated for HIV positive patients with a CD4 count below 50 cells per microlitre not on antiretroviral therapy. Discontinue once the CD4 count rises above 100 cells per microlitre for three months on effective treatment.

Throughout the prolonged course, monitor for ethambutol associated optic neuropathy (baseline and periodic visual acuity and colour vision testing). Also monitor for rifamycin drug interactions, particularly with antiretroviral therapy in HIV positive patients.