11/30 TB and Mycobacteria - McAuliffe Flashcards
Mycobacterium tuberculosis
- aerobic bacillus
- non-spore forming
- non-motile
- cell wall containing mycolic acid → retains acid-fast stain
- doubling time: 15-20h, needs 3-8wk for growth on solid Lowenstein-Jensen media
non-tuberculous Mycobacteria
more than 100 species; 60 can cause disease in humans
no evidence of person–to-person spread → pts dont need to be isolated, not public health issue
clinical syndromes including:
- pulmonary disease
- skin, soft tissue, bone/joint disease
- lymphadenitis
- disseminated disease
- catheter-related infections
pathogenesis of MTB
inhalation → phagocytosis by alveolar macrophages → intracellular multiplication → spread to regional lymph nodes via lymphatic system of hematogenous dissemination
immune response → granuloma formation to contain infection
- cell death in granuloma → caseous necrosis
- bacteria can remain dormant in granuloma
10% of infected with normal immune systems develop TB at some point in life
- certain metical conditions incr risk that TB inf progresses to TB disease
- HIV is strongest risk factor
- chronic renal failure
- diabetes
- silicosis
- leukemias/lymphomas
- carcinoma of head/neck, lung
- weight loss > 10% of ideal body weight
TB testing
PPD (purified protein derivative) of tuberculin
- antigenic, resulting in delayed type hypersensitivity rxn
- indicates TB infection; no distinction between active and latent
- PPD may not become + until 3mo following exposure
immunosuppressed: PPD greater than/equal to 5mm
not immunosuppressed but higher risk: PPD greater than/equal to 10mm
not immunosuppressed, low risk: PPD greater than/equal to 15mm
false + : non-tuberculous mycobacterial inf, BCG vaccine
false - : HIV, malnutrition, steroid tx, recent TB inf or overwhelming TB disease
BCG vaccine
Bacille Calmette-Guerin vaccination
- line attenuated mycobacterial strain from M. bovis
- used in countries with high prevalence rates to prevent childhood TB
- can yield false + PPD (less likely further from vaccination)
- if rxn > 20mm, prob true +
IGRAs
interferon gamma release assays (IGRAs)
whole blood in vitro test assessing lymphocytic release of interferon gamma in presence of TB antigen
positive in presence of latent or active TB
advantages
- no error in interp
- no 48-72h follow up
- no boosting
- not affected by BCG vaccine
disadvantages
- must be processed within 12h
- false + with nonTB mycobacteria
- can give some indeterminate results
- poss less reliable in pregnant women, children, immunocompromised
- does not distinguish between active and latent TB
active TB vs latent TB
active TB
- positive test (skin test or IFNgamma release assay)
- signs, sx (fever, night sweat, cough, hemoptysis, pleurisy, anorexia, weight loss, fatigue)
- most commonly affects lungs/pleura, but can also affect several other organs
- abnormal CXR
latent TB
- positive test (skin test or IFNgamma release assay)
- no signs, sx
- normal CXR
- EXCEPTIONS: nodules, pleural scarring
miliary TB
hematogenous dissemination of TB
- can occur with primary inf or with reactivation
- commonly affects lungs, liver, spleen, bone marrow, kidneys, adrenals
- CXR: diffuse nodules < 2mm
- if sputum testing is neg, can try bone marrow/liver biopsy
CXR findings
primary vs reactivated vs latent TB
primary TB
- lower or middle lobe infiltrates
reactivated TB
- apical infiltrates
- cavitation
latent TB
- usually normal
- nodules in hilar area or upper lobes
- pleural scarring/thickening
antituberculosis drugs
first line (6)
second line (9)
first line drugs
- isoniazid (INH)
- rifampin (RIF)
- pyrazinamide (PZA)
- ethambutol (EMB)
- rifabutin*
- rifapentine (RPT)
second line drugs
- streptomycin (SM)
- cycloserine
- p-aminosalicylic acid
- ethionamide
- amikacin or kanamycin
- capreomycin
- levofloxacin
- moxifloxacin
- gatifloxacin
not approved by FDA for tx of TB
treatment of active TB
first 2 months: four drug regimen
- isoniazid, rifampin, pyrazinamide, ethambutol or streptomycin
- *if TB non resistant (or there’s less than 4% resistance in comm), INH/RIF/PZA can be used for first two months
next 4 months: two drug regimen
- isoniazid, rifampin
drug resistant TB
multi-drug resistance (MDR) : resistance to INH and RIF
eXtnesive-drug resistance (XDR) : resistance to INH, RIF, fluoroquinolones and EITHER capreomycin, amikacin, kanamycin
overall, more common in foreigners
tx based on susceptibilities
higher risk of mortality
why treat latent TB?
decrease risk of reactivation!
- protective for at least 20y, prob for life
if all meds taken, 90% efficacy
if drugs self-admin, 60-70% efficacy
regimen: INH daily (or 2x weekly) for 9mo (at least 6mo, 12 mo if interrupted)
- if INH resistant: RIF daily for 4mo
that said, have to weigh risks and benefits of tx in low risk pts
- possibility of drug-induced hepatitis
- contraindications: end stage liver disease, active hepatitis
TB in kids
- less likely to see lung cavitation
- more likely to see intrathoracic adenopathy
- gastric aspirate used instead of sputum culture
- kids < 5y at greater risk for dissemination (meningitis, miliary TB)
TB infection prevention
if active pulmo TB suspected…
-
AIRBORNE ISOLATION
- negative pressure room
- particulate respirator masks
discontinue isolation when…
- AFB smears negative x3
- PCR negative
- alt dx reached
if confirmed active TB…
- isolate until clinical improvement on TB tx and AFB smears negative x3
isolation not required for latent TB and extrapulmonary TB