Non-tuberculous mycobacteria: Difference between revisions

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***May grow in blood culture if mycobacteremic
***May grow in blood culture if mycobacteremic
**Slow-growers produce colonies after more than 7 days on solid media
**Slow-growers produce colonies after more than 7 days on solid media
***MAC, ''M. xenopi'', and ''M. kansasii'' are the three most important
***[[MAC]], [[Mycobacterium xenopi]], and [[Mycobacterium kansasii]] are the three most important
***Grows optimally at 35-37ΒΊ C except ''M. haemophilum'' (28-30 ΒΊC) and ''M. xenopi'' (42-45 ΒΊC)
***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
*Media includes blood or chocolate agar, MTBC media, etc
*Species-level identifiation requires molecular tests
*Species-level identification requires molecular tests


===Species===
===Species===


*More than 200 species of ''Mycobacterium'' spp. that are not in ''M. tuberculosis'' complex or ''M. leprae''
*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)
*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
*Slow-growers are further classified by production of yellow-orange pigment
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| rowspan="10" |rapid
| rowspan="10" |rapid
| rowspan="10" |nonchromogen
| rowspan="10" |nonchromogen
| rowspan="3" |''M. fortuitum'' complex
| rowspan="3" |[[Mycobacterium fortuitum complex]]
| ''M. fortuitum''
| [[Mycobacterium fortuitum]]
|
|
|-
|-
| ''M. peregrinum''
| [[Mycobacterium peregrinum]]
|
|
|-
|-
| ''M. porcinum''
| [[Mycobacterium porcinum]]
|
|
|-
|-
| colspan="2" |[[Mycobacterium chelonae]]
|
|''M. chelonae''
|
|
|-
|-
| rowspan="4" |[[Mycobacterium abscessus complex]]
|
|''[[M. abscessus]]''
|''[[Mycobacterium abscessus]]''
|
|
|-
|-
|''[[M. abscessus]]''
|[[Mycobacterium abscessus]] subsp. ''abscessus''
|''M. abscessus'' subsp. ''abscessus''
|
|
|-
|-
|''[[M. abscessus]]''
| [[Mycobacterium abscessus]] subsp. ''bolletii''
| ''M. abscessus'' subsp. ''bolletii''
|
|
|-
|-
|''[[M. abscessus]]''
| [[Mycobacterium abscessus]] subsp. ''massiliense''
| ''M. abscessus'' subsp. ''massiliense''
|
|
|-
|-
| colspan="2" |[[Mycobacterium smegmatis]]
|
|''M. smegmatis''
|
|
|-
|-
| colspan="2" |[[Mycobacterium mucogenicum]]
|
|''M. mucogenicum''
|
|
|-
|-
| rowspan="16" |slow
| rowspan="16" |slow
| rowspan="2" |photochromogen
| rowspan="2" |photochromogen
| colspan="2" |[[Mycobacterium kansasii]]
|
| ''M. kansasii''
|Always assumed to be pathogenic, never colonizer.
|Always assumed to be pathogenic, never colonizer.
|-
|-
| colspan="2" |[[Mycobacterium marinum]]
|
| ''M. marinum''
|Intermediate-grower (7-10 days).
|Intermediate-grower (7-10 days).
|-
|-
| rowspan="2" |scotochromogen
| rowspan="2" |scotochromogen
| colspan="2" |[[Mycobacterium gordonae]]
|
| ''M. gordonae''
|Intermediate-grower (7-10 days). Common tap-water contaminant.
|Intermediate-grower (7-10 days). Common tap-water contaminant.
|-
|-
| colspan="2" |[[Mycobacterium scrofulaceum]]
|
|''M. scrofulaceum''
|
|
|-
|-
| rowspan="12" |nonchromogen
| rowspan="12" |nonchromogen
| rowspan="4" |[[M. avium complex]]
| rowspan="4" |[[Mycobacterium avium complex]]
|[[M. avium complex]]
|[[Mycobacterium avium complex]]
|In HIV, rarely pulmonary and almost always disseminated.
|In HIV, rarely pulmonary and almost always disseminated.
|-
|-
|''M. avium''
|[[Mycobacterium avium]]
|Most common subspecies.
|Most common subspecies.
|-
|-
|''M. intracellulare''
|[[Mycobacterium intracellulare]]
|
|
|-
|-
|''[[Mycobacterium chimaera|M. chimaera]]''
|[[Mycobacterium chimaera]]
|Associated with contaminated heater-cooler units in cardiac bypass machines.
|Associated with contaminated heater-cooler units in cardiac bypass machines.
|-
|-
|''M. terrae'' complex
|[[Mycobacterium terrae complex]]
|''M. terrae'' complex
|[[Mycobacterium terrae complex]]
|
|
|-
|-
| colspan="2" |[[Mycobacterium ulcerans]]
|
|''M. ulcerans''
|
|
|-
|-
| colspan="2" |[[Mycobacterium xenopi]]
|
|''M. xenopi''
|Grows optimally at 42-45 ΒΊC.
|Grows optimally at 42-45 ΒΊC.
|-
|-
| colspan="2" |[[Mycobacterium simiae]]
|
|''M. simiae''
|
|
|-
|-
| colspan="2" |[[Mycobacterium malmoense]]
|
|''M. malmoense''
|
|
|-
|-
| colspan="2" |[[Mycobacterium szulgai]]
|
|''M. szulgai''
|
|
|-
|-
| colspan="2" |[[Mycobacterium asiaticum]]
|
|''M. asiaticum''
|
|
|-
|-
| colspan="2" |[[Mycobacterium haemophilum]]
|
|''M. haemophilum''
|Grows optimally at 28-30 ΒΊC.
|Grows optimally at 28-30 ΒΊC.
|}
|}
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*NTMs are distributed worldwide, present in soil, household water, vegetable matter, animals, and birds
*NTMs are distributed worldwide, present in soil, household water, vegetable matter, animals, and birds
**Also tap water (especially ''M. gordonae'', ''M. kansasii'', ''M. xenopi'', ''M. simiae'', MAC, and ''M. mucogenicum'')
**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
*90% of patients with NTM infections have underlying pulmonary disease
*No person-to-person transmission
*No person-to-person transmission
*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"
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! colspan="2" |Pulmonary Disease
! colspan="2" |Pulmonary Disease
|-
|-
|''M. abscessus''
|[[Mycobacterium abscessus]]
|Worldwide; may be found concomitant with MAC
|Worldwide; may be found concomitant with MAC
|-
|-
|''M. avium'' complex
|[[Mycobacterium avium complex]]
|Worldwide; most common NTM pathogen in US
|Worldwide; most common NTM pathogen in US
|-
|-
|''M. kansasii''
|[[Mycobacterium kansasii]]
|US, Europe, South Africa, and coal-mining regions
|US, Europe, South Africa, and coal-mining regions
|-
|-
|''M. malmoense''
|[[Mycobacterium malmoense]]
|UK, northern Europe; uncommon in US
|UK, northern Europe; uncommon in US
|-
|-
|''M. xenopi''
|[[Mycobacterium xenopi]]
|Europe, Canada; uncommon in US; associated with pseudoinfection
|Europe, Canada; uncommon in US; associated with pseudoinfection
|-
|-
! colspan="2" |Lymphadenitis
! colspan="2" |Lymphadenitis
|-
|-
|''M. avium'' complex
|[[Mycobacterium avium complex]]
|Worldwide; most common NTM pathogen in US
|Worldwide; most common NTM pathogen in US
|-
|-
|''M. malmoense''
|[[Mycobacterium malmoense]]
|UK, northern Europe (especially Scandinavia)
|UK, northern Europe (especially Scandinavia)
|-
|-
|''M. scrofulaceum''
|[[Mycobacterium scrofulaceum]]
|Worldwide; previously common, now rarely isolated in US
|Worldwide; previously common, now rarely isolated in US
|-
|-
! colspan="2" |Disseminated Disease
! colspan="2" |Disseminated Disease
|-
|-
|''M. avium'' complex
|[[Mycobacterium avium complex]]
|Worldwide; AIDS; most common NTM pathogen in US
|Worldwide; AIDS; most common NTM pathogen in US
|-
|-
|''M. chelonae''
|[[Mycobacterium chelonae]]
|US; non-AIDS immunosuppressed skin lesions
|US; non-AIDS immunosuppressed skin lesions
|-
|-
|''M. haemophilum''
|[[Mycobacterium haemophilum]]
|AIDS; US, Australia; non-AIDS immunosuppressed
|AIDS; US, Australia; non-AIDS immunosuppressed
|-
|-
|''M. kansasii''
|[[Mycobacterium kansasii]]
|AIDS; US, South Africa
|AIDS; US, South Africa
|-
|-
! colspan="2" |SSTI and MSK
! colspan="2" |SSTI and MSK
|-
|-
|''M. abscessus''
|[[Mycobacterium abscessus]]
|Penetrating injury
|Penetrating injury
|-
|-
|''M. chelonae''
|[[Mycobacterium chelonae]]
|US, associated with keratitis and disseminated disease
|US, associated with keratitis and disseminated disease
|-
|-
|''M. fortuitum''
|[[Mycobacterium fortuitum]]
|Penetrating injury, footbaths
|Penetrating injury, footbaths
|-
|-
|''M. marinum''
|[[Mycobacterium marinum]]
|Worldwide, fresh- and saltwater
|Worldwide, fresh- and saltwater
|-
|-
|''M. ulcerans''
|[[Mycobacterium ulcerans]]
|Australia, tropics, Africa, Southeast Asia, not US
|Australia, tropics, Africa, Southeast Asia, not US
|-
|-
! colspan="2" |Contaminant
! colspan="2" |Contaminant
|-
|-
|''M. gordonae''
|[[Mycobacterium gordonae]]
|Most common NTM contaminant
|Most common NTM contaminant
|-
|-
|''M. haemophilum''
|[[Mycobacterium haemophilum]]
|
|
|-
|-
|''M. mucogenicum''
|[[Mycobacterium mucogenicum]]
|
|
|-
|-
|''M. nonchromogenicum''
|[[Mycobacterium nonchromogenicum]]
|
|
|-
|-
|''M. terrae'' complex
|[[Mycobacterium terrae complex]]
|
|
|}
|}
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|-
|-
|Pulmonary disease
|Pulmonary disease
|MAC, ''M. kansasii'', ''M. xenopi'', ''M. abscessus''
|MAC, [[Mycobacterium kansasii]], [[Mycobacterium xenopi]], [[Mycobacterium abscessus]]
|
|
|-
|-
| style="padding-left:2em;" |Upper lobe cavitary
| style="padding-left:2em;" |Upper lobe cavitary
|MAC, ''M. kansasii''
|[[MAC]], [[Mycobacterium kansasii]]
|Male smokers, often alcohol use, usually early 50s
|Male smokers, often alcohol use, usually early 50s
|-
|-
| style="padding-left:2em;" |RML/lingular nodular bronchiectasis
| style="padding-left:2em;" |RML/lingular nodular bronchiectasis
|MAC, ''M. abscessus'', ''M. absessus'' subsp. ''massiliense''
|[[MAC]], [[Mycobacterium abscessus]], [[Mycobacterium abscessus]] subsp. ''massiliense''
|Female nonsmokers, usually older than 60
|Female nonsmokers, usually older than 60
|-
|-
| style="padding-left:2em;" |Localized alveolar/cavitary
| style="padding-left:2em;" |Localized alveolar/cavitary
|''M. abscessus'', MAC
|[[Mycobacterium abscessus]], [[MAC]]
|Prior granulomatous dz (usually TB) with bronchiectasis
|Prior [[granulomatous disease]] (usually [[TB]]) with [[bronchiectasis]]
|-
|-
| style="padding-left:2em;" |Reticulonodular or alveolar bilateral lower lobe
| style="padding-left:2em;" |Reticulonodular or alveolar bilateral lower lobe
|''M. fortuitum''
|[[Mycobacterium fortuitum]]
|Achalasia, chronic vomiting, exogenous lipoid pneumonia
|[[Achalasia]], chronic vomiting, exogenous lipoid pneumonia
|-
|-
| style="padding-left:2em;" |Reticulonodular
| style="padding-left:2em;" |Reticulonodular
|MAC, ''M. abscessus'' subsp. ''abscessus'', ''M. abscessus'' subsp. ''massiliense''
|[[MAC]], [[Mycobacterium abscessus]] subsp. ''abscessus'', [[Mycobacterium abscessus]] subsp. ''massiliense''
|Adolescents with CF, HIV-positive patients, prior bronchiectasis
|Adolescents with CF, HIV-positive patients, prior bronchiectasis
|-
|-
| style="padding-left:2em;" |Hypersensitivity pneumonitis
| style="padding-left:2em;" |Hypersensitivity pneumonitis
|''M. immunogenum'', ''M. avium''
|[[Mycobacterium immunogenum]], [[Mycobacterium avium]]
|Metal workers, indoor hot tubs
|Metal workers, indoor hot tubs
|-
|-
|Cervical lymphadenitis
|Cervical lymphadenitis
|MAC
|[[MAC]]
|
|
|-
|-
|SSTI
|SSTI
|''M. fortuitum'', ''M. marinum'', ''M. chelonae'', ''M. ulcerans''
|[[Mycobacterium fortuitum]], [[Mycobacterium marinum]], [[Mycobacterium chelonae]], [[Mycobacterium ulcerans]]
|
|
|-
|-
|MSK
|MSK
|''M. marinum'', MAC, ''M. kansasii'', ''M. fortuitum'', ''M. abscessus'', ''M. chelonae''
|[[Mycobacterium marinum]], [[MAC]], [[Mycobacterium kansasii]], [[Mycobacterium fortuitum]], [[Mycobacterium abscessus]], [[Mycobacterium chelonae]]
|
|
|-
|-
|Disseminated
|Disseminated
|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]]
|
|
|-
|-
|Catheter-related
|Catheter-related
|''M. fortuitum'', ''M. abscessus'', ''M. chelonae''
|[[Mycobacterium fortuitum]], [[Mycobacterium abscessus]], [[Mycobacterium chelonae]]
|
|
|}
|}
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*Risk factors include COPD and CF[[CiteRef::honda2015pa]]
*Risk factors include COPD and CF[[CiteRef::honda2015pa]]
*Most common clinical manifestation of NTM
*Most common clinical manifestation of NTM
*Most commonly caused by MAC, ''M. kansasii'', ''M. xenopi'', and ''M. abscessus''
*Most commonly caused by MAC, [[Mycobacterium kansasii]], [[Mycobacterium xenopi]], and [[Mycobacterium abscessus]]
*Nonspecific chronic or subacute respiratory syndrome with prominent cough
*Nonspecific chronic or subacute respiratory syndrome with prominent cough


====Fibrocavitary Disease====
====Fibrocavitary Disease====


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


====Nodular Bronchiectatic Disease====
====Nodular Bronchiectatic Disease====


*Lady Windermere syndrome
*"Lady Windermere syndrome"
*RML/lingula with discrete nodules and bronchiectasis
*RML/lingula with discrete nodules and bronchiectasis
*Usually no preexisting lung disease, non-smoker, women
*Usually no preexisting lung disease, non-smoker, women
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*Almost always needs CT; may repeat to monitor for progression
*Almost always needs CT; may repeat to monitor for progression
*3 sputums for AFB; may treat ''M. kansasii'' based on only a single colony but everything else needs 2-3 positives
*3 sputums for AFB; may treat [[Mycobacterium kansasii]] based on only a single colony but everything else needs 2-3 positives
**Rule out [[tuberculosis]]
**Rule out [[tuberculosis]]


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*From direct inoculation
*From direct inoculation
*''M. abscessus'', ''M. fortuitum'', ''M. chelonae'', ''M. marinum'', ''M. ulcerans''
*[[Mycobacterium abscessus]], [[Mycobacterium fortuitum]], [[Mycobacterium chelonae]], [[Mycobacterium marinum]], [[Mycobacterium ulcerans]]
*Dx: tissue biopsy culture (best) or culture of discharge
*Dx: tissue biopsy culture (best) or culture of discharge


====''M. marinum''====
====[[Mycobacterium marinum]]====


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


===Other Infections===
===Other Infections===
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*Usually in AIDS or other significant cell-mediated immunosuppression
*Usually in AIDS or other significant cell-mediated immunosuppression


====''M. chimaera'' Infection====
====[[Mycobacterium chimaera]] Infection====


*Outbreaks associated with heater units used in cardiac surgery
*Outbreaks associated with heater units used in cardiac surgery
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***Goals of care
***Goals of care
*All rapid-growers are resistant to first-line TB treatment (RIPE), and have aspiration as an underlying risk factor
*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
**Need susceptibilities for [[macrolides]] in MAC; needs to be specifically requested


===Pulmonary Disease===
===Pulmonary Disease===


====''Mycobacterium avium'' Complex====
====[[Mycobacterium avium complex|''Mycobacterium avium'' Complex]]====


*MAC is the prototype
*[[MAC]] is the prototype
*Macrolide (azithro/clarithro) backbone, with 2 to 3 other agents depending on the disease type and severity
*[[Macrolide]] ([[azithromycin]]/[[clarithromycin]]) backbone, with 2 to 3 other agents depending on the disease type and severity
*Rifampin and clarithromycin interact, so prefer rifamycin
*[[Rifampin]] and [[clarithromycin]] interact, so prefer [[rifamycin]]
*Treat until 12 months after negative cultures
*Treat until 12 months after negative cultures


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|}
|}


====''M. kansasii''====
====[[Mycobacterium kansasii]]====


*''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)
*Patients should be treated until culture negative on therapy for 1 year
*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
*Could consider treating based on a single positive colony, as it is rarely a colonizer


====''M. abscessus''====
====[[Mycobacterium abscessus]]====


*There are no drug regimens of proven or predictable efficacy for treatment of M. abscessus lung disease
*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
*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
*Surgical resection of localized disease combined with multidrug clarithromycin-based therapy offers the best chance for cure of this disease


===Non-Pulmonary Disease===
===Non-Pulmonary Disease===


====Rapid Growers (''M. abscessus'', ''M. chelonae'', ''M. fortuitum'')====
====Rapid Growers====


*Includes [[Mycobacterium abscessus]], [[Mycobacterium chelonae]], and [[Mycobacterium fortuitum]]
*Based on in vitro susceptibilities
*Antimicrobial selection is based on in vitro susceptibilities
*For ''M. abscessus'', a macrolide-based regimen is frequently used
*For ''Mycobacterium abscessus'', a macrolide-based regimen is frequently used
*Surgical debridement may be necessary
*Surgical debridement may be necessary


====Skin and Soft Tissue Infection====
====Skin and Soft Tissue Infection====


*3 to 6 months for ''M. marinum'', 6 to 12 months for MAC
*3 to 6 months for [[Mycobacterium marinum]], 6 to 12 months for [[MAC]]


====Cervical Lymphadenitis====
====Cervical Lymphadenitis====


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


===Monitoring===
===Monitoring===


*Depends on the antibiotics used
*Depends on the antibiotics used
*Audiology for aminoglycosides
*Audiology for [[aminoglycosides]]
*Liver enzymes monthly for many others
*Liver enzymes monthly for many others


Latest revision as of 14:49, 2 May 2024

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

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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