Mycobacterium avium complex: Difference between revisions
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Mycobacterium avium complex
m (Aidan moved page Non-tuberculous Mycobacterium avium complex (MAC) to Mycobacterium avium complex (MAC) without leaving a redirect) |
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== Background == |
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= ''Mycobacterium avium'' complex (MAC) = |
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=== Microbiology === |
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* A slow-growing [[non-tuberculous mycobacterium]] |
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== Microbiology == |
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* A slow-growing [non-tuberculous mycobacterium](Non-tuberculous mycobactera (NTM).md) |
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* Comprises ''M. avium'' (subspecies ''hominissuis'' in humans) and ''M. intracellulaire'' |
* Comprises ''M. avium'' (subspecies ''hominissuis'' in humans) and ''M. intracellulaire'' |
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** 28 serovars between the two |
** 28 serovars between the two |
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* Can colonize airways and GI tract as well as causing disease |
* Can colonize airways and GI tract as well as causing disease |
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== Differential Diagnosis == |
=== Differential Diagnosis === |
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* Pulmonary disease |
* Pulmonary disease |
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** ''M. kansasii'' |
** ''M. kansasii'' |
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** ''M. abscessus'' |
** ''M. abscessus'' |
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== Epidemiology == |
=== Epidemiology === |
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* Common in the environment, likely acquired by inhalation or ingestion (not person-to-person) |
* Common in the environment, likely acquired by inhalation or ingestion (not person-to-person) |
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** Water, soil, and animals |
** Water, soil, and animals |
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** Natural water, indoor water, pools, hot tubs |
** Natural water, indoor water, pools, hot tubs |
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* Risk factors |
* Risk factors |
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** Pulmonary disease: COPD, |
** Pulmonary disease: [[COPD]], prior [[pneumonia]], prior [[TB]], [[Corticosteroids|steroid]] use, [[silicosis]], [[scoliosis]], [[pectus excavatum]] |
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** Disseminated disease: HIV, interferon-gamma defects |
** Disseminated disease: [[HIV]], interferon-gamma defects |
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** Cervical lymphadenitis: children 1-5 years old, HIV with IRIS |
** [[Cervical lymphadenitis]]: children 1-5 years old, [[HIV]] with [[IRIS]] |
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== Pathophysiology == |
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=== Pathophysiology === |
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* In pulmonary disease, likely inhalation ± microaspiration |
* In pulmonary disease, likely inhalation ± microaspiration |
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* In disseminated disease in AIDS, likely GI colonization then replication and dissemination |
* In disseminated disease in [[AIDS]], likely GI colonization then replication and dissemination |
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== Clinical Presentation == |
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=== Pulmonary disease === |
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== Clinical Manifestations == |
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* Incubation months to years |
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=== Pulmonary Disease === |
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* Incubation period [[Usual incubation period::months to years]] |
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* Typically presents with non-specific subacute to chronic respiratory syndrome |
* Typically presents with non-specific subacute to chronic respiratory syndrome |
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** Productive cough, weight loss, fevers, night sweats |
** Productive cough, weight loss, fevers, night sweats |
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** Hot tub lung disease: a hypersensitivity pneumonitis associated with inhalation |
** Hot tub lung disease: a hypersensitivity pneumonitis associated with inhalation |
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=== Disseminated |
=== Disseminated Disease === |
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* Almost exclusive to HIV patients with CD4 <100 |
* Almost exclusive to HIV patients with CD4 <100 |
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** Median CD4 was 13 |
** Median CD4 was 13 |
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* Mortality 50% at 4 months |
* Mortality 50% at 4 months |
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=== Cervical |
=== Cervical Lymphadenitis === |
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* Disease of children, usually <3 (80% aged 1 to 5 years) |
* Disease of children, usually <3 (80% aged 1 to 5 years) |
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* Presents as painless unilateral lymph node enlargement |
* Presents as painless unilateral lymph node enlargement |
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== Investigations == |
== Investigations == |
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=== Pulmonary disease === |
=== Pulmonary disease === |
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* (1) chest radiograph or, in the absence of cavitation, chest high-resolution computed tomography (HRCT) scan |
* (1) chest radiograph or, in the absence of cavitation, chest high-resolution computed tomography (HRCT) scan |
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* (2) three or more sputum specimens for acid-fast bacilli (AFB) analysis |
* (2) three or more sputum specimens for acid-fast bacilli (AFB) analysis |
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== Diagnosis == |
== Diagnosis == |
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=== Pulmonary Disease === |
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=== Pulmonary disease === |
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* Diagnosis based on presence of both clinical and microbiological evidence |
* Diagnosis based on presence of both clinical and microbiological evidence |
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* Clinical: |
* Clinical: |
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** Transbronchial or other lung biopsy with mycobacterial histopathologic features, and either positive culture for NTM or one or more sputum or BALs positive for NTM |
** Transbronchial or other lung biopsy with mycobacterial histopathologic features, and either positive culture for NTM or one or more sputum or BALs positive for NTM |
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=== Disseminated |
=== Disseminated Disease === |
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* Diagnosis based on MAC in culture of sterile site |
* Diagnosis based on MAC in culture of sterile site |
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== Management == |
== Management == |
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=== Pulmonary Disease === |
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=== Pulmonary disease === |
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* Nodular/bronchiectatic disease: |
* Nodular/bronchiectatic disease: |
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** Clarithromycin (1,000 mg) or azithromycin (500 mg) |
** [[Clarithromycin]] (1,000 mg) or [[azithromycin]] (500 mg) |
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** Rifampin (600 mg) |
** [[Rifampin]] (600 mg) |
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** Ethambutol (25 mg/kg) |
** [[Ethambutol]] (25 mg/kg) |
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** Three times weekly (because daily never tolerated) |
** Three times weekly (because daily never tolerated) |
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* If fibrocavitary MAC lung disease or severe nodular/bronchiectatic disease: |
* If fibrocavitary MAC lung disease or severe nodular/bronchiectatic disease: |
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** Clarithromycin (500–1,000 mg) or azithromycin (250 mg) daily |
** [[Clarithromycin]] (500–1,000 mg) or [[azithromycin]] (250 mg) daily |
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** Rifampin (600 mg) or rifabutin (150–300 mg) daily |
** [[Rifampin]] (600 mg) or [[rifabutin]] (150–300 mg) daily |
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** Ethambutol (15 mg/kg) daily |
** [[Ethambutol]] (15 mg/kg) daily |
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** And consider adding three-times-weekly amikacin or streptomycin early in therapy |
** And consider adding three-times-weekly [[amikacin]] or [[streptomycin]] early in therapy |
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* Duration is until culture negative on therapy for at least 1 year |
* Duration is until culture negative on therapy for at least 1 year |
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* Refer to Ophthalmology for monitoring while on ethambutol |
* Refer to Ophthalmology for monitoring while on [[ethambutol]] |
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=== Disseminated disease === |
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=== Disseminated Disease === |
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* Antibiotics |
* Antibiotics |
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** Clarithromycin (1,000 mg/d) or azithromycin (250 mg/d) |
** [[Clarithromycin]] (1,000 mg/d) or [[azithromycin]] (250 mg/d) |
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** Ethambutol (15 mg/kg/d) |
** [[Ethambutol]] (15 mg/kg/d) |
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** ± rifabutin (150–350 mg/d) |
** ± [[rifabutin]] (150–350 mg/d) |
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* Duration is until resolution of symptoms and reconstitution of cell-mediated immune function (e.g. CD4 >100) |
* Duration is until resolution of symptoms and reconstitution of cell-mediated immune function (e.g. CD4 >100) |
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=== Dosing === |
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{| class="wikitable" |
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!Disease |
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!Drugs |
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!Preferred Regimen |
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!Daily Dose |
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!Thrice-Weekly Dose |
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|- |
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| rowspan="5" |Nodular-bronchiectatic |
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| rowspan="5" |3 |
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|[[azithromycin]], or |
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|250-500 mg |
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|500 mg |
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|- |
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|[[clarithromycin]]; and |
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|500 mg bid |
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|N/A |
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|- |
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|[[rifampin]], or |
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|450-600 mg (10 mg/kg) |
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|600 mg |
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|- |
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|[[rifabutin]]; and |
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|150-300 mg (150 mg if with clarithromycin) |
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|300 mg |
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|- |
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|[[ethambutol]] |
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|15 mg/kg |
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|25 mg/kg |
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|- |
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| rowspan="6" |Cavitary |
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| rowspan="6" |3+ |
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|[[azithromycin]], or |
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|250-500 mg |
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|500 mg |
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|- |
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|[[clarithromycin]]; and |
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|500 mg bid |
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|N/A |
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|- |
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|[[rifampin]], or |
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|450-600 mg (10 mg/kg) |
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|600 mg |
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|- |
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|[[rifabutin]]; and |
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|150-300 mg (150 mg if with clarithromycin) |
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|300 mg |
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|- |
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|[[ethambutol]]; and consider |
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|15 mg/kg |
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|25 mg/kg |
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|- |
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|[[amikacin]] IV |
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|10-15 mg/kg |
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|15-25 mg/kg |
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|- |
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| rowspan="2" |Salvage |
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| rowspan="2" | |
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|liposomal inhaled [[amikacin]] |
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|590 mg |
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| |
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|- |
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|[[clofazimine]] |
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|100 mg |
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| |
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|} |
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=== Prophylaxis === |
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* Indicated for adults with (AIDS) with CD4 <50; but not done and no longer in the HIV guidelines |
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* Antibiotics: [[azithromycin]] 1,200 mg/week or [[clarithromycin]] 1,000 mg/day |
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* Second-line: [[rifabutin]] 300 mg/day (less well tolerated) |
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== Further Reading == |
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* Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. ''Eur Respir J''. 2020 Jul 7;56(1):2000535. doi: [https://doi.org/10.1183/13993003.00535-2020 10.1183/13993003.00535-2020]. PMID: [https://pubmed.ncbi.nlm.nih.gov/32636299/ 32636299]; PMCID: [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8375621/ PMC8375621].{{DISPLAYTITLE:''Mycobacterium avium'' complex}} |
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* Indicated for adults with (AIDS) with CD4 <50; but not done and no longer in the HIV guidelines |
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[[Category:Non-tuberculous mycobacteria]] |
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* Antibiotics: azithromycin 1,200 mg/week or clarithromycin 1,000 mg/day |
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* Second-line: rifabutin 300 mg/day (less well tolerated) |
Latest revision as of 19:23, 1 December 2023
Background
Microbiology
- A slow-growing non-tuberculous mycobacterium
- Comprises M. avium (subspecies hominissuis in humans) and M. intracellulaire
- 28 serovars between the two
- Can colonize airways and GI tract as well as causing disease
Differential Diagnosis
- Pulmonary disease
- M. kansasii
- M. abscessus
Epidemiology
- Common in the environment, likely acquired by inhalation or ingestion (not person-to-person)
- Water, soil, and animals
- Natural water, indoor water, pools, hot tubs
- Risk factors
Pathophysiology
- In pulmonary disease, likely inhalation ± microaspiration
- In disseminated disease in AIDS, likely GI colonization then replication and dissemination
Clinical Manifestations
Pulmonary Disease
- Incubation period months to years
- Typically presents with non-specific subacute to chronic respiratory syndrome
- Productive cough, weight loss, fevers, night sweats
- CXR often shows upper-lobe infiltrates ± cavitations ± pleural thickening
- Bronchiectasis on CT in 94%
- Mortality is 15% within 2 to 10 years
- Specific populations/presentations:
- Smokers/COPD/alcohol: typical presentation as above
- Lady Windermere syndrome: slower progression
- Hot tub lung disease: a hypersensitivity pneumonitis associated with inhalation
Disseminated Disease
- Almost exclusive to HIV patients with CD4 <100
- Median CD4 was 13
- Typically presents with high fevers, weight loss, night sweats, anemia
- Also abdo pain, diarrhea, intraabdo lymphadenopathy, hepatosplenomegaly, and elevated ALP
- Organ-specific involvement: spleen, lymph nodes, liver, adrenals, stomach, CNS
- Often not lung involvement
- Mortality 50% at 4 months
Cervical Lymphadenitis
- Disease of children, usually <3 (80% aged 1 to 5 years)
- Presents as painless unilateral lymph node enlargement
- 10% bilateral
Investigations
Pulmonary disease
- (1) chest radiograph or, in the absence of cavitation, chest high-resolution computed tomography (HRCT) scan
- (2) three or more sputum specimens for acid-fast bacilli (AFB) analysis
- (3) exclusion of other disorders, such as tuberculosis
Diagnosis
Pulmonary Disease
- Diagnosis based on presence of both clinical and microbiological evidence
- Clinical:
- Pulmonary symptoms, nodular or cavitary opacities on chest radiograph, or an HRCT scan that shows multifocal bronchiectasis with multiple small nodules; and
- Appropriate exclusion of other diagnoses.
- Microbiological:
- Positive cultures from at least two separate expectorated sputum samples; or
- Positive culture from at least one bronchial wash or lavage; or
- Transbronchial or other lung biopsy with mycobacterial histopathologic features, and either positive culture for NTM or one or more sputum or BALs positive for NTM
Disseminated Disease
- Diagnosis based on MAC in culture of sterile site
Management
Pulmonary Disease
- Nodular/bronchiectatic disease:
- Clarithromycin (1,000 mg) or azithromycin (500 mg)
- Rifampin (600 mg)
- Ethambutol (25 mg/kg)
- Three times weekly (because daily never tolerated)
- If fibrocavitary MAC lung disease or severe nodular/bronchiectatic disease:
- Clarithromycin (500–1,000 mg) or azithromycin (250 mg) daily
- Rifampin (600 mg) or rifabutin (150–300 mg) daily
- Ethambutol (15 mg/kg) daily
- And consider adding three-times-weekly amikacin or streptomycin early in therapy
- Duration is until culture negative on therapy for at least 1 year
- Refer to Ophthalmology for monitoring while on ethambutol
Disseminated Disease
- Antibiotics
- Clarithromycin (1,000 mg/d) or azithromycin (250 mg/d)
- Ethambutol (15 mg/kg/d)
- ± rifabutin (150–350 mg/d)
- Duration is until resolution of symptoms and reconstitution of cell-mediated immune function (e.g. CD4 >100)
Dosing
Disease | Drugs | Preferred Regimen | Daily Dose | Thrice-Weekly Dose |
---|---|---|---|---|
Nodular-bronchiectatic | 3 | azithromycin, or | 250-500 mg | 500 mg |
clarithromycin; and | 500 mg bid | N/A | ||
rifampin, or | 450-600 mg (10 mg/kg) | 600 mg | ||
rifabutin; and | 150-300 mg (150 mg if with clarithromycin) | 300 mg | ||
ethambutol | 15 mg/kg | 25 mg/kg | ||
Cavitary | 3+ | azithromycin, or | 250-500 mg | 500 mg |
clarithromycin; and | 500 mg bid | N/A | ||
rifampin, or | 450-600 mg (10 mg/kg) | 600 mg | ||
rifabutin; and | 150-300 mg (150 mg if with clarithromycin) | 300 mg | ||
ethambutol; and consider | 15 mg/kg | 25 mg/kg | ||
amikacin IV | 10-15 mg/kg | 15-25 mg/kg | ||
Salvage | liposomal inhaled amikacin | 590 mg | ||
clofazimine | 100 mg |
Prophylaxis
- Indicated for adults with (AIDS) with CD4 <50; but not done and no longer in the HIV guidelines
- Antibiotics: azithromycin 1,200 mg/week or clarithromycin 1,000 mg/day
- Second-line: rifabutin 300 mg/day (less well tolerated)
Further Reading
- Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Eur Respir J. 2020 Jul 7;56(1):2000535. doi: 10.1183/13993003.00535-2020. PMID: 32636299; PMCID: PMC8375621.