Nontuberculous Mycobacterioses (overview) A31.9

Author: Prof. Dr. med. Peter Altmeyer

Co-Autor: Dr. med. Eva Kämmerer

All authors of this article

Last updated on: 13.03.2021

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Synonym(s)

Atypical mycobacterioses; atypical mycobacteriosis; MOTT; Mycobacteria other than tubercle bacilli (MOTT); Mycobacterioses non-tuberculous; Mycobacteriosis atypical; Mycobacteriosis other than tuberculosis; Nontuberculous mycobacterial infections; Non-tuberculous mycobacterioses

Definition
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Infectious diseases caused by "nontuberculous mycobacteria" (NTM), which have become increasingly important in recent years. The terms "atypical mycobacteria" or "mycobacteria other than tuberculosis" (MOTT) are outdated, as the bacteria in this group are by no means "atypical".

The term "atypical mycobacterioses" was most often understood to be synonymous with Mycobacterium avium complex (MAC) infections. Although MAC is by far the most common pathogen, there are a large number of other atypical mycobacteria that cause similar clinical pictures. In this respect, the term "atypical mycobacteriosis" should also be abandoned for this disease complex. In addition to several human pathogenic species, there are many species that occur in the environment.

Pathogen
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Mycobacteria that do not produce tuberculosis or leprosy -NTMs-(previously called atpic mycobacteria). NTMs: transmission from human to human does not occur. Occurrence in dust, dirt, fresh and salt water, in birds, pigs, sheep, cattle, in milk and eggs. The most significant representative of NTMs for Central Europe is M. marinum.

Classification
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Runyon classification of "non-tuberculous mycobacteria" NTMs:

  • Photochromogenic NTM (pigment formation under light):
    • M. marinum (see below swimming pool granuloma)
    • M. kansasii (causes mainly pneumonia, rare are sporotrichoid nodules of the skin, disseminated infections in AIDS)
  • Scotochromogenic NTM (pigmentation without light):
    • M. scrofulaceum (cervical lymphadenitis of the child; clinically indistinguishable from scrophuloderma)
    • M. szulgai
  • Nonchromogenic NTM (no pigment formation):
    • M. ulcerans ( Buruli ulcer)
    • M. avium-intracellulare complex (pneumonia, disseminated course with skin involvement in immunodeficiency)
    • M. malmoense
    • M. xenopi
  • Fast-growing NTM(Mycobacterium fortuitum complex):
    • M. chelonae and M. fortuitum (skin and soft tissue abscesses after inoculation, disseminated course with skin involvement in immunodeficiency)
    • M. smegmatis
    • M. abscessus

Occurrence/Epidemiology
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Atypical mycobacteria are species-rich microorganisms that occur worldwide, are very stable in the environment and are found as aerobic, immobile, mostly harmless environmental saprophytes in both soil and water. To date, well over 100 species are known.

Etiopathogenesis
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While MAC may be detectable in the sputum or stool of asymptomatic individuals (colonization), almost only patients with massive immune deficiency and less than < 50 CD4 cells/µl become ill. In the pre-HAART era this was up to 40% of AIDS patients. In the meantime, the infection has become rather rare. MAC infections used to be almost always disseminated. In the course of an immune reconstitution syndrome under HAART, however, localized lymph node abscesses, which take a long time to heal, have become almost more common nowadays. Localized forms include osteomyelitis (spine! joints!) and skin lesions.

Clinical features
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The clinic can be very variable depending on the pathogen. For dermatology, the swimming pool granuloma caused by Mycobacterium marinum is the most important: 2-3 weeks after contact, circumscribed skin changes appear in the form of a solitary, asymptomatic or painful, red or reddish-brown nodule or a smooth or verrucous plaque with a possible tendency to ulceration. The lesions always occur on fingers, backs of hands or forearms, i.e. at "working contact points". Since the diagnosis is often made months later, other nodules or plaques may be added to the "primary nodule" in the direction of lymphatic flow.

Buruli ulcer is a disease of tropical areas, Africa, Asia and America. The infection occurs by inoculation.

In other infections caused by atypical mycobacteria, the skin is a projection organ only in disseminated infections of immunocompromised individuals.

In children < 5 years of age, cervical adenitis (A31.8) is the NTM-induced mycobacteriosis. There are localized forms, especially cutaneous, as well as generalized forms (especially lung, gastrointestinal tract) occurring almost exclusively in immunosuppressed patients.

Skin and soft tissue infections:

Diagnostics
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Histology, PCR, culture from tissue biopsy.

Laboratory
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The AP is often elevated. In case of newly occurring anemia and constitutional symptoms, infection with atypical mycobacteria should always be considered.

Differential diagnosis
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Tuberculosis; malignant lymphomas.

Therapy
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Individual skin lesions can be excised; in the case of uncomplicated lymph node involvement, lymph node extirpation may be performed. In case of deep infections and fistula tracts, incision and drainage, usually combined with antibiosis.

The individual mycobacteria respond differently to the tuberculostatic drugs (see tuberculostatics), prior determination of resistance is therefore essential. Long-term treatment (sometimes up to 2 years) necessary. The duration of therapy should be continued for some time even after clinical healing. In case of disseminated infestation, antibiotic combination treatment. Since patients are often immunosuppressed, these cases are usually fatal.

For general therapy regimens, see Tables 2 and 3. For special dosages in chemotherapeutic treatment, see below for the respective clinical picture.

Tables
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Differentiation of the common ubiquitous mycobacteria according to their treatability with conventional tuberculostatics (according to Fätkenheuer/Diehl/Schrappe)

Relatively sensitive mycobacteria

Relatively resistant mycobacteria

M. kansasii: RMP + INH + EMB or SM

(good response)

M. avium complex

M. marinum: RMP + EMB

M. scrofulaceum

M. szulgai: RMP + EMB + ETA or SM

(good response)

M. fortuitum-chelonei

M. xenopi: INH + RMP + SM

M. simiae

Clinic and therapy of frequent infections with atypical mycobacteria

Bacterium

Occurrence

Clinic

Therapy

M. kansasii

Earth, dust and water, biosynthetic surfaces (e.g. silicone tubes, intravenous cannula)

Mainly pulmonary, rarely extrapulmonary manifestations.

Combination with RMP + INH + EMB + Levofloxacin or SM over several months to 2 years. Successes have also been described with kanamycin, clarithromycin or minocyclin.

Variable on the skin, e.g. abscess formation; localized oropharyngeal infection and others; disseminated infections in immunosuppressive patients.

In circumscribed foci additional surgical procedure.

M. marinum (swimming pool granuloma)

Sea, lake, rivers, swimming pool, fountains, aquariums

Cutaneous manifestations.

Usually spontaneous healing within 1-2 years. If necessary, excision or incision with drainage, cryosurgery, electric snare. Cotrimoxazole, tetracycline, minocycline if necessary. In case of persistence RMP + EMB.

2-3 weeks after contact occurrence of circumscribed skin changes in the form of a livid nodule, plaques or verrucous lesions. Ulcerations are possible. Asymptomatic or painful skin changes.

M. ulcerans (Buruli ulcer)

Minor injuries e.g. thorn bites, insect bites, mainly in water-rich subtropical areas.

Cutaneous manifestations.

Excision and plastic covering. Therapy trial with Cotrimoxazol + SM. If necessary, additional local heat therapy and hyperbaric therapy. Spontaneous healing after years.

Approximately 3 months after contact a subcutaneous swelling develops, which expands and may ulcerate. Expansion to the entire extremity is possible (painless!), otherwise the patient feels comfortable.

M. chelonei (M. fortuitum-chelonei complex)

Water (also tap water), soil, dust.

Pulmonary, rarely cutaneous manifestations.

Therapy of choice for circumscribed processes is excision in toto. The pathogen responds well to erythromycin. Agents such as clarithromycin, cefocitin, amikacin, doxycycline, sulfamethoxazole alone or in combination have been described as successful. In case of doubt, antituberculous drug therapy. No special scheme known. Spontaneous healing possible.

Transmission often after minor injuries, operations, punctures, intravenous catheters.

On the skin as dermal deep red subcutaneous nodules, possibly with ulceration or abscess formation or erythematous keratotic plaques. In case of immunosuppression, possibly dissemination.

M. avium-intracellulare (M. avium complex)

Occurs in dust, dirt, fresh and salt water, in birds, pigs, sheep, cattle, milk and eggs.

Pulmonary, rarely extrapulmonary.

Transcribed lesions are excised. In case of disseminated infestation: clarithromycin + rifabutin + EMB, clofazimines.

On the skin granulomatous synovitis, panniculitis, subcutaneous nodes. In immunosuppressive patients possibly dissemination. Primary skin diseases have been described sporadically.

M. scrofulaceum

Milk, oysters, earth and water. Occurrence in children (1-3 years) and immunocompromised patients. Sources of infection are often unclear.

Cutaneous manifestations, lymph node involvement.

Lymphadenitis: Excision of the affected lymnode areas is curative. In case of large extent excision, possibly incision and drainage combined with systemic treatment. Clarithromycin + EMB + Rifabutin.

Typical (cervical) lymphadenitis with long existing symptomless plaques or sporotrichoid nodes. Disseminated forms with immunosuppression.

M. szulgai

Cutaneous manifestations, lymph node involvement.

In the case of circumscribed changes, lymph nodes and affected skin are surgically removed. In case of persistence RMP + EMB + ETA or SM.

Typical is the (cervical) lymphadenitis with appearance of nodules and plaques on the skin.

Literature
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  1. Aubry A et al (2002) Sixty-three cases of Mycobacterium marinum infection: clinical features, treatment, and antibiotic susceptibility of causative isolates. Arch Intern Med 162: 1746-1752
  2. Chemlal K et al (2003) Molecular diagnosis of nontuberculous mycobacteria. Curr Opin Infect Dis 16: 77-83
  3. Düzgünes N et al (1991) Treatment of mycobacterium avium-intracellulare complex infection in beige mice with free and liposome-encapsulated streptomycin: role of liposome type and duration of treatment. J Infect Dis 164: 143-151
  4. Fabri M (2015) Atypical mycobacterioses, JDDG 13 (Suppl.1): 7-8.

  5. Fätkenheuer G et al (1995) Clinic and therapy of ubiquitous mycobacterioses. Internist 36: 987-994
  6. Franco-Paredes C et al (2018) Cutaneous mycobacterial infections.
    Clin Microbiol Rev 32. pii: e00069-18. doi: 10.1128/CMR.00069-18.
  7. Lamb SR et al (2004) Disseminated cutaneous infection with Mycobycterium chelonae in a patient with steroid-dependent rheumatoid arthritis. Clin Exper Dermatol 29: 254-257
  8. McGarvey J et al (2002) Pathogenesis of nontuberculous mycobacteria infections. Clin Chest Med 23: 569-583
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  10. Paech V et al (2002) Remission of cutaneous Mycobacterium haemophilum infection as a result of antiretroviral therapy in a human immunodeficiency virus--infected patient. Clin Infect Dis 34: 1017-1019
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  14. Weitzul S et al (2000) Nontuberculous mycobacterial infections of the skin. Dermatol Clin 18: 359-377
  15. Wölfer LU (2009) Atypical mycobacterioses of the skin. Act Dermatol 35: 295-299

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Last updated on: 13.03.2021