This document discusses atypical mycobacteria (also known as nontuberculous mycobacteria or environmental mycobacteria), which are ubiquitous in the environment and can cause opportunistic infections in humans. It notes there are over 150 known species and describes their epidemiology, pathophysiology, taxonomy, and laboratory diagnosis. The document also provides details on treatment approaches for different atypical mycobacteria species/strains, including the use of multidrug regimens involving macrolides, rifamycins, and others.

1. Atypical Mycobacteria
Dr. Sandeep G Huilgol
MBBS, DNB(Internal Medicine)MMedSci(Nephro)

2. Atypical Mycobacteria
• Known by several terms—
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Nontuberculous mycobacteria (NTM)
Atypical mycobacteria,
Mycobacteria other than tuberculosis,
Environmental mycobacteria—all refer to mycobacteria
other than Mycobacterium tuberculosis, its close relatives
(M. bovis, M. caprae, M. africanum, M. pinnipedii, M.
canetti), and M. leprae.
• The number of known species currently exceeds 150.
NTM are highly adaptable and can inhabit hostile
environments, including industrial solvents.

3. Epidemiology
• The true international epidemiology of infections due to NTM is
hard to determine.
• NTM are ubiquitous in soil and water.
• Most NTM cause disease in humans only rarely unless some aspect
of host defense is impaired, as in bronchiectasis, or breached, as by
inoculation (e.g., liposuction, trauma).
• Human-to-human transmission of NTM is not known.
• Disseminated disease denotes significant immune dysfunction
(e.g., advanced HIV infection), whereas pulmonary disease, which is
much more common, is highly associated with pulmonary epithelial
defects but not with systemic immunodeficiency.

4. Pathophysiology
• Because exposure to NTM is essentially universal and
disease is rare
• Normal host defenses against these organisms must be
strong and that otherwise healthy individuals in whom
significant disease develops are highly likely to have
specific susceptibility factors that permit NTM to
become established, multiply, and cause disease.
– HIV infection
– CD4+ T lymphocytopenia.
– Potent inhibitors of tumor necrosis factor (TNF-), such as
infliximab, adalimumab, certolizumab, and etanercept

5. Taxonomy
• Earlier Runyon classification was used.
• This was based on growth characteristics and
pigment formation.
• Presently more 150 species have been isolated

6. Runyon Classsification
• Slow growing
– Photochromogens, which develop pigments in or after being exposed
to light. Examples include M. kansasii, M. simiae and M. marinum.
– Scotochromogens, which become pigmented in darkness. Examples
include M. scrofulaceum and M. szulgai.
– Non-chromogens, which includes 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.
• Rapid growers include four well recognized pathogenic rapidly growing
non-chromogenic species: M. chelonae, M. abscessus, M.
fortuitum and M. peregrinum. Other examples cause disease rarely, such
as M. smegmatis and M. flavescens.

7. Am J of Resp Crit Care Med Vol 175, 367-416, 2007

8. Am J of Resp Crit Care Med Vol 175, 367-416, 2007

9. Laboratory Diagnosis
• Strong suspicion
• The optimal way is culture of tissue. This should
be performed at multiple temperatures
25°, 37°, and 42° to grow out all possible
pathogens.
• PCR.
• Imaging Studies
– The characteristic radiologic features of nonclassic
atypical mycobacteria infection include bronchiectasis
and centrilobular nodules isolated to or most severe
in the lingula and the middle lobe. In patients with
acquired immunodeficiency syndrome, mediastinal or
hilar adenopathy is the most common radiographic
finding.

10. • A biopsy of the skin, the cervical nodes, and the lung can be used to
diagnose atypical mycobacteria. The tissue obtained can be used for
cultures of the tissue and for histopathologic examination.
• Histopathologic examination of tissue can reveal
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tuberculoid, palisading, and sarcoidlike granulomas;
a diffuse infiltrate of histiocytic foamy cells;
acute and chronic panniculitis;
nonspecific chronic inflammation;
cutaneous abscesses;
suppurative granulomas; and
necrotizing folliculitis.
Suppurative granulomas are the most characteristic feature in skin
biopsy specimens from cutaneous atypical mycobacteria infections.

11. Treatment
• MAC infection often requires multidrug therapy, one is a macrolide
(clarithromycin or azithromycin), ethambutol, and a rifamycin (rifampin or
rifabutin).
• For disseminated nontuberculous mycobacterial disease in HIV-infected
patients, the use of rifamycins poses special problems—i.e., rifamycin
interactions with protease inhibitors.
• For pulmonary MAC disease, thrice-weekly administration of a
macrolide, a rifamycin, and ethambutol has been successful.
• Therapy is prolonged, generally continuing for 12 months after culture
conversion; typically, a course lasts for at least 18 months. Other drugs
with activity against MAC organisms include IV and aerosolized
aminoglycosides, fluoroquinolones, and clofazimine.

12. • M. kansasii lung disease is similar to tuberculosis and is also
effectively treated with isoniazid (300 mg/d), rifampin (600
mg/d), and ethambutol (15 mg/kg per day).
• Other drugs with very high-level activity against M. kansasii
include clarithromycin, fluoroquinolones, and
aminoglycosides.
• Treatment should continue until cultures have been negative
for at least 1 year.
• M. kansasii infection is easily cured.

13. • Rapidly growing mycobacteria :Extrapulmonary disease in an
immunocompetent host is usually due to inoculation (e.g., via
surgery, injections, or trauma) or to line infection
• Treated successfully with a macrolide and another drug (with the choice
based on in vitro susceptibility), along with removal of the offending focus
• Pulmonary disease, especially that caused by M. abscessus, is extremely
difficult to cure.
• Therapy generally includes a macrolide along with an IV-administered
agent such as amikacin, a carbapenem, cefoxitin, or tigecycline.
• Other oral fluoroquinolones, doxycycline, and linezolid. Because
nontuberculous mycobacterial infections are chronic, care must be taken
in the long-term use of drugs with neurotoxicities, such as linezolid and
ethambutol

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• Treatment of the other NTM is less well defined, but
macrolides and aminoglycosides are usually effective.

15. References
• Am J of Resp Crit Care Med Vol 175, 367416, 2007
• Harrisons Principles of Internal Medicine, 18th
edition.
• CDC, Atlanta (Web reference)
• American Thoracic Society guidelines