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Mycobacteriosis

Mycobacteriosis. Clinical correlations. Mycobacteria. Tuberculosis Leprosy (Hansen Disease) BCG hypersensitivity and infection MOTT AIDS related disseminated MAC Immune reconstitution disease. Mycobacteria. All species resist decoloration, i.e. acid fast

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Mycobacteriosis

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  1. Mycobacteriosis Clinical correlations

  2. Mycobacteria • Tuberculosis • Leprosy (Hansen Disease) • BCG hypersensitivity and infection • MOTT • AIDS related disseminated MAC • Immune reconstitution disease

  3. Mycobacteria • All species resist decoloration, i.e. acid fast • All cause granulomatous inflammation • All are more common and/or more severe with cell mediated immune dysfunction • Delayed diagnosis if not specifically sought • Only TB spread person to person

  4. When to suspect Mycobacterial disease • Cavitary, reticulonodular or tree-in-bud pattern on CXR • Underlying structural lung disease* • Cellular immune dysfunction • Subacute or chronic fever, sweats or weight loss, esp. along with CBC abnormality • Any unexplained respiratory symptom/sign in patient with HIV • Cosmetic, plastics esp. breast, or bioprosthetic valve surgery • Granulomatous inflammation * May coexist with other active or inactive lung process

  5. Dx of Mycobacteria • Smear- acid fast stains (Kinyoun, auramine) – rare false positives • Culture – all species other than M.tb and M. leprae must be correlated clinically • PCR – currently only for interpretation respiratory secretion: smear (+) and PCR (+) means TB, smear (+) but PCR (-) means MOTT, smear (-) but PCR (+) means TB • Histology – granulomatous inflammation narrows differential greatly even if stains (-) for AFB

  6. Mycobacterium leprae • Unique infection able to manifest full spectrum from nearly absent to intense granulomatous immune response • Temperate climates worldwide; La., Ark., Tx., Miss. in USA • Not grown in vitro • Respiratory tract entry, seeks cooler areas • Infects schwann cells causing neuropathy

  7. Histology of Leprosy

  8. Acid-Fast Stain: M. leprae

  9. MOTT • Over 100 species, most of little, no or unknown virulence • Similar to TB in histology and staining, trained technicians can distinguish • All can be normal flora except M.kansasii • None person to person • Diagnosis requires more than simply recovering from non-sterile specimen

  10. MOTT Classification • Growth-rate /morphologic system obsolete • Clinically useful to classify by host, organ system (pulmonary vs. lymphatic, cutaneous, disseminated) • Treatment varies greatly with species

  11. MOTT Risk Factors • Structural lung disease (MAC, kansasii,) • Trauma/surgical (M.marinum, rapid growers) • Cellular immune defect (rapid growers, MAC) • Gamma interferon/IL-12 defect • AIDS (MAC, rapid growers, genevensa, hemophilum) • Recurrent aspiration, achalasia (MAC, rapid growers) • Fish tank (M.marinum) • Reptiles ( M chelonei) • Children – Scrofula (M. scrofula, MAC) • Hot-Tubs – Hypersensitivity pneumonitis (MAC)

  12. TABLE 4 Characteristics of patients with nontuberculous mycobacteria pulmonary infections MAC M.xenopi M. kansasii RGM/non-CF Subjects n 125 66 34 16 Underlying conditions Pre-existing pulmonary disease 89 (71.2) 28 (42.4) 7 (20.6) 8 (50) Previous M. tuberculosis 35 (28) 17 (25.8) 9 (26.5) 3 (18.7) Immunosupression/transplantation 34 (27.7) 17 (25.8) 5 (14.7) 1 (6.2) None/anorexia 14 (11.2) 18 (27.3) 15 (44.1) 4 (25) Radiographic abnormalities Infiltrates 46 (36.8) 1 (31.8) 12 (35.3) 8 (50) Nodules 28 (22.4) 21 (31.8) 10 (29.4) 3 (18.7) Cavitation 13 (10.4) 11 (16.7) 13 (38.2) 1 (6.2) Nonspecific 4 (35.2) 19 (28.8) 4 (11.7) 7 (43.7) No symptoms 35 (28) 22 (33.3) 10 (29.4) 0 (0) Data are presented as n, mean (range) or n (%), unless otherwise stated. MAC: Mycobacterium avium-intracellulare complex; M. xenopi: Mycobacterium xenopi; M. Adapted from Dailloux et.al. Eur.Respir.J.,2006;28:1211

  13. AIDS related MAC • CD4 less than 70 • Hectic chronic fever, GI complaints, esp. with very high alkaline phosphatase or severe anemia • Blood culture slow, insensitive; other secretions not specific • Can be pulmonary like with COPD • Antibiotics without antiretrovirals often insufficient

  14. MAC • M. avium complex; includes M. intracellulare, other clinically insignificant ones • By far main MOTT in AIDS • 4 types in relatively competent hosts: 1) fibrocavitary – COPD, etc. 2) fibronodular –older women, collagen defect* 3) cystic fibrosis 4) hypersensitivity (hot tub) pneumonitis * Presumed by assoc. with mitral valve prolapse, scoliosis,joint hypermobility,pectus excavatum

  15. Fibronodular MAC with bronchiectasis

  16. Tree–in–Bud Appearance of Mycobacterial Pneumonitis

  17. Rx of MOTT • Very little correlation or predictive data from susceptibilty testing except for: M.kansasii - rifampin MAC – clarithromycin M.chelonei, fortuitum, abscessus – per mic’s • None susceptible to PZA • Susceptible to macrolides, amikacinimipenem; often quinolones • M. abscessus- need IV drug • 2 and usually 3 drugs preferred • Duration varies; usually at least 1- 11/2 year after sputum smears turn negative • Patients without prescription coverage may not be treatable

  18. Risk Factors for TB • EtOH • Head/Neck, hematologic cancers • Silicosis • HIV - roughly 1 in 14 TB cases have HIV • Medications-transplant, corticosteroid, TNF inhibitors • Gastrectomy • Fe excess, Vit D deficiency • ESRD, DM( Hb A1c> 7) • Celiac Disease • Age

  19. Acid-Fast Staining: Limitations • Non-mycobacterial bacteria can stain positive • Smear-positive respiratory secretion implies contagious individual • Approximately 50% sensitive (sputum) • 3, (and possibly only 1 if suspicion low) sputa rules out contagion but NOT active disease • If AFB (+) respiratory specimen is negative for TB by PCR -TB ruled out, (+) smear due to MOTT

  20. Pathogenesis of TB: Anatomic event Clinical event Calcified lesion (eventually) seen on xray Miliary, endobronchial spread (ARDS, hypersensitivity pneumonitis), late extrapulmonary disease Cavitary pneumonia • Granuloma forms to contain – walls off, creates environment not condusive to growth • Granuloma enlarges, ruptures into bronchus, artery etc. • Liquefaction of granuloma, extracellular growth, inflammatory response lead to necrosis of parenchyma

  21. TB: Miliary, Extra-Pulmonary Disease • Non –specific symptoms may dominate miliary or disseminated TB • Psoas abscess, with or without vertebral osteomyelitis, CNS disease relatively common • May occur with or without active pulmonary disease

  22. Extra- Pulmonary TB* CID 2009,49:1350 * Excludes disseminated or concurrent pulmonary/extra pulmonary disease

  23. Dx. Of TB • PPD – very limited role in dx of active disease due to high rate of false (-) and true - but –unrelated phenomenon • Can help in CNS disease, pericarditis • Definition of (+) PPD depends on circumstances (size, prior tests, host etc.) • Prior BCG – must assume positive skin test could be due to subsequent TB infection • Interferon based assays – M.tb specific immune response to TB proteins, identifies PPD reaction as TB rather than MOTT, more sensitive than PPD for screening, less for active disease

  24. Reading TST Result • Read 48–72 hrs after placement • If HCW returns after >72 hrs, place and read another TST* • Do not let HCWs read their own results • Find and measure induration • Measure diameter of induration across the arm • Do not measure redness

  25. Positive PPD: Interpretation

  26. Criteria for Initiating Respiratory Precautions Patient has symptoms or signs of TB disease Or Patient has documented infectious TB disease and has not completed anti-TB treatment Or HIV and unexplained respiratory sign/symptom

  27. General Points on Tb Rx • INH resistance alone does not affect efficacy of standard 4 drug regimen • Rifabutin preferred over rifampin in HIV • Extra – pulmonary TB Rx 1 year • 2 or more new/active agents for suspected/proven resistance • Steroids for meningitis, pericarditis, ARDS

  28. Rx. of TB Standard regimen for all unless: -Suspected resistance ( foreign born, failed prior Rx) -Pregnancy, coexistent liver disease, drug interaction concerns, intolerance Direct observed Rx when possible Some strains not treatable

  29. Immune Reconstitution Inflammatory Syndrome (IRIS) • Occurs in setting of immune system recovery, usually AIDS and initiation of HAART* • Exuberant or poorly coordinated reactions to antigen, probably larger amount than usually seen in less compromised hosts • Usually mycobacteria, Cryptococcus or CMV retinitis • High fever, lymphadenitis, or paradoxical worsening of primary lesion • Can be worse than initial presentation

  30. Summary • Mycobacteria like lung and lymphatics and weak cell mediated immunity; causing subacute to chronic granulomatous infection • MOTT also like skin and anatomically abnormal lungs, TB likes CNS, vertebrae • Patients with MOTT usually less ill • Size and circumstance matter for PPD • Imaging can’t distinguish MOTT vs TB • Rx requires 2 or more drugs for >6 months, guided by MIC’s

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