Mycobacterium avium complex: Difference between revisions

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Mycobacterium avium complex
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== Microbiology ==
+
== Background ==
  +
=== Microbiology ===
 
* A slow-growing [[Non-tuberculous mycobacteria (NTM)|non-tuberculous mycobacterium]]
+
* A slow-growing [[non-tuberculous mycobacterium]]
 
* Comprises ''M. avium'' (subspecies ''hominissuis'' in humans) and ''M. intracellulaire''
 
* Comprises ''M. avium'' (subspecies ''hominissuis'' in humans) and ''M. intracellulaire''
 
** 28 serovars between the two
 
** 28 serovars between the two
 
* Can colonize airways and GI tract as well as causing disease
 
* Can colonize airways and GI tract as well as causing disease
   
== Differential Diagnosis ==
+
=== Differential Diagnosis ===
 
 
* Pulmonary disease
 
* Pulmonary disease
 
** ''M. kansasii''
 
** ''M. kansasii''
 
** ''M. abscessus''
 
** ''M. abscessus''
   
== Epidemiology ==
+
=== Epidemiology ===
 
 
* 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)
 
** Water, soil, and animals
 
** Water, soil, and animals
 
** Natural water, indoor water, pools, hot tubs
 
** Natural water, indoor water, pools, hot tubs
 
* Risk factors
 
* Risk factors
** Pulmonary disease: COPD, preior pneumonia, prior TB, steroid use, silicosis, scoliosis, pectus excavatum
+
** Pulmonary disease: [[COPD]], prior [[pneumonia]], prior [[TB]], [[Corticosteroids|steroid]] use, [[silicosis]], [[scoliosis]], [[pectus excavatum]]
** Disseminated disease: HIV, interferon-gamma defects
+
** Disseminated disease: [[HIV]], interferon-gamma defects
** Cervical lymphadenitis: children 1-5 years old, HIV with IRIS
+
** [[Cervical lymphadenitis]]: children 1-5 years old, [[HIV]] with [[IRIS]]
 
== Pathophysiology ==
 
   
  +
=== Pathophysiology ===
 
* In pulmonary disease, likely inhalation ± microaspiration
 
* In pulmonary disease, likely inhalation ± microaspiration
* In disseminated disease in AIDS, likely GI colonization then replication and dissemination
+
* In disseminated disease in [[AIDS]], likely GI colonization then replication and dissemination
 
== Clinical Presentation ==
 
 
=== Pulmonary disease ===
 
   
  +
== Clinical Manifestations ==
* Incubation months to years
 
  +
=== Pulmonary Disease ===
  +
* Incubation period [[Usual incubation period::months to years]]
 
* Typically presents with non-specific subacute to chronic respiratory syndrome
 
* Typically presents with non-specific subacute to chronic respiratory syndrome
 
** 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
   
=== Disseminated disease ===
+
=== Disseminated Disease ===
 
 
* Almost exclusive to HIV patients with CD4 <100
 
* Almost exclusive to HIV patients with CD4 <100
 
** Median CD4 was 13
 
** Median CD4 was 13
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* Mortality 50% at 4 months
 
* Mortality 50% at 4 months
   
=== Cervical lymphadenitis ===
+
=== Cervical Lymphadenitis ===
 
 
* Disease of children, usually <3 (80% aged 1 to 5 years)
 
* Disease of children, usually <3 (80% aged 1 to 5 years)
 
* Presents as painless unilateral lymph node enlargement
 
* Presents as painless unilateral lymph node enlargement
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== Investigations ==
 
== Investigations ==
 
 
=== Pulmonary disease ===
 
=== Pulmonary disease ===
 
 
* (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
 
* (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 ==
  +
=== Pulmonary Disease ===
 
=== Pulmonary disease ===
 
 
 
* Diagnosis based on presence of both clinical and microbiological evidence
 
* Diagnosis based on presence of both clinical and microbiological evidence
 
* 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
   
=== Disseminated disease ===
+
=== Disseminated Disease ===
 
 
* Diagnosis based on MAC in culture of sterile site
 
* Diagnosis based on MAC in culture of sterile site
   
 
== Management ==
 
== Management ==
  +
=== Pulmonary Disease ===
 
=== Pulmonary disease ===
 
 
 
* Nodular/bronchiectatic disease:
 
* Nodular/bronchiectatic disease:
** Clarithromycin (1,000 mg) or azithromycin (500 mg)
+
** [[Clarithromycin]] (1,000 mg) or [[azithromycin]] (500 mg)
** Rifampin (600 mg)
+
** [[Rifampin]] (600 mg)
** Ethambutol (25 mg/kg)
+
** [[Ethambutol]] (25 mg/kg)
 
** Three times weekly (because daily never tolerated)
 
** Three times weekly (because daily never tolerated)
 
* If fibrocavitary MAC lung disease or severe nodular/bronchiectatic disease:
 
* If fibrocavitary MAC lung disease or severe nodular/bronchiectatic disease:
** Clarithromycin (500–1,000 mg) or azithromycin (250 mg) daily
+
** [[Clarithromycin]] (500–1,000 mg) or [[azithromycin]] (250 mg) daily
** Rifampin (600 mg) or rifabutin (150–300 mg) daily
+
** [[Rifampin]] (600 mg) or [[rifabutin]] (150–300 mg) daily
** Ethambutol (15 mg/kg) daily
+
** [[Ethambutol]] (15 mg/kg) daily
** And consider adding three-times-weekly amikacin or streptomycin early in therapy
+
** And consider adding three-times-weekly [[amikacin]] or [[streptomycin]] early in therapy
 
* Duration is until culture negative on therapy for at least 1 year
 
* Duration is until culture negative on therapy for at least 1 year
* Refer to Ophthalmology for monitoring while on ethambutol
+
* Refer to Ophthalmology for monitoring while on [[ethambutol]]
 
=== Disseminated disease ===
 
   
  +
=== Disseminated Disease ===
 
* Antibiotics
 
* Antibiotics
** Clarithromycin (1,000 mg/d) or azithromycin (250 mg/d)
+
** [[Clarithromycin]] (1,000 mg/d) or [[azithromycin]] (250 mg/d)
** Ethambutol (15 mg/kg/d)
+
** [[Ethambutol]] (15 mg/kg/d)
** ± rifabutin (150–350 mg/d)
+
** ± [[rifabutin]] (150–350 mg/d)
 
* 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)
  +
  +
=== Dosing ===
  +
{| class="wikitable"
  +
!Disease
  +
!Drugs
  +
!Preferred Regimen
  +
!Daily Dose
  +
!Thrice-Weekly Dose
  +
|-
  +
| rowspan="5" |Nodular-bronchiectatic
  +
| rowspan="5" |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
  +
|-
  +
| rowspan="6" |Cavitary
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| rowspan="6" |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
  +
|-
  +
| rowspan="2" |Salvage
  +
| rowspan="2" |
  +
|liposomal inhaled [[amikacin]]
  +
|590 mg
  +
|
  +
|-
  +
|[[clofazimine]]
  +
|100 mg
  +
|
  +
|}
   
 
=== Prophylaxis ===
 
=== 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 ==
* 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)
 
   
  +
* 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}}
{{DISPLAYTITLE:''Mycobacterium avium'' complex}}
 
[[Category:Mycobacteria]]
+
[[Category:Non-tuberculous mycobacteria]]

Latest revision as of 15:23, 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

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

Disseminated Disease

  • Antibiotics
  • 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.