Non-tuberculous mycobacteria: Difference between revisions
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*Mycobacteria that excludes tuberculosis and leprosy |
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==Background== |
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===Microbiology=== |
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* Acid-fast bacilli, free-living in the environment |
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** Direct microscopy with auremine rodhamine fluorochrome stain (better than Ziehl-Neelsen) |
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* Broadly divided into slow-growers and fast-growers |
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** Fast-growers produce colonies within 7 days on solid media |
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*** Grows optimally at 28-30º C, with some preferring 35º C |
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*** May grow in blood culture if mycobacteremic |
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** Slow-growers produce colonies after more than 7 days on solid media |
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*** MAC, ''M. xenopi'', and ''M. kansasii'' are the three most important |
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*** Grows optimally at 35-37º C except ''M. haemophilum'' (28-30º C) and ''M. xenopi'' (42-45º C) |
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* Media includes blood or chocolate agar, MTBC media, etc |
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* Species-level identifiation requires molecular tests |
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*Acid-fast bacilli, free-living in the environment |
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=== Species === |
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**Direct microscopy with auremine rodhamine fluorochrome stain (better than Ziehl-Neelsen) |
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* More than 200 species of ''Mycobacterium'' spp. that are not in ''M. tuberculosis'' complex or ''M. leprae'' |
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*Broadly divided into slow-growers and fast-growers |
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**Fast-growers produce colonies within 7 days on solid media |
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***Grows optimally at 28-30º C, with some preferring 35º C |
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***May grow in blood culture if mycobacteremic |
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**Slow-growers produce colonies after more than 7 days on solid media |
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***MAC, ''M. xenopi'', and ''M. kansasii'' are the three most important |
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***Grows optimally at 35-37º C except ''M. haemophilum'' (28-30º C) and ''M. xenopi'' (42-45º C) |
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*Media includes blood or chocolate agar, MTBC media, etc |
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*Species-level identifiation requires molecular tests |
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===Species=== |
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*More than 200 species of ''Mycobacterium'' spp. that are not in ''M. tuberculosis'' complex or ''M. leprae'' |
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{| class="wikitable" |
{| class="wikitable" |
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!Species |
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!Notes |
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! colspan=2 | |
! colspan="2" |Rapid-growers (visible in culture in <7 days) |
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|''M. fortuitum'' complex |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. fortuitum'' |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. peregrinum'' |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. porcinum'' |
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|''M. chelonae'' |
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|''[[M. abscessus]]'' |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. abscessus'' subsp. ''abscessus'' |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. abscessus'' subsp. ''bolletii'' |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. abscessus'' subsp. ''massiliense'' |
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|''M. smegmatis'' |
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|''M. mucogenicum'' |
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! colspan=2 | |
! colspan="2" |Slow-growers (visible in culture in >7 days) |
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| colspan=2 | |
| colspan="2" |Photochromogens (develop pigments in light) |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. kansasii'' |
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|Always assumed to be pathogenic, never colonizer. |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. marinum'' |
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|Intermediate-grower (7-10 days). |
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| Scotochromogens |
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|Develop pigments in darkness. |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. gordonae'' |
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|Intermediate-grower (7-10 days). Common tap-water contaminant. |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. scrofulaceum'' |
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| colspan=2 | |
| colspan="2" |Nonchromogens (do not develop pigments in light) |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |[[M. avium complex]] |
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|In HIV, rarely pulmonary and almost always disseminated. |
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| style="padding-left:2.5em;" | |
| style="padding-left:2.5em;" |''M. avium'' |
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|Most common subspecies. |
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| style="padding-left:2.5em;" | |
| style="padding-left:2.5em;" |''M. intracellulare'' |
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| style="padding-left:2.5em;" | |
| style="padding-left:2.5em;" |''M. chimaera'' |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. terrae'' complex |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. ulcerans'' |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. xenopi'' |
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|Grows optimally at 42-45º C. |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. simiae'' |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. malmoense'' |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. szulgai'' |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. asiaticum'' |
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| style="padding-left:1.5em;" | |
| style="padding-left:1.5em;" |''M. haemophilum'' |
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|Grows optimally at 28-30º C. |
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=== |
===Pathophysiology=== |
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* Inhalation ± microaspiration, likely from water source |
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** Environmental organisms that are essentially unavoidable |
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* Response is cell-mediated with pulmonary macrophages, with assistance from CD4, IL-2, and IFN-γ |
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*Inhalation ± microaspiration, likely from water source |
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=== Epidemiology === |
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**Environmental organisms that are essentially unavoidable |
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* NTMs are distributed worldwide, present in soil, household water, vegetable matter, animals, and birds |
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*Response is cell-mediated with pulmonary macrophages, with assistance from CD4, IL-2, and IFN-γ |
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** Also tap water (especially ''M. gordonae'', ''M. kansasii'', ''M. xenopi'', ''M. simiae'', MAC, and ''M. mucogenicum'') |
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* 90% of patients with NTM infections have underlying pulmonary disease |
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===Epidemiology=== |
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* In Ontario: ''M. avium'' complex (25%), ''M. xenopi'' (10%), ''M. abscessus''/''M. chelonae'', ''M. fortuitum'' |
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*NTMs are distributed worldwide, present in soil, household water, vegetable matter, animals, and birds |
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**Also tap water (especially ''M. gordonae'', ''M. kansasii'', ''M. xenopi'', ''M. simiae'', MAC, and ''M. mucogenicum'') |
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*90% of patients with NTM infections have underlying pulmonary disease |
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*In Ontario: ''M. avium'' complex (25%), ''M. xenopi'' (10%), ''M. abscessus''/''M. chelonae'', ''M. fortuitum'' |
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{| class="wikitable" |
{| class="wikitable" |
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! |
!Presentation and Species |
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! |
!Distribution |
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! colspan=2 | |
! colspan="2" |Pulmonary disease |
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|''M. abscessus'' |
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|Worldwide; may be found concomitant with MAC |
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|''M. avium'' complex |
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|Worldwide; most common NTM pathogen in US |
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|''M. kansasii'' |
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|US, Europe, South Africa, and coal-mining regions |
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|''M. malmoense'' |
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|UK, northern Europe; uncommon in US |
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|''M. xenopi'' |
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|Europe, Canada; uncommon in US; associated with pseudoinfection |
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! colspan=2 | |
! colspan="2" |Lymphadenitis |
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|''M. avium'' complex |
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|Worldwide; most common NTM pathogen in US |
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|''M. malmoense'' |
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|UK, northern Europe (especially Scandinavia) |
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|''M. scrofulaceum'' |
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|Worldwide; previously common, now rarely isolated in US |
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! colspan=2 | |
! colspan="2" |Disseminated disease |
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|''M. avium'' complex |
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|Worldwide; AIDS; most common NTM pathogen in US |
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|''M. chelonae'' |
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|US; non-AIDS immunosuppressed skin lesions |
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|''M. haemophilum'' |
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|AIDS; US, Australia; non-AIDS immunosuppressed |
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|''M. kansasii'' |
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|AIDS; US, South Africa |
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! colspan=2 | |
! colspan="2" |SSTI and MSK |
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|''M. abscessus'' |
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|Penetrating injury |
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|''M. chelonae'' |
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|US, associated with keratitis and disseminated disease |
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|''M. fortuitum'' |
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|Penetrating injury, footbaths |
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|''M. marinum'' |
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|Worldwide, fresh- and saltwater |
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|''M. ulcerans'' |
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|Australia, tropics, Africa, Southeast Asia, not US |
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! colspan=2 | |
! colspan="2" |Contaminant |
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|''M. gordonae'' |
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|Most common NTM contaminant |
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|''M. haemophilum'' |
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|''M. mucogenicum'' |
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|''M. nonchromogenicum'' |
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|''M. terrae'' complex |
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== |
==Clinical Manifestations== |
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{| class="wikitable" |
{| class="wikitable" |
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!Syndrome |
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!Species |
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!Description |
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|Pulmonary disease |
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|MAC, ''M. kansasii'', ''M. xenopi'', ''M. abscessus'' |
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| style="padding-left:2em;" | |
| style="padding-left:2em;" |Upper lobe cavitary |
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|MAC, ''M. kansasii'' |
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|Male smokers, often alcohol use, usually early 50s |
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| style="padding-left:2em;" | |
| style="padding-left:2em;" |RML/lingular nodular bronchiectasis |
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|MAC, ''M. abscessus'', ''M. absessus'' subsp. ''massiliense'' |
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|Female nonsmokers, usually older than 60 |
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| style="padding-left:2em;" | |
| style="padding-left:2em;" |Localized alveolar/cavitary |
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|''M. abscessus'', MAC |
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|Prior granulomatous dz (usually TB) with bronchiectasis |
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| style="padding-left:2em;" | |
| style="padding-left:2em;" |Reticulonodular or alveolar bilateral lower lobe |
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|''M. fortuitum'' |
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|Achalasia, chronic vomiting, exogenous lipoid pneumonia |
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| style="padding-left:2em;" |Reticulonodular |
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|MAC, ''M. abscessus'' subsp. ''abscessus'', ''M. abscessus'' subsp. ''massiliense'' |
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|Adolescents with CF, HIV-positive patients, prior bronchiectasis |
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| style="padding-left:2em;" | |
| style="padding-left:2em;" |Hypersensitivity pneumonitis |
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|''M. immunogenum'', ''M. avium'' |
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|Metal workers, indoor hot tubs |
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|Cervical lymphadenitis |
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|MAC |
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|SSTI |
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|''M. fortuitum'', ''M. marinum'', ''M. chelonae'', ''M. ulcerans'' |
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|MSK |
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|''M. marinum'', MAC, ''M. kansasii'', ''M. fortuitum'', ''M. abscessus'', ''M. chelonae'' |
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|Disseminated |
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|HIV-positive: ''M. avium'' and ''M. kansasii'', HIV-negative: ''M. abscessus'' and ''M. chelonae'' |
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|Catheter-related |
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|''M. fortuitum'', ''M. abscessus'', ''M. chelonae'' |
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=== |
===Pulmonary Disease=== |
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* Risk factors include COPD and CF [[CiteRef::honda2015pa]] |
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* Most common clinical manifestation of NTM |
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* Most commonly caused by MAC, ''M. kansasii'', ''M. xenopi'', and ''M. abscessus'' |
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* Nonspecific chronic or subacute respiratory syndrome with prominent cough |
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*Risk factors include COPD and CF [[CiteRef::honda2015pa]] |
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==== Fibrocavitary disease ==== |
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*Most common clinical manifestation of NTM |
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* Usually preexisting lung disease (COPD etc), men |
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*Most commonly caused by MAC, ''M. kansasii'', ''M. xenopi'', and ''M. abscessus'' |
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* Upper-lobe predominant, focal, cavitary |
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*Nonspecific chronic or subacute respiratory syndrome with prominent cough |
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* DDx includes TB and lung cancer |
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====Fibrocavitary Disease==== |
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==== Nodular bronchiectatic disease ==== |
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* Lady Windermere syndrome |
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* RML/lingula with discrete nodules and bronchiectasis |
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* Usually no preexisting lung disease, non-smoker, women |
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*Usually preexisting lung disease (COPD etc), men |
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==== Investigations ==== |
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*Upper-lobe predominant, focal, cavitary |
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* Almost always needs CT; may repeat to monitor for progression |
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*DDx includes TB and lung cancer |
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* 3 sputums for AFB; may treat ''M. kansasii'' based on only a single colony but everything else needs 2-3 positives |
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** Rule out TB |
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==== |
====Nodular Bronchiectatic Disease==== |
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* Requires both clinical and microbiological evidence of disease |
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* Clinical diagnosis |
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** Pulmonary symptoms, or |
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** Presence of nodules or cavities as seen on chest radiograph, or |
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** HRCT scan with multifocal bronchiectasis with multiple small nodules, and |
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** Exclusion of other diagnoses |
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* Microbiologic diagnosis |
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** At least 2 (of 3) expectorated sputa (or at least 1 bronchial wash or lavage) with positive cultures for NTM |
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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. |
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*Lady Windermere syndrome |
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=== Skin and soft tissue infections (SSTI) === |
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*RML/lingula with discrete nodules and bronchiectasis |
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* From direct inoculation |
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*Usually no preexisting lung disease, non-smoker, women |
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* ''M. abscessus'', ''M. fortuitum'', ''M. chelonae'', ''M. marinum'', ''M. ulcerans'' |
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* Dx: tissue biopsy culture (best) or culture of discharge |
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==== |
====Investigations==== |
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* "Fish tank granuloma" |
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* Incubation 2 to 3 weeks |
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* Small violet papular lesions on hands, which can ulcerate |
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* Can also cause sporotrichoid disease |
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*Almost always needs CT; may repeat to monitor for progression |
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=== Other Infections === |
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*3 sputums for AFB; may treat ''M. kansasii'' based on only a single colony but everything else needs 2-3 positives |
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==== Superficial lymphadenitis ==== |
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**Rule out TB |
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* Children, usually submandibular |
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* May be from eating dirt |
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==== |
====Diagnosis==== |
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* Usually in AIDS or other significant cell-mediated immunosuppression |
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*Requires both clinical and microbiological evidence of disease |
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==== ''M. chimaera'' infection ==== |
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*Clinical diagnosis |
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* Outbreaks associated with heater units used in cardiac surgery |
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**Pulmonary symptoms, or |
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* Present with IE, sternal wound infections, mediastinitis, etc. |
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**Presence of nodules or cavities as seen on chest radiograph, or |
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**HRCT scan with multifocal bronchiectasis with multiple small nodules, and |
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**Exclusion of other diagnoses |
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*Microbiologic diagnosis |
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**At least 2 (of 3) expectorated sputa (or at least 1 bronchial wash or lavage) with positive cultures for NTM |
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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. |
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===Skin and Soft Tissue Infection=== |
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== Diagnosis == |
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* Sputum smear and culture for AFB |
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** Spontaneous, induced, or BAL |
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** PCR/NAAT can be done for TB and MAC, but only done on smear positive samples unless specifically requested |
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*From direct inoculation |
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== Management == |
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*''M. abscessus'', ''M. fortuitum'', ''M. chelonae'', ''M. marinum'', ''M. ulcerans'' |
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* Treatment decisions |
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*Dx: tissue biopsy culture (best) or culture of discharge |
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** First is to decide whether or not to treat; must weigh the risks and benefits |
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** NTM can represent contamination, colonization, or infection/invasion |
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** The mycobacteria are inherently resistant to many bacteria, sometimes require IV therapy, multiple agents with toxicity, prolonged treatment |
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** Treatment often ineffective |
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** Recurrence is common; 50% of patients need a second course within 5 years of the first one |
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** Decide to start based on shared decision-making model, reviewing: |
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*** Meets diagnostic criteria |
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*** Comorbidities |
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*** Toxicities |
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*** Goals of care |
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* All rapid-growers are resistant to first-line TB treatment (RIPE), and have aspiration as an underlying risk factor |
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** Need susceptibilities for macrolides in MAC; needs to be specifically requested |
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====''M. marinum''==== |
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=== MAC pulmonary infection === |
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* MAC is the prototype |
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*"Fish tank granuloma" |
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* Macrolide (azithro/clarithro) backbone, with 2 to 3 other agents depending on the disease type and severity |
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*Incubation 2 to 3 weeks |
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* Rifampin and clarithromycin interact, so prefer rifamycin |
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*Small violet papular lesions on hands, which can ulcerate |
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* Treat until 12 months after negative cultures |
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*Can also cause sporotrichoid disease |
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===Other Infections=== |
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====Superficial Lymphadenitis==== |
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*Children, usually submandibular |
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*May be from eating dirt |
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====Disseminated Disease==== |
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*Usually in AIDS or other significant cell-mediated immunosuppression |
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====''M. chimaera'' Infection==== |
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*Outbreaks associated with heater units used in cardiac surgery |
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*Present with IE, sternal wound infections, mediastinitis, etc. |
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==Diagnosis== |
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*Sputum smear and culture for AFB |
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**Spontaneous, induced, or BAL |
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**PCR/NAAT can be done for TB and MAC, but only done on smear positive samples unless specifically requested |
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==Management== |
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*Treatment decisions |
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**First is to decide whether or not to treat; must weigh the risks and benefits |
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**NTM can represent contamination, colonization, or infection/invasion |
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**The mycobacteria are inherently resistant to many bacteria, sometimes require IV therapy, multiple agents with toxicity, prolonged treatment |
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**Treatment often ineffective |
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**Recurrence is common; 50% of patients need a second course within 5 years of the first one |
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**Decide to start based on shared decision-making model, reviewing: |
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***Meets diagnostic criteria |
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***Comorbidities |
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***Toxicities |
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***Goals of care |
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*All rapid-growers are resistant to first-line TB treatment (RIPE), and have aspiration as an underlying risk factor |
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**Need susceptibilities for macrolides in MAC; needs to be specifically requested |
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=== Pulmonary Disease === |
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====''Mycobacterium avium'' Complex==== |
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*MAC is the prototype |
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*Macrolide (azithro/clarithro) backbone, with 2 to 3 other agents depending on the disease type and severity |
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*Rifampin and clarithromycin interact, so prefer rifamycin |
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*Treat until 12 months after negative cultures |
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{| class="wikitable" |
{| class="wikitable" |
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! |
!Class |
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!Nodular |
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!Cavitary or Advanced |
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|[[Macrolide]] |
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|[[Clarithromycin]] 1000 tiw or [[azithromycin]] 500 tiw |
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|[[Clarithromycin]] 500 bid or [[azithromycin]] 250 daily |
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|[[Ethambutol]] |
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|25 mg/kg tiw |
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|15 mg/kg/day |
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|[[Rifamycin]] |
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|TMP 600 tiw |
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|RMP 450-600 mg OD, or RFB 150-300 mg daily |
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|[[Amikacin]] |
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|— |
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|Consider 10-15 mg/kg/day IV |
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=== |
====''M. kansasii''==== |
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* ''M. kansasii'' pulmonary disease: daily isoniazid (300 mg/d), rifampin (600 mg/d), and ethambutol (15 mg/kg/d) |
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*''M. kansasii'' pulmonary disease: daily isoniazid (300 mg/d), rifampin (600 mg/d), and ethambutol (15 mg/kg/d) |
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* Patients should be treated until culture negative on therapy for 1 year |
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*Patients should be treated until culture negative on therapy for 1 year |
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* Could consider treating based on a single positive colony, as it is rarely a colonizer |
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*Could consider treating based on a single positive colony, as it is rarely a colonizer |
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====''M. abscessus''==== |
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*There are no drug regimens of proven or predictable efficacy for treatment of M. abscessus lung disease |
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*Multidrug regimens that include clarithromycin 1,000 mg/day may cause symptomatic improvement and disease regression |
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*Surgical resection of localized disease combined with multidrug clarithromycin-based therapy offers the best chance for cure of this disease |
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=== Non-Pulmonary Disease === |
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==== Rapid Growers (''M. abscessus'', ''M. chelonae'', ''M. fortuitum'') ==== |
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*Based on in vitro susceptibilities |
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*For ''M. abscessus'', a macrolide-based regimen is frequently used |
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*Surgical debridement may be necessary |
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====Skin and Soft Tissue Infection==== |
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*3 to 6 months for ''M. marinum'', 6 to 12 months for MAC |
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====Cervical Lymphadenitis==== |
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=== ''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''): |
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* Based on in vitro susceptibilities |
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* For ''M. abscessus'', a macrolide-based regimen is frequently used |
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* Surgical debridement may be necessary |
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*Mostly due to MAC |
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=== ''M. marinum'' SSTI === |
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*Treated primarily by surgical excision, with a greater than 90% cure rate |
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* 3 to 6 months for ''M. marinum'', 6 to 12 months for MAC |
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*A macrolide-based regimen should be considered for patients with extensive MAC lymphadenitis or poor response to surgical therapy |
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===Monitoring=== |
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=== NTM cervical lymphadenitis === |
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* Mostly due to MAC |
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* Treated primarily by surgical excision, with a greater than 90% cure rate |
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* A macrolide-based regimen should be considered for patients with extensive MAC lymphadenitis or poor response to surgical therapy |
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*Depends on the antibiotics used |
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=== Monitoring === |
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*Audiology for aminoglycosides |
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* Depends on the antibiotics used |
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*Liver enzymes monthly for many others |
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* Audiology for aminoglycosides |
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* Liver enzymes monthly for many others |
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[[Category:Mycobacteria]] |
[[Category:Mycobacteria]] |
Revision as of 15:31, 18 August 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 28-30º C, with some preferring 35º 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 35-37º C except M. haemophilum (28-30º C) and M. xenopi (42-45º C)
- Fast-growers produce colonies within 7 days on solid media
- 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 42-45º C. |
M. simiae | |
M. malmoense | |
M. szulgai | |
M. asiaticum | |
M. haemophilum | Grows optimally at 28-30º C. |
Pathophysiology
- Inhalation ± 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-γ
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 Manifestations
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 1
- 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 Infection
- 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
Pulmonary Disease
Mycobacterium avium Complex
- 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 | 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 | — | Consider 10-15 mg/kg/day IV |
M. kansasii
- 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
- 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
Non-Pulmonary Disease
Rapid Growers (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
Skin and Soft Tissue Infection
- 3 to 6 months for M. marinum, 6 to 12 months for MAC
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
- ^ 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.