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TB and Mycobacterium Treatment
Terms in this set (57)
Why use multi-drug therapy with active TB?
-enhances rates of response/cure
-reduces emergence of resistance
What are methods of increasing adherence/Rx completion?
-shortest possible course of therapy
Why do you need an adequate duration of TB therapy?
-increase cure rate
How is Isoniazid HCL used clinically?
-first line drug for active pulmonary TB
-used in combo with at least 2 other active drugs, except for when treating LTBI
What is the MOA of INH?
-pro drug that is activated by catalase peroxidase
-targets inhA gene products (cell wall my colic acid)
Is INH cidal or static?
-cidal for replicating organisms
-static for resting organisms
what is the gene which encodes catalase peroxidase?
TB katG gene
How dose INH resistance develop?
-mutations in the katG gene
-mtuations in the inha gene
how is INH acetylation rate controlled?
genetics (slow, rapid, nl)
does INH reach the CNS?
What is INH toxicity?
How can you reduce neurotoxicity in INH therapy?
-give them Vitamin B6 (pyridoxine)
What are some notable INH drug interactions?
-Dilantin (reduced clearance)
-intraconazole and levadopa (dec. levels)
What are the clinical uses of Rifampin?
-first line for TB (in combo , xc for LTBI)
-Gram + like S. aureus in combo
-N. meningitidis (alone)
Why can't you use Rifampin alone?
-rapid development of resistance
what is the MOA of Rifampin?
-inhibits DNA dependent RNA polymerase
-endocded by rpoB gene
How does resistance to Rifampin develop?
-mutations in the rpoB gene
is Rifampin bactericidal or static?
cidal all the way
Does Rifampin get to the CNS?
what are some adverse effects of Rifampin?
-Red discoloration of body fluids
-ARF, interstitial nephritis
What are drug interactions in Rifampin?
-too many to count (over 100!)
-coumadin, estrogen, anticonvulsants, antiretrovral drugs, etc.
What is the clinical use of Ethambutol?
-first line TB therapy
-helper drug to inhibit resistance to other drugs
What is the MOA of Ethambutol?
-inhibits TB arabinosyl transferase encoded by the embB gene
-effects wall synthesis
is Ethambutol tidal or static?
Does Ethambutol reach the CNS
What are adverse effects of Ethambutol?
What is the clinical use of Pyrazinamide?
-first line TB drug for the FIRST TWO MONTHS OF THERAPY
-always used in combo
what is the MOA of Pyrazinamide?
-prodrug activated by TB pyrazinamidase encoded by pncA gene
How dose PZA resistance occur?
-mutations of the pncA gene
is PZA cidal or static?
Does PZA reach the CNS?
What are adverse effects of PZA?
inc. serum uric acid (but no gout)
What are clinical uses of Streptomycin?
-second line TB drug
What is the MOA of Streptomycin?
-inhibits protein synthesis by binding to ribosome
how dose resistance to Streptomycin occur?
-mutation of ribosomal binding site
-not cross resistant to amikacin, kanamycin, capreomycin
Does Streptomycin enter the CNS?
only in the presence of inflamed meninges
What are adverse effects of Streptomycin?
What is Primary Resistance?
infection by a source case with drug resistant TB
What is secondary resistance?
From ineffective therapy (poor treatment design or adherence)
-too few drugs to prevent emergence of resistance
-suboptinal drug dosing or absorption
How do you calculate the risk of evolution of resistance to two drugs?
the product of the risk of the development of resistance to each drug
resistance to both INH and Rifampin
-more common with HIV infected patients
What will it mean for therapy if Rifampin resistance develops?
you will not be able to use short course (6month) TB therapy and will need therapy for 18-24 months
-Resistance to INH and rifampin
-Resistance to fluorquinolone antibiotic
-resistance to one of three injectable antibiotics (amikacin, kanamycin, capreomycin)
How effective is 6 month TB treatment?
95% cure rate
What is the 4 drug regimen for 6 month TB therapy?
-rifampin, INH, PZA, and Ethambutol
When can you use intermittent therapy plans?
only with DOT
When can 6 month therapy be used?
-Adherence is high
-Sputum cultures convert by 2 months
-no major cavitary lung disease
-no rifampin resistance
How do you treat a latent TB infection?
-INH mono therapy for 9 mo
-Rifampin for 4 mo
-INH + Rifampin for 3 mo (DOT)
Which drugs can be used to treat Mycobacterium avium-intracellular (MAI, MAC)?
-calirthromycin or azithromycin
Which drugs can be used to treat Mycobacterium kansasii?
-rifampin, ethambutol, INH
Which drugs can be used to treat rapidly growing mycobacteria like Mycobacterium abbessus?
-completely different than TB therapy
-clarithromycin or azithromycin and a fluoroquinolone
Which drugs are only active against TB?
which drugs are active against TB and NTM?
Which drugs are only active against NTM?
How does the treatment of leprosy compare to the treatment of TB?
it's very different
How do you treat Paucibacillary leprosy?
Rifampin and dapson daily for 12 mo
How do you treat multibacillary leprosy?
rifampin and dapson and clofazimine daily for 24 months
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