Tuberculosis Flashcards
TB is the leading infectious cause of death globally
wow
Tuberculosis Incidence is on a __________ decline
(very) slow
It will take 200 years for TB incidence in high-burden countries to reach current levels in the U.S.
risk of reactivation of LTBI
Half of that risk in the first 2 years after infection
Injection of TB antigens
PPD- tuberculin skin test
Interferon gamma release assays (IGRAs):
Detects interferon release from monocytes exposed to TB antigens
Whom to test for latent TB infection:
1, High risk of exposure (i.e. infection) such as recent contact of person with TB, high prevalence countries, homeless/prisoners, HIV infection
- High risk of disease (low immunity) if infected- HIV, end-stage renal disease or immunosuppressive meds
what is wrong with the PPD with HIV pt.?
Weak cell-mediated immunity (can’t produce large reaction)
TB requires ____________ in hospital
airborne isolation; (N95 mask and negative air pressure room)
symptoms of TB
- productive cough for more than 2-3 weeks
- blood in sputum
- weight loss
- fevers/chills
- nightsweats more than 2-3 weeeks
**** epi is critical!!!!
what type of lesions do we see in lungs of TB pt.
apical lesions increases suspicion but TB can show up in any lobe
pulmonary tb diagnosis
- smear microscopy (only 50% sensitive)
- TB culture (95 % sensitive but takes weeks to grow)
- PCR (80-90% sensitive and there is immediate dx)
multidrug restistant to TB
resistance to BOTH Isoniazid and Rifampicin
resistant to Isoniazid and Rifampicin PLUS resistant to two core classes of drugs used to treat MDR TB
Extensively drug-resistant (XDR)
HIV TB
- more atypical presentations
2. latent TB infection is missed a lot
ART and “treatment as prevention” for HIV without CD4 cut-offs for starting ART is likely to also have a big impact on reducing TB
yep
why is TB so hard to kill?
thick cell wall and they are slow growing (doubling time is about 20hr in laboratory culture)
__________have highest concentration (>108 organisms) of actively metabolizing organisms that are extracellular in a neutral or alkaline pH.
Cavities - very happy bacteria
what do we form following TB infection
granuloma less number of bacteria than in cavities
treatment response is dependent on
lesion type (very heterogeneous)
one drug is unlikely to be effective for TB cure.
yep
RIPE and what is the Order of bactericial activity
first line therapy:
- rifampin
- isoniazid
- pyrazinamide
- ethambutol
INH>EMB>RIF>PZA
*** INH best for rapid growth in cavitary disease.
isoniazid MOA
Rate of elimination depends of ______________. Autosomal recessive trait can lead to deficiency in this enzyme. This will ____ INH acetylation and lead to _________ concentrations and _________ in those with the trait.
inhibits mycolic scid synthesis used for both latent and active
Rate of elimination depends of N-acetyltransferase-2 enzyme (NAT2). Autosomal recessive trait can lead to deficiency in this enzyme. This will slow INH acetylation and lead to higher concentrations and toxicity in those with the trait.
Toxicities associated with isoniazid
safe in pregnancy?
- peripheral neuropathy
- elvated LFTs with hepatitis
- lupus like syndrome
- CNS issues
- fever/rash/acne
safe in pregnancy
rifampin MOA
Bactericida compared to INH.
toxicities associated
binds to RNA pol and prevents DNA directed mRNA synthesis
Bactericidal activity half of that of INH.
toxicities include renal and liver
Has better activity against semi dormant populations
rifampin
rifampin induces
p450
PZA MOA and what is it used for?
caveat
unknown and Best for dormant and semidormant organisms and good activity in acid pH
Hepatic toxicity rare but can lead to fatal hepatic necrosis.
Ethambutol MOA
inhibits arabinogalactan synthesis and it is used to prevent emergence of resistance to the other drugs used
major issue of ethambutol
RETROBULBAR NEURITIS. Decreased acuity and red-green discrimination.
Active TB treatment principles:
- Decrease infectiousness by using _____ up front (EBA high).
- Other drugs to__________.
- Long duration of meds that have good sterilizing properties.
- Most regimes ______ months long.
- ALWAYS USE MORE THAN ONE DRUG AND NEVER ADD ONE DRUG TO FAILING REGIME.
- Decrease infectiousness by using INH up front (EBA high).
- Other drugs to prevent drug resistance.
- Long duration of meds that have good sterilizing properties. Rifampin best with PZA (PZA for first two months only).
- Most regimes 6 months long.
- ALWAYS USE MORE THAN ONE DRUG AND NEVER ADD ONE DRUG TO FAILING REGIME.
latent TB treatment
Patients have a much lower bacterial burden compared to active disease (104 vs 109 bacilli)
only one drug is needed- isoniazid for 9 months
drug resistance
- MDR. Resistant to at least _______
- XDR-TB MDR plus r to kanamycin, amikacin or capreomycin (INJECTABLES) plus any __________
- TDR or XXDR (4 cases in India, 2 Italy)
- MDR. Resistant to at least INH and Rifampin
- XDR-TB MDR plus r to kanamycin, amikacin or capreomycin (INJECTABLES) plus any quinolone.
- TDR or XXDR (4 cases in India, 2 Italy)
what is the strategy for active TB treatment?
RIPE/DOTS
RIPE for first two months
RI for four more months
Drug resistance is on the rise – never add just one drug at a time to a failing regimen.
yep
