abx concept

Question 1

empiric vs directed therapy

Answer 1

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

directed = based on MICs from culture

Question 2

how to choose an antibiotic empirically

Answer 2

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

Question 3

pros and cons of using broad spectrum drugs

Answer 3

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

Question 4

MIC

Answer 4

lowest concentration that inhibits growth after 18-24 hrs

Question 5

methods for determining MIC

Answer 5

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

Question 6

MIC breakpoint

Answer 6

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

Question 7

pharmacokinetics vs pharmacodynamics

Answer 7

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

Question 8

PK/PD principles to consider in antibiotic selection

Answer 8

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

Question 9

what are “protected” sites in the body?

Answer 9

• csf
• eye
• prostate
• biofilm

Question 10

concentration dependent killing

Answer 10

• 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]

Question 11

time dependent killing

Answer 11

• 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

Question 12

concentration and time dependent killing

Answer 12

• AUC/MIC

- vanco, dapto, tetracyclines, macrolides

Question 13

which antibiotics require therapeutic drug monitoring and why?

Answer 13

• 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

Question 14

cidal vs static

Answer 14

cidal kill bugs

static inhibit growth but depend on host defense to kill organism

Question 15

when are cidal drugs necessary?

Answer 15

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

- septic shock, meningitis, endocarditis

Question 16

pros and cons of double coverage

Answer 16

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

Question 17

adverse consequences of abx use

Answer 17

• antibiotic associated diahrea
• c diff colitis
• damage to microbiome

Question 18

common mechanisms of antimicrobial resistance

Answer 18

• 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

Question 19

how is resistance spread?

Answer 19

horizontal gene transfer via transformation, transduction, and conjugation

Question 20

most urgent threats by resistant bugs

Answer 20

CRE, C. diff, resistant neisseria gonorrhoeae

Question 21

B-lactam ADE

Answer 21

allergic reactions and anaphylaxis

Question 22

aminoglycoside ADE

Answer 22

nephrotoxicity

Question 23

vancomycin ADE

Answer 23

red man’s syndrome

Question 24

fluoroquinolone ADE

Answer 24

achilles’ tendon rupture

Question 25

linezolid ADE

Answer 25

bone marrow suppression (leukopenia, thromocytopenia)

Question 26

daptomycin ADE

Answer 26

myopathy

Question 27

TMP-SMX ADE

Answer 27

stevens-johnson syndrome

Question 28

type I hypersensitivity to drug

Answer 28

- immediate - IgE mediated - urticaria, angioedema, anaphylaxis

Question 29

type II hypersensitivity to drug

Answer 29

- cytotoxic; IgG mediated | - immune hemolytic anemia, thromocytopenia

Question 30

type III hypersensitivity to drug

Answer 30

- immune complex mediated (IgG bound drug) | - serum sickness, drug fever, vasculitis

Question 31

type IV hypersensitivity to drug

Answer 31

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

Question 32

B-lactam cross-reactivity

Answer 32

- 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)

Question 33

death toll and $ cost of antibiotic resistance

Answer 33

- 2 million infections with 23,000 deaths annually in US | - $20 billion in healthcare costs + $35 billion in lost productivity