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Foundations III > abx concept > Flashcards

abx concept Flashcards

1
Q

empiric vs directed therapy

A

empiric = founded on practical experience but not proven scientifically (initiation of treatment prior to determination of firm diagnosis)

directed = based on MICs from culture

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2
Q

how to choose an antibiotic empirically

A
  • guidelines
  • knowledge of what bugs cause what infections
  • knowledge of susceptibilities of bugs in different settings
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3
Q

pros and cons of using broad spectrum drugs

A

pros: improve odds of favorable outcome, reduce odds of bad outcome, lessen suffering
cons: cost, toxicity, stewardship

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4
Q

MIC

A

lowest concentration that inhibits growth after 18-24 hrs

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5
Q

methods for determining MIC

A
  • microbroth dilution
  • automated susceptibility testing
  • disk diffusion + ZOI
  • E-test
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6
Q

MIC breakpoint

A

concentration of an antibiotic that determines whether a species of bacteria is susceptible or resistant (MIC <= breakpoint is susceptible)

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7
Q

pharmacokinetics vs pharmacodynamics

A

what the body does to the drug (ADME) vs what the drug does to the body

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8
Q

PK/PD principles to consider in antibiotic selection

A
  • oral bioavailability
  • distribution to different compartments (central vs peripheral)
  • clearance
  • Vd
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9
Q

what are “protected” sites in the body?

A
  • csf
  • eye
  • prostate
  • biofilm
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10
Q

concentration dependent killing

A
  • aminoglycosides, fluoroquinolones, metronidazole
  • rate of bactericidal killing maximized at Cmax in serum
  • when [drug] < MIC, persistent growth suppression due to post-abx effect (PAE)
  • high, extended interval dosing to maximize peak [drug]
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11
Q

time dependent killing

A
  • B-lactams
  • bacterial killing based on amount of time where serum [drug] > MIC…must be > 40-50% of the time for effective killing
  • peak serum concentration irrelevant and no PAE
  • increased frequency with lower dosing to maximize time > MIC
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12
Q

concentration and time dependent killing

A
  • AUC/MIC

- vanco, dapto, tetracyclines, macrolides

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13
Q

which antibiotics require therapeutic drug monitoring and why?

A
  • vancomycin and gentamicin
  • direct relationship between [drug] and efficacy/toxicity
  • inter-patient variability in serum [drug] with standard dosing
  • low TI
  • efficacy/toxicity delayed or hard to measure
  • available assay
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14
Q

cidal vs static

A

cidal kill bugs

static inhibit growth but depend on host defense to kill organism

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15
Q

when are cidal drugs necessary?

A
  • can’t rely on host immune response (immunocompromised)

- septic shock, meningitis, endocarditis

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16
Q

pros and cons of double coverage

A

pros: synergy, anticipate resistance and presence of multiple organisms, prevent emergence of resistance
cons: more adverse effects, increased risk of colonization with resistant bugs, antagonism, cost

17
Q

adverse consequences of abx use

A
  • antibiotic associated diahrea
  • c diff colitis
  • damage to microbiome
18
Q

common mechanisms of antimicrobial resistance

A
  • reduced entry of abx into cell
  • efflux pumps (esp in gram negatives)
  • production of microbial enzymes that destroy the drug
  • modification of target
  • decoy binding sites
  • alteration of microbial proteins needed to activate prodrugs
  • alternative pathways
19
Q

how is resistance spread?

A

horizontal gene transfer via transformation, transduction, and conjugation

20
Q

most urgent threats by resistant bugs

A

CRE, C. diff, resistant neisseria gonorrhoeae

21
Q

B-lactam ADE

A

allergic reactions and anaphylaxis

22
Q

aminoglycoside ADE

A

nephrotoxicity

23
Q

vancomycin ADE

A

red man’s syndrome

24
Q

fluoroquinolone ADE

A

achilles’ tendon rupture

25
Q

linezolid ADE

A

bone marrow suppression (leukopenia, thromocytopenia)

26
Q

daptomycin ADE

A

myopathy

27
Q

TMP-SMX ADE

A

stevens-johnson syndrome

28
Q

type I hypersensitivity to drug

A
  • immediate
  • IgE mediated
  • urticaria, angioedema, anaphylaxis
29
Q

type II hypersensitivity to drug

A
  • cytotoxic; IgG mediated

- immune hemolytic anemia, thromocytopenia

30
Q

type III hypersensitivity to drug

A
  • immune complex mediated (IgG bound drug)

- serum sickness, drug fever, vasculitis

31
Q

type IV hypersensitivity to drug

A
  • delayed (days)
  • T cell mediated
  • maculopapular rash, contact dermatitis, fixed rug eruption, stevens-johnson, toxic epidermal necrolysis
32
Q

B-lactam cross-reactivity

A
  • more likely with similar side chains
  • type I reaction to penicillin => 5-10% with cephalosporin
  • azetreonam is not cross reactive (unique side chain)
  • if reaction to one B-lactam is a rash, likely to be reaction to all (unlikely that a different one will cause anaphylaxis)
33
Q

death toll and $ cost of antibiotic resistance

A
  • 2 million infections with 23,000 deaths annually in US

- $20 billion in healthcare costs + $35 billion in lost productivity

Foundations III (26 decks)

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