TB Tx Flashcards
Mycobacteria general resistance
slow growth
lipid rich mycobacterial cell wall
abundance of efflux pumps
quickly develop single-agent resistance
latent TB (LTBI)
Isoniazid (INH) for 9 months
or
Rifapentine and INH for 3 months
or rifampin for 4 months
active disease
2-month initial phase
continuation phase of 4 or 7 months
initial therapy
INH
rifampin
pyrazinamide
ethambutol (once susceptibility of above confirmed drop this drug)
risk for Tx failure
cavitary disease at presentation
positive sputum culture at 2 months
drug susceptible infection with 1 or no risk factors
continuation phase should be INH and rifampin for 4 months
both risk factors
continuation phase 7 months
TB osteomyelitis
6-9months
TB menigitis
9-12 months
add corticosteroid
TB pericarditis
add corticosteroid
pyrazinamide added to INH-rifampin
only needed for 2 months
shortens Tx to 6 months
but pyrazinamide is most nephrotoxic
resistance to INH
Tx w/rifampin, pyrazinamide, ethambutol
can add FQ
resistance to rifamycns
at least 12months of Tx with INH, ehtambutol, and FQ
pyrazinamide for 2 months
MDR and XDR
daily DOT therapy
INH, rifampin, ethambutol, pyrazinamide, aminoglycoside, FQ, PAS
LTBI + HIV
daily INH for 9 months
active TB +HIV
INH
rifamycin
ethambutol
pyrazinamide
ART +TB
rifampin largest drug interaction, inhibits ART
CD4 <50
initiate ART asap
CD4>50
wait until after initial phase of TB Tx
LTBI + TNF alpha inhibitor
high risk for developing active TB
patients should always be screened for TB
LTBI and prego
delay Tx for LTBI for 2-3 months after delivery
active TB and prego
requires Tx b/c of risk of TB to fetus
agents to avoid while Tx TB in prego
streptomycin -> deafness
kanamycin, amikacin, capreomycin
1st line against TB
INH rifampin pyrazinamide ethambutol streptomycin
INH
prodrug activated by KatG
INH MOA
complex w/KasA which inhibits synthesis of mycolic acids, a cell wall component, killing cell
INH resistance
overexpression of inhA
mutation or deletion in katG
overexpression of aphC
mutations in kasA
INH adverse rxns
- hepatitis, age dependent, rare under 20, increased risk w/alcoholics and pregnancy
- minor increases in liver aminotransferases (benign)
- peripheral neurophathy and other CNS issues due to vit B deficiency, supplementation helps
- drug fever
- rashes
- drug induced SLE
INH CI
hepatitis
serious rxns
rifampin
readily penetrates into phagocytic cells and can kill organisms that are poorly accessible to other agents
rifampin MOA
binds to beta-subunit of DNA dependent RNA polymerase inhibiting RNA synthesis
bactericidal
rifampin resistance
several points of mutation in rpoB gene
rifampin uses
mycobacterial infections menigococcal carriers prophylaxis of children exposed to H. influenza B staphylococcal carriers serious staphylococcal infections
adverse rxns to rifampin
strong P450 inducer extreme caution in HIV harmless red/orange color to urine, feces, saliva, sweat, tears, CSF, contact lenses rashes GI thrombocytopenia nephritis hepatotoxicity (not as common as INH) less then 2x/wk flu like symptoms
pyrazinamide
prodrug converted to pyrazinoic acid by pncA
pyrazinamide resistance
imparied uptake of pyrazinamide
mutations in pncA
adverse rxns to pyrazinamide
hepatotoxicity (most of all 1st line agents)
GI
hyperuricemia
drug rash (most of all 1st line agents)
ethambutol MOA
inhibits mycobacterial arabinosyl transferases encoded by embCAB, essential part of cell wall
ethambutol resistance
overexpression of emb gene
mutations w/embB gene
adverse rxns ethambutol
retrobulbar neuritis-> loss of visual acuity, red-green color blindness
CI in children where acuity and color vision cannot be assessed
streptomycin
aminoglycoside
well absorbed as IM, typically administered
streptomycin MOA
irreversibly inhibitor of protein synthesis
30S
streptomycin resistance
mutations in rpsL gene
mutations in rrs gene
TB, MAC, and M. kansasii only mycobacteria that are susceptible
streptomycin adverse effects
ototoxicity
nephrotoxicity
relative CI in prego
Second line use for TB
1st line resistance
failure w/traditional therapy
serious adverse effects of traditional therapy
second line drugs
ethionamide capreomycin cycloserine aminosalicyli acid (PAS) kanamycin and amikacin FQs linezolid rifabutin rifapentine
ehtionamide
blocks synthesis of mycolic acids oral hepatotoxicity intense GI thyroid and neuro adverse effects single agent -> rapid resistance
capreomycin
peptide protein synthesis inhibitor IM injections resistance due to rrs mutations nephro and ototoxic significant pain and abscesses at injection site
cycloserine
inhibits cell wall synthesis
peripheral neuropathy and CNS dysfnx
aminosalicylic acid
folate synthesis inhibitor
active exclusively against TB
GI adverse effects
severe hypersensativity rxns
kanamycin and amikacin
protein synthesis inhibitors
amikan less toxic
used w/MDR and streptomycin resistant TB
adverse effects- nephro and ototoxicity
FQs
block bacterial DNA synthesis via DNA gyrase and toposiomerase IV
also active against atypical myco
resistance due to point mutations in grase A
used when resistant to first line agents
GI and CNS disturbances can occur
impaired glucose control
linezolid
significant and potentially life-threatening adverse effects
bone marrow suppresion, irreversible peripheral and optic neuropathy
rifabutin
rifabutin
TB MAI M. fortuitum patients with HIV on ARV expensive
rifapentine
active against TB and MAI
M. leprae
dapsone
rifampin
clofazimine
dapsone
similar to sulfonamides, inhibits folate synthesis
hemolysis and methemoglobinemia common
P. jiroveci in AIDs Tx as well
clofazimine
half life up to 2 months
sulfone resistant leprosy
skin discoloration, GI intolerance
M. kansasii clinical
resembles TB
M. kansasii Tx
cipro clarithromycin ethambutol INH rifampin trimethoprim-sulfamethoxazole
M. marinum clinical
granulomatous cutaneous disease
M. marium Tx
Amikacin clarithromycin ethambutol doxycycline minocycline rifampin trimethoprim-sulfamethoxazole
M. scrofulaceum clinical
cervical adenitis in kids
M. scrofulaceum Tx
amikacin, erythromycin, rifampin, streptomycin
surgical excision Tx of choice
M. avium complex clinical
pulmonary disease in patients w/chronic lung disease, disseminated in AIDs
M. avium complex Tx
amikacin azithromycin clarithromycin cipro ethambutol rifabutin
M. chelonae clinical
abscess
sinus ract
ulcer
bone, joint, or tendon infection
M. chelonae Tx
amikacin, doxy, imipenem, macrolide, tobramycin
M. fortuitum clinical
abscess
sinus ract
ulcer
bone, joint, or tendon infection
M. fortuitum Tx
amikacin cefoxitin cipro doxy ofloxacin trimethoprim-sulfamethoxazole
M. ulcers clinical
skin ulcers
M. ulcers Tx
INH, streptomycin, rifampin, minocycline,
surgical excision
