Atypical mycobacteria

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  • 1. Atypical Mycobacteria Dr. Sandeep G Huilgol MBBS, DNB(Internal Medicine)MMedSci(Nephro)
  • 2. Atypical Mycobacteria • Known by several terms— – – – – 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 – – – – – – – • 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
  • 14. . • 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