Non-tuberculous mycobacteria: Difference between revisions
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− | * |
+ | *Mycobacteria that excludes tuberculosis and leprosy |
− | == |
+ | ==Background== |
− | === |
+ | ===Microbiology=== |
− | * 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 |
− | ! |
+ | !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'' |
− | | |
+ | |Always assumed to be pathogenic, never colonizer. |
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− | | style="padding-left:1.5em;" | |
+ | | style="padding-left:1.5em;" |''M. marinum'' |
− | | |
+ | |Intermediate-grower (7-10 days). |
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− | | |
+ | | Scotochromogens |
− | | |
+ | |Develop pigments in darkness. |
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− | | style="padding-left:1.5em;" | |
+ | | style="padding-left:1.5em;" |''M. gordonae'' |
− | | |
+ | |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]] |
− | | |
+ | |In HIV, rarely pulmonary and almost always disseminated. |
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− | | style="padding-left:2.5em;" | |
+ | | style="padding-left:2.5em;" |''M. avium'' |
− | | |
+ | |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'' |
− | | |
+ | |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'' |
− | | |
+ | |Grows optimally at 28-30º C. |
|} |
|} |
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− | === |
+ | ===Pathophysiology=== |
− | * 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 |
− | ! |
+ | !Distribution |
|- |
|- |
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− | ! colspan=2 | |
+ | ! colspan="2" |Pulmonary disease |
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− | | |
+ | |''M. abscessus'' |
− | | |
+ | |Worldwide; may be found concomitant with MAC |
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− | | |
+ | |''M. avium'' complex |
− | | |
+ | |Worldwide; most common NTM pathogen in US |
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− | | |
+ | |''M. kansasii'' |
− | | |
+ | |US, Europe, South Africa, and coal-mining regions |
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− | | |
+ | |''M. malmoense'' |
− | | |
+ | |UK, northern Europe; uncommon in US |
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− | | |
+ | |''M. xenopi'' |
− | | |
+ | |Europe, Canada; uncommon in US; associated with pseudoinfection |
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− | ! colspan=2 | |
+ | ! colspan="2" |Lymphadenitis |
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− | | |
+ | |''M. avium'' complex |
− | | |
+ | |Worldwide; most common NTM pathogen in US |
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− | | |
+ | |''M. malmoense'' |
− | | |
+ | |UK, northern Europe (especially Scandinavia) |
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− | | |
+ | |''M. scrofulaceum'' |
− | | |
+ | |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 |
− | | |
+ | |Worldwide; AIDS; most common NTM pathogen in US |
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− | | |
+ | |''M. chelonae'' |
− | | |
+ | |US; non-AIDS immunosuppressed skin lesions |
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− | | |
+ | |''M. haemophilum'' |
− | | |
+ | |AIDS; US, Australia; non-AIDS immunosuppressed |
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− | | |
+ | |''M. kansasii'' |
− | | |
+ | |AIDS; US, South Africa |
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− | ! colspan=2 | |
+ | ! colspan="2" |SSTI and MSK |
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− | | |
+ | |''M. abscessus'' |
− | | |
+ | |Penetrating injury |
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− | | |
+ | |''M. chelonae'' |
− | | |
+ | |US, associated with keratitis and disseminated disease |
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− | | |
+ | |''M. fortuitum'' |
− | | |
+ | |Penetrating injury, footbaths |
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− | | |
+ | |''M. marinum'' |
− | | |
+ | |Worldwide, fresh- and saltwater |
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− | | |
+ | |''M. ulcerans'' |
− | | |
+ | |Australia, tropics, Africa, Southeast Asia, not US |
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− | ! colspan=2 | |
+ | ! colspan="2" |Contaminant |
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− | | |
+ | |''M. gordonae'' |
− | | |
+ | |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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|} |
|} |
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− | == |
+ | ==Clinical Manifestations== |
{| class="wikitable" |
{| class="wikitable" |
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− | ! |
+ | !Syndrome |
− | ! |
+ | !Species |
− | ! |
+ | !Description |
|- |
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− | | |
+ | |Pulmonary disease |
− | | |
+ | |MAC, ''M. kansasii'', ''M. xenopi'', ''M. abscessus'' |
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− | | style="padding-left:2em;" | |
+ | | style="padding-left:2em;" |Upper lobe cavitary |
− | | |
+ | |MAC, ''M. kansasii'' |
− | | |
+ | |Male smokers, often alcohol use, usually early 50s |
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− | | style="padding-left:2em;" | |
+ | | style="padding-left:2em;" |RML/lingular nodular bronchiectasis |
− | | |
+ | |MAC, ''M. abscessus'', ''M. absessus'' subsp. ''massiliense'' |
− | | |
+ | |Female nonsmokers, usually older than 60 |
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− | | style="padding-left:2em;" | |
+ | | style="padding-left:2em;" |Localized alveolar/cavitary |
− | | |
+ | |''M. abscessus'', MAC |
− | | |
+ | |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 |
− | | |
+ | |''M. fortuitum'' |
− | | |
+ | |Achalasia, chronic vomiting, exogenous lipoid pneumonia |
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− | | style="padding-left:2em;" | |
+ | | style="padding-left:2em;" |Reticulonodular |
− | | |
+ | |MAC, ''M. abscessus'' subsp. ''abscessus'', ''M. abscessus'' subsp. ''massiliense'' |
− | | |
+ | |Adolescents with CF, HIV-positive patients, prior bronchiectasis |
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− | | style="padding-left:2em;" | |
+ | | style="padding-left:2em;" |Hypersensitivity pneumonitis |
− | | |
+ | |''M. immunogenum'', ''M. avium'' |
− | | |
+ | |Metal workers, indoor hot tubs |
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− | | |
+ | |Cervical lymphadenitis |
− | | |
+ | |MAC |
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− | | |
+ | |SSTI |
− | | |
+ | |''M. fortuitum'', ''M. marinum'', ''M. chelonae'', ''M. ulcerans'' |
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− | | |
+ | |MSK |
− | | |
+ | |''M. marinum'', MAC, ''M. kansasii'', ''M. fortuitum'', ''M. abscessus'', ''M. chelonae'' |
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− | | |
+ | |Disseminated |
− | | |
+ | |HIV-positive: ''M. avium'' and ''M. kansasii'', HIV-negative: ''M. abscessus'' and ''M. chelonae'' |
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− | | |
+ | |Catheter-related |
− | | |
+ | |''M. fortuitum'', ''M. abscessus'', ''M. chelonae'' |
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|} |
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− | === |
+ | ===Pulmonary Disease=== |
− | * 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==== |
− | * 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==== |
− | * "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==== |
− | * 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=== |
||
+ | ====Superficial Lymphadenitis==== |
||
+ | |||
+ | *Children, usually submandibular |
||
+ | *May be from eating dirt |
||
+ | |||
+ | ====Disseminated Disease==== |
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+ | |||
+ | *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="wikitable" |
{| class="wikitable" |
||
− | ! |
+ | !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) |
||
+ | *''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 |
||
− | * Could consider treating based on a single positive colony, as it is rarely a colonizer |
||
+ | *Could consider treating based on a single positive colony, as it is rarely a colonizer |
||
+ | |||
+ | ====''M. abscessus''==== |
||
+ | |||
+ | *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==== |
||
− | === ''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 |
||
+ | *Mostly due to MAC |
||
− | === ''M. marinum'' SSTI === |
||
+ | *Treated primarily by surgical excision, with a greater than 90% cure rate |
||
− | * 3 to 6 months for ''M. marinum'', 6 to 12 months for MAC |
||
+ | *A macrolide-based regimen should be considered for patients with extensive MAC lymphadenitis or poor response to surgical therapy |
||
+ | ===Monitoring=== |
||
− | === 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 |
||
+ | *Depends on the antibiotics used |
||
− | === Monitoring === |
||
+ | *Audiology for aminoglycosides |
||
− | * Depends on the antibiotics used |
||
+ | *Liver enzymes monthly for many others |
||
− | * Audiology for aminoglycosides |
||
− | * Liver enzymes monthly for many others |
||
[[Category:Mycobacteria]] |
[[Category:Mycobacteria]] |
Revision as of 11:31, 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.