Non-tuberculous mycobacteria: Difference between revisions

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* Mycobacteria that excludes tuberculosis and leprosy
* Mycobacteria that excludes tuberculosis and leprosy


== Microbiology ==
== Background ==
=== Microbiology ===

* Acid-fast bacilli, free-living in the environment
* Acid-fast bacilli, free-living in the environment
** Direct microscopy with auremine rodhamine fluorochrome stain (better than Ziehl-Neelsen)
** Direct microscopy with auremine rodhamine fluorochrome stain (better than Ziehl-Neelsen)
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* Species-level identifiation requires molecular tests
* Species-level identifiation 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 ''M. tuberculosis'' complex or ''M. leprae''


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== 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 ''M. gordonae'', ''M. kansasii'', ''M. xenopi'', ''M. simiae'', MAC, and ''M. mucogenicum'')
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== Clinical Presentation ==
== Clinical Presentation ==

{| class="wikitable"
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! Syndrome
! Syndrome
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== Pulmonary disease ==
=== Pulmonary disease ===

* Risk factors include COPD and CF
* Risk factors include COPD and CF
** [https://doi.org/10.1016/j.ccm.2014.10.001 Review article]
** [https://doi.org/10.1016/j.ccm.2014.10.001 Review article]
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* 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


=== 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 ''M. kansasii'' based on only a single colony but everything else needs 2-3 positives
** Rule out TB
** Rule out TB


=== Diagnosis ===
==== Diagnosis ====

* Requires both clinical and microbiological evidence of disease
* Requires both clinical and microbiological evidence of disease
* Clinical diagnosis
* Clinical diagnosis
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** 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.
** 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.


== Skin and soft tissue infections (SSTI) ==
=== Skin and soft tissue infections (SSTI) ===

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


=== ''M. marinum'' ===
==== ''M. 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 disease


== Other Infections ==
=== Other Infections ===
⚫
==== Superficial lymphadenitis ====

⚫
=== Superficial lymphadenitis ===

* Children, usually submandibular
* Children, usually submandibular
* May be from eating dirt
* May be from eating dirt


=== Disseminated disease ===
==== Disseminated disease ====

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


=== ''M. chimaera'' infection ===
==== ''M. chimaera'' infection ====

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


== Diagnosis ==
== Diagnosis ==

* Sputum smear and culture for AFB
* Sputum smear and culture for AFB
** Spontaneous, induced, or BAL
** Spontaneous, induced, or BAL
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== Management ==
== Management ==

* Treatment decisions
* Treatment decisions
** First is to decide whether or not to treat; must weigh the risks and benefits
** First is to decide whether or not to treat; must weigh the risks and benefits
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=== MAC pulmonary infection ===
=== 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 (azithro/clarithro) backbone, with 2 to 3 other agents depending on the disease type and severity
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=== ''M. kansasii'' pulmonary disease ===
=== ''M. kansasii'' pulmonary disease ===

* ''M. kansasii'' pulmonary disease: daily isoniazid (300 mg/d), rifampin (600 mg/d), and ethambutol (15 mg/kg/d)
* ''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
* Patients should be treated until culture negative on therapy for 1 year
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=== ''M. abscessus'' pulmonary disease ===
=== ''M. abscessus'' pulmonary disease ===

* 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 M. 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
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=== ''M. marinum'' SSTI ===
=== ''M. marinum'' SSTI ===

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


=== NTM 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
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=== Monitoring ===
=== Monitoring ===

* Depends on the antibiotics used
* Depends on the antibiotics used
* Audiology for aminoglycosides
* Audiology for aminoglycosides

Revision as of 17:24, 31 January 2020

  • Mycobacteria that excludes tuberculosis and leprosy

Background

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

Species

  • More than 200 species of Mycobacterium spp. that are not in M. tuberculosis complex or M. leprae
Species Notes
Rapid-growers (visible in culture in <7 days)
M. fortuitum complex
M. fortuitum
M. peregrinum
M. porcinum
M. chelonae
M. abscessus
M. abscessus subsp. abscessus
M. abscessus subsp. bolletii
M. abscessus subsp. massiliense
M. smegmatis
M. mucogenicum
Slow-growers (visible in culture in >7 days)
Photochromogens (develop pigments in light)
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
Nonchromogens (do not develop pigments in light)
M. avium complex In HIV, rarely pulmonary and almost always disseminated.
M. avium Most common subspecies.
M. intracellulare
M. chimaera
M. terrae complex
M. ulcerans
M. xenopi Grows optimally at 42-45ΒΊ C.
M. simiae
M. malmoense
M. szulgai
M. asiaticum
M. haemophilum Grows optimally at 28-30ΒΊ C.

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 M. gordonae, M. kansasii, M. xenopi, M. simiae, MAC, and M. mucogenicum)
  • 90% of patients with NTM infections have underlying pulmonary disease
  • In Ontario: M. avium complex (25%), M. xenopi (10%), M. abscessus/M. chelonae, M. fortuitum
Presentation and Species Distribution
Pulmonary disease
M. abscessus Worldwide; may be found concomitant with MAC
M. avium complex Worldwide; most common NTM pathogen in US
M. kansasii US, Europe, South Africa, and coal-mining regions
M. malmoense UK, northern Europe; uncommon in US
M. xenopi Europe, Canada; uncommon in US; associated with pseudoinfection
Lymphadenitis
M. avium complex Worldwide; most common NTM pathogen in US
M. malmoense UK, northern Europe (especially Scandinavia)
M. scrofulaceum Worldwide; previously common, now rarely isolated in US
Disseminated disease
M. avium complex Worldwide; AIDS; most common NTM pathogen in US
M. chelonae US; non-AIDS immunosuppressed skin lesions
M. haemophilum AIDS; US, Australia; non-AIDS immunosuppressed
M. kansasii AIDS; US, South Africa
SSTI and MSK
M. abscessus Penetrating injury
M. chelonae US, associated with keratitis and disseminated disease
M. fortuitum Penetrating injury, footbaths
M. marinum Worldwide, fresh- and saltwater
M. ulcerans Australia, tropics, Africa, Southeast Asia, not US
Contaminant
M. gordonae Most common NTM contaminant
M. haemophilum
M. mucogenicum
M. nonchromogenicum
M. terrae complex

Clinical Presentation

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

Pulmonary disease

  • Risk factors include COPD and CF
  • Most common clinical manifestation of NTM
  • Most commonly caused by MAC, M. kansasii, M. xenopi, and M. abscessus
  • Nonspecific chronic or subacute respiratory syndrome with prominent cough

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 M. kansasii based on only a single colony but everything else needs 2-3 positives
    • Rule out TB

Diagnosis

  • Requires both clinical and microbiological evidence of disease
  • Clinical diagnosis
    • 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.

Skin and soft tissue infections (SSTI)

  • From direct inoculation
  • M. abscessus, M. fortuitum, M. chelonae, M. marinum, M. ulcerans
  • Dx: tissue biopsy culture (best) or culture of discharge

M. 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

M. 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

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

MAC pulmonary infection

  • MAC is the prototype
  • Macrolide (azithro/clarithro) 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 Nodular Cavitary or Advanced
Macrolide Clari 1000 tiw or azi 500 tiw Clari 500 bid or azi 250 OD
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

M. kansasii 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

M. abscessus pulmonary disease

  • There are no drug regimens of proven or predictable efficacy for treatment of M. 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
  • 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

  • 3 to 6 months for M. marinum, 6 to 12 months for MAC

NTM 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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