Atypical Mycobacterial Diseases

Updated: Nov 12, 2019
  • Author: Erisa Alia, MD; Chief Editor: Dirk M Elston, MD  more...
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Overview

Practice Essentials

Mycobacteria are a large group of aerobic bacteria that produce filamentous pellicles similar to molds when grown in liquid media. The family Mycobacteriaceae consists of a single genus, Mycobacterium, which are thin, slightly curved-to-straight, non–spore-forming, nonmotile acid-fast bacilli. The genus consists of more than 190 species, [1] many of which are ubiquitous and can be found in water (including tap water), soil, animals, birds, plants, food (dairy products), vegetation, and human feces. [2] Mycobacterium fortuitum has been reported as a commensal on human skin. They can also be found as colonizers of medical equipment [3] such as endoscopes and surgical solutions. Mycobacterial species other than Mycobacterium tuberculosis and Mycobacterium leprae are classified as atypical mycobacteria, nontuberculous mycobacteria (NTM), or environmental mycobacteria.

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Background

Nontuberculous mycobacteria (NTM) are aerobic, generally free-living organisms that do not form spores. Mycobacterial species reside in a wide variety of environments, owing to multiple adaptations. More than 190 species of NTM have been identified, most of which are not pathogenic to humans. These environmental, ubiquitous bacteria are transmitted by inhalation, ingestion, and percutaneous penetration.

Four distinct clinical syndromes account for most infections with NTM [4] and include (1) pulmonary disease, (2) lymphadenitis, (3) skin or soft-tissue infections (SSTIs), [5] and (4) disseminated disease. As reported in 2019, NTM are being implicated in a few challenging cases of eye infections. [6] Person-to-person spread is extremely uncommon, although in 2012 the first known outbreak of respiratory Mycobacterium abscessus subsp massiliense disease occurring in a population of patients with cystic fibrosis (CF) was reported. [7] Studies from multiple countries indicate that the incidence of NTM infection is increasing globally [8] and that Mycobacterium avium and Mycobacterium intracellulare (known together as M avium complex [MAC]) infections are the main driver of this increase. [9] Meanwhile, Mycobacterium marinum, the causative organism of the fish-tank granuloma as well as swimming pool granuloma, given its resistance to chlorine, [10] remains the most common atypical bacteria causing skin involvement. See the image below.

Mycobacterium marinum is an atypical mycobacteria Mycobacterium marinum is an atypical mycobacteria found in water with a wide range of temperatures and salinities

The type of disease depends on the species of mycobacteria, the route and degree of exposure, and the immune status of the host.

Classification

Traditionally, NTM have been classified according to the Runyon system, into four broad categories based on their growth rates, pigment production, and colony morphology. Groups I-III are categorized as slow-growing NTM and group IV is known as the fast growers (detectable in culture within 7 days).

  • Group 1: Photochromogens; pigment producers in the presence of light (eg, Mycobacterium kansasii, M marinum, Mycobacterium simiae)
  • Group 2: Scotochromogens; pigment producers in the absence of light ((eg, Mycobacterium scrofulaceum, Mycobacterium szulgai, Mycobacterium gordonae)
  • Group 3: Nonphotochromogens; nonpigment producers (eg, M avium, M intracellulare, Mycobacterium ulcerans, Mycobacterium haemophilum, Mycobacterium genavense, Mycobacterium malmoense, Mycobacterium xenopi, Mycobacterium terrae)
  • Group 4: Fast growers; produces mature colonies in culture media in less than 7 days (eg, M fortuitum, Mycobacterium chelonae, M abscessus, Mycobacterium peregrinum, Mycobacterium smegmatis, Mycobacterium cosmeticum, Mycobacterium mucogenicum)

NTM have been known since the time of Robert Koch, but historically they have been overshadowed by tuberculosis and dismissed as contaminants. NTM were first isolated by Pinners in 1931, who found that these organisms were different from M tuberculosis in their lack of virulence for guinea pigs and poor response to antituberculous therapy. The importance of NTM as human pathogens was not generally appreciated until the 1950s. [11] In 1996, Horsburgh [12] noted clinically important NTM, including M avium, M intracellulare, M kansasii, M marinum, M scrofulaceum, M haemophilum, M ulcerans, M abscessus, M chelonae, M fortuitum, M genavense, M xenopi, M malmoense, M simiae, M szulgai, and M smegmatis. Approximately 60 species of NTM are now recognized as true pathogens and important causes of human infection. [13]

Disseminated NTM infections occur almost exclusively in immunocompromised patients. Disease in patients who are immunocompetent usually consists of localized SSTIs.

Tap water is considered the major reservoir for NTM pathogens in humans and, as such, is of increasing public health concern. [14]

NTM develop and are protected within biofilms, which makes them difficult to eradicate with common decontamination techniques and relatively resistant to standard disinfectants such as chlorine, glutaraldehyde, gigasept, and Virkon. [15] They can grow in hot and cold water systems.

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Pathophysiology

In the human host, mycobacterial infections may affect multiple anatomical sites, but since they enter through the skin and mucosal barriers, they lead mostly to pulmonary or cutaneous infections. [16, 17] Infections with atypical mycobacteria usually occur mostly in immunocompromised hosts (eg those with HIV, transplant recipients, those on tumor necrosis factor [TNF]–alpha inhibitors). Normal host defense mechanisms are sufficient to prevent NTM infection.

While the lungs are the most common site of infection, NTM can colonize and infect any other organ systems, including lymph nodes, skin, sinuses, eyes, ears, bones, the CNS, [18] and the urinary tract. The main host-derived risk factor for pulmonary NTM infection is a preexisting lung disease such as chronic obstructive pulmonary disease, asthma, alpha-1 antitrypsin deficiency, cystic fibrosis (CF), non-CF bronchiectasis, primary ciliary dyskinesia, or allergic bronchopulmonary aspergillosis, which may predispose to NTM infection by causing chronic epithelial cell inflammation and impaired mucociliary clearance. [19]

The most common cutaneous forms of acquisition of NTM involve direct inoculation through skin barrier breaks, trauma, [20] postsurgical infections, iatrogenic acquisition with indwelling medical devices, plastic surgery, cosmetic procedures, prosthetic implants, tattoos, acupuncture, and body piercings. [21]

In current practice, immunodeficiency remains a known risk factor for all NTM infections. A number of immunodeficiencies have been associated with NTM infection, [22] including inherited disorders of interferon (IFN)γ-IL12 pathway (eg, IFNγR1 mutations), [23] other cytokine signalling (eg, STAT mutations), [24] and macrophage and dendritic cell function (eg, GATA2 [25] , NRAMP1 [26] ), as well as acquired immunodeficiencies including HIV infection [27] and functional anti–interferon-gamma autoantibodies. [28] Patient with the above disorders are predisposed to severe and disseminated infections with NTM.

Common immunosuppressive drugs have been associated with acquisition of NTM infection, and these include oral and inhaled corticosteroids, [29] TNF-alpha inhibitors, [30] immunosuppression used in solid organ transplantation, [31] and cancer chemotherapy. [27]

The ability of some NTM to survive sterilization procedures and to even contaminate antiseptic solutions can lead to infections in surgical patients. [32]

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Etiology

Tap water is considered the major reservoir for nontuberculous mycobacteria (NTM) pathogens in humans and, as such, is of increasing public health concern. [14] Mycobacteria were found in up to 90% of samples taken from piped water systems in 1992. [33]

Exposure to contaminated water, injections, surgical and cosmetic procedures, and trauma have been linked to infection with atypical mycobacteria.

Immunodeficiency is a known risk factor for all NTM infections, and it usually predisposes to severe localized forms or disseminated visceral disease. A number of immunodeficiencies have been associated with NTM infection, [22] including inherited disorders of IFNγ-IL12 pathway (eg, IFNγR1 mutations), [23] other cytokine signalling (eg, STAT mutations), [24] and macrophage and dendritic cell function (eg, GATA2 [25] , NRAMP1 [26] ), as well as acquired immunodeficiencies including HIV infection [27] and functional anti–interferon-gamma autoantibodies. [28] Patients with the above disorders are predisposed to severe and disseminated infections with NTM.

Common immunosuppressive drugs have been associated with acquisition of NTM infection, including oral and inhaled corticosteroids, [29] TNF-alpha inhibitors, [30] immunosuppression used in solid organ transplantation, [31] and cancer chemotherapy. [27]

In a hospital in Taiwan, [34] 12 cockroaches (Periplaneta americana) were found to be infected with the following organisms:

  • Four with M kansasii
  • Three with M xenopi
  • Two with M gordonae
  • One with M haemophilum
  • One with M fortuitum
  • One with M avium

Because cockroach infestation commonly occurs in the hospital environment, cockroaches might be implicated as a cause of hospital-acquired infections due to atypical mycobacteria.

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Epidemiology

Frequency

The most common nontuberculous mycobacteria (NTM) species causing human disease are the slowly growing species of the M avium complex (MAC) and M kansasii and the rapidly growing mycobacteria, M abscessus subsp abscessus.

Determining the incidence and prevalence of NTM lung disease remains difficult because disease reporting to health authorities is not mandatory. M kansasii, although the second most common cause of lung disease after MAC, has been considered the most virulent NTM species, and the presence of a single M kansasii isolate in a sputum sample has been believed to be clinically significant. [4]

Approximately 85% of NTM infections involve the pulmonary system; the remaining 15% involve lymph nodes, skin and soft tissue, bones, and, less frequently, eye, ears, and disseminated infection. [35, 36, 37]

Cutaneous infections with atypical mycobacteria are rare in the United States and worldwide. They are mostly seen in immunocompromised hosts, in particular those with HIV infection, leukemia, or undergoing immunosuppressive therapy.

Race

No apparent difference in race exists with regard to the course of atypical mycobacteria infection.

Sex

Atypical mycobacteria infection is more common in men than in women. Middle-class, middle-aged, white men of urban origin are most commonly affected from pulmonary and skin and soft tissue disease. [38]

Age

Atypical mycobacteria infections are more commonly reported in older patients. This probably relates to the decline in health and the presence of other predisposing conditions.

The predominant NTM disease in children is cervical lymphadenitis due to MAC and M scrofulaceum and less common cutaneous disease due to M marinum and M ulcerans, although rare cases of disseminated disease have been reported. [39] NTM lymphadenitis usually affects children younger than 5 years. [40]

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Prognosis

The prognosis is good with proper medical and surgical treatment. Atypical mycobacteria infections cause little mortality. They can cause morbidity, especially when they are not diagnosed and not treated effectively. Often times, cutaneous atypical mycobacteria infection can resolve on its own without intervention. In children, cervical lymphadenitis caused by atypical mycobacteria can result in facial nerve injury, and the incidence of hypertrophic scarring varies among the different treatments.

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Patient Education

Patients should avoid exposure to atypical mycobacteria by contaminated injections or materials.

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