1. Ali Somily MD

2.  All mycobacterial species except those that cause tuberculosis (TB)  Mycobacterium tuberculosis complex includes M. tuberculosis  including M. tuberculosis subsp canetti  M.bovis  M. bovis BCG strain  M. africanum  M. caprae  M. microti  M. pinnipedii  Leprosy (M. leprae).

3.  1954 Runyon first NTM classification  >100 NTM species  Other names  Mycobacteria other than tuberculosis (MOTT)  Atypical  Environmental  Opportunistic  Variable pathogenicity and geographic regions  40% cause diseases in human  Immunosuppressed host

4.  Water, soil, food and animals  Does not spread from person to another  Relatively resistant to chlorination and ozonization  Outbreak and Pseudo-outbreak in the hospital  HIV and dialysis patients  Improve laboratory methods  reporting  MAC 40%,rapidly growing 10%,15% unknown,25% M.gordonae,2.5% M.kansasii(MW USA and UK) and 1% M.xenopi (Ontario)

5.  Rapid Growers  Days in broth and < 1 week in solid media  M.abscessus  M.chelonae  M.fortutum  Slow Growers  1-2 weeks in broth and 2-4 weeks in solid media  M.avium  M.kansasii  M.scrofulaceum  M.ulcerans  M.xenopi  M.gordonae

6.  M.leprae cannot be cultured  M.marinum lower temperature required  M.haemophilum lower temperature required and iron need to be added  M.ulcerans lower temperature required  M.genavense very slow growth in broth  DNA probes for MAC, M. kansasii and M. gordonae available  Identification and sensitivity

7.  Risk factors  Immunosuppression ( HIV, Medications )  Aging   BCG vaccination  Cystic fibrosis  Fibronodular bronchiectasis

8.  Common clinical syndromes: 1. Lymphadenopathy 2. Chronic pulmonary disease 3. Skin and soft tissue infections (often associated with trauma or a foreign body) sometimes with extension to bone and joint 4. Disseminated disease.

9.  Pulmonary disease  Definition  Usually adults  Symptoms of cough, sputum production, weight loss  Two or more sputum isolates or one isolate from,BAL,Bx, sterile site  Distribution of isolates varies regionally

10.  Pulmonary disease  Common etiological agents  M. avium complex(MAC)  M. kansasii  M. abscessus  M. xenopi

12.  Elderly men with COPD  Middle aged to elderly Non- smoking women  CF patients  Hypersensitivity pneumonitis

13.  M.Kansasii  Similar to TB  US midwest and south  AFB positive  Probe positive  HIV CD4 <200 pulmonary and disseminated  M..xenopi  UK, Northern Europe and Canada, less common in US  Rural /farm area  Very good outcome

14.  Pulmonary disease  Treatment  Treatment with combined antimicrobials  Resection if localized

15.  Lymph node disease  Definition  Usually < 5 years of age  Unilateral, submandibular site most common  Onset of symptoms subacute  Skin induration and sinus tract formation may occur  R/O TB  MAC (80%) is the most common followed by M. scrofulaceum  Dx Fine needle or excisional Bx

16.  Lymph node disease  Common etiological agents  MAC  M. kansasii  M. malmoense  M. haemophilum  Uncommon etiological agents  M. scrofulaceum  M.fortuitum/ peregrinum  M.abscessus/ chelonae

18.  Lymph node disease  Treatment  Surgical resection is usually curative

19.  Skin/soft tissue/bone/joint and tendons  Definition  History of trauma or superficial laceration  Presence of a foreign body

20.  Skin/soft tissue/bone/joint and tendons  Common etiological agents  M. marinum  M. fortuitum/peregrinu m  M. abscessus/chelonae  M. ulcerans  Uncommon etiological agents  MAC  M. kansasii  M. terrae  M. haemophilum

21.  Water,fish  Lake, bay,ocean,pool,aquarium  1-2 month IP  granulomatous nodular – ulcerative lesions (hands)  Bx for diagnosis

22. Fish tank granuloma/ M.marinum

23. Buruli ulcer /M.ulcerans  Chronic cutanous ulcer  Africa mostly  Debridment

24.  Skin/soft tissue/bone/joint and tendons  Treatment  Debridement plus combined drug therapy

25.  Disseminated  Definition  HIV or other immunosuppressive disease  Symptoms: fever, weight loss, diarrhea  Any site possible  No trauma necessary

26.  Disseminated  Prevention & treatment  Prevention of MAC in HIV by prophylaxis  Treat positive blood culture aggressively

27.  Disseminated  Common etiological agents  MAC  M. genavense  M. abscessus/chelonae  M. haemophilum  Any mycobacterium may cause disease in association with significant immunosuppression HIV CD4 < 50), and any localized lesion may disseminate.

28.  M.fortutum  M.abscessus  M.chelonae  Skin and soft tissue infection after truma, post-op,cardiac,mammoplasty and cosmotic  Pulmonary M.abscessus>M.fortutum  Indolent, progressive  Cavitary uncommon  Mild systemic symptoms

29.  Worldwide –esp in tropical countries  Transmission rout unknown  Can not be cultured  Syndromes  Lepromatous  Tuberculoid  Mixed  Treatment 6-months to 2 years  Dapsone + Rif +/- clofazimine

33.  Principles of Treatment of NTM Disease  1. Patients should be carefully evaluated to determine the significance of an NTM isolate. The presence of the organism in a sterile site or repeatedly from airway secretions in association with a compatible clinical and radiologic picture confirms the diagnosis.  2. Treatment of rapidly growing mycobacteria should be guided by in vitro susceptibilities. Other drug susceptibility testing is not standardized.

34.  3. Treatment should usually combine at least two drugs of proven efficacy.  4. Contact follow-up is not necessary since NTM are not transmitted from person to person.  5. Duration of therapy has not been determined; in general, 6-12 months is required following negative cultures.

35.  6. In soft tissue infections, because of rapidly growing mycobacteria, a combination of debridement and treatment with antimicrobials is recommended. For selection of antimicrobial agents, consultation with the laboratory should be undertaken regarding the reliability of in vitro testing.

36.  MAC Clarithromycin or azithromycin + ethambutol+Rifampin  M. xenopi Rifampin+Ethambiotol +INH  M. kansasii Rifampin + Ethambutol  M. malmoense Rifampin or Ethambutol  M. marinum Rifampin or Clari + Ethambutol 2-3 months  Rapid growers doxycycline, amikacin, imipenem, quinolones, sulfonamides, cefoxitin, clarithromycin

37.  M. haemophilum Clarithromycin, Rifampin Cipro or Amikacin  M. genavense Clarithromycin, Rifabutin or AmikacinEthambutol  M. ulcerans Clarithromycin, Rifampin, Ethambutol or PAS ( Paraaminosalicylic acid)  MAC prophylaxis Azithromycin, Clarithromycin or Rifabutin 300 if CD4 <50x 106/L