Therapeutics - General Principles Pt 2 Flashcards
what is MIC (minimum inhibitory concentration)
an indicator of antibiotic potency
It’s the lowest ab concentration that prevents visible growth of the bacteria after spending 24 hours in vitro
true or false
MIC values are very specific
TRUE
very specific— 1 drug-1 bug
3 methods of antimicrobial suceptibility testing
broth microdilution
E-test
Kirby-bauer test (zone of inhibition)
who establishes the MIC breakpoints (reference values) for each organism to each antibiotic
CLSI (clinical laboratory standards institute)
organisms can be _____,_______, or ______ to the antibiotic
susceptible, intermediate, or resistant
what is the name of the cumulative antibiotic “report card” specific for each hospital
an antibiogram
an antibiogram is useful for deciding ______ antimicrobial therapy
empiric
in an antibiogram, if the antibiotic has a high value to the organism, is it good or bad?
GOOD
means that it works against the organism a high % of the time
(% susceptibility)
when staph epi comes back in the sample, what are some important considerations
-could be a contaminant
-may be actual infection tho - NEED TO SEE IF THEY HAVE RISK FACTORS (ie: IV drug user or use medical devices often)
gram negative rods, non lactose fermenting
pseudomonas
which class of antibiotics cover pseudomonas (aerobic gram negative) but do not penetrate the lungs well
aminoglycosides
is pipercillin-tazobactam a good empiric choice for pseudomonas
yes - but need to look at antibiogram to confirm
organism MIC is 2 and MIC susceptibility breakpoint, according to CLSI, is less than or equal to 1
does this mean the organism is susceptible or resistant to the antibiotic?
RESISTANT
MIC of organism is 4 and MIC susceptibility breakpoint is less than or equal to 4
is it susceptible or resistant to the antibiotic
technically susceptible, but not preferred to use because it’s just at the breakpoint
does cefepime penetrate into the lungs and can it be used for a respiatory infection
YES
true allergy, toxicity, or intolerance
diarrhea with doxycycline
intolerance
true allergy, toxicity, or intolerance
thrombocytopenia with linezolid
toxicity
true allergy, toxicity, or intolerance
SJS with bactrim
true allergy
true allergy, toxicity, or intolerance
nephrotoxicity with gentamicin
toxicity
true allergy, toxicity, or intolerance
hives and SOB with penicillin
true allergy
IGE mediated hypersensitivity reactions – what is onset time?
what is an example?
within 1 hour - SUPER QUICK
ex - anaphylaxis
around ______% of US pts report having pen allergy, but only ___% are truly allergic
10%, less than 1%
important consideration for someone that had an IGE-mediated pen allergy years ago
around 80% of pts with this allergy lose their sensitivity after 10 yrs!!!
decreases by 10% each year you avoid penicillin
cephalosporin cross reactivity with pen allergy is around ___%
which generations is it less common
3%
as you move up to 5th gen, cross reactivity rate keeps decreasing
why are false pen allergies so detrimental
suboptimal treatment, more expensive, antiobitc resistance, unnecessary broadspectrum
most ab’s are eliminated how?
renally
how is age a consideration when giving antibiotics
likely pathogen can differ based on age (ie - bacterial meningitis)
ceftriaxone avoided in neonates bc of hyperbilirubinemia
ability to eliminate certain drugs (ie over 65 = decline in renal function)
how can hepatic function be estimated
child pugh score
3 pregnancy and lactation concerns with antibiotics
teratogencity
altered pharmacokinetics
antibiotic conc in breast milk
name 3 drugs that can cause hemolytic anemia in patients with GDPDH deficiency
dapsone
nitrofurantoin
primaquine
how are pts with diabetes a special consideration when giving antibiotics
poor peripheral blood flow — more difficult to treat
chronic lung disease, cystic firosis, and immunosuppressive diseases - how are they a consideration in antibiotic treatment
different pathogens
immunosuppressed have higher risk of infection
concern with fluoroquinolones and antacids
they can chelate
how is rifampin a major concern with drug interactions
its a major CYP450 inducer
linezolid + _______ is a big DDI
SSRIs – risk of serotonin syndrome
which 2 antibiotic classes have a side effect of QT prolongation
macrolides and quinolones
give an example of how dosing of aminoglycosides can differ based on the location of the infection
uncomplicated UTI vs severe infection
aminoglycosides penetrate into the urine well – dont need a veru high dose
differentiate between the ability of cefepime vs pipercillin-tazobactam to penetrate into the CNS
cefepime is much better
pipercillin-tazobactam is too big
differentiate between the ability of colistin vs polymyxin B to get into the urine
polymyxin does not
colistin is better
can we use daptomycin in pneumonia??
why or why not
NO
it gets inactivated by the lung surfactants
first and second line for MRSA pneumonia
vancomycin
2nd line is linezolid
DO NOT USE DAPTOMYCIN!!!!!!!!!! gets inactivated by lung surfactants
pt spent 14 days in the hospital
what is 1 bacteria we definitely need to cover for and what are 2 choices
pseudomonas
use pipercillin-tazobactam or cefepime
if a very severe infection, do we use IV or PO
explain
we can start IV and then switch to PO once controlled
beta lactams use conc or time dependent killing
time dependent
differentiate between the dosing frequency of time dependent killing vs concentration dependent
time dependent - DOSED MORE FRWQUENTLY (like Q8 or Q6)
conc dependent dosed less frequently
a very high MIC means more or less resistant
more resistant
name 2 antibiotic classes that use concentration dependent killing
aminoglycosides and fluoroquinolones
how do we want the infusion of beta lactams to be and why
PROLONGED INFUSION of 304 hours over traditional 30mins- it’s time dependent!!
want to maximize duration that the pathogen is exposed to the beta lactam
time over MIC - want maximal time
prolonged infusion of beta lactams is particularly beneficial in what 2 scenarios
crtically ill patients
pathogens with high MIC
aminoglycosides are time or concentration dependent killing
therefore, how are they administered
concentration
at a HIGH DOSE once daily
ie: gentamicin is 5-7mg/kg Q24H instead of 1-2mg/kg Q8H
aminoglycosides are conc dependent killing and thus give higher doses less frequently
give specific EX with amikacin
15mg/kg Q24H instead of 7.5mg/kg Q12H
3 benefits of administering aminoglycosides Q24H instead of more frequently
easier to administer
easier drug monitoring
decreased nephrotoxicity of aminoglycosides
give 2 secnarios when we may use combination therapy to broaden the spectrum of coverage
-mixed infection
-nosocomial infection
3 ex when we may use combination antimicrobial therapy
-broaden spectrum
-synergy
-prevent resistance
give an example of combination therapy for enterococcal endocarditis
beta lactam + aminoglycoside
gives more RAPID KILLING - SYNERGY
true or false
combination antimicrobial therapy can be used to prevent resistance
true
4 disadvantages of combination antimicrobial therapy
-superinfection risk
-toxicities
-antagonist
-cost
when monitoring the therapeutic response to antibiotics, _____________ improvement may lag
radiologic
do we repeat chest x rays to check for therapeutic response improvement
NO - only if pt not improving
give 2 ab’s where we do therapeutic drug monitoring
vancomycin or aminoglycosides
4 scenarios when we can do IV-PO switch
-overall clinical improvement
-no fever for 24 hrs
-decreased WBC
-functioning GI tract
true or false
IV to PO switch does not decrease infection rates
FALSE - it does
there’s no open IV line
1st 2nd and 3rd line for HOSPITAL ACQUIRED MRSA
also, name how they come
which has interaction with statin and can increase CPK (creatinine phosphokinase)
vancomycin (IV and PO, but PO only for c diff)
linezolid (PO and IV)
daptomycin (NOT FOR LUNGS) (IV only)
dapto
what is the ONLY cephalosporin with MRSA coverage
Ceftaroline (5th gen)
name 3 main ABs mainly used for community acquired MRSA (not hospital)
bactrim
clindamycin
doxycycline
does ceftaroline have pseudomonas coverage
NO
has MRSA coverage tho
“cousin” of linezolid that has less thrombocytopenia issues and no DDI with SSRIs
tedizolid
2 “cousins” of vanco that are very long acting glycopeptides (1-2 weeks)
dalbavancin
oritavancin
true or false
tigecyciline does not have MRSA coverage
FALSE - it does
fluoroquinolone not really used but has MRSA coverage and pseudomonas coverage
delafloxacin
differentiate between intrinsic and acquired resistance and give ex
intrinsic - vanco has always and will always be ineffective against gram negative, cephalosporins will never work against enterococcus
acquired - due to inappropriate abx use (ie: decreased permeability, efflux pump, drug inactivation, altered target)
drug of choice for MRSA and 3 alternatives
vancomycin
daptomycin, linezolid, and ceftaroline
what is VRE and explain it
what are drugs of choice
vancomycin resistant enterococcus
altered target site
D-alanyl-D-alanine switched to D-alanyl-D-lactate
linezolid and daptomycin are drugs of choice
what are ESBLs and what are the drugs of choice
extended spectrum beta lactamases - they hydrolyze the beta lactam ring and inactivate most beta lactams (penicillin, cephalosporin, and monobactam)
CARBAPENEMS are drug of choice
ESBLs are produced by gram positive or negative bacteria
NEGATIVE
what are CREs
carbapenem resistant enterobacterales
produce carbapenamases that inhibit ALL BETA LACTAMS - INCLUDING CARBAPENEMS
drugs of choice for CREs
tailored to whatever is most susceptible, but there’s
polymyxin, ceftazidime/avibactam, meropenem/vaborbactam
(newer beta lactams)
primary and secondary goal of antimicrobial stewardship
primary - optimize clinical outcomes while minimizing unintendend consequences (c diff diarrhea, resistance)
secondary - decrease healthcare costs
antimicrobial stewardship was a mandate made by _______-
the joint commission
