Non-tuberculous mycobacteria: Difference between revisions

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==Background==
* Mycobacteria that excludes tuberculosis and leprosy


*Mycobacteria that excludes tuberculosis and leprosy
== Microbiology ==


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


*Acid-fast bacilli, free-living in the environment
== Species ==
**Direct microscopy with auremine rodhamine fluorochrome stain (better than Ziehl-Neelsen)
*Broadly divided into slow-growers and fast-growers
**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 ''M. tuberculosis'' complex or ''M. leprae''


*More than 200 species of ''Mycobacterium'' spp. that are not in [[Mycobacterium tuberculosis]] complex or [[Mycobacterium leprae]]
{| class="wikitable"
*Often divided into rapid growers (visible in culture in less than 5-7 days) and slow growers (more than 7 days)
! Species
*Slow-growers are further classified by production of yellow-orange pigment
! Notes
**Photochromagens produce pigment when exposed to light
|-
**Scotochromogens produce pigment regardless of light
| '''Rapid-growers'''
**Nonchromogens do not produce pigment
| ''Visible in culture in <7 days''

{| class="wikitable sortable"
!Slow or Rapid
!Pigmentation
!Complex
!Species
!Notes
|-
|-
| rowspan="10" |rapid
|  ''M. fortuitum'' complex
| rowspan="10" |nonchromogen
| rowspan="3" |[[Mycobacterium fortuitum complex]]
| [[Mycobacterium fortuitum]]
|
|
|-
|-
| [[Mycobacterium peregrinum]]
|   ''M. fortuitum''
|
|
|-
|-
| [[Mycobacterium porcinum]]
|   ''M. peregrinum''
|
|
|-
|-
| colspan="2" |[[Mycobacterium chelonae]]
|   ''M. porcinum''
|
|
|-
|-
| rowspan="4" |[[Mycobacterium abscessus complex]]
|  ''M. chelonae''
|''[[Mycobacterium abscessus]]''
|
|
|-
|-
|  ''[[M. abscessus]]''
|[[Mycobacterium abscessus]] subsp. ''abscessus''
|
|
|-
|-
|   ''M. abscessus'' subsp. ''abscessus''
| [[Mycobacterium abscessus]] subsp. ''bolletii''
|
|
|-
|-
|   ''M. abscessus'' subsp. ''bolletii''
| [[Mycobacterium abscessus]] subsp. ''massiliense''
|
|
|-
|-
| colspan="2" |[[Mycobacterium smegmatis]]
|   ''M. abscessus'' subsp. ''massiliense''
|
|
|-
|-
| colspan="2" |[[Mycobacterium mucogenicum]]
|  ''M. smegmatis''
|
|
|-
|-
| rowspan="16" |slow
|  ''M. mucogenicum''
| rowspan="2" |photochromogen
|
| colspan="2" |[[Mycobacterium kansasii]]
|Always assumed to be pathogenic, never colonizer.
|-
|-
| colspan="2" |[[Mycobacterium marinum]]
| '''Slow-growers'''
|Intermediate-grower (7-10 days).
| ''Visible in culture in >7 days''
|-
|-
| rowspan="2" |scotochromogen
|  Photochromogens
| colspan="2" |[[Mycobacterium gordonae]]
| Develop pigments in light.
|Intermediate-grower (7-10 days). Common tap-water contaminant.
|-
|-
| colspan="2" |[[Mycobacterium scrofulaceum]]
|   ''M. kansasii''
| Always assumed to be pathogenic, never colonizer.
|-
|   ''M. marinum''
| Intermediate-grower (7-10 days).
|-
|  Scotochromogens
| Develop pigments in darkness.
|-
|   ''M. gordonae''
| Intermediate-grower (7-10 days). Common tap-water contaminant.
|-
|   ''M. scrofulaceum''
|
|
|-
|-
| rowspan="12" |nonchromogen
|  Nonchromogens
| rowspan="4" |[[Mycobacterium avium complex]]
|
|[[Mycobacterium avium complex]]
|In HIV, rarely pulmonary and almost always disseminated.
|-
|-
|   [[M. avium complex]]
|[[Mycobacterium avium]]
|Most common subspecies.
| In HIV, rarely pulmonary and almost always disseminated.
|-
|-
|[[Mycobacterium intracellulare]]
|    ''M. avium''
| Most common subspecies.
|-
|    ''M. intracellulare''
|
|
|-
|-
|    ''M. chimaera''
|[[Mycobacterium chimaera]]
|Associated with contaminated heater-cooler units in cardiac bypass machines.
|
|-
|-
|   ''M. terrae'' complex
|[[Mycobacterium terrae complex]]
|[[Mycobacterium terrae complex]]
|
|
|-
|-
|   ''M. ulcerans''
| colspan="2" |[[Mycobacterium ulcerans]]
|
|
|-
|-
|   ''M. xenopi''
| colspan="2" |[[Mycobacterium xenopi]]
| Grows optimally at 42-45ΒΊ C.
|Grows optimally at 42-45 ΒΊC.
|-
|-
|   ''M. simiae''
| colspan="2" |[[Mycobacterium simiae]]
|
|
|-
|-
|   ''M. malmoense''
| colspan="2" |[[Mycobacterium malmoense]]
|
|
|-
|-
|   ''M. szulgai''
| colspan="2" |[[Mycobacterium szulgai]]
|
|
|-
|-
|   ''M. asiaticum''
| colspan="2" |[[Mycobacterium asiaticum]]
|
|
|-
|-
|   ''M. haemophilum''
| colspan="2" |[[Mycobacterium haemophilum]]
| Grows optimally at 28-30ΒΊ C.
|Grows optimally at 28-30 ΒΊC.
|}
|}


== Pathophysiology ==
===Pathophysiology===


* Inhalation Β± microaspiration, likely from water source
*Inhalation Β± microaspiration, likely from water source
** Environmental organisms that are essentially unavoidable
**Environmental organisms that are essentially unavoidable
* 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 ==
===Epidemiology===


* 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
* 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"
! Presentation and Species
!Species
! Distribution
!Distribution
|-
|-
| 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
|-
|-
| 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
|-
|-
| 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
|-
|-
| 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
|-
|-
| 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]]
|
|
|}
|}


== Clinical Presentation ==
==Clinical Manifestations==
{| class="wikitable"

!Syndrome
{|
!Species
! Syndrome
!Description
! Species
! Description
|-
|-
| Pulmonary disease
|Pulmonary disease
| MAC, ''M. kansasii'', ''M. xenopi'', ''M. abscessus''
|MAC, [[Mycobacterium kansasii]], [[Mycobacterium xenopi]], [[Mycobacterium abscessus]]
|
|
|-
|-
|  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
|-
|-
|  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
|-
|-
|  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]]
|-
|-
|  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
|  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
|-
|-
|  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]]
|
|
|}
|}


== Pulmonary disease ==
===Pulmonary Disease===


* Risk factors include COPD and CF
*Risk factors include COPD and CF[[CiteRef::honda2015pa]]
*Most common clinical manifestation of NTM
** [https://doi.org/10.1016/j.ccm.2014.10.001 Review article]
*Most commonly caused by MAC, [[Mycobacterium kansasii]], [[Mycobacterium xenopi]], and [[Mycobacterium abscessus]]
* Most common clinical manifestation of NTM
*Nonspecific chronic or subacute respiratory syndrome with prominent cough
* Most commonly caused by MAC, ''M. kansasii'', ''M. xenopi'', and ''M. abscessus''
* 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


=== Investigations ===
====Investigations====


* 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 TB
**Rule out [[tuberculosis]]


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


*From direct inoculation
* Requires both clinical and microbiological evidence of disease
*[[Mycobacterium abscessus]], [[Mycobacterium fortuitum]], [[Mycobacterium chelonae]], [[Mycobacterium marinum]], [[Mycobacterium ulcerans]]
* Clinical diagnosis
*Dx: tissue biopsy culture (best) or culture of discharge
** Pulmonary symptoms, or
** Presence of nodules or cavities as seen on chest radiograph, or
** HRCT scan with multifocal bronchiectasis with multiple small nodules, and
** Exclusion of other diagnoses
* Microbiologic diagnosis
** At least 2 (of 3) expectorated sputa (or at least 1 bronchial wash or lavage) with positive cultures for NTM
** 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.


====[[Mycobacterium marinum]]====
== Skin and soft tissue infections (SSTI) ==


*"Fish tank granuloma"
* From direct inoculation
*Incubation 2 to 3 weeks
* ''M. abscessus'', ''M. fortuitum'', ''M. chelonae'', ''M. marinum'', ''M. ulcerans''
*Small violet papular lesions on hands, which can ulcerate
* Dx: tissue biopsy culture (best) or culture of discharge
*Can also cause [[Sporotrichoid lesions|sporotrichoid disease]]


=== ''M. marinum'' ===
===Other Infections===
====Superficial Lymphadenitis====


*Children, usually submandibular
* "Fish tank granuloma"
*May be from eating dirt
* Incubation 2 to 3 weeks
* Small violet papular lesions on hands, which can ulcerate
* Can also cause sporotrichoid disease


====Disseminated Disease====
== Other Infections ==


*Usually in AIDS or other significant cell-mediated immunosuppression
=== Superficial lymphadenitis ===


====[[Mycobacterium chimaera]] Infection====
* Children, usually submandibular
* May be from eating dirt


*Outbreaks associated with heater units used in cardiac surgery
=== Disseminated disease ===
*Present with IE, sternal wound infections, mediastinitis, etc.


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


*Sputum smear and culture for AFB
=== ''M. chimaera'' infection ===
**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===
* Outbreaks associated with heater units used in cardiac surgery
* Present with IE, sternal wound infections, mediastinitis, etc.


*Diagnosis requires clinical, radiologic, and microbiologic criteria
== Diagnosis ==
*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==
* 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


*Treatment decisions
== Management ==
**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===
* 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


====[[Mycobacterium avium complex|''Mycobacterium avium'' Complex]]====
=== MAC pulmonary infection ===


* 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


{| class="wikitable"
{|
! Class
!Class
! Nodular
!Nodular
! Cavitary or Advanced
!Cavitary or Advanced
|-
|-
| Macrolide
|[[Macrolide]]
| Clari 1000 tiw or azi 500 tiw
|[[Clarithromycin]] 1000 tiw or [[azithromycin]] 500 tiw
| Clari 500 bid or azi 250 OD
|[[Clarithromycin]] 500 bid or [[azithromycin]] 250 daily
|-
|-
| Ethambutol
|[[Ethambutol]]
| 25 mg/kg tiw
|25 mg/kg tiw
| 15 mg/kg/day
|15 mg/kg/day
|-
|-
| Rifamycin
|[[Rifamycin]]
| TMP 600 tiw
|TMP 600 tiw
| RMP 450-600 mg OD, or RFB 150-300 mg daily
|RMP 450-600 mg OD, or RFB 150-300 mg daily
|-
|-
| Amikacin
|[[Amikacin]]
| β€”
|β€”
| Consider 10-15 mg/kg/day IV
|Consider 10-15 mg/kg/day IV
|}
|}


=== ''M. kansasii'' pulmonary disease ===
====[[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===
* ''M. 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


====Rapid Growers====
=== ''M. abscessus'' pulmonary disease ===


*Includes [[Mycobacterium abscessus]], [[Mycobacterium chelonae]], and [[Mycobacterium fortuitum]]
* There are no drug regimens of proven or predictable efficacy for treatment of M. abscessus lung disease
*Antimicrobial selection is based on in vitro susceptibilities
* Multidrug regimens that include clarithromycin 1,000 mg/day may cause symptomatic improvement and disease regression
*For ''Mycobacterium abscessus'', a macrolide-based regimen is frequently used
* Surgical resection of localized disease combined with multidrug clarithromycin-based therapy offers the best chance for cure of this disease
*Surgical debridement may be necessary
* Nonpulmonary disease caused by RGM (''M. abscessus'', ''M. chelonae'', ''M. fortuitum''):
* Based on in vitro susceptibilities
* For ''M. abscessus'', a macrolide-based regimen is frequently used
* Surgical debridement may be necessary


=== ''M. marinum'' SSTI ===
====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====
=== NTM 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


[[Category:Mycobacteria]]
[[Category:Mycobacteria]]

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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