L33 TB and Nontuberculous mycobacterial (NTM) pulmonary disease

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jknell
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202348
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L33 TB and Nontuberculous mycobacterial (NTM) pulmonary disease
Updated:
2013-02-21 18:59:55
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Pulmonary II
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TB (latent and active) non Tuberculous Mycobacterial disease
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  1. Latent TB
    classic model, Dx, Tx
    • "classic" model:
    • -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)
    • 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

    • 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

    • Reactive (post primary)
    • -Upper lobe disease
    • -Cavitation common in later stages

    • Disseminated
    • -aka miliary
    • -local organ involvement

    • 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
    • -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

    • 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

    • 3. One or more masses: usually in young women
    • -+/- adenopathy

    • 4. Pectus excavatum:
    • -squeezes the heart, mitral valve prolapse

    • 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

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