atypical organism

1. ATYPICAL MYCOBACTERIA
BY
DR.MD ABDULLAH SALEEM
MBBS, MD (PULMONOLGY)

2. 1)INTRODUCTION
2)CHARACTERISTICS
3)EPIDEMIOLOGY
4)CLASSIFICATION
5)PATHOGENESIS & RISK FACTORS
6)CLINICAL MANIFESTATIONS
7)DIAGNOSIS
8)TREATMENT

3. INTRODUCTION
Infections caused by Mycobacterium other than
tuberculosis, leprae or bovis.
Also known as:
• Non Tuberculous Mycobacteria
• Environmental
• Anonymous
• Oppurtunistic mycobacteria
• MOTT
• In 1959 Timple & Runyon classified Mycobacteria

4. CHARACTERISTICS
• Ubiquitous but infections are less common than
Tuberculosis
• Both Immmunocompetent &
Immunocompromised persons.
• Saprophytes
• No Animal to Human or Human to Human
Transmission
• Resistant to Disinfectants.

5. EPIDEMIOLOGY
• Exact incidence in india is not known varies from
<1 to 28%.
• Over shadowed by high incidence of M.tb
• Mc isolates in India are M.fortuitum, M.avium,
M.chelonae
• Infections are comparable to iceberg.
• It comprises of 33% of total mycobacterial
infections in USA.

6. CLASSIFICATION
• Runyon-pigment production, rate of growth
• Slow growing- >7 days
• Rapid growing- <7 days

7. Classification according to Timpe and
Runyon

8. PULMONARY
LYMPH NODE
CUTANEOUS /
MUSCULOSKELETAL
DISSEMINATED
M avium complex
M kansasii
M xenopi
M abscessus
M malmoense
M fortuitum
M celatum
M asiaticum
M sulgai
M avium complex
M scrofulaceum
M malmoense
M genavense
M marinum
M ulcerans
M fortuitum
M abscessus
M chelonae
M avium complex
M kansasii
M malmoense
M terrae
M avium complex
M kansasii
M chelonae
M abscessus
M haemophilum
M genavense
M scrofulaceum
M celatum
M simiae
M malmoense
ENVIRONMENTAL /
ATYPICAL / OPPORTUNIST / NON-TUBERCULOUS
MYCOBACTERIA

9. PATHOGENESIS
Virulence:
• Prevention of phagolysosome fusion.
• Ability to scavenge O2 free radicals
• Ability to replicate within macrophages
• Resistance to disinfectants.
Portal of entry:
Respiratory,GIT,Skin & soft tissue.

10. Risk factors:
1) Altered local or systemic immunity
2)Congenital defects of immunity:
A)Dec production of TNFA,IFN-G
B) Mutations in the gene for IFN-G receptor-
disseminated MAC
3)Acquired defects of immunity
• A) HIV/AIDS
B) Hairy cell leukemia

11. CLINICAL MANIFESTATIONS
• Most of the NTM are associated with both
localised/disseminated disease depending upon
the degree of host immunity.

12. PULMONARY DISEASE
• Common causes-M.avium complex, M.kansasii,
M.xenopii, M.absessus
• Mimics pulmonary tuberculosis
• MC manifestation of NTM in western world.
• MC –in persons with pre-existing lung disease,
Elderly males
• Chronic cough with sputum, fatigue are
common.
• Fever, Hemoptysis is less common

13. Radiological findings:
• B/L linear nodular opacities.
• Thin walled Cavity & pleural thickening is more
common.
• Less parenchymal infiltration.
• Miliary disease,pleural effusions,adenopathy are
rare.

14. Criteria For Diagnosing Nontuberculous
Mycobacterial Lung Disease
1)Clinical criteria:
A) Compatible signs/symptoms
B) Reasonable exclusion of other diseases.
2)Microbiological criteria:
A)atleast 3 available sputum/bronchial wash
samples
• 3 +ve cultures with -ve AFB smears or
• 2 +ve cultures with one smear for AFB +ve

15. B)Single available bronchial wash & inability to obtain
sputum samples
• +ve culture with 2+,3+,or 4+ growth
• +ve culture with a 2+,3+, or 4+ AFB smear
OR Tissue biopsy
• Any growth on bronchopulmonary tissue biopsy
• Granuloma & or AFB on lung biopsy with 1 or more
+ve cultures from sputum or Br wash
• Any growth from usually sterile EP site

16. RADIOLOGICAL CRITERIA
A)CXR:Any of the following CXR abnormalities;if baseline films
are more than 1 yr old there should be evidence of
progression.
• Infiltrates with or without nodules persistant for _> 2 m or
progressive
• Cavitation(often thin walled)
• Nodules (multiple)
B)HRCT:
• Multiple small nodules
• Multifocal bronchiectasis with or without small lung nodules

17. • None of these differences, however, is
sufficiently specific to exclude the diagnosis of
TB on the basis of the radiographic appearance.

18. LYMPHADENITIS
• Lymphadenitis is the most common manifestation of
NTM disease in children.
• Involvement of the submandibular, sub-maxillary,
cervical, or preauricular lymph nodes in children
between 1-5 yrs old is the typical presentation.
• Approx. 80% of culture-proven cases of NTM
lymphadenitis are due to MAC, other causes are
M.scrofulaceum,M.hemophilum

19. • The disease occurs generally without systemic
symptoms; the child is afebrile, and the involved
nodes are generally unilateral and nontender.
• It follows an insidious course, and the lymph
node(s) may be swollen for weeks or even
months.
.

20. Diagnosis is difficult
Positive cultures occur in 50-85% of cases
A negative or weakly reactive PPD skin test
Fine needle aspiration is controversial.
Excisional biopsy is both diagnostic and
probably the best treatment option currently

21. Skin, Soft Tissue, and Bone
Disease
• SSTI:Common causes are M.fortuitum chelonae
complex,M.hemophilum,
M.ulcerans,M.marinum.
• Occurs after trauma or surgery, mc by
M.fortuitum.
• Cellulitis with nodule & serosanguinous
discharge seen.

22. • M. marinum- swimming pool granuloma.
• M.ulcerans- Buruli ulcer seen in tropical &
subtropical countries, minor trauma, painless
ulcer with ragged undermined edges.
• Scrofula- skin infection caused by M.ulcerans
involves submental & submaxillary LN.

23. Nguyen C. N Engl J Med 2004;350:e8
A small, raised, erythematous lesion developed on the dorsum of the
hand of a 35-year-old man who worked in a pet shop by M.marinum

24. Disseminated Disease
• One of the MC and severe infections in persons with
advanced HIV infection.
• MAC and M. kansasii isolates are more common
• Occurs only in patients who are severely immuno-
compromised, (<50 CD4+T cells/μl).
• M. abscessus causes lung disease in similar clinical
settings to MAC, but is not associated with
disseminated infection in patients with AIDS.

25. • It is very rare with any form of immunosuppression other than
advanced HIV disease, but there have been reports in patients
with renal or cardiac transplantation, chronic corticosteroid
use, and leukemia.
Clinical presentation
• Classic complaints in persons with disseminated MAC are fever
( 80%), night sweats ( 35%), and weight loss ( 25%).
• many patients with MAC develop abdominal pain or diarrhea.
.

26. Physical findings
• nonspecific, and may include abdominal
tenderness or hepatosplenomegaly, although
palpable lymphadenopathy is not common.

27. • 90% of persons diagnosed with disseminated MAC
have positive blood cultures.
• Asymptomatic pt + low CD4+T cells - routine cultures
are not recommended.
• Symptomatic pts + 2 negative blood cultures - biopsy
and culture of bone marrow or liver are sometimes
indicated.

28. • If lymphadenopathy + - excision of the node for
histopathology and culture is frequently
indicated (usually bacteremia is absent)
• Patients with intrathoracic, intraabdominal, or
retroperitoneal adenopathy may require fine
needle aspiration of the involved lymph nodes
for diagnosis.

29. Identification of Isolates
• Niacin production:Negative for NTM
• Nitrate Reduction: Positive for M.tb,m.kansasii,
M.fortuitum, M.phlei,M.smegmatis
• Tween 80 degradation(hydrolysis):
M.tb,M.scrofulaceum gives –ve result whereas
M.gordonae & M.flavescens gives +ve result
• Aryl sulphatase test:Rapid growers gives +ve
result except M.smegmatis,M.phlei.

30. RAPID DIAGNOSTIC METHODS
• Genetic methods_ Highly sensitive & specific & rapid
Gene probes
DNA finger printing techniques
-Pulsed field Gel electrophoresis
-PCR
• Gene amplification methods-PCR assay
• Amplification followed by restriction analysis of 65KD-
M.avium
• Thin Pressure Liquid Chromatography
• HPLC based on mycolic acid content of cell wall (Guanine
& Cytosine residues) pattern.

31. CULTURE
• Tissue biopsy with positive culture is the Gold
Standard.
• Grows on L.J Media
• Liquid media are Dubos medium, Middle brooks
medium.
• M.hemophilum-Choclate agar (requires hemin)
• M.genavense,M.paratuberculosis- requires
supplementation with mycobactin J
• MAC-Radiometric methods

32. • Different Incubation temperatures are:
• 30 C for M.ulcerans,M.marinum
• 45 C for M.xenopi,M.avium
• 37 C for all others.

33. Mycobacterium Avium Complex
(MAC)
• Includes at least two mycobacterial species, M. avium
and M. intracellulare.
• These two species cannot be differentiated on the
basis of traditional physical &biochemical tests.>95%
of MAC in HIV/AIDS is M.avium.
• MAC has been found to colonize natural water
sources, indoor water systems, pools, and hot tubs.
• They are relatively resistant to chemical disinfection
by chlorine, chloramine, and ozone.

34. Mycobacterium Avium Complex
(MAC)
• M. avium, which is by far the most common
species to infect patients with HIV, is probably
acquired via the gastrointestinal tract.
• Immunocompetent patients with pulmonary MAC
are usually infected with M. Intracellulare (as
opposed to M. avium), and most likely acquire
their infection by the respiratory route.

35. Spectrum of Pulmonary Disease
Caused by MAC
Type of Disease Host Characteristics Demographics Radiographic Features
Classical
Underlying lung disease,
especially chronic
obstructive pulmonary
disease
Males over 50
Cavitation, often upper
lobes involved,
fibronodular infiltrates
New
No underlying lung
disease, possibly
associated with thoracic
deformities
Elderly females
Multiple nodules
associated with areas of
bronchiectasis;
predilection for right
middle lobe/lingula
Pediatric Healthy children
Usually under 5 years
of age, no
gender/racial proclivity
Intrathoracic
lymphadenopathy, focal
atelectasis

36. Spectrum of Pulmonary Disease
Caused by MACType of Disease Host Characteristics Demographics
Radiographic
Features
Pulmonary/
disseminated
Late-stage HIV
infection, bone marrow
transplants, other
immuno-deficiency
(severe combined
immunodeficiency,
interleukin-12 or g-
interferon deficiency)
No age /gender/
racial proclivity
Multiple nodules,
diffuse interstitial
infiltrate, cavitation in
setting of
disseminated MAC
Hot tub lung
Generally
immunocompetent
No age /gender/
racial proclivity
Bilateral interstitial +/-
alveolar infiltrates,
ground glass
appearance on CT
scan

37. Disseminated MAC
• Substantial morbidity & mortality
• >15% of AIDS pts develop MAC in USA but it is
uncommon in Africa
Pathogenesis:
• CD4<50-annual risk of bacteremia is 10 to 20 %
• Disseminated MAC is almost always present if
CD4<20
• Prior oppurtunistic infection like CMV
• High plasma RNA levels(>1Lakh copies/ml)

38. • Early symptoms are minimal,Insiduous in onset
• Fever,night sweats,wt loss, diarrhoea.
• Anemia,Increased liver Alk phosohatase,
Albumin & Hepatospleenomegaly
• CXR-cavitary lesions with extensive
inflitrations,PLEF, Focal pneumonia,
endobronchial lesions.

39. • Dx:Blood,Bone marrow other normally sterile
body fluids in presence of compatible clinical
settings.
• Single +ve culture from above sites-
dissemination.

40. Initial Therapy for
Nodular/
Bronchiectatic
Disease
Initial Therapy
for Cavitary
Disease
Advanced (Severe) or
Previously Treated
Disease
Macrolide
Clarithromycin 1,000
mg TIW or
azithromycin 500–600
mg TIW
Clarithromycin 500 –
1,000 mg/d
or azithromycin 250–
300 mg/d
Clarithromycin 500 –
1,000 mg/d or
azithromycin
250–300 mg/d
Ethambutol 25 mg/kg TIW 15 mg/kg/d 15 mg/kg/d
Rifamycin Rifampin 600 mg TIW
Rifampin 450–600
mg/d
Rifabutin 150–300 mg/d
or rifampin 450–600
mg/d
Aminoglycoside None
Streptomycin or
amikacin or none
Streptomycin or amikacin
Therapy For Mycobacterium Avium Complex Lung Disease
Official ATS/IDSA Statement Am J Respir Crit Care Med Vol 175. (2007)

41. TreatmentandpreventionofDisseminatedMycobacterium
aviuminHIV-infectedPatients
Preferred Alternative
Treatment
Clarithromycin 500 mg orally twice daily
+
Ethambutol 15 mg/kg orally daily
±
Rifabutin 300 mg orally daily
Azithromycin 500 mg daily
Ethambutol 15 mg/kg daily
Rifabutin 300–450 mg
orally daily
Prevention
Azithromycin 1,200 mg orally weekly
Clarithromycin 500 mg orally twice daily
or
Rifabutin 300 mg orally daily

42. Monitoringofdisease
• The goals of therapy include symptomatic, radiographic, and
microbiologic improvement.
• AFB smears and cultures of sputum should be obtained
monthly during therapy for pulmonary MAC disease to assess
response.
• Patients should show clinical improvement within 3 to 6
months and should convert their sputum to negative within 12
months on macrolide-containing regimens.
• 12 months of culture-negative sputum as a reasonable
treatment endpoint.

43. Surgical treatment of MAC lung
disease
Recommendations
1. Surgical resection of limited (focal) disease in a patient with
adequate cardiopulmonary reserve to withstand partial or
complete lung resection can be successful in combination
with multidrug treatment regimens for treating MAC lung
disease.
2. Surgical resection of a solitary pulmonary nodule due to
MAC is considered curative.
3. Mycobacterial lung disease surgery should be performed in
centers with expertise in both medical and surgical
management of mycobacterial diseases.
Official ATS/IDSA Statement Am J Respir Crit Care Med Vol 175. (2007)

44. Guidelines for prevention of MAC in
HIV/AIDS
• Begin prophylaxis for pts with CD4 counts <50
• Rule out active tuberculosis by clinical
examination & appropriate laboratory studies.
• Obtain mycobacterial blood culture to R/o
subclinical bacteremia
• Regimens:
Azithromycin 1200 mg weekly
Clarithromycin 500 mg twice daily
Rifabutin 300 mg daily

45. Advantages of chemoprophylaxis are:
• Decreased risk of development of bacteremia.
• Azithromycin/ Clarithromycin more efficacious
than Rifabutin.
• Emergence of drug resistance is not a major
problem.

46. Mycobacterium Kansasii
• Mycobacterium kansasii is an environmental
organism which can be isolated from a wide variety of
sources including tap water.
• It can be readily isolated from clinical specimens
where it is present as a casual contaminant; however
in patients with preexisting lung damage, it can
cause serious pulmonary disease and in a small
number of patients, it has affected lymph nodes,
tendon sheaths and skin.
• The infectivity of M. kansasii is low.

47. Mycobacterium Kansasii
• M. kansasii lung disease most closely parallels the
clinical course of M. tuberculosis.
• Middle-old aged men present with a subacute or
chronic pattern of symptoms which may include one
or more of cough with Sputum,hemoptysis,
breathlessness, night sweats, malaise, fatigue and
weight loss, but between 10- 40% may be
asymptomatic.

48. • Majority have coexisting lung disease .
• Peptic ulcer, previous gastroduodenal surgery,
and conditions associated with reduction in
immune response are said to predispose to M.
kansasii infection .

49. Mycobacterium Kansasii -
Radiology
• The chest radiographic abnormalities are also very
similar to reactivation pulmonary TB, including
cavitary infiltrates with an upper lobe predilection.
• Noncavitary or nodular/ bronchiectatic lung disease,
similar to that seen with MAC.
• Thin Layer chromatography confirms the dx.

50. Mycobacterium Abscessus
• M. abscessus is the third most frequently recovered
NTM respiratory pathogen in the United States.
• The largest group of patients with this lung disease
are white, female nonsmokers, and older than 60
years, with no predisposing conditions or previously
recognized lung disease.
• Other rare predisposing conditions include
gastroesophageal disorders with chronic vomiting,
lipoid pneumonia, and CF.

51. • The chest radiograph from patients with M. abscessus lung
disease usually shows multilobar, patchy, reticulonodular, or
mixed interstitial–alveolar opacities with an upper lobe
predominance.
• Cavitation occurs in only approximately 15% of cases.
• Overall, the radiographic pattern is similar to the nodular
bronchiectatic form of MAC lung disease.

52. Posteroanterior chest radiograph
shows reticulonodular opacities
throughout both lungs.
Axial thin-section CT scan obtained
at level of main bronchi shows
nodules (arrow) smaller than 10 mm
in diameter in both lungs.

53. Mycobacterium Abscessus -
Treatment
• The only predictably curative therapy of limited
(focal) M. abscessus lung disease is surgical resection
of involved lung combined with multidrug
chemotherapy.
• Periodic administration of multidrug therapy,
including a macrolide and one or more parenteral
agents (amikacin, cefoxitin, or imipenem) or a
combination of parenteral agents over several
months may help control symptoms and progression
of M. abscessus lung disease.

54. • The amikacin combined with high-dose cefoxitin (up to 12 g/d
given intravenously in divided doses) is recommended for
initial therapy (minimum, 2 wk) until clinical improvement is
evident.
• For serious disease, a minimum of 4 months of therapy is
necessary.
• For bone infections, 6 months of therapy is recommended.
• Surgery is generally indicated with extensive disease, abscess
formation, or where drug therapy is difficult.

55. • Disseminated skin Infection:
• Pts on chronic steroid therapy-
M.chelonae,multiple non contiguous nodular
skin lesions
• Leukemias,lymphomas-M.abscessus
• Catheter related infections-M.fortuitum

56. • M.abcessus- Clarithromycin,Cefoxitin &
Amikacin.
Some isolates respond to
Imipenem,Linizolid,Tigycycline

57. REFERENCES
• Sharmas text book of Tuberculosis-2/e
• Fishman’s Pulmonary Diseases & Disorders -4/e
• Tuberculosis and nontuberculous mycobacterial
infections - -5th Edition (2006) – David Schlossberg
• ZUMLAM TEXT OF MYCOBACTRIUM
• UPTODATE online medical encephalopedia

58. • THANK YOU