Nontuberculous mycobacteria

Nontuberculous mycobacteria (NTM), also known as environmental mycobacteria, atypical mycobacteria[1] and mycobacteria other than tuberculosis (MOTT), are mycobacteria which do not cause tuberculosis or leprosy (also known as Hansen's disease). NTM do cause pulmonary diseases that resemble tuberculosis.[2] Mycobacteriosis is any of these illnesses, usually meant to exclude tuberculosis. They occur in many animals, including humans and are commonly found in soil and water.[3]

## Contents

* 1 Classification
* 2 Taxonomy
* 3 Research
* 4 Infection
* 4.1 Diagnosis
* 4.2 Epidemiology
* 5 References
* 6 Further reading
* 7 External links

## Classification[edit | edit source]

Mycobacteria are a family of small, rod-shaped bacilli that can be classified into three main groups for the purpose of diagnosis and treatment:

* Mycobacterium tuberculosis complex, which can cause tuberculosis: M. tuberculosis, M. bovis, M. africanum, M. microti and M. canetti
* M. leprae and M. lepromatosis, which cause Hansen's disease, also called leprosy
* Nontuberculous mycobacteria (NTM) are all the other mycobacteria that can cause pulmonary disease resembling tuberculosis, lymphadenitis, skin disease, or disseminated disease. Although over 150 different species of NTM have been described, pulmonary infections are most commonly due to Mycobacterium avium complex (MAC), Mycobacterium kansasii, and Mycobacterium abscessus .

## Taxonomy[edit | edit source]

In 1959, botanist Ernest Runyon put these human disease-associated bacteria into four groups (Runyon classification):[4]

* Photochromogens develop pigments in or after being exposed to light. Examples include M. kansasii, M. simiae, and M. marinum.[4]
* Scotochromogens become pigmented in darkness. Examples include M. scrofulaceum and M. szulgai.[4]
* Nonchromogens include a group of prevalent opportunistic pathogens called M. avium complex (MAC). Other examples are M. ulcerans, M. xenopi, M. malmoense, M. terrae, M. haemophilum, and M. genavense.[5]
* Rapid growers include four well-recognized, pathogenic, rapidly growing, nonchromogenic species: M. chelonae, M. abscessus, M. fortuitum, and M. peregrinum. Other examples cause disease rarely, such as M. smegmatis and M. flavescens.[5]

The number of identified and cataloged NTM species has been increasing rapidly, from about 50 in 1997 to over 125 by January 2007. The surge is mainly due to improved isolation and identification techniques.[6]

Even with these new techniques, though, the Runyon classification is still sometimes used to organize the mycobacteria into categories.[7]

## Research[edit | edit source]

French researchers finalized the genome sequence of M. abscessus in March 2008[8]

## Infection[edit | edit source]

The most common clinical manifestation of NTM disease is lung disease, but lymphatic, skin/soft tissue, and disseminated diseases are also important.[9]

Pulmonary disease caused by NTM is most often seen in postmenopausal women and patients with underlying lung disease such as cystic fibrosis, bronchiectasis, and prior tuberculosis. It is not uncommon for alpha 1-antitrypsin deficiency, Marfan syndrome, and primary ciliary dyskinesia patients to have pulmonary NTM colonization and/or infection. Pulmonary NTM can also be found in individuals with AIDS and malignant disease. It can be caused by many NTM species, which depends on region, but most frequently MAC and M. kansasii.[10]

Clinical symptoms vary in scope and intensity, but commonly include chronic cough, often with purulent sputum. Hemoptysis may also be present. Systemic symptoms include malaise, fatigue, and weight loss in advanced disease.[11] The diagnosis of M. abscessus pulmonary infection requires the presence of symptoms, radiologic abnormalities, and microbiologic cultures.

Lymphadenitis can be caused by various species that differ from one place to another, but again, MAC is the main cause worldwide. Most patients are aged less than 5 years, but the incidence is rare for children having BCG vaccine. The disease has a high curability.[12]

Soft-tissue disease due to NTM infection include post-traumatic abscesses (caused by rapid growers), swimming pool granuloma (caused by M. marinum) and Buruli ulcer (caused by M. ulcerans or M. shinshuense). Post-traumatic abscesses most commonly occur after injection.[12]

Disseminated mycobacterial disease was common in US and European AIDS patients in the 1980s and early 1990s, though the incidence has declined in developed nations since the introduction of highly active antiretroviral therapy. It can also occur in individuals after having renal transplantation.[10]

### Diagnosis[edit | edit source]

A) Neck and chest of a 53-year-old woman 14 days after fractionated CO2 laser resurfacing, showing nontuberculous mycobacterial infection B) Neck of the patient after five months of multidrug therapy and pulsed dye laser treatment.

Diagnosis of opportunistic mycobacteria is made by repeated isolation and identification of the pathogen with compatible clinical and radiological features. Similar to M. tuberculosis, most nontuberculous mycobacteria can be detected microscopically and grow on Löwenstein-Jensen medium.[10] Many reference centres now use a nucleic acid-based method such as sequence differences detection in the gene coding for 16S ribosomal RNA to identify the species.[13]

Pulmonary NTM disease diagnosis requires both identification of the mycobacterium in the patient's lung(s), as well as a high-resolution CT scan of the lungs.

### Epidemiology[edit | edit source]

Distribution of nontuberculous mycobacteria strains in Turkey.

NTM are widely distributed in the environment, particularly in wet soil, marshland, streams, rivers and estuaries. Different species of NTM prefer different types of environment.[13] Human disease is believed to be acquired from environmental exposures. Unlike tuberculosis and leprosy, animal-to-human or human-to-human transmission of NTM rarely occurs.[14]

NTM diseases have been seen in most industrialized countries, where incidence rates vary from 1.0 to 1.8 cases per 100,000 persons. Recent studies, including one done in Ontario, Canada, suggest that incidence is much higher.[citation needed] Pulmonary NTM is estimated by some experts in the field to be at least ten times more common than TB in the U.S., with at least 150,000 cases per year.

Most NTM disease cases involve the species known as Mycobacterium avium complex or MAC for short, M. abscessus, M. fortuitum and M. kansasii. M. abscessus is being seen with increasing frequency and is particularly difficult to treat.[9]

Mayo Clinic researchers found a three-fold increased incidence of cutaneous NTM infection between 1980 and 2009 in a population-based study of residents of Olmsted County, Minnesota. The most common species were M. marinum, accounting for 45% of cases and M. chelonae and M. abscessus, together accounting for 32% of patients.[15] M. chelonae infection outbreaks, as a consequence of tattooing with infected ink, have been reported in the United Kingdom[16] and the United States.[17]

Rapidly growing NTMs are implicated in catheter infections, post-LASIK, skin and soft tissue (especially post-cosmetic surgery) and pulmonary infections.[18]

## References[edit | edit source]

1. ↑ Nontuberculous Mycobacteria at the US National Library of Medicine Medical Subject Headings (MeSH)
2. ↑ American Thoracic Society (1997). "Diagnosis and treatment of disease caused by nontuberculous mycobacteria. This official statement of the American Thoracic Society was approved by the Board of Directors, March 1997. Medical Section of the American Lung Association". American Journal of Respiratory and Critical Care Medicine. 156 (2 Pt 2): S1–25. doi:10.1164/ajrccm.156.2.atsstatement. PMID 9279284.
3. ↑ Foote, Sydney L.; Lipner, Ettie M.; Prevots, D. Rebecca; Ricotta, Emily E. (2021). "Environmental predictors of pulmonary nontuberculous mycobacteria (NTM) sputum positivity among persons with cystic fibrosis in the state of Florida". PLOS ONE. 16 (12): e0259964. Bibcode:2021PLoSO..1659964F. doi:10.1371/journal.pone.0259964. PMC 8659685. PMID 34882686.
4. ↑ 4.0 4.1 4.2 Grange, J. M. (2007). "Environmental mycobacteria". In Greenwood, David; Slack, Richard; Peitherer, John; & Barer, Mike (Eds.), Medical Microbiology (17th ed.), pp. 221–227. Elsevier. ISBN 978-0-443-10209-7, p. 221
5. ↑ 5.0 5.1 Grange, J. M. (2007). "Environmental mycobacteria". In Greenwood, David; Slack, Richard; Peitherer, John; & Barer, Mike (Eds.), Medical Microbiology (17th ed.), pp. 221–227. Elsevier. ISBN 978-0-443-10209-7., p. 222
6. ↑ American Thoracic Society, p.369
7. ↑ Tortoli E (April 2003). "Impact of genotypic studies on mycobacterial taxonomy: the new mycobacteria of the 1990s". Clinical Microbiology Reviews. 16 (2): 319–54. doi:10.1128/CMR.16.2.319-354.2003. PMC 153139. PMID 12692101.
8. ↑ "abscessus - Genome - NCBI". www.ncbi.nlm.nih.gov. Archived from the original on 18 July 2023. Retrieved 16 July 2023.
9. ↑ 9.0 9.1 American Thoracic Society, p. 370
10. ↑ 10.0 10.1 10.2 Grange, p. 225
11. ↑ Johnson, Margaret M.; Odell, John A. (March 2014). "Nontuberculous mycobacterial pulmonary infections". Journal of Thoracic Disease. 6 (3): 210–220. doi:10.3978/j.issn.2072-1439.2013.12.24. PMC 3949190. PMID 24624285.
12. ↑ 12.0 12.1 Grange, p. 223
13. ↑ 13.0 13.1 Grange, J. M. (2007). "Environmental mycobacteria". In Greenwood, David; Slack, Richard; Peitherer, John; & Barer, Mike (Eds.), Medical Microbiology (17th ed.), pp. 221–227. Elsevier. ISBN 978-0-443-10209-7.p. 226"
14. ↑ Bryant, Josephine M; Grogono, Dorothy M; Greaves, Daniel; Foweraker, Juliet; Roddick, Iain; Inns, Thomas; Reacher, Mark; Haworth, Charles S; Curran, Martin D (May 2013). "Whole-genome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis: a retrospective cohort study". The Lancet. 381 (9877): 1551–1560. doi:10.1016/s0140-6736(13)60632-7. ISSN 0140-6736. PMC 3664974. PMID 23541540.
15. ↑ Wentworth, A.B.; Drage L.A.; Wengenack N.L.; Wilson J.W.; Lohse C.M. (4 December 2012). "Increased Incidence of Cutaneous Nontuberculous Mycobacterial Infection, 1980 to 2009: A Population-Based Study". Mayo Clinic Proceedings. 88 (1): 38–45. doi:10.1016/j.mayocp.2012.06.029. PMC 3690780. PMID 23218797.
16. ↑ Sergeant, A.; Conaglen P.; Laurenson I.F.; Claxton P.; Mathers M.E.; Kavanagh G.M.; Tidman M.J. (25 July 2012). "Mycobacterium chelonae infection: a complication of tattooing". Clinical and Experimental Dermatology. 38 (2): 140–2. doi:10.1111/j.1365-2230.2012.04421.x. PMID 22831709. S2CID 205280965.
17. ↑ Centers for Disease Control and Prevention (CDC) (24 August 2012). "Tattoo-associated nontuberculous mycobacterial skin infections--multiple states, 2011-2012". MMWR. Morbidity and Mortality Weekly Report. 61 (33): 635–6. PMID 22914227.
18. ↑ De Groote, M. A.; Huitt, G. (2006-06-15). "Infections Due to Rapidly Growing Mycobacteria". Clinical Infectious Diseases. 42 (12): 1756–1763. doi:10.1086/504381. PMID 16705584.

## Further reading[edit | edit source]

* Griffith David E.; Aksamit Timothy; Brown-Elliott Barbara; et al. (2007). "American Thoracic Society Guidelines: Diagnosis, Treatment and Prevention of Nontuberculous Mycobacterial Diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–417. doi:10.1164/rccm.200604-571st. PMID 17277290. Archived from the original on 2007-06-09. Retrieved 2023-01-29.
* New BTS Guideline has been published in 2017, https://www.brit-thoracic.org.uk/standards-of-care/guidelines/bts-guidelines-for-non-tuberculous-mycobacteria/ Archived 2017-07-06 at the Wayback Machine
* Grange, J. M. (2007). "Environmental mycobacteria". In Greenwood, David; Slack, Richard; Peitherer, John; & Barer, Mike (Eds.), Medical Microbiology (17th ed.), pp. 221–227. Elsevier. ISBN 978-0-443-10209-7.
* Deppisch C et al. (2016). Gaseous nitric oxide to treat antibiotic resistant bacterial and fungal lung infections in patients with cystic fibrosis: a phase I clinical study. Infection. 44(4):513-20. pmid= 26861246.
* Meng-Rui Lee et al., (2015). Mycobacterium abscessus Complex Infections in Humans. Emerg Infect Dis.; 21(9): 1638–1646. PMC 4550155.

## External links[edit | edit source]

* NTM Info & Research, a nonprofit research and patient support organization Archived 2023-02-03 at the Wayback Machine
* Lung, Nontuberculous Mycobacterial Infections from eMedicine Radiology Archived 2023-01-18 at the Wayback Machine

* v
* t
* e

Gram-positive bacterial infection: Actinobacteria

Actinomycineae|

| Actinomycetaceae|

* Actinomyces israelii
* Actinomycosis
* Cutaneous actinomycosis
* Tropheryma whipplei
* Whipple's disease
* Arcanobacterium haemolyticum
* Arcanobacterium haemolyticum infection
* Actinomyces gerencseriae

|

Propionibacteriaceae|

* Propionibacterium acnes

Corynebacterineae|

| Mycobacteriaceae|

| M. tuberculosis/
M. bovis|

* Tuberculosis: Ghon focus/Ghon's complex
* Pott disease
* brain
* Meningitis
* Rich focus
* Tuberculous lymphadenitis
* Tuberculous cervical lymphadenitis
* cutaneous
* Scrofuloderma
* Erythema induratum
* Lupus vulgaris
* Prosector's wart
* Tuberculosis cutis orificialis
* Tuberculous cellulitis
* Tuberculous gumma
* Lichen scrofulosorum
* Tuberculid
* Papulonecrotic tuberculid
* Primary inoculation tuberculosis
* Miliary
* Tuberculous pericarditis
* Urogenital tuberculosis
* Multi-drug-resistant tuberculosis
* Extensively drug-resistant tuberculosis

|

M. leprae|

* Leprosy: Tuberculoid leprosy
* Borderline tuberculoid leprosy
* Borderline leprosy
* Borderline lepromatous leprosy
* Lepromatous leprosy
* Histoid leprosy

Nontuberculous|

| R1:|

* M. kansasii
* M. marinum
* Aquarium granuloma

|

R2:|

* M. gordonae

R3:|

* M. avium complex/Mycobacterium avium/Mycobacterium intracellulare/MAP
* MAI infection
* M. ulcerans
* Buruli ulcer
* M. haemophilum

R4/RG:|

* M. fortuitum
* M. chelonae
* M. abscessus

Nocardiaceae|

* Nocardia asteroides/Nocardia brasiliensis/Nocardia farcinica
* Nocardiosis
* Rhodococcus equi

Corynebacteriaceae|

* Corynebacterium diphtheriae
* Diphtheria
* Corynebacterium minutissimum
* Erythrasma
* Corynebacterium jeikeium
* Group JK corynebacterium sepsis

Bifidobacteriaceae|

* Gardnerella vaginalis

* v
* t
* e

Mycobacteria (including Nontuberculous)

Slowly growing
(R1P=photochromogenic;
R2S=scotochromogenic;
R3N=nonchromogenic)|

| Long helix 18
(TKHGC)|

| M. tuberculosis group|

MTC
M. tuberculosis
M. bovis
M. africanum
M. microti
M. canetti
M. caprae
M. pinnipedii

MPM
R1P

M. marinum
R2S

M. pseudoshottsii
R3N

M. ulcerans
M. shottsii
M. ulcerans liflandii

Leprosy
M. leprae
M. lepraemurium
M. lepromatosis

R3N
other

M. lacus
M. kumamotonense

|

K/H groups|

| M. kansasii group|

MAC
R3N

M. intracellulare/M. avium
M. avium subp. paratuberculosis
M. chimaera
R2S

M. bohemicum

R1P

M. kansasii
R3N

M. gastri

R2S

M. nebraskense
M. seoulense
R3N

M. scrofulaceum

|

M. haemophilum group|

* M. haemophilum
* R2S
* M. szulgai
* R3N
* M. malmoense

M. gordonae group|

* R1P
* M. asiaticum
* R2S
* M. gordonae

M. conspicuum group|

* R2S
* M. conspicuum

Long helix 18
(other)|

| M. xenopi group|

* M. botniense
* M. shimoidei/M. xenopi
* M. heckeshornense
* M. hassiacum

|

M. celatum group|

* R2S
* M. cookii
* R3N
* M. branderi
* M. celatum

M. hiberniae group|

* M. terrae
* M. hiberniae
* M. nonchromogenicum/M. arupense

Short helix 18|

| M. simiae clade|

M. simiae group
R3N

M. genavense/M. triplex
M. florentinum/M. montefiorense
M. heidelbergense/M. parmense
M. simiae
R2S

M. lentiflavum

M. kubicae group
R3N

M. parascrofulaceum
R2S

M. palustre/M. kubicae

M. interjectum group
M. interjectum
M. saskatchewanense

|

M. intermedium group|

* M. intermedium

Ungrouped|

* M. triviale
* M. doricum
* M. tusciae
* M. arosiense

Rapidly growing/
Runyon IV|

| M. neoaurum group|

* M. mageritense
* M. wolinskyi

* M. canariasense
* M. cosmeticum
* M. diernhoferi
* M. hodleri
* M. frederiksbergense
* M. neoaurum

* M. brisbanense

* M. fluoroanthenivorans

|

F/T groups|

| M. fortuitum group|

* M. chitae/M. fallax/M. gadium

* M. rhodesiae
* M. houstonense

* M. neworleansense/M. boenickei/M. fortuitum/M. porcinum/M. senegalense

* M. septicum/M. peregrinum/M. alvei

* M. farcinogenes

|

M. vaccae group|

* M. obuense/M. gilvum/M. parafortuitum

* M. chlorophenolicum/M. chubuense
* M. psychrotolerans/M. sphagni
* M. aubagnense/M. mucogenicum/M. phocaicum

* AV
* M. aurum
* M. vanbaalenii
* M. vaccae
* M. austroafricanum
* M. pyrenivorans

* M. poriferae

M. smegmatis group|

* M. agri/M. thermoresistibile
* M. duvalii/M. flavescens
* M. monacense
* M. pulveris/M. conceptionense/M. moriokaense

* M. novocastrense/M. brumae/M. phlei

* M. confluentis/M. madagascariense

* M. smegmatis/M. goodii

M. chelonae group|

* M. komossense
* M. murale/M. tokaiense
* M. aichiense
* M. chelonae
* M. abscessus
* M. immunogenum
* M. massiliense
* M. bolletii

M. elephantis group|

* M. elephantis
* M. holsaticum

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