Antimycobacterial Agents (Linger DSA) Flashcards
what are the mechanisms by which mycobacterial cells confer resistance? and how does this effect the duration of drugs and number of different drugs used
a) the lipid-rich mycobacterial cell wall, which is not easily penetrated by drugs,
b) the tendency to hide as intracellular pathogens (primarily within macrophages),
c) an abundance of efflux pumps in the cell membrane, which pump drugs out of the mycobacterial cytoplasm back into the extracellular space, and
d) the ability to develop single-agent resistance.
e) As a result, treatment almost always includes more than one agent and is administered for months to years depending on which drugs are used.
what is the standard treatment for latent TB and how long is this treatment
what is an equivalent to this therapy
INH for 9 months daily or intermittently
INH and rifapentine given weekly for 12 weeks is an equal alternative
what should be used for INH resistant strains
rifampin alone for 4 months
what is the standard therapy of active TB
2 month initial phase and a continuation phase of either 4 or 7 months
initial therapy *until susceptibility results are in... -INH rifampin pyrazinamide ethambutol
when susceptibility results are in, what drug can be removed
ethambutol
(if the drug is susceptible to INH, rifampin, or pyrazinamide)
patients who can’t take pyrazinamide (those with severe liver disease) should take -INH, rifampin and ethambutol
for patients with drug susceptible infection and one or no risk factors (cavitary disease at presentation and a positive sputum culture taken at 2 months) should take what for continuation therapy and how long
INH
rifampin
4 months
for patients with both risk factors ((cavitary disease at presentation and a positive sputum culture taken at 2 months), the continuation phase therapy should include what
INH and rifampin for 7 months
if sputum cultures remain positive after 4 months of treatment , what should be considered
malabsorption, nonadherence to treatment, or infection with drug-resistant TB should be considered and treatment duration extended
why is it not useful to use single -agent therapy
b/c resistance mutants are readily selected out
(4) Two or more active agents should always be used to treat active TB to prevent emergence of resistance during therapy
the addition of pyrazinamide to an INH-rifampin combination for the first 2 months allows for what?
total duration of therapy to be reduced to 6 months without the loss of efficacy
what is the 4 drug therapy that is initiated first until susceptibility of clinical isolate has been determined
INH
rifampin
pyrazinamide
and either ethambutol or streptomycin
what is MD resistance TB resistant to
both INH and rifampin
what 3 first line drugs cause drug induced hepatitis and which one is the most hepatotoxic
INH, rifampin, and pyrazinamide (pyrazinamide is probably the most hepatotoxic)
(3) If hepatitis (serum AST >3x the upper limit of normal with symptoms or >5x the upper limit of normal with or without symptoms) occurs during the initial phase of treatment, isoniazid, pyrazinamide and rifampin should be stopped; when serum AST levels decrease to <2x the upper limit of normal and symptoms improve, rifampin, isoniazid, and pyrazinamide can be restarted sequentially, one week apart
ocular toxicity occurs from which first line therapy
ethambutol
what should you use to treat a patient with drug resistant TB to INH?
for patients who can’t take pyrazinamide?
(1) Treat with rifampin, pyrazinamide, and ethambutol for 6 months
(2) Rifampin and ethambutol for 12 months for patients who cannot take pyrazinamide
(3) A fluoroquinolone (levofloxacin or moxifloxacin) may be added as they are well tolerated in patients with drug-induced hepatic dysfunction
what should be used in patients with DR-TB to rifamycin
(1) At least 12 months of treatment with INH, ethambutol, and a fluoroquinolone
(2) Pyrazinamide should also be used during the initial 2 months of therapy
what is the empiric therapy for suspected MDR-TB
(5) Empiric therapy for suspected MDR-TB often includes isoniazid, rifampin, ethambutol, pyrazinamide, an aminoglycoside (streptomycin) or capreomycin, a fluoroquinolone and, if needed, cycloserine, ethionamide and/or p-aminosalicylic acid (PAS)
testing for what is recommended for all pt’s with TB
HIV
ii) Patients with HIV, once infected with M. tuberculosis, are at markedly greater increased risk of developing active TB disease
what is the problem with giving anti-TB drugs to patients who are taking antiretroviral therapy (ART) for HIV?f
rifamycins induce CYP450’s and can accelerate the metabolism of protease inhibitors (PI’s) and some NNRTI’s thus reducing their antiviral efficacy
rifampin is the MOST potent inducer
rifabutin is the LEAST
what is meant by the statement “TB is an AID’s defining illness”
in what patients (what CD4 level) should ART be started with TB treatment and when
(a) TB is an AIDS-defining illness, meaning that an HIV-positive patient who is relatively asymptomatic and not on ART progresses to an AIDS diagnosis when TB is confirmed, thus ART is recommended
(c) In patients with CD4 counts 50 cells/mm3) should probably wait until after the initial phase of TB treatment to begin ART in order to reduce the risk of adverse events and IRIS
what is the role of TNF in TB
plays a major role in the initial and long-term control of tuberculosis
so patients who have LTBI who are taking a TNF alpha inhibitor are at high risk for development of active TB disease
TNF alpha inhibitors are usually stopped in patients with active TB
for a pregnant patient with LTBI , when should you start treatment?
UNLESS WHAT
2-3 months after delivery due to risk of hepatotoxicity and lack of data on teratogenicity
UNLESS the woman is HIV positive or has been recently infected with TB (DO NOT DELAY)
what if a patient is pregnant and has active TB
treat!!!!
INH, rifampin, and ethambutol (all cross placenta but none are known to be teratogenic) for two months
followed by isoniazid and rifampin for seven months
vi) Pregnant or post-partum women receiving isoniazid for LTBI or active TB disease and their breastfeeding infants should take pyridoxine
what TB drugs should be avoided in prego mom’s
streptomycin – causes congenital deafness
(2) Kanamycin, amikacin, and capreomycin are assumed to share the toxicity of streptomycin
what is KatG
it is the mycobacterial catalase peroxidase that activates isoniazid prodrug into active drug
