1. Dr . Jalal Mohsin Uddin MBBS, DTCD, FCPS (Pulmonology)
MOTT an unseen story
Dr . Jalal Mohsin Uddin
MBBS, DTCD, FCPS (Pulmonology)

2. What is MOTT ?
MOTT
Mycobacteria other than M tuberculosis . An acronym for non-TB mycobacteria–eg, M avium-intracellulare complex, M chelonei, M kansasii, M malmoense, M xenopi .
Nontuberculous mycobacteria (NTM), also known as environmental mycobacteria ,opportunistic mycobacteria, atypical mycobacteria .

3. Are all the AFB +ve mean tuberculosis ?
AFB +ve report evaluated by culture
False positive AFB may be found in following condition
1) Food particles
2) Scratch mark over slide
3) Dead bacilli
4) Atypical mycobacteria
5) Fungal spore
6) Nocardia etc

4. Why they are atypical ?
They are acid-fast mycobacteria but do not cause tuberculosis or leprosy. These mycobacteria or atypical mycobacteria exist in almost all habitats.
Mycobacterium fortuitum

6. Why are they important ?
Nontuberculous mycobacteria (NTM) can cause pulmonary disease resembling tuberculosis, lymphadenitis, skin disease, or disseminated disease.
Most of them are resistant to conventional anti TB drug .
They cause disease more in immunocompromised host and diseased lung .
Atypical mycobacteria have been known to colonize tap water, natural waters, and soil and thus can easily contaminate solutions and disinfectants used in hospital settings.

7. Source of infection : Atypical mycobacteria are obligate aerobes
Your bathroom may be source of infection
Atypical mycobacteria are obligate aerobes
Although Mycobacterium tuberculosis and nontuberculous mycobacteria (NTM) cause chronic lung infections, only tuberculosis (TB) spreads from person to person by inhalation of organisms expectorated into the air.
NTM infections are acquired directly from the environment, where they are often present in soil and various water sources.

8. Although there are more than a dozen species of atypical mycobacteria, the two most common are Mycobacterium kansasii and M. avium-intracellulare. These microbes are found in many places in the environment: tap water, fresh and ocean water, milk, bird droppings, soil, and house dust.

9. Prevalence :
The prevalence of NTM disease is reported to be increasing and is likely greater than that of TB in the United States .
The incidence of infection by mycobacteria, other than tubercle bacilli (MOTT) is also increasing in the United Kingdom other countries of Europe . These diseases increase morbidity and are an increasing public health concern. However, the epidemiology of disease due to these species is not well characterized.
MAC is more common in the United States , M abscessus and M avium are reported to be more common in Europe.

11. Pathophysiology :
In immunocompromised patients, the intestinal tract is the primary route for MAC infection, followed by the respiratory tract as a secondary portal of entry.

12. Who are affected most ?
Mycobacterium avium complex (MAC) and Mycobacterium scrofulaceum are associated with lymphadenitis in immunocompetent children .
Disseminated infections are usually associated with HIV infection .
NTM more common in older age groups. NTM disease usually more commonly associated with old TB infection and with bed ridden patients on tracheostomy.

13. a variety of manifestations of NTM infection have been described, but the lungs remain the most commonly involved site.
In one study investigators found approximately 80% of pulmonary NTM infections are caused by M avium complex (MAC), and M abscessus accounts for 6-13%.
Pulmonary NTM disease occurs more frequently in patients with chronic underlying disease, such as chronic obstructive pulmonary disease (COPD) and bronchiectasis.

14. Atypical mycobacterial infection has been described in children with cystic fibrosis (CF).
MAC has also been associated with the pulmonary infection and bronchiectasis in elderly women without a preexisting lung disease. Pulmonary MAC infection in this population is believed to be due to voluntary cough suppression that results in stagnation of secretions, which is suitable for growth of the organisms. This particular type of infection is also referred to as Lady Windermere syndrome.

15. One of the most common infection is the so-called case of fish tank granuloma, which is caused by Mycobacterium marinum .
Mycobacterium avium-intracellulare is the most common etiology of systemic disease in humans.
Atypical mycobacterial infections at the laparoscopic port site are a frequent problem encountered in patients undergoing laparoscopic surgery and should be treated with a combination of oral clarithromycin and ciprofloxacin. For prevention of infection, proper sterilization and storage of instruments is recommended.

16. Diagnostic guidelines
Diagnostic guidelines from the American Thoracic Society suggest that the presence of symptoms and radiographic evidence of infiltrates (nodular or cavitary disease) are essential adjuncts to the microbiologic diagnosis.
if smear is positive for AFB and PCR (eg. Gene X-pert) is negative NTM should be suspected.
Gene X-pert machine

17. Radiological tools for diagnosis
The most common CT findings of pulmonary NTM infection in immunocompromised patients (ICPs) are bronchiectasis and ill-defined nodules . Ill-defined nodules with cavity and large opacity >2 cm with/without cavity are more frequently found in ICPs.

18. patients with MAI infection may be distinguished from those with Mycobacterium tuberculosis (MTB) by the presence of widespread bronchiectasis, particularly if it involves the right middle lobe and the lingula. Cavitation is usually associated with positive sputum results.

19. Images in a 50-year-old man with chronic obstructive pulmonary disease (COPD), a worsening cough, and a low-grade fever of 3 months' duration show cavitating consolidation and volume loss, the primary pattern associated with nontuberculous mycobacterial infections. This particular patient had a Mycobacterium kansasii infection.

20. Chest CT scans in a patient with Mycobacterium avium- intracellulare complex (MAI complex) infection show nodules and multifocal bronchiectasis in the middle lobe and lingula.

21. Microbiological aspect of diagnosis

22. Positive culture results from at least two separate expectorated sputum samples. Or
Positive culture results from at least one bronchial wash or lavage. Or
Transbronchial or other lung biopsy with mycobacterial histopathologic features (granulomatous inflammation or AFB) and positive culture for NTM .

23. How will you isolate individual NTM ?
NTM should be identified to the species level.
Methods of rapid species identification include commercial DNA probes (MAC, M. kansasii, and M. gordonae) and high-performance liquid chromatography (HPLC).
For some NTM isolates, especially rapidly growing mycobacterial (RGM) isolates (M. fortuitum, M abscessus, and M. chelonae), other identification techniques may be necessary including extended antibiotic in vitro susceptibility testing.eg DNA sequencing or polymerase chain reaction (PCR), restriction endonuclease assay (PRA).

24. Susceptibility test :
Routine susceptibility testing of MAC is recommended for clarithromycin only.
Routine susceptibility testing of M. kansasii is recommended for rifampin only.
Routine susceptibility testing for treatment of M. fortuitum, M abscessus, and M. chelonae.
amikacin, imipenem for M. fortuitum only,
doxycycline, quinolones, sulfonamide or trimethoprim- sulfamethoxazole, cefoxitin, clarithromycin, linezolid, and tobramycin for M. chelonae only.

25. Decision of treatment

26. Expert consultation should be obtained when NTM are recovered that are either infrequently encountered or that usually represent environmental contamination.
Patients who are suspected of having NTM lung disease but who do not meet the diagnostic criteria should be followed until the diagnosis is firmly established or excluded.
Making the diagnosis of NTM lung disease does not, necessitate the institution of therapy, which is a decision based on potential risks and benefits of therapy for individual patients.

27. Basic concept of management :
Clarithromycin has shown good efficacy against a broad range of atypical mycobacteria.
Effective treatment of M kansasii infection can usually be accomplished with a rifampin-based regimen, or a rifabutin-based regimen .
M chelonae treated with rescue treatment with interferon gamma.
M abscessus was the most resistant species and that Mycobacterium mucogenicum was most susceptible.
In some cases based on clinical assessment, successful treatment requires aggressive debridement of all infected subcutaneous tissues and skin.

28. Treatment of MAC pulmonary disease :
For patients with nodular/bronchiectatic disease, a three-times- weekly regimen of clarithromycin (1,000 mg) or azithromycin (500 mg), rifampin (600 mg), and ethambutol (25 mg/kg) is recommended.
For patients with fibrocavitary MAC lung disease or severe nodular/bronchiectatic disease, a daily regimen of clarithromycin (500–1,000 mg) or azithromycin (250 mg), rifampin (600 mg) or rifabutin (150–300 mg), and ethambutol (15 mg/kg) with consideration of three-times-weekly amikacin or streptomycin early in therapy is recommended.
Patients should be treated until culture negative on therapy for 1 year.

29. Treatment of M. kansasii pulmonary disease :
A regimen of daily isoniazid (300 mg/d), rifampin (600 mg/d), and ethambutol (15 mg/kg/d).
Patients should be treated until culture negative on therapy for 1 year.

30. Treatment of M. abscessus pulmonary disease
Multidrug regimens that include clarithromycin 1,000 mg/day may cause symptomatic improvement and disease regression.
Surgical resection of localized disease combined with multidrug clarithromycin-based therapy offers the best chance for cure of this disease.

31. Treatment of NTM cervical lymphadenitis :
NTM cervical lymphadenitis is due to MAC in the majority of cases and treated primarily by surgical excision, with a greater than 90% cure rate.
A macrolide-based regimen should be considered for patients with extensive MAC lymphadenitis or poor response to surgical therapy.

32. Take home message :
Non Tuberculous Mycobacteria (NTM) can cause severe infection in selected groups of patients and is very difficult to be differentiated from TB infection clinically or radiologically leading to miss diagnosis and wrong treatment in these cases.
Expert consultation should be obtained when NTM are recovered that are either causing disease or that usually represent environmental contamination.
Suggestive clinical manifestations with positive culture for atypical mycobacteria is diagnostic.

33. Thank You All