Nontubercular mycobacterium, Mycobacterium other than Tuberculosis

1. Nontubercular
Mycobacteria
Sayantan Banerjee
AIIMS Kalyani

2. NTM : Overview
• Nontuberculous mycobacteria (NTM) refers to mycobacteria other than the
Mycobacterium tuberculosis complex and M. leprae.
• NTM are ubiquitous in the environment, including household
• water, natural water sources, and soil
• Human disease due to NTM is classified into 4 clinical syndromes:
1. chronic pulmonary disease
2. Lymphadenitis
3. Cutaneous disease
4. Disseminated disease

3. Portal of Entry
• Most NTM disease is assumed to originate from environmental NTM
• Airborne NTM play an important role in respiratory disease
• NTM are quite resistant to commonly used water disinfectants, such as chlorine, and
persist in urban water supplies
• Unlike with pulmonary tuberculosis, person-to-person transmission is considered unlikely
• Ingestion in children can cause NTM cervical lymphadenitis and for the majority of HIV-
infected patients, in whom M. avium dissemination begins as gastrointestinal
colonization
• Direct inoculation of NTM organisms from water or some other material is likely to be a
source of infection for those with skin and soft tissue infections

4. Runyon Classification – based on Growth Rate
and Pigment production
Type I
Pigment is produced
only on exposure to
light –
photochromogen
M. Kansasii
M. marinum
Type II
Pigment is produced
even if grown in the
dark –
scotochromogen
M. scrofulaceum
M. szulgai
M. gordonae
Type III
Not strongly
pigmented -
nonphotochromogen
M. avium complex
M. ulcerans
M. xenopi
Type IV
Rapidly growing
mycobacteria (type
IV) grew in less than
7 days but more
slowly than most
bacteria
M. abscessus complx
M. chelonae
M. fortuitum complx

5. Clinical Syndromes caused by NTM
Pulmonary
disease
• M. avium
complex
• M. abscessus
complex
• M. kansasii
Lymphadenitis
• M. avium
complex
• M.
scrofulaceum
Skin, soft tissue
infecton
• M. abscessus
complex
• M. chelonae
• M. fortuitum
complex
• M. marinum
• M. ulcerans
Bone infection
• M. avium
complex
• M. abscessus
complex
• M. fortuitum
complex
• M. marinum
• M. kansasii

6. Epidemiology
• NTM are found everywhere - soil, surface and tap water, animals, milk, foods
• As such, they were considered colonizers or contaminant in cultures until the
latter half of 20th century
• True incidence is difficult to determine as this is not a reportable disease
• On the rise by 5-10% per year, primarily due to increasing number of
immunosuppressed

7. Epidemiology
• Serious complication of advanced HIV disease particularly in Asia and the
Pacific
• 127 NTM species are known to have been isolated from clinical specimens
• MAC accounts for 95% of disseminated NTM diseases among HIV+ patients
• Hospital-based estimates suggest that 30-50% of immunosuppressed
individuals develop MAC
• There is HIV aided constant upsurge of NTM
• Limitations of current diagnostics for NTM

8. Four Syndromes of NTM Infection
• Progressive pulmonary disease
• Favors older males with underlying lung disease
• Superficial lymphadenitis (scrofula)
• Most common in children
• Disseminated infection
• Typically only seen in immunocompromised
• Skin and soft tissue infection

9. Pulmonary disease
• Due to the ubiquity of these organisms, it is important to associate a positive
culture with true clinical disease
• Non-tuberculous mycobacteria are NOT known to cause latent infection as TB
does

10. NTM Pulmonary Pathogens
Common
M. avium
M. intracellulare
M. kansasii
M. abscessus
M. chelonae
Infrequent
M. xenopi
M. szulgai
M. malmoense
M. fortuitum
}MAC
Rare
M. celatum
M. scrofulaceum
M. simiae
M. terrae
M. immunogenum

11. Common Features of NTM Lung Disease
• Insidious onset of cough; initially dry, then variably productive of mucopurulent
secretions
• Occasional hemoptysis
• Dyspnea
• Fever, chills, night sweats are not uncommon
• Recurrent “bronchitis”
• Vague malaise and diminished energy
• Occasionally, focal chest discomfort

12. • Chest X-rays typically reveal amorphous, lower zone shadowing
• Upper lobe cavitary disease (like TB) is less common; however, cavities may
be present in other zones
• HRCT scans are the primary diagnostic aid in recognizing NTM disease
• HRCT scans often reveal predominantly right middle lobe and/or lingular
disease
Common Features of NTM Lung Disease

13. 54-year-old man with mild emphysema,
cough, and fever. Cultures from sputum
and resected surgical specimen showed
Mycobacterium avium-intracellulare
Martinez S et al. AJR 2007;189:177-186

14. 36-year-old woman with chronic cough,
weight loss, and fatigue. Cultures
from sputum showed Mycobacterium
avium-intracellulare complex organisms
Martinez S et al. AJR 2007;189:177-186

15. 37-year-old man with chronic
cough. Cultures of bronchoalveolar
lavage fluid showed Mycobacterium
chelonei
Martinez S et al. AJR 2007;189:177-186

16. NTM: Risk factors
• HIV, Immunosuppressive drugs, Anti TNF-α
• Cystic Fibrosis, including adult-onset variants
• Primary ciliary dyskinesia (immotile cilia or Kartagener’s Syndrome)
• Alpha-1 antitrypsin anomalies
• GERD with aspiration
• Prior histoplasmosis or TB

17. Elements of NTM Disease Diagnosis
• Clinical history
• Radiography
• Microbiology
A. Spontaneous sputum sample
B. Induced sample (hypertonic saline nebulization)
C. Bronchoscopy, if A and B fail to yield results
D. Culture for other potential bacterial / fungal pathogens
• Since NTM are widespread in the environment, a single isolation is usually
NOT sufficient for diagnosis or initiation of therapy

18. Diagnosis of NTM disease
• Compatible clinical and radiologic profile
AND
• Sputum: at least two positive cultures
• Bronchial wash / lavage: at least one positive culture
• Bronchoscopic lung biopsy:
• Granuloma/AFB + and culture +
• Granuloma/AFB + and sputum culture +
AND
• Exclusion of other diagnosis
AJRCCM 175: 367-416, 2007

19. • Actually includes two species
• M. avium
• M. intracellulare
• Cause similar clinical syndromes, treatment is identical
• Although these organisms are ubiquitous, environmental and
clinical/pathogenic isolates are different serovars
• Isolates that are most easily aerosolized are most common in clinical practice
• No documented cases of human-human transmission
Mycobacterium Avium Complex

20. Spectrum of MAC Disease
• Cavitary lung disease
• elderly male alcoholics with underlying lung disease
• also seen in immunocompromised
• Mid-lung field nodular bronchiectasis
• Seen in “normal” individuals
• MAC in association with cystic fibrosis
• Hypersensitivity pneumonitis (“Hot tub lung”)

21. NTM Postoperative skin & soft tissue infection
• Quite common in developing countries with
inadequate surgical asepsis
• Usually through contaminated Laparoscopic
instruments or surgical instruments
• Source is hospital water in the Laparoscopic
instrument tubs
• Usually, the infection develops after a latent
period of 2-3 weeks after the initial surgical
wound is healed well
• In histopathology, granulomatous infection and
AFB may be present – mislead to TB treatment
• M.C. agents – Rapid growers – MABC, MF, MC