Tuberculosis Flashcards
True or false: tuberculosis is not curable
false
tuberculosis is preventable and curable
Which population is impacted by tuberculosis the most in Saskatchewan?
Indigenous
-6x higher than the provincial rates
-42% of cases in SK living in First Nations communities
Which organism causes tuberculosis?
mycobacterium tuberculosis
How is tuberculosis spread?
spread is airborne via coughing or sneezing
-host inhales droplet nuclei
-close contacts most likely to be infected
-prolonged contact: risk of infection can be up to 30%
Describe mycobacterium tuberculosis.
acid fast bacillus
-impervious to gram staining (can appear weakly gram +)
slow growing (doubling time 20hrs)
What are the risk factors for tuberculosis?
foreign born from highly endemic area
Canadian Indigenous population
close contact
homeless
incarceration
alcoholism, IVDU, malnutrition
co-infection with HIV (synergism)
What are the risk factors for active TB disease?
once infected with M. tuberculosis: lifetime risk of active TB is 10%
risk greatest during first 2 years after infection
<2yo and >65yo: greater risk of active disease
immunosuppression
HIV infected
What increases the probability of transmission of tuberculosis?
# of infectious droplets per volume of air and length of time spent breathing that air
bacterial burden in source
upper lung disease in source
laryngeal disease in source
severity and amount of cough in source
crowding and poor ventilation
duration of exposure
proximity to source
delayed diagnosis and tx of source
What is involved in the host response of a tuberculosis infection?
T-lymphocyte response (mainly CD4+)
-active macrophages that engulf and kill mycobacterium
TNF-a and TNF-y are important cytokines in coordinating immune response
organism has many mechanisms to evade immune response
How does a primary infection of tuberculosis occur?
inhalation of droplet nuclei which reach alveoli
What does the progression of clinical tuberculosis depend upon?
infecting dose (# of organisms inhaled)
virulence of the organism
cell-mediated immune response
-macrophages kill: infection controlled
-organism not killed: macrophages rupture, bacteria spill out
What occurs roughly 3 weeks after tuberculosis infection?
T-lymphocytes are presented with M. tuberculosis antigen
T-cells become active and secrete INF-Y
-this stimulates macrophages to become -cidal
large # of -cidal macrophages surround the tuberculosis foci
What is the process called for creating activated microbiocidal macrophages?
cell mediated immunity
What is occurring at the same time as CMI?
DTH (delayed-type hypersensitivity)
-cytotoxic immune response that kills nonactivated immature macrophages that allow bacillary replication
-occurs via T lymphocytes
-released bacteria then killed by activated macrophages
What can the inflammatory response to tuberculosis result in?
tissue necrosis
calcification
lymph node enlargement
When is the tuberculin skin test positive?
when activated lymphocytes reach an adequate number and tissue hypersensitivity results
Describe reactivation of disease for tuberculosis.
occurs in 10% of cases
most often in apices of lung (high O2, poor local immunity)
organisms within granulomas emerge and multiply extracellularly
granulomas liquefy and spread producing cavities
if untreated, destroy the lung - hypoxia, resp acidosis, death
What are extrapulmonary sites or diseases that can be caused by tuberculosis?
lymphatic and pleural disease most common
bone (often vertebrae), joint, GU, meningeal
large # of organisms in bloodstream (miliary TB)=emergency
HIV (destroys CD4+ cells = depleting cells that control TB)
What are the signs and symptoms of tuberculosis?
gradual onset
may not seek medical attention until hemoptysis
fever, cough, fatigue, night sweats, weight loss
Frank hemoptysis
chest exam: dullness to percussion, rales
moderate increase in WBC (mainly lymphocytes)
CXR: nodular infiltrates (apices), cavitations
How is tuberculosis diagnosed?
Mantoux test (TB skin test)
-read in 48-72h
-measure the induration (bump), not redness
sputum culture and sensitivity
In general, what is the treatment for tuberculosis?
isolation to prevent spread
drugs to cure
adherence: directly observed therapy (DOT)
identification of contacts
What is required for active tuberculosis?
combination therapy
Explain the differences in drug susceptibility within the 3 subpopulations of microorganisms.
extracellular:
-isoniazid, rifampin, streptomycin
within granulomas:
-pyrazinamide best drug
-isoniazid and rifampin
intracellular within macrophages:
-rifampin, isoniazid, quinolones
What is the treatment for latent tuberculosis?
rifampin daily x 4 months (4R)
-#1 option
rifapentine and isoniazid once weekly x 3 months (3HP)
unable to use rifamycin regimen:
-isoniazid daily x 9 months (6 month is alt)
What is the standard treatment for active tuberculosis?
rifampin, isoniazid, ethambutol and pyrazinamide for 2 months followed by rifampin and isoniazid for 4 months
= 6 months total
What can be done if the bacteria is sensitive to rifampin and isoniazid?
ethambutol can be stopped at any time
How long is treatment of active tuberculosis if pyrazinamide is not used?
9 months of isoniazid and rifampin required
Differentiate the initial phase and continuation phase of active tuberculosis.
initial phase:
-3 to 4 effective drugs daily x 2 months
continuation phase:
-minimum 2 drugs, daily preferred but option of intermittent with DOT
How long is treatment of active tuberculosis when rifampin and isoniazid are not used?
2 years or more
What is the MOA of isoniazid?
inhibit bacterial wall synthesis
-powerful early bactericidal activity
How should isoniazid be taken?
on an empty stomach
Which patients are at higher risk of neurotoxicity with isoniazid?
slow acetylators
many other comorbidities
What are the adverse effects of isoniazid?
elevations in transaminases common
hepatotoxicity
neurotoxicity
other: GI, rash, hematologic abnormalities
What are drug interactions of isoniazid?
inhibits metabolism of phenytoin, carbamazepine, primidone, valproic acid, warfarin
-monitor and adjust doses as needed
increased risk of hepatotoxicity with acetaminophen
What is the MOA of rifampin?
inhibits bacterial RNA synthesis by binding to the beta subunit of DNA-dependent RNA polymerase
-blocking RNA transcription
How should rifampin be taken?
on an empty stomach
If a strain is resistant to rifampin, what else is the strain likely resistant to?
isoniazid
How long is tuberculosis treatment without rifampin?
minimum 12-18 months
What are the adverse effects of rifampin?
liver enzyme elevations
hepatotoxicity
rash, fever, GI, colors body secretions orange/red
allergic rxn (esp with intermittent dosing)
flu-like sx
hemolytic anemia, acute renal failure
What are the drug interactions of rifampin?
MANY
potent enzyme inducer, esp 3A4
-macrolides, azoles, protease inhibitors, simv, phenytoin, cyclosporine, steroids, warfarin
oral contraceptives
What is an advantage of rifabutin?
less drug interactions than rifampin
When is rifabutin preferentially used?
with some antivirals and immunosuppressives
What are the adverse effects of rifabutin?
arthralgia, myalgia
less common:
-hepatotoxicity
-neutropenia
-thrombocytopenia
-rash
-uveitis
What is an advantage of rifapentine?
longer t1/2 than rifampin
What are the adverse effects of rifapentine?
rash, hematologic, arthralgias, increased liver enzymes
more hypersensitivity rxns
How long is tuberculosis treatment when pyrazinamide is on board?
when used in first 2 months, shortens duration to 6 months
-not used: duration is at least 9 months
What are the adverse effects of pyrazinamide?
GI, arthralgias, increased uric acid
hepatotoxicity (major, dose related)
What is the role of ethambutol?
generally bacteriostatic, prevents resistance
What are the adverse effects of ethambutol?
GI most common
retrobulbar neuritis
Which drugs should be avoided while on ethambutol?
antacids
What is the role of quinolones for tuberculosis?
alt when 1st line agent has to be d/c
-levofloxacin and moxifloxacin
Describe the BCG vaccine.
attenuated, hybridized strain of M. bovis
produces subclinical infection resulting in sensitization of T lymphocytes and cross-immunity to M. tuberculosis
primary benefit: prevention of severe forms of TB in children
not routinely given in Canada with exceptions
What are some drugs where concentration may be substantially decreased with rifamycins?
hormone therapy
-add a barrier method of contraception
levothyroxine
-monitor TSH
SSRIs
-may need dose increase
corticosteroids
-monitor clinically, may need dose increase
DOACs
-some combos CI
warfarin
-monitor PT, may need dose increase
methadone
-may need dose increase
anticonvulsants
-may need dose increase
antiretrovirals
-rifabutin preferred
What are the patient monitoring parameters for tuberculosis?
initial: physical, weight, visual acuity, color vision testing, CXR
baseline labs:
-CBC, AST, ALT, bilirubin, SCr, HIV serology, Hep C serology, HbA1C
sputum
-for efficacy (q1-2 wks until 2 consecutive negatives)
-monthly until 2 consecutive negatives
drug sensitivity testing
adherence (DOT)
monthly weight, vision testing (EMB), CBC, SCr, AST, ALT, bilirubin
drug interactions
