L33 TB and Nontuberculous mycobacterial (NTM) pulmonary disease

  1. Latent TB
    classic model, Dx, Tx
    • "classic" model:
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    • -90% remain well
    • -10% reactivate (aka Post-Primary TB)

    • Dx: delayed type hypersensitivity reaction
    • 1. TST (TB Skin Test) - many false positives
    • 2. Interferon Gamma Release Assay - eliminates false positives (99.7% negative predictive value)
    • -positive for M tuberculosis, M africanum, M bovis, M kansasii, M marinum, and M szulgai
    • -aka QFT, T spot (backup), QFT GIT (automated)
    • -works by determining IFN-γ levels


    • Tx: of latent TB infection (LTBI)
    • -Not everyone who has LTBI requires treatment: look at other factors such as epidemiological factors (healthcare workers, alcoholics,...)
    • -reactivation can be prevented (~60% reduced) when treated with INH (isoniazid)
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    • Tx options:
    • -INH 300mg/day for 6-9 mos
    • -Rifampin 600mg/day for 4 mos
    • -INH 900mg +Rifapentine 900mg Qweek x 12 weeks (must be given under direct observation)
  2. Latent TB
    current model
    • LTBI isn't really 'latent' - waxes and wanes
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    • Distinguishing factors:
    • 1. Host (innate/acquired immune response
    • -Vulnerability to infection
    • -Infection/disease status
    • 2. Microbe
    • -Strain
    • -Metabolic activity
    • 3. Environment
    • -likelihood of exposure/re-exposure
    • -other mycobacteria
    • -other infections

    • Tx: not everyone requires treatment
    • -look to epidemiology, recent infections, co-morbidities to determine who should get LTBI treatment
  3. Active Tuberculosis
    Epidemiology and clinical suspicio
    • Epidemiology:
    • -US-born rates are declining
    • -Foreign-born rates have stayed flat
    • -In San Diego: Mexico, Viet Nam, Philippines make up >80% of cases
    • -In US: Mexico, philippines, Viet Nam make up >40% of cases

    • M bovis:
    • -5-10% of TB in San Diego County
    • -transmission through unpasturized dairy
  4. TB
    Clinical suspicion
    • Clinical suspicion of TB
    • 1. Risk factor analysis
    • -Demographics: country of birth
    • -Social history: homeless, prison, alcoholic
    • -TB history: exposures, history of BCG, LTBI

    • 2. Clinical presentation
    • -Cough > three weeks
    • -minimal symptoms with highly abnl CXR (out of proportion to sx)
    • -other sx tend to be minimal: fever, chills, night sweats, anorexia, weight loss, hemoptysis, chest pain, dyspnea
    • -PE: rales, wheezes, adenopathy, splenomegaly, pleural changes

    • 3. Comorbidity
    • -Conditions: HIV (with low CD4 count), DM, Malignancy, chronic renal failure, immunosuppressive disease
    • -Immunosuppressive medications: steroids, Anti-TNF preparations, etc.

    • 4. Radiology
    • (next slide)
    • 5. Microbiology
    • (next slide)
    • -recommendation is to collect multiple sputum on the first day (Q8hrs), and one on each of the following two days

    • Clinical suspicion:
    • -Low suspicion --> 4% probability
    • -Intermediate-->28% probability
    • -High--> 85% probability
  5. TB radiology
    • Primary TB: 50% of cases in US
    • -Lower lobe disease
    • -Adenopathy common
    • -No cavitation unless progressive
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    • Reactive (post primary)
    • -Upper lobe disease
    • -Cavitation common in later stages
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    • Disseminated
    • -aka miliary
    • -local organ involvement
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    • HIV: have radiographic changes
    • -atypical presentation predominate:
    • pleural effusion, atypical infiltrate, reticulo-Nodular, adenopathy
    • -extrapulmonary involvement is common
  6. TB microbiology
    • Microscopy:
    • -6,000-10,000 organisms per ml to see 3 AFB on slide
    • -Repeat 3 times
    • -Sensitivity: 55%
    • -Specificity: 5-50%

    • Culture:
    • -100 organisms per ml to get 1 colony
    • -Sensitivity: 80%
    • -Specificity: 1-2% false-positives

    • Nucleic Acid Amplification:
    • -get answer in ~1day!
    • -sensitivity ~ that of culture
  7. TB - drug resistance
    • Large problem around the world (former Soviet Union); not a big problem in the US
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    • -10-12% are isoniazid resistant
    • -1-2% are MDR TB

    • Risk factors:
    • -Prior tx for TB
    • -Foreign born in high incidence country
    • -Close contact with pt who had drug resistant TB
    • -Host  factors: HIV/immunosuppressed, homeless

    • Dx of drug resistant TB:
    • -Clinical suspicion (bedside epidemiology)
    • -Lab:
    • 1. Growth based test - standard drug susceptibility testing
    • -can take up to 1 week

    • 2. Genetic Based - results in 1day!
    • -Xpert: rtPCR that tests for Rifampin resistnace
    • -Hain Test: line probe assay that tests for MDR TB, second line drugs
  8. TB
    Standard pulmonary treatment
    "4 for 2, and 2 for 4"

    • Induction phase: QD 2 months, start as direct observed therapy (DOT)
    • -Rifampin
    • -Isoniazid
    • -PZA
    • -Ethambutol

    • Consolidation phase: QD to BIW for 4 months
    • -Isonizid
    • -Rifampin or Rifapentine

    • In HIV patients:
    • -initiation of ART as soon as possible (earlier the better); as soon as patient is tolerating all TB meds
  9. Extrapulmonary TB
    treatment
    • -RIPE therapy for 6 months
    • -9-12 months for menengitis
    • -Corticosteroids added for pericarditis (Prednisone), meningitis (Dexamethisone)
  10. Reasons for persistently positive cultures
    • Poor compliance with medications
    • Extensive cavitations and extensive fibrosis
    • co-morbidity (HIV, malnutrition, DM, immonocompromising diseases or meds)
    • Biological variation
    • -Drug resistant TB
    • -Poor drug absorption
  11. Non Tuberculous Mycobacterium
    aka NTM
    aka Mycobacteria other than tuberculosis (MOTT)
    aka Atypical mycobacteria
    • More common NTMs: relative frequencies
    • -M avium intracellular complex (MAC) 61%
    • -M kansasii 10%
    • -M fortuitum/cheloni/abcessus complex 19%
    •     (rapidly growing mycrobacterium [RGM])
    • frequency of disease when NTM is isolated:
    • -MAC: 45%
    • -Kansasii: 75%!!
    • -fortuitum/cheloni: 18%
    • ...few people who are colonized get disease

    • Less common:
    • -M gordonae
    • -M malmoense
    • -M simiae
    • -M szulgai
    • -M smegmatis
    • -M xenopi
  12. MAC
    pathogenesis, disease spectrum, co-morbid conditions
    • -Ubiquitous, especially in the southeast US
    • -Pathogenesis: oral or inhaled (in water)

    • spectrum of disease:
    • -adenitis
    • -acute pneumonia
    • -chronic pulmonary changes

    • Co-morbid conditions:
    • -CF
    • -T cell deficiencies
    • -Cytokine web dysfunction
    • -Anatomic disruption
  13. Pulmonary MAC
    sx, main types
    • Sx:
    • -fatigue, afternoon naps
    • -weight loss (with good intake)
    • -fever & chills, night sweats
    • -cough/sputum production
    • -hemoptysis
    • -chest pain
    • -SOB/DOE

    • Main types of pulmonary MAC
    • 1. Fibro cavity: "classic infection" cause it looks like TB
    • -not the most common
    • -nodular areas of increased opacity; upper lobes
    • -calcified pulmonary nodules with hilar nodes
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    • 2. Lady Windemere syndrome:
    • -old ladies who suppress cough
    • -lingual/middle lobe bronchiectasis
    • -multiple 1-3 mm diameter centrilobular nodules
    • -"tree in bud" appearance on CT
    • -adeonpathy
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    • 3. One or more masses: usually in young women
    • -+/- adenopathy
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    • 4. Pectus excavatum:
    • -squeezes the heart, mitral valve prolapse
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    • 5. Hot tub lung:
    • -Sx: dyspnea, cough, hypoxia, fever
    • -Hot tub users; immunocompetent
    • -CxR shows diffuse infiltrative lung disease, no bronchiectasis
    • -Bx: exuberant nonnecrotizing, frequent bronchilocentric, granulomatous inflammation
  14. NTM
    Treatment
    • Considerations:
    • -Evaluate sx, microbiology, radiographs
    • -Comorbidities: past lung injury, smoking, CF, GERD
    • -Determine goal of tx

    • Tx:
    • 1. Clarithromycin (or azithromycin)
    • +
    • 2. Rifabutin (or rifampin)
    • +
    • 3. Ethambutol

    -also consider Moxifloxacin or Amikacin

    • **Duration and frequency of treatments depend on extent of diseases:
    • -Pts should be treated till they are culture negative for >12 months

    • Surgical treatment:
    • -Indications: localized disease, adequate lung function, poor response to medical therapy or resistant
    • -High incidence of complications
  15. M. Kansasii
    • Tx:
    • -INH
    • -Rifampin
    • -Ethambutol

    -must be culture negative for 12 mos
Author
jknell
ID
202348
Card Set
L33 TB and Nontuberculous mycobacterial (NTM) pulmonary disease
Description
TB (latent and active) non Tuberculous Mycobacterial disease
Updated