Tb Flashcards
Tb caused by
Mycobacterium tuberculosis
Define latent Tb
exposed but immune system keeps in check.
asymptomatic
+/- PPD and granulomas on CXR
define Active Tb
organisms released from granulomas and begin mutltiplying extracellularly
usually within 2 years of infection
symptomatic
2 main risk factors for active Tb
recently exposed
weakened immune system
5 categories of recently exposed
close contacts of TB cases
immigrants from contries with high TB rates
Children
factors for weakened immune system
hiv substance abuse transplant recipients DM renal failure malignancies immunosuppressive drugs
s/s of TB
weight loss
productive cough
fever/night sweats
hemoptysis
PE findings for TB
dullness in chest percussion
rales
vocal fremitus
CXR findings in TB
patchy or nodular infiltrates
cavitation
miliary tb
% of patients with active TB who will be negative on PPD
20%
dose of PPD
5 tuberculin unit
alternate names for PPD
mantoux test
tuberculin skin test
tuberculin purified protien derivative
5 categories who are PPD + with 5 mm induration
HIV +
recent contact with TB case
fibrotic changes on CXR suggesting prior TB
Organ transplant recipients
> or = 15 mg/day of prednisone or equivalent for at least 1 month
categories who are PPD+ with 10 mm induration
Recent immigrants (within 5 years, from high prevalence countries)
IVDU
residents of institutions (prisons, nursing homes, long term hospital, AIDS residences, homeless shelters)
mycobacteria lab personnel
DM, CRF, malignancies
children
categories who are PPD+ with > or = 15 mm induration
no risk factors
employees of institutions as long as otherwise low risk and negative PPD at start of employment
categories who are PPD+ with > or = 15 mm induration
no risk factors
employees of institutions as long as otherwise low risk and negative PPD at start of employment
Alternative tests to PPD
Interferon gamma release assays:
Quantiferon - TB gold
T-spot
when is interferon gamma release assay preferred
unlikely to return for PPD reading
received BCG vaccine
when is PPD preferred
children
treatment of choice for latent TB
isoniazide
300 mg daily x 6/9 months
900 mg twice weekly x 6/9 months
who receives 9 months of treatment for active tb
HIV
fibrotic lesions
children
alternative treatments for latent TB
isonazide and rifapentine (weekly) x 3 months
Rigampin or rifabutin x 4 months
what is not recommended for latent TB treatment
rifampin and pyrazinamide
when is DOT used
any regiment that is less than once daily
what is the purpose of DOT
reduce public health implications
reduce risk of resistance
what is the purpose of DOT
reduce public health implications
reduce risk of resistance
First line treatment for active TB
Rifampin/rifabutin x 6 months +
isoniazide x 6 months +
pyrazindamide x 2 months +
Ethambutol x 2 months (or until susceptibility to RIF and INH is known)
Who is ineligble for weekly INH + rifapentine for continuation
HIV positive
extrapulmonary TB
cavitary lesions on initial CXR
AFB smear positive after initial phase
Who is ineligble for weekly INH + rifapentine for continuation
HIV positive
extrapulmonary TB
cavitary lesions on initial CXR
AFB smear positive after initial phase
Rifampin MOA
inhibits bacterial RNA synthesis
dose dependent killing
bactericidal
rifampin AEs
elevated LFTs Hyperbilirubinemia Rash Flu-like symptoms (dose dependent) Thrombocytopenia, leukopenia, anemia Allergic reactions
Rifampin metabolism
substrate of: PGP and SLCO1B1
inducer of: 3A4, 1A2, 2A6, 2B6, 2C19, 2C8, 2C9, and PGP
Rifampin monitoring
LFTs and bilirubin at baseline and q2-4 weeks
CBC at baseline and q2-4 weeks
rifampin counseling
empty stomach orange-red secretions flu-like symptoms jaundice fatigue N/V
which rifamycin is choice in HIV+ patients on ARVs
rifabutin
When is rigapentine used
in continuation phase only
When is rifapentine used
in continuation phase only
Isoniazid MOA
inhibits mycolic acid synthesis -> cell wall disruption
bactericidal - rapid growing
bacteristatic - slow growing
isoniazid BBW
hepatitis within first 3 months
age related
other risk factors
Isoniazid AEs
Peripheral neuropathy (dose related) Elevated LFTs
What is given to prevent isoniazid peripheral neuropathy
pyridoxine -> HIV, DM, pregnancy, alcoholics
Isoniazid metabolism
substrate and inducer of 2E1
Drug interactions with isoniazid
carbamezapine citalopram clopidogrel phenytoin warfarin
isoniazid monitoring
LFTs at baseline + if increased risk for hepatotoxicity
isoniazid counseling
empty stomach
s/s of hepatitis (fatigue, weakness, malaise, anorexia, N/V, abdominal pain, jaundice)
Prazinamide MOA
lowers pH of environment
static/cidal depending on growth phase and concentration
Pyrazinamide dose adjust
renal impairment CrCl
Pyrazinamide dose adjust
renal impairment CrCl
Pyrazinamide AEs
hepatotoxicity (dose related)
GI distress
arthralgias
increased uric acid
Pyrazinamide drug interactions
increased hepatotoxicity with rifampin
monitoring for pyrazinamide
LFTs
serum uric acid
counseling for pyrazinamide
N/V loss of appetite jaundice joint pain blood in urine/easy bruising
counseling for pyrazinamide
N/V loss of appetite jaundice joint pain blood in urine/easy bruising
ethambutol MOA
inhibits arabinosyl transferase -> cell wall synthesis
bacteriostatic
dose adjust for ethambutol
CrCl
dose adjust for ethambutol
CrCl
Ethambutol AEs
optic neuritis (acuity / color green) GI upset dizziness malaise hepatic/renal toxicity
ethambutol drug interations
antacids decrease absorption
ethambutol monitoring
baseline and monthly visual exams
renal and hepatic function at baseline
Ethambutol counseling
take with meals - not antacids
GI distress, dizziness, drowsiness
report visual changes
when is active TB treated for 9 months
cavitary disease
initial phase excludes PZA
INH and rifapentine weekly used for continuation with positive culture at end of inital phase
HIV infected with positive culture after initial phase
when is active TB treated for 9 months
cavitary disease
initial phase excludes PZA
INH and rifapentine weekly used for continuation with positive culture at end of inital phase
HIV infected with positive culture after initial phase
Monitoring TB treatment
sputum q2weeks sputum monthly - AFB smear and culture repeat drug susceptibilities if culture positive after 3 months repeat CXR if culture negative Adherence and AE assessments SCr, LFTs, bilirubin, plts
Monitoring TB treatment
sputum q2weeks sputum monthly - AFB smear and culture repeat drug susceptibilities if culture positive after 3 months repeat CXR if culture negative Adherence and AE assessments SCr, LFTs, bilirubin, plts
define relapse
cultures become negative with treatment, but when finished treatment: cultures become positive again / s/s of active TB
when does relapse normally occur
first 6-12 months after treatment completion
Who is at risk for relapse
cavitation on initial CXR
culture positive at the end of initial phase
Who is at risk for relapse
cavitation on initial CXR
culture positive at the end of initial phase
define treatment failure
cultures positive after 4 months of treatment with ensured ingestion
how to manage treatment failure
add at least 2 second-line drugs
drug susceptibilitt
define MDR-TB
resistant to at least isoniazid and rifampin
risk factors of MDR-TB
prior TB treatment, failure, or relapse areas of high TB resistance homelessness institutionalized IVDU HIV+ sputum positive for AFB after 1-2 months of therapy positive cultures after 2-4 months of therapy known exposure to MDR-TB
areas of high TB resistance
south africa mexico southeast asia baltic countries former soviet states
define XDR-TB
resistant to at least isoniazid, rifampin, 1 FQ, and one second-line injectable: amikacin/kanamycin
streptomycin
capreomycin
second line agents for Active TB
levofloxacin moxifloxacin amikacin kanamycin streptomycin
options for drug resistant TB
capreomycin ethionamide cycloserine p-aminosalicylic acid bedaquiline
aminoglycosides cross resistance
only between amikacin/kanamycin
AE concerns with aminoglycosides
nephrotoxicity
ototoxicity
AEs of capreomycin
nephrotoxicity
ototoxicity
eosinophilia (dose related)
Ethionamide MOA
inhibits peptide synthesis
bacteriostatic
Ethionamide AEs
GI toxicity (dose limiting) goiter hypothyroid gynecomastia alopecia impotence menorrhagia photodermatitis acne hyperglycemia
Ethionamide AEs
GI toxicity (dose limiting) goiter hypothyroid gynecomastia alopecia impotence menorrhagia photodermatitis acne hyperglycemia
cycloserine moa
inhibits cell wall synthesis
cidal or static
cycloserine AEs
dose limiting CNS toxicity lethargy confusion unusual behavior seizure
p-Aminosalicylic acid MOA
competitive antagonism of PABA
static
P-aminosalicylic acid AEs
GI (diarrhea x 1-2 weeks)
goiter
hypersensitivity
hepatitis
bedaquiline fumurate brand name
sirturo
bedaquiline moa
inhibits proton transfer chain of ATP synthase required for energy genration
static at low conc. cidal at high
When is DOT required for bedaquiline
ALWAYS!!!!
bedaquiline BBW
arrhythmia - QT prolongation
increase in mortality
bedaquiline AEs
hepatotoxicity HA arthralgia N/V hyperuricemia
Bedaquiline metabolism
CYP 3A4
drugs not used for TB
macrolides
beta lactams
when are corticosteroids used for TB
reduce inflammation -
CNS/pericaridal TB
treating children with TB
same as adults without EMB
dose on mg/kg
DOT
treatings preggos with TB
Treat active only.
Isoniazid, rifampin, ethambutol x 9 months
avoid streptomycin and FQs
