Non-tuberculous mycobacteria: Difference between revisions

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==Background==
βˆ’
* Mycobacteria that excludes tuberculosis and leprosy
  
   
  +
*Mycobacteria that excludes tuberculosis and leprosy
βˆ’
== Background ==
  
βˆ’
=== Microbiology ===
  
βˆ’
* Acid-fast bacilli, free-living in the environment
  
βˆ’
** Direct microscopy with auremine rodhamine fluorochrome stain (better than Ziehl-Neelsen)
  
βˆ’
* Broadly divided into slow-growers and fast-growers
  
βˆ’
** Fast-growers produce colonies within 7 days on solid media
  
βˆ’
*** Grows optimally at 28-30ΒΊ C, with some preferring 35ΒΊ C
  
βˆ’
*** May grow in blood culture if mycobacteremic
  
βˆ’
** Slow-growers produce colonies after more than 7 days on solid media
  
βˆ’
*** MAC, ''M. xenopi'', and ''M. kansasii'' are the three most important
  
βˆ’
*** Grows optimally at 35-37ΒΊ C except ''M. haemophilum'' (28-30ΒΊ C) and ''M. xenopi'' (42-45ΒΊ C)
  
βˆ’
* Media includes blood or chocolate agar, MTBC media, etc
  
βˆ’
* Species-level identifiation requires molecular tests
  
   
βˆ’
=== Species ===
 +
===Microbiology===
βˆ’
* More than 200 species of ''Mycobacterium'' spp. that are not in ''M. tuberculosis'' complex or ''M. leprae''
  
   
  +
*Acid-fast bacilli, free-living in the environment
βˆ’
{| class="wikitable"
  
  +
**Direct microscopy with auremine rodhamine fluorochrome stain (better than Ziehl-Neelsen)
βˆ’
! Species
  
  +
*Broadly divided into slow-growers and fast-growers
βˆ’
! Notes
  
  +
**Fast-growers produce colonies within 7 days on solid media
  +
***Grows optimally at 28-30ΒΊ C, with some preferring 35 ΒΊC
  +
***May grow in blood culture if mycobacteremic
  +
**Slow-growers produce colonies after more than 7 days on solid media
  +
***[[MAC]], [[Mycobacterium xenopi]], and [[Mycobacterium kansasii]] are the three most important
  +
***Grows optimally at 35-37ΒΊ C except [[Mycobacterium haemophilum]] (28-30 ΒΊC) and [[Mycobacterium xenopi]] (42-45 ΒΊC)
  +
*Media includes blood or chocolate agar, MTBC media, etc
  +
*Species-level identification requires molecular tests
  +
  +
===Species===
  +
  +
*More than 200 species of ''Mycobacterium'' spp. that are not in [[Mycobacterium tuberculosis]] complex or [[Mycobacterium leprae]]
  +
*Often divided into rapid growers (visible in culture in less than 5-7 days) and slow growers (more than 7 days)
  +
*Slow-growers are further classified by production of yellow-orange pigment
  +
**Photochromagens produce pigment when exposed to light
  +
**Scotochromogens produce pigment regardless of light
  +
**Nonchromogens do not produce pigment
  +
  +
{| class="wikitable sortable"
  +
!Slow or Rapid
  +
!Pigmentation
  +
!Complex
  +
!Species
  +
!Notes
 
|-
  
|-
  +
| rowspan="10" |rapid
βˆ’
! colspan=2 | Rapid-growers (visible in culture in <7 days)
  
  +
| rowspan="10" |nonchromogen
  +
| rowspan="3" |[[Mycobacterium fortuitum complex]]
  +
| [[Mycobacterium fortuitum]]
  +
|
 
|-
  
|-
  +
| [[Mycobacterium peregrinum]]
βˆ’
| ''M. fortuitum'' complex
  
 
|
  
|
 
|-
  
|-
  +
| [[Mycobacterium porcinum]]
βˆ’
| style="padding-left:1.5em;" | ''M. fortuitum''
  
 
|
  
|
 
|-
  
|-
  +
|
βˆ’
| style="padding-left:1.5em;" | ''M. peregrinum''
  
  +
|[[Mycobacterium chelonae]]
 
|
  
|
 
|-
  
|-
  +
| rowspan="4" |[[Mycobacterium abscessus complex]]
βˆ’
| style="padding-left:1.5em;" | ''M. porcinum''
  
  +
|''[[Mycobacterium abscessus]]''
 
|
  
|
 
|-
  
|-
  +
|[[Mycobacterium abscessus]] subsp. ''abscessus''
βˆ’
| ''M. chelonae''
  
 
|
  
|
 
|-
  
|-
βˆ’
| ''[[M. abscessus]]''
 +
| [[Mycobacterium abscessus]] subsp. ''bolletii''
 
|
  
|
 
|-
  
|-
βˆ’
| style="padding-left:1.5em;" | ''M. abscessus'' subsp. ''abscessus''
 +
| [[Mycobacterium abscessus]] subsp. ''massiliense''
 
|
  
|
 
|-
  
|-
  +
|
βˆ’
| style="padding-left:1.5em;" | ''M. abscessus'' subsp. ''bolletii''
  
  +
|[[Mycobacterium smegmatis]]
 
|
  
|
 
|-
  
|-
  +
|
βˆ’
| style="padding-left:1.5em;" | ''M. abscessus'' subsp. ''massiliense''
  
  +
|[[Mycobacterium mucogenicum]]
 
|
  
|
 
|-
  
|-
  +
| rowspan="16" |slow
βˆ’
| ''M. smegmatis''
  
  +
| rowspan="2" |photochromogen
 
|
  
|
  +
| [[Mycobacterium kansasii]]
  +
|Always assumed to be pathogenic, never colonizer.
 
|-
  
|-
βˆ’
| ''M. mucogenicum''
  
 
|
  
|
  +
| [[Mycobacterium marinum]]
  +
|Intermediate-grower (7-10 days).
 
|-
  
|-
  +
| rowspan="2" |scotochromogen
βˆ’
! colspan=2 | Slow-growers (visible in culture in >7 days)
  
  +
|
  +
| [[Mycobacterium gordonae]]
  +
|Intermediate-grower (7-10 days). Common tap-water contaminant.
 
|-
  
|-
  +
|
βˆ’
| colspan=2 | Photochromogens (develop pigments in light)
  
  +
|[[Mycobacterium scrofulaceum]]
βˆ’
|-
  
  +
|
βˆ’
| style="padding-left:1.5em;" | ''M. kansasii''
  
βˆ’
| Always assumed to be pathogenic, never colonizer.
  
βˆ’
|-
  
βˆ’
| style="padding-left:1.5em;" | ''M. marinum''
  
βˆ’
| Intermediate-grower (7-10 days).
  
 
|-
  
|-
  +
| rowspan="12" |nonchromogen
βˆ’
|  Scotochromogens
  
  +
| rowspan="4" |[[Mycobacterium avium complex]]
βˆ’
| Develop pigments in darkness.
  
  +
|[[Mycobacterium avium complex]]
  +
|In HIV, rarely pulmonary and almost always disseminated.
 
|-
  
|-
  +
|[[Mycobacterium avium]]
βˆ’
| style="padding-left:1.5em;" | ''M. gordonae''
  
  +
|Most common subspecies.
βˆ’
| Intermediate-grower (7-10 days). Common tap-water contaminant.
  
 
|-
  
|-
  +
|[[Mycobacterium intracellulare]]
βˆ’
| style="padding-left:1.5em;" | ''M. scrofulaceum''
  
 
|
  
|
 
|-
  
|-
  +
|[[Mycobacterium chimaera]]
βˆ’
| colspan=2 | Nonchromogens (do not develop pigments in light)
  
  +
|Associated with contaminated heater-cooler units in cardiac bypass machines.
 
|-
  
|-
βˆ’
| style="padding-left:1.5em;" | [[M. avium complex]]
 +
|[[Mycobacterium terrae complex]]
  +
|[[Mycobacterium terrae complex]]
βˆ’
| In HIV, rarely pulmonary and almost always disseminated.
  
βˆ’
|-
  
βˆ’
| style="padding-left:2.5em;" | ''M. avium''
  
βˆ’
| Most common subspecies.
  
βˆ’
|-
  
βˆ’
| style="padding-left:2.5em;" | ''M. intracellulare''
  
 
|
  
|
 
|-
  
|-
  +
|
βˆ’
| style="padding-left:2.5em;" | ''M. chimaera''
  
  +
|[[Mycobacterium ulcerans]]
 
|
  
|
 
|-
  
|-
βˆ’
| style="padding-left:1.5em;" | ''M. terrae'' complex
  
 
|
  
|
  +
|[[Mycobacterium xenopi]]
  +
|Grows optimally at 42-45 ΒΊC.
 
|-
  
|-
  +
|
βˆ’
| style="padding-left:1.5em;" | ''M. ulcerans''
  
  +
|[[Mycobacterium simiae]]
 
|
  
|
 
|-
  
|-
βˆ’
| style="padding-left:1.5em;" | ''M. xenopi''
  
βˆ’
| Grows optimally at 42-45ΒΊ C.
  
βˆ’
|-
  
βˆ’
| style="padding-left:1.5em;" | ''M. simiae''
  
 
|
  
|
  +
|[[Mycobacterium malmoense]]
βˆ’
|-
  
βˆ’
| style="padding-left:1.5em;" | ''M. malmoense''
  
 
|
  
|
 
|-
  
|-
  +
|
βˆ’
| style="padding-left:1.5em;" | ''M. szulgai''
  
  +
|[[Mycobacterium szulgai]]
 
|
  
|
 
|-
  
|-
  +
|
βˆ’
| style="padding-left:1.5em;" | ''M. asiaticum''
  
  +
|[[Mycobacterium asiaticum]]
 
|
  
|
 
|-
  
|-
  +
|
βˆ’
| style="padding-left:1.5em;" | ''M. haemophilum''
  
  +
|[[Mycobacterium haemophilum]]
βˆ’
| Grows optimally at 28-30ΒΊ C.
  
  +
|Grows optimally at 28-30 ΒΊC.
 
|}
  
|}
   
βˆ’
=== Pathophysiology ===
 +
===Pathophysiology===
  +
βˆ’
* Inhalation Β± microaspiration, likely from water source
  
  +
*Inhalation Β± microaspiration, likely from water source
βˆ’
** Environmental organisms that are essentially unavoidable
  
  +
**Environmental organisms that are essentially unavoidable
βˆ’
* Response is cell-mediated with pulmonary macrophages, with assistance from CD4, IL-2, and IFN-Ξ³
  
  +
*Response is cell-mediated with pulmonary macrophages, with assistance from CD4, IL-2, and IFN-Ξ³
  +
  +
===Epidemiology===
   
  +
*NTMs are distributed worldwide, present in soil, household water, vegetable matter, animals, and birds
βˆ’
=== Epidemiology ===
  
  +
**Also tap water (especially ''Mycobacterium gordonae'', ''Mycobacterium kansasii'', ''Mycobacterium xenopi'', ''Mycobacterium simiae'', MAC, and ''Mycobacterium mucogenicum'')
βˆ’
* NTMs are distributed worldwide, present in soil, household water, vegetable matter, animals, and birds
  
  +
*90% of patients with NTM infections have underlying pulmonary disease
βˆ’
** Also tap water (especially ''M. gordonae'', ''M. kansasii'', ''M. xenopi'', ''M. simiae'', MAC, and ''M. mucogenicum'')
  
  +
*No person-to-person transmission
βˆ’
* 90% of patients with NTM infections have underlying pulmonary disease
  
βˆ’
* In Ontario: ''M. avium'' complex (25%), ''M. xenopi'' (10%), ''M. abscessus''/''M. chelonae'', ''M. fortuitum''
 +
*In Ontario: ''Mycobacterium avium'' complex (25%), ''Mycobacterium xenopi'' (10%), ''Mycobacterium abscessus''/''Mycobacterium chelonae'', ''Mycobacterium fortuitum''
   
 
{| class="wikitable"
  
{| class="wikitable"
βˆ’
! Presentation and Species
 +
!Species
βˆ’
! Distribution
 +
!Distribution
 
|-
  
|-
βˆ’
! colspan=2 | Pulmonary disease
 +
! colspan="2" |Pulmonary Disease
 
|-
  
|-
βˆ’
| ''M. abscessus''
 +
|[[Mycobacterium abscessus]]
βˆ’
| Worldwide; may be found concomitant with MAC
 +
|Worldwide; may be found concomitant with MAC
 
|-
  
|-
βˆ’
| ''M. avium'' complex
 +
|[[Mycobacterium avium complex]]
βˆ’
| Worldwide; most common NTM pathogen in US
 +
|Worldwide; most common NTM pathogen in US
 
|-
  
|-
βˆ’
| ''M. kansasii''
 +
|[[Mycobacterium kansasii]]
βˆ’
| US, Europe, South Africa, and coal-mining regions
 +
|US, Europe, South Africa, and coal-mining regions
 
|-
  
|-
βˆ’
| ''M. malmoense''
 +
|[[Mycobacterium malmoense]]
βˆ’
| UK, northern Europe; uncommon in US
 +
|UK, northern Europe; uncommon in US
 
|-
  
|-
βˆ’
| ''M. xenopi''
 +
|[[Mycobacterium xenopi]]
βˆ’
| Europe, Canada; uncommon in US; associated with pseudoinfection
 +
|Europe, Canada; uncommon in US; associated with pseudoinfection
 
|-
  
|-
βˆ’
! colspan=2 | Lymphadenitis
 +
! colspan="2" |Lymphadenitis
 
|-
  
|-
βˆ’
| ''M. avium'' complex
 +
|[[Mycobacterium avium complex]]
βˆ’
| Worldwide; most common NTM pathogen in US
 +
|Worldwide; most common NTM pathogen in US
 
|-
  
|-
βˆ’
| ''M. malmoense''
 +
|[[Mycobacterium malmoense]]
βˆ’
| UK, northern Europe (especially Scandinavia)
 +
|UK, northern Europe (especially Scandinavia)
 
|-
  
|-
βˆ’
| ''M. scrofulaceum''
 +
|[[Mycobacterium scrofulaceum]]
βˆ’
| Worldwide; previously common, now rarely isolated in US
 +
|Worldwide; previously common, now rarely isolated in US
 
|-
  
|-
βˆ’
! colspan=2 | Disseminated disease
 +
! colspan="2" |Disseminated Disease
 
|-
  
|-
βˆ’
| ''M. avium'' complex
 +
|[[Mycobacterium avium complex]]
βˆ’
| Worldwide; AIDS; most common NTM pathogen in US
 +
|Worldwide; AIDS; most common NTM pathogen in US
 
|-
  
|-
βˆ’
| ''M. chelonae''
 +
|[[Mycobacterium chelonae]]
βˆ’
| US; non-AIDS immunosuppressed skin lesions
 +
|US; non-AIDS immunosuppressed skin lesions
 
|-
  
|-
βˆ’
| ''M. haemophilum''
 +
|[[Mycobacterium haemophilum]]
βˆ’
| AIDS; US, Australia; non-AIDS immunosuppressed
 +
|AIDS; US, Australia; non-AIDS immunosuppressed
 
|-
  
|-
βˆ’
| ''M. kansasii''
 +
|[[Mycobacterium kansasii]]
βˆ’
| AIDS; US, South Africa
 +
|AIDS; US, South Africa
 
|-
  
|-
βˆ’
! colspan=2 | SSTI and MSK
 +
! colspan="2" |SSTI and MSK
 
|-
  
|-
βˆ’
| ''M. abscessus''
 +
|[[Mycobacterium abscessus]]
βˆ’
| Penetrating injury
 +
|Penetrating injury
 
|-
  
|-
βˆ’
| ''M. chelonae''
 +
|[[Mycobacterium chelonae]]
βˆ’
| US, associated with keratitis and disseminated disease
 +
|US, associated with keratitis and disseminated disease
 
|-
  
|-
βˆ’
| ''M. fortuitum''
 +
|[[Mycobacterium fortuitum]]
βˆ’
| Penetrating injury, footbaths
 +
|Penetrating injury, footbaths
 
|-
  
|-
βˆ’
| ''M. marinum''
 +
|[[Mycobacterium marinum]]
βˆ’
| Worldwide, fresh- and saltwater
 +
|Worldwide, fresh- and saltwater
 
|-
  
|-
βˆ’
| ''M. ulcerans''
 +
|[[Mycobacterium ulcerans]]
βˆ’
| Australia, tropics, Africa, Southeast Asia, not US
 +
|Australia, tropics, Africa, Southeast Asia, not US
 
|-
  
|-
βˆ’
! colspan=2 | Contaminant
 +
! colspan="2" |Contaminant
 
|-
  
|-
βˆ’
| ''M. gordonae''
 +
|[[Mycobacterium gordonae]]
βˆ’
| Most common NTM contaminant
 +
|Most common NTM contaminant
 
|-
  
|-
βˆ’
| ''M. haemophilum''
 +
|[[Mycobacterium haemophilum]]
 
|
  
|
 
|-
  
|-
βˆ’
| ''M. mucogenicum''
 +
|[[Mycobacterium mucogenicum]]
 
|
  
|
 
|-
  
|-
βˆ’
| ''M. nonchromogenicum''
 +
|[[Mycobacterium nonchromogenicum]]
 
|
  
|
 
|-
  
|-
βˆ’
| ''M. terrae'' complex
 +
|[[Mycobacterium terrae complex]]
 
|
  
|
 
|}
  
|}
   
βˆ’
== Clinical Presentation ==
 +
==Clinical Manifestations==
 
{| class="wikitable"
  
{| class="wikitable"
βˆ’
! Syndrome
 +
!Syndrome
βˆ’
! Species
 +
!Species
βˆ’
! Description
 +
!Description
 
|-
  
|-
βˆ’
| Pulmonary disease
 +
|Pulmonary disease
βˆ’
| MAC, ''M. kansasii'', ''M. xenopi'', ''M. abscessus''
 +
|MAC, [[Mycobacterium kansasii]], [[Mycobacterium xenopi]], [[Mycobacterium abscessus]]
 
|
  
|
 
|-
  
|-
βˆ’
| style="padding-left:2em;" | Upper lobe cavitary
 +
| style="padding-left:2em;" |Upper lobe cavitary
βˆ’
| MAC, ''M. kansasii''
 +
|[[MAC]], [[Mycobacterium kansasii]]
βˆ’
| Male smokers, often alcohol use, usually early 50s
 +
|Male smokers, often alcohol use, usually early 50s
 
|-
  
|-
βˆ’
| style="padding-left:2em;" | RML/lingular nodular bronchiectasis
 +
| style="padding-left:2em;" |RML/lingular nodular bronchiectasis
βˆ’
| MAC, ''M. abscessus'', ''M. absessus'' subsp. ''massiliense''
 +
|[[MAC]], [[Mycobacterium abscessus]], [[Mycobacterium abscessus]] subsp. ''massiliense''
βˆ’
| Female nonsmokers, usually older than 60
 +
|Female nonsmokers, usually older than 60
 
|-
  
|-
βˆ’
| style="padding-left:2em;" | Localized alveolar/cavitary
 +
| style="padding-left:2em;" |Localized alveolar/cavitary
βˆ’
| ''M. abscessus'', MAC
 +
|[[Mycobacterium abscessus]], [[MAC]]
βˆ’
| Prior granulomatous dz (usually TB) with bronchiectasis
 +
|Prior [[granulomatous disease]] (usually [[TB]]) with [[bronchiectasis]]
 
|-
  
|-
βˆ’
| style="padding-left:2em;" | Reticulonodular or alveolar bilateral lower lobe
 +
| style="padding-left:2em;" |Reticulonodular or alveolar bilateral lower lobe
βˆ’
| ''M. fortuitum''
 +
|[[Mycobacterium fortuitum]]
βˆ’
| Achalasia, chronic vomiting, exogenous lipoid pneumonia
 +
|[[Achalasia]], chronic vomiting, exogenous lipoid pneumonia
 
|-
  
|-
βˆ’
| style="padding-left:2em;" | Reticulonodular
 +
| style="padding-left:2em;" |Reticulonodular
βˆ’
| MAC, ''M. abscessus'' subsp. ''abscessus'', ''M. abscessus'' subsp. ''massiliense''
 +
|[[MAC]], [[Mycobacterium abscessus]] subsp. ''abscessus'', [[Mycobacterium abscessus]] subsp. ''massiliense''
βˆ’
| Adolescents with CF, HIV-positive patients, prior bronchiectasis
 +
|Adolescents with CF, HIV-positive patients, prior bronchiectasis
 
|-
  
|-
βˆ’
| style="padding-left:2em;" | Hypersensitivity pneumonitis
 +
| style="padding-left:2em;" |Hypersensitivity pneumonitis
βˆ’
| ''M. immunogenum'', ''M. avium''
 +
|[[Mycobacterium immunogenum]], [[Mycobacterium avium]]
βˆ’
| Metal workers, indoor hot tubs
 +
|Metal workers, indoor hot tubs
 
|-
  
|-
βˆ’
| Cervical lymphadenitis
 +
|Cervical lymphadenitis
βˆ’
| MAC
 +
|[[MAC]]
 
|
  
|
 
|-
  
|-
βˆ’
| SSTI
 +
|SSTI
βˆ’
| ''M. fortuitum'', ''M. marinum'', ''M. chelonae'', ''M. ulcerans''
 +
|[[Mycobacterium fortuitum]], [[Mycobacterium marinum]], [[Mycobacterium chelonae]], [[Mycobacterium ulcerans]]
 
|
  
|
 
|-
  
|-
βˆ’
| MSK
 +
|MSK
βˆ’
| ''M. marinum'', MAC, ''M. kansasii'', ''M. fortuitum'', ''M. abscessus'', ''M. chelonae''
 +
|[[Mycobacterium marinum]], [[MAC]], [[Mycobacterium kansasii]], [[Mycobacterium fortuitum]], [[Mycobacterium abscessus]], [[Mycobacterium chelonae]]
 
|
  
|
 
|-
  
|-
βˆ’
| Disseminated
 +
|Disseminated
βˆ’
| HIV-positive: ''M. avium'' and ''M. kansasii'', HIV-negative: ''M. abscessus'' and ''M. chelonae''
 +
|HIV-positive: [[Mycobacterium avium]] and [[Mycobacterium kansasii]];
  +
HIV-negative: [[Mycobacterium abscessus]] and [[Mycobacterium chelonae]]
 
|
  
|
 
|-
  
|-
βˆ’
| Catheter-related
 +
|Catheter-related
βˆ’
| ''M. fortuitum'', ''M. abscessus'', ''M. chelonae''
 +
|[[Mycobacterium fortuitum]], [[Mycobacterium abscessus]], [[Mycobacterium chelonae]]
 
|
  
|
 
|}
  
|}
   
βˆ’
=== Pulmonary disease ===
 +
===Pulmonary Disease===
βˆ’
* Risk factors include COPD and CF [[CiteRef::honda2015pa]]
  
βˆ’
* Most common clinical manifestation of NTM
  
βˆ’
* Most commonly caused by MAC, ''M. kansasii'', ''M. xenopi'', and ''M. abscessus''
  
βˆ’
* Nonspecific chronic or subacute respiratory syndrome with prominent cough
  
   
  +
*Risk factors include COPD and CF[[CiteRef::honda2015pa]]
βˆ’
==== Fibrocavitary disease ====
  
  +
*Most common clinical manifestation of NTM
βˆ’
* Usually preexisting lung disease (COPD etc), men
  
  +
*Most commonly caused by MAC, [[Mycobacterium kansasii]], [[Mycobacterium xenopi]], and [[Mycobacterium abscessus]]
βˆ’
* Upper-lobe predominant, focal, cavitary
  
  +
*Nonspecific chronic or subacute respiratory syndrome with prominent cough
βˆ’
* DDx includes TB and lung cancer
  
   
  +
====Fibrocavitary Disease====
βˆ’
==== Nodular bronchiectatic disease ====
  
βˆ’
* Lady Windermere syndrome
  
βˆ’
* RML/lingula with discrete nodules and bronchiectasis
  
βˆ’
* Usually no preexisting lung disease, non-smoker, women
  
   
  +
*Usually preexisting lung disease ([[COPD]] etc), men
βˆ’
==== Investigations ====
  
  +
*Upper-lobe predominant, focal, cavitary
βˆ’
* Almost always needs CT; may repeat to monitor for progression
  
  +
*DDx includes [[TB]] and [[lung cancer]]
βˆ’
* 3 sputums for AFB; may treat ''M. kansasii'' based on only a single colony but everything else needs 2-3 positives
  
βˆ’
** Rule out TB
  
   
βˆ’
==== Diagnosis ====
 +
====Nodular Bronchiectatic Disease====
βˆ’
* Requires both clinical and microbiological evidence of disease
  
βˆ’
* Clinical diagnosis
  
βˆ’
** Pulmonary symptoms, or
  
βˆ’
** Presence of nodules or cavities as seen on chest radiograph, or
  
βˆ’
** HRCT scan with multifocal bronchiectasis with multiple small nodules, and
  
βˆ’
** Exclusion of other diagnoses
  
βˆ’
* Microbiologic diagnosis
  
βˆ’
** At least 2 (of 3) expectorated sputa (or at least 1 bronchial wash or lavage) with positive cultures for NTM
  
βˆ’
** Transbronchial or other lung biopsy showing the presence of granulomatous inflammation or AFB with 1 or more sputum or bronchial washings that are culture positive for NTM.
  
   
  +
*"Lady Windermere syndrome"
βˆ’
=== Skin and soft tissue infections (SSTI) ===
  
  +
*RML/lingula with discrete nodules and bronchiectasis
βˆ’
* From direct inoculation
  
  +
*Usually no preexisting lung disease, non-smoker, women
βˆ’
* ''M. abscessus'', ''M. fortuitum'', ''M. chelonae'', ''M. marinum'', ''M. ulcerans''
  
βˆ’
* Dx: tissue biopsy culture (best) or culture of discharge
  
   
βˆ’
==== ''M. marinum'' ====
 +
====Investigations====
βˆ’
* "Fish tank granuloma"
  
βˆ’
* Incubation 2 to 3 weeks
  
βˆ’
* Small violet papular lesions on hands, which can ulcerate
  
βˆ’
* Can also cause sporotrichoid disease
  
   
  +
*Almost always needs CT; may repeat to monitor for progression
βˆ’
=== Other Infections ===
  
  +
*3 sputums for AFB; may treat [[Mycobacterium kansasii]] based on only a single colony but everything else needs 2-3 positives
βˆ’
==== Superficial lymphadenitis ====
  
  +
**Rule out [[tuberculosis]]
βˆ’
* Children, usually submandibular
  
βˆ’
* May be from eating dirt
  
   
  +
===Skin and Soft Tissue Infection===
βˆ’
==== Disseminated disease ====
  
βˆ’
* Usually in AIDS or other significant cell-mediated immunosuppression
  
   
  +
*From direct inoculation
βˆ’
==== ''M. chimaera'' infection ====
  
  +
*[[Mycobacterium abscessus]], [[Mycobacterium fortuitum]], [[Mycobacterium chelonae]], [[Mycobacterium marinum]], [[Mycobacterium ulcerans]]
βˆ’
* Outbreaks associated with heater units used in cardiac surgery
  
  +
*Dx: tissue biopsy culture (best) or culture of discharge
βˆ’
* Present with IE, sternal wound infections, mediastinitis, etc.
  
   
  +
====[[Mycobacterium marinum]]====
βˆ’
== Diagnosis ==
  
βˆ’
* Sputum smear and culture for AFB
  
βˆ’
** Spontaneous, induced, or BAL
  
βˆ’
** PCR/NAAT can be done for TB and MAC, but only done on smear positive samples unless specifically requested
  
   
  +
*"Fish tank granuloma"
βˆ’
== Management ==
  
  +
*Incubation 2 to 3 weeks
βˆ’
* Treatment decisions
  
  +
*Small violet papular lesions on hands, which can ulcerate
βˆ’
** First is to decide whether or not to treat; must weigh the risks and benefits
  
  +
*Can also cause [[Sporotrichoid lesions|sporotrichoid disease]]
βˆ’
** NTM can represent contamination, colonization, or infection/invasion
  
βˆ’
** The mycobacteria are inherently resistant to many bacteria, sometimes require IV therapy, multiple agents with toxicity, prolonged treatment
  
βˆ’
** Treatment often ineffective
  
βˆ’
** Recurrence is common; 50% of patients need a second course within 5 years of the first one
  
βˆ’
** Decide to start based on shared decision-making model, reviewing:
  
βˆ’
*** Meets diagnostic criteria
  
βˆ’
*** Comorbidities
  
βˆ’
*** Toxicities
  
βˆ’
*** Goals of care
  
βˆ’
* All rapid-growers are resistant to first-line TB treatment (RIPE), and have aspiration as an underlying risk factor
  
βˆ’
** Need susceptibilities for macrolides in MAC; needs to be specifically requested
  
   
  +
===Other Infections===
βˆ’
=== MAC pulmonary infection ===
  
  +
====Superficial Lymphadenitis====
βˆ’
* MAC is the prototype
  
  +
βˆ’
* Macrolide (azithro/clarithro) backbone, with 2 to 3 other agents depending on the disease type and severity
  
  +
*Children, usually submandibular
βˆ’
* Rifampin and clarithromycin interact, so prefer rifamycin
  
  +
*May be from eating dirt
βˆ’
* Treat until 12 months after negative cultures
  
  +
  +
====Disseminated Disease====
  +
  +
*Usually in AIDS or other significant cell-mediated immunosuppression
  +
  +
====[[Mycobacterium chimaera]] Infection====
  +
  +
*Outbreaks associated with heater units used in cardiac surgery
  +
*Present with IE, sternal wound infections, mediastinitis, etc.
  +
  +
==Diagnosis==
  +
  +
*Sputum smear and culture for AFB
  +
**Spontaneous, induced, or BAL
  +
**PCR/NAAT can be done for TB and MAC, but only done on smear positive samples unless specifically requested
  +
  +
===Diagnostic Criteria for Pulmonary Disease===
  +
  +
*Diagnosis requires clinical, radiologic, and microbiologic criteria
  +
*Clinical: pulmonary or systemic symptoms
  +
*Radiologic: nodular or cavitary opacities on chest radiograph, or a high-resolution cCT scan that shows bronchiectasis with multiple small nodules
  +
*Microbiologic:
  +
**Positive cultures from at least 2 separate expectorate sputums, or
  +
**One positive culture from bronchial wash or lavage
  +
**Transbronchial or other lung biopsy with mycobacterial histologic features (granulomatous inflammation or AFB) and positive culture for NTM or biopsy showing mycobacterial histologic features (granulomatous inflammation or AFB) and one or more sputum or bronchial washings that are culture positive for NTM
  +
*Exclusion of other diagnoses
  +
  +
==Management==
  +
  +
*Treatment decisions
  +
**First is to decide whether or not to treat; must weigh the risks and benefits
  +
**NTM can represent contamination, colonization, or infection/invasion
  +
**The mycobacteria are inherently resistant to many bacteria, sometimes require IV therapy, multiple agents with toxicity, prolonged treatment
  +
**Treatment often ineffective
  +
**Recurrence is common; 50% of patients need a second course within 5 years of the first one
  +
**Decide to start based on shared decision-making model, reviewing:
  +
***Meets diagnostic criteria
  +
***Comorbidities
  +
***Toxicities
  +
***Goals of care
  +
*All rapid-growers are resistant to first-line TB treatment (RIPE), and have aspiration as an underlying risk factor
  +
**Need susceptibilities for [[macrolides]] in MAC; needs to be specifically requested
  +
  +
===Pulmonary Disease===
  +
  +
====[[Mycobacterium avium complex|''Mycobacterium avium'' Complex]]====
  +
  +
*[[MAC]] is the prototype
  +
*[[Macrolide]] ([[azithromycin]]/[[clarithromycin]]) backbone, with 2 to 3 other agents depending on the disease type and severity
  +
*[[Rifampin]] and [[clarithromycin]] interact, so prefer [[rifamycin]]
  +
*Treat until 12 months after negative cultures
   
 
{| class="wikitable"
  
{| class="wikitable"
βˆ’
! Class
 +
!Class
βˆ’
! Nodular
 +
!Nodular
βˆ’
! Cavitary or Advanced
 +
!Cavitary or Advanced
 
|-
  
|-
βˆ’
| [[Macrolide]]
 +
|[[Macrolide]]
βˆ’
| [[Clarithromycin]] 1000 tiw or [[azithromycin]] 500 tiw
 +
|[[Clarithromycin]] 1000 tiw or [[azithromycin]] 500 tiw
βˆ’
| [[Clarithromycin]] 500 bid or [[azithromycin]] 250 daily
 +
|[[Clarithromycin]] 500 bid or [[azithromycin]] 250 daily
 
|-
  
|-
βˆ’
| [[Ethambutol]]
 +
|[[Ethambutol]]
βˆ’
| 25 mg/kg tiw
 +
|25 mg/kg tiw
βˆ’
| 15 mg/kg/day
 +
|15 mg/kg/day
 
|-
  
|-
βˆ’
| [[Rifamycin]]
 +
|[[Rifamycin]]
βˆ’
| TMP 600 tiw
 +
|TMP 600 tiw
βˆ’
| RMP 450-600 mg OD, or RFB 150-300 mg daily
 +
|RMP 450-600 mg OD, or RFB 150-300 mg daily
 
|-
  
|-
βˆ’
| [[Amikacin]]
 +
|[[Amikacin]]
βˆ’
| β€”
 +
|β€”
βˆ’
| Consider 10-15 mg/kg/day IV
 +
|Consider 10-15 mg/kg/day IV
 
|}
  
|}
   
βˆ’
=== ''M. kansasii'' pulmonary disease ===
 +
====[[Mycobacterium kansasii]]====
  +
βˆ’
* ''M. kansasii'' pulmonary disease: daily isoniazid (300 mg/d), rifampin (600 mg/d), and ethambutol (15 mg/kg/d)
  
  +
*[[Mycobacterium kansasii]] pulmonary disease: daily [[isoniazid]] (300 mg/d), [[rifampin]] (600 mg/d), and [[ethambutol]] (15 mg/kg/d)
βˆ’
* Patients should be treated until culture negative on therapy for 1 year
  
  +
*Patients should be treated until culture negative on therapy for 1 year
βˆ’
* Could consider treating based on a single positive colony, as it is rarely a colonizer
  
  +
*Could consider treating based on a single positive colony, as it is rarely a colonizer
  +
  +
====[[Mycobacterium abscessus]]====
  +
  +
*There are no drug regimens of proven or predictable efficacy for treatment of [[Mycobacterium abscessus]] lung disease
  +
*Multidrug regimens that include [[clarithromycin]] 1,000 mg/day may cause symptomatic improvement and disease regression
  +
*Surgical resection of localized disease combined with multidrug clarithromycin-based therapy offers the best chance for cure of this disease
  +
  +
===Non-Pulmonary Disease===
  +
  +
====Rapid Growers ([[Mycobacterium abscessus]], [[Mycobacterium chelonae]], [[Mycobacterium fortuitum]])====
  +
  +
*Based on in vitro susceptibilities
  +
*For ''Mycobacterium abscessus'', a macrolide-based regimen is frequently used
  +
*Surgical debridement may be necessary
  +
  +
====Skin and Soft Tissue Infection====
  +
  +
*3 to 6 months for [[Mycobacterium marinum]], 6 to 12 months for [[MAC]]
   
  +
====Cervical Lymphadenitis====
βˆ’
=== ''M. abscessus'' pulmonary disease ===
  
βˆ’
* There are no drug regimens of proven or predictable efficacy for treatment of M. abscessus lung disease
  
βˆ’
* Multidrug regimens that include clarithromycin 1,000 mg/day may cause symptomatic improvement and disease regression
  
βˆ’
* Surgical resection of localized disease combined with multidrug clarithromycin-based therapy offers the best chance for cure of this disease
  
βˆ’
* Nonpulmonary disease caused by RGM (''M. abscessus'', ''M. chelonae'', ''M. fortuitum''):
  
βˆ’
* Based on in vitro susceptibilities
  
βˆ’
* For ''M. abscessus'', a macrolide-based regimen is frequently used
  
βˆ’
* Surgical debridement may be necessary
  
   
  +
*Mostly due to [[MAC]]
βˆ’
=== ''M. marinum'' SSTI ===
  
  +
*Treated primarily by surgical excision, with a greater than 90% cure rate
βˆ’
* 3 to 6 months for ''M. marinum'', 6 to 12 months for MAC
  
  +
*A [[macrolide]]-based regimen should be considered for patients with extensive MAC lymphadenitis or poor response to surgical therapy
   
  +
===Monitoring===
βˆ’
=== NTM cervical lymphadenitis ===
  
βˆ’
* Mostly due to MAC
  
βˆ’
* Treated primarily by surgical excision, with a greater than 90% cure rate
  
βˆ’
* A macrolide-based regimen should be considered for patients with extensive MAC lymphadenitis or poor response to surgical therapy
  
   
  +
*Depends on the antibiotics used
βˆ’
=== Monitoring ===
  
  +
*Audiology for [[aminoglycosides]]
βˆ’
* Depends on the antibiotics used
  
  +
*Liver enzymes monthly for many others
βˆ’
* Audiology for aminoglycosides
  
βˆ’
* Liver enzymes monthly for many others
  
   
 
[[Category:Mycobacteria]]
  
[[Category:Mycobacteria]]

Revision as of 12:00, 21 November 2023

Background

  • Mycobacteria that excludes tuberculosis and leprosy

Microbiology

  • Acid-fast bacilli, free-living in the environment
    • Direct microscopy with auremine rodhamine fluorochrome stain (better than Ziehl-Neelsen)
  • Broadly divided into slow-growers and fast-growers
  • Media includes blood or chocolate agar, MTBC media, etc
  • Species-level identification requires molecular tests

Species

  • More than 200 species of Mycobacterium spp. that are not in Mycobacterium tuberculosis complex or Mycobacterium leprae
  • Often divided into rapid growers (visible in culture in less than 5-7 days) and slow growers (more than 7 days)
  • Slow-growers are further classified by production of yellow-orange pigment
    • Photochromagens produce pigment when exposed to light
    • Scotochromogens produce pigment regardless of light
    • Nonchromogens do not produce pigment
Slow or Rapid Pigmentation Complex Species Notes
rapid nonchromogen Mycobacterium fortuitum complex Mycobacterium fortuitum
Mycobacterium peregrinum
Mycobacterium porcinum
Mycobacterium chelonae
Mycobacterium abscessus complex Mycobacterium abscessus
Mycobacterium abscessus subsp. abscessus
Mycobacterium abscessus subsp. bolletii
Mycobacterium abscessus subsp. massiliense
Mycobacterium smegmatis
Mycobacterium mucogenicum
slow photochromogen Mycobacterium kansasii Always assumed to be pathogenic, never colonizer.
Mycobacterium marinum Intermediate-grower (7-10 days).
scotochromogen Mycobacterium gordonae Intermediate-grower (7-10 days). Common tap-water contaminant.
Mycobacterium scrofulaceum
nonchromogen Mycobacterium avium complex Mycobacterium avium complex In HIV, rarely pulmonary and almost always disseminated.
Mycobacterium avium Most common subspecies.
Mycobacterium intracellulare
Mycobacterium chimaera Associated with contaminated heater-cooler units in cardiac bypass machines.
Mycobacterium terrae complex Mycobacterium terrae complex
Mycobacterium ulcerans
Mycobacterium xenopi Grows optimally at 42-45 ΒΊC.
Mycobacterium simiae
Mycobacterium malmoense
Mycobacterium szulgai
Mycobacterium asiaticum
Mycobacterium haemophilum Grows optimally at 28-30 ΒΊC.

Pathophysiology

  • Inhalation Β± microaspiration, likely from water source
    • Environmental organisms that are essentially unavoidable
  • Response is cell-mediated with pulmonary macrophages, with assistance from CD4, IL-2, and IFN-Ξ³

Epidemiology

  • NTMs are distributed worldwide, present in soil, household water, vegetable matter, animals, and birds
    • Also tap water (especially Mycobacterium gordonae, Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium simiae, MAC, and Mycobacterium mucogenicum)
  • 90% of patients with NTM infections have underlying pulmonary disease
  • No person-to-person transmission
  • In Ontario: Mycobacterium avium complex (25%), Mycobacterium xenopi (10%), Mycobacterium abscessus/Mycobacterium chelonae, Mycobacterium fortuitum
Species Distribution
Pulmonary Disease
Mycobacterium abscessus Worldwide; may be found concomitant with MAC
Mycobacterium avium complex Worldwide; most common NTM pathogen in US
Mycobacterium kansasii US, Europe, South Africa, and coal-mining regions
Mycobacterium malmoense UK, northern Europe; uncommon in US
Mycobacterium xenopi Europe, Canada; uncommon in US; associated with pseudoinfection
Lymphadenitis
Mycobacterium avium complex Worldwide; most common NTM pathogen in US
Mycobacterium malmoense UK, northern Europe (especially Scandinavia)
Mycobacterium scrofulaceum Worldwide; previously common, now rarely isolated in US
Disseminated Disease
Mycobacterium avium complex Worldwide; AIDS; most common NTM pathogen in US
Mycobacterium chelonae US; non-AIDS immunosuppressed skin lesions
Mycobacterium haemophilum AIDS; US, Australia; non-AIDS immunosuppressed
Mycobacterium kansasii AIDS; US, South Africa
SSTI and MSK
Mycobacterium abscessus Penetrating injury
Mycobacterium chelonae US, associated with keratitis and disseminated disease
Mycobacterium fortuitum Penetrating injury, footbaths
Mycobacterium marinum Worldwide, fresh- and saltwater
Mycobacterium ulcerans Australia, tropics, Africa, Southeast Asia, not US
Contaminant
Mycobacterium gordonae Most common NTM contaminant
Mycobacterium haemophilum
Mycobacterium mucogenicum
Mycobacterium nonchromogenicum
Mycobacterium terrae complex

Clinical Manifestations

Syndrome Species Description
Pulmonary disease MAC, Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium abscessus
Upper lobe cavitary MAC, Mycobacterium kansasii Male smokers, often alcohol use, usually early 50s
RML/lingular nodular bronchiectasis MAC, Mycobacterium abscessus, Mycobacterium abscessus subsp. massiliense Female nonsmokers, usually older than 60
Localized alveolar/cavitary Mycobacterium abscessus, MAC Prior granulomatous disease (usually TB) with bronchiectasis
Reticulonodular or alveolar bilateral lower lobe Mycobacterium fortuitum Achalasia, chronic vomiting, exogenous lipoid pneumonia
Reticulonodular MAC, Mycobacterium abscessus subsp. abscessus, Mycobacterium abscessus subsp. massiliense Adolescents with CF, HIV-positive patients, prior bronchiectasis
Hypersensitivity pneumonitis Mycobacterium immunogenum, Mycobacterium avium Metal workers, indoor hot tubs
Cervical lymphadenitis MAC
SSTI Mycobacterium fortuitum, Mycobacterium marinum, Mycobacterium chelonae, Mycobacterium ulcerans
MSK Mycobacterium marinum, MAC, Mycobacterium kansasii, Mycobacterium fortuitum, Mycobacterium abscessus, Mycobacterium chelonae
Disseminated HIV-positive: Mycobacterium avium and Mycobacterium kansasii;

HIV-negative: Mycobacterium abscessus and Mycobacterium chelonae

Catheter-related Mycobacterium fortuitum, Mycobacterium abscessus, Mycobacterium chelonae

Pulmonary Disease

Fibrocavitary Disease

  • Usually preexisting lung disease (COPD etc), men
  • Upper-lobe predominant, focal, cavitary
  • DDx includes TB and lung cancer

Nodular Bronchiectatic Disease

  • "Lady Windermere syndrome"
  • RML/lingula with discrete nodules and bronchiectasis
  • Usually no preexisting lung disease, non-smoker, women

Investigations

  • Almost always needs CT; may repeat to monitor for progression
  • 3 sputums for AFB; may treat Mycobacterium kansasii based on only a single colony but everything else needs 2-3 positives

Skin and Soft Tissue Infection

Mycobacterium marinum

  • "Fish tank granuloma"
  • Incubation 2 to 3 weeks
  • Small violet papular lesions on hands, which can ulcerate
  • Can also cause sporotrichoid disease

Other Infections

Superficial Lymphadenitis

  • Children, usually submandibular
  • May be from eating dirt

Disseminated Disease

  • Usually in AIDS or other significant cell-mediated immunosuppression

Mycobacterium chimaera Infection

  • Outbreaks associated with heater units used in cardiac surgery
  • Present with IE, sternal wound infections, mediastinitis, etc.

Diagnosis

  • Sputum smear and culture for AFB
    • Spontaneous, induced, or BAL
    • PCR/NAAT can be done for TB and MAC, but only done on smear positive samples unless specifically requested

Diagnostic Criteria for Pulmonary Disease

  • Diagnosis requires clinical, radiologic, and microbiologic criteria
  • Clinical: pulmonary or systemic symptoms
  • Radiologic: nodular or cavitary opacities on chest radiograph, or a high-resolution cCT scan that shows bronchiectasis with multiple small nodules
  • Microbiologic:
    • Positive cultures from at least 2 separate expectorate sputums, or
    • One positive culture from bronchial wash or lavage
    • Transbronchial or other lung biopsy with mycobacterial histologic features (granulomatous inflammation or AFB) and positive culture for NTM or biopsy showing mycobacterial histologic features (granulomatous inflammation or AFB) and one or more sputum or bronchial washings that are culture positive for NTM
  • Exclusion of other diagnoses

Management

  • Treatment decisions
    • First is to decide whether or not to treat; must weigh the risks and benefits
    • NTM can represent contamination, colonization, or infection/invasion
    • The mycobacteria are inherently resistant to many bacteria, sometimes require IV therapy, multiple agents with toxicity, prolonged treatment
    • Treatment often ineffective
    • Recurrence is common; 50% of patients need a second course within 5 years of the first one
    • Decide to start based on shared decision-making model, reviewing:
      • Meets diagnostic criteria
      • Comorbidities
      • Toxicities
      • Goals of care
  • All rapid-growers are resistant to first-line TB treatment (RIPE), and have aspiration as an underlying risk factor
    • Need susceptibilities for macrolides in MAC; needs to be specifically requested

Pulmonary Disease

Mycobacterium avium Complex

Class Nodular Cavitary or Advanced
Macrolide Clarithromycin 1000 tiw or azithromycin 500 tiw Clarithromycin 500 bid or azithromycin 250 daily
Ethambutol 25 mg/kg tiw 15 mg/kg/day
Rifamycin TMP 600 tiw RMP 450-600 mg OD, or RFB 150-300 mg daily
Amikacin β€” Consider 10-15 mg/kg/day IV

Mycobacterium kansasii

  • Mycobacterium kansasii pulmonary disease: daily isoniazid (300 mg/d), rifampin (600 mg/d), and ethambutol (15 mg/kg/d)
  • Patients should be treated until culture negative on therapy for 1 year
  • Could consider treating based on a single positive colony, as it is rarely a colonizer

Mycobacterium abscessus

  • There are no drug regimens of proven or predictable efficacy for treatment of Mycobacterium abscessus lung disease
  • Multidrug regimens that include clarithromycin 1,000 mg/day may cause symptomatic improvement and disease regression
  • Surgical resection of localized disease combined with multidrug clarithromycin-based therapy offers the best chance for cure of this disease

Non-Pulmonary Disease

Rapid Growers (Mycobacterium abscessus, Mycobacterium chelonae, Mycobacterium fortuitum)

  • Based on in vitro susceptibilities
  • For Mycobacterium abscessus, a macrolide-based regimen is frequently used
  • Surgical debridement may be necessary

Skin and Soft Tissue Infection

Cervical Lymphadenitis

  • Mostly due to MAC
  • Treated primarily by surgical excision, with a greater than 90% cure rate
  • A macrolide-based regimen should be considered for patients with extensive MAC lymphadenitis or poor response to surgical therapy

Monitoring

  • Depends on the antibiotics used
  • Audiology for aminoglycosides
  • Liver enzymes monthly for many others

References

  1. ^  Jennifer R. Honda, Vijaya Knight, Edward D. Chan. Pathogenesis and Risk Factors for Nontuberculous Mycobacterial Lung Disease. Clinics in Chest Medicine. 2015;36(1):1-11. doi:10.1016/j.ccm.2014.10.001.

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