Ch.30: Principles of Antibiotic Therapy (Vickroy)

Question 1

Principle of Selective Toxicity

Answer 1

agents can have selective actions on microbes vs. the host animal because they target a process that is unique to the microorganism that the host doesn’t have

Question 2

Can agents be bacteristatic AND bactericidal?

Answer 2

Y

Question 3

antibiotic

Answer 3

a substance produce by bacteria or fungi that, at low concentrations, inhibits or kills other microorganisms

Question 4

antimicrobial

Answer 4

any substance of natural, semi-synthetic, or synthetic origin that kills or inhibits the growth of a microorganism, but CAUSES LITTLE OR NO HOST DAMAGE

Question 5

chemotherapeutic triangle

Answer 5

Points in triangle: Drug, Patient, Microbe

1) Drug elicits antimicrobial actions on microbe, microbe elicits drug resistance on drug
2) Drug elicits side effects on patient, patient elicits drug elimination (PK) on drug
3) Patient elicits host defense responses on microbe, microbe elicits infection on patient

Question 6

broad-spectrum agent

Answer 6

agent that is highly effective against an array of BOTH gram + and gram - organisms

• does NOT include all members of an abx class
• shouldn’t be universal first choice!
• higher risk of disruptimg normal flora**
• greater risk of resistance

Question 7

Narrow-spectrum agent

Answer 7

• effective against specific families of bacteria

- provide targeted approach to tx

Question 8

broader the spectrum of drug, the more/less likely side effects will be

Answer 8

more

Question 9

bacteriostatic drug

Answer 9

agent that attenuates or stops replication but does NOT kill sensitive microbes

• have slower onset of clinical action
• very reliant on host immune response (don’t use in immunocompromised patients!)

Question 10

bactericidal drug

Answer 10

agent that causes IRREPARABLE damage an DEATH of sensitive microbes

• exert faster clinical effect
• less reliant on host immune system
• bacterioSTATIC at low doses**

Question 11

classifications of cidal or static depend on 3 things:

Answer 11

1) drug conc.
2) exposure time to drug
3) target organism

Question 12

most commonly used abx that target DNA replication

Answer 12

fluoroquinolones

Question 13

how do cell-wall targeting abx work?

Answer 13

inhibit cross-linking –> cell wall weakness –> cell wall bursting under osmotic pressure

Question 14

which abx/classes of abx target ribosomes?

Answer 14

tetracyclines (tetracycline, doxy)
aminoglycosides (gentamicin, amakacin)
macrolides (erythromycin, azithromycin)
phenicols (chloramphenicol, florfenicol)

Question 15

how do ribosome-targeting abx work?

Answer 15

inhibit protein synthesis in ribosomes

Question 16

Name REVERSIBLE ribosome-targeting abx***

Answer 16

phenicols
tetracyclines
macrolides

Question 17

Name IRREVERSIBLE ribosome-targeting abx***

Answer 17

aminoglycosides

macrolides

Question 18

sulfonamides site of action

Answer 18

anti-metabolites (DNA)

Question 19

penicillins MOA

Answer 19

cell wall inhibitors

Question 20

which abx are bacteriostatic***

Answer 20

phenicols
tetracyclines
macrolides
sulfonamides

Question 21

which abx are bacteriocidal***

Answer 21

penicillins
aminoglycosides
macrolides
fluoroquinolones
cephalosporins
carbapenems

Question 22

what happens when you combine static + static agent?

Answer 22

additive action

Question 23

what happens when you combine cidal + cidal agent?***

Answer 23

synergistic action

Question 24

what happens when you combine static + cidal agent?

Answer 24

antagonistic action

Question 25

Will be exam question on which combo of antimicrobial agents best to give? (pick 2 cidal agents)***

Answer 25

:)

Question 26

2 basic patterns for bacterial killing

Answer 26

1) conc.-dependent killing (dose-dependent) 2) time-dependent killing "hybrid agents" exhibit both 1 and 2

Question 27

conc-dependent killing

Answer 27

kill rate relates to aggregate drug exposure (AUC/MIC) or peak plasma drug conc

Question 28

time-dependent killing

Answer 28

kill rate determined by net time above MIC

Question 29

MIC =

Answer 29

minimum inhibitory concentration

Question 30

AUC =

Answer 30

area under curve

Question 31

Why is kill pattern important?**

Answer 31

influences clinical dosing regimen in frequency and drug dose

Question 32

If you are treating an infection by an organism that is less sensitive to an abx and the agent exhibits dose-dependent killing, the best way to enhance clinical efficacy would be to administer:***

Answer 32

higher doses at usual or less frequent intervals

Question 33

If you want to maximize the efficacy of a time-dependent abx, you should administer:***

Answer 33

higher doses at the usual intervals, or same doses at more frequent intervals

Question 34

kill rate for conc.-dependent drugs is related to the ___ of a drug

Answer 34

intensity

Question 35

preferred dosing regimen for a conc-dependent drug

Answer 35

high and less frequent doses. Goal = maximize Cpmax relative to MIC - TIME PDC remains above MIC less important * if conc. well below target, it promotes resistance!

Question 36

kill rate for time-dependent agents is dependent on:

Answer 36

TIME that drug conc. remains at or above MIC Goal = maximize time for PDC > MIC during tx (should be at least 25% of the time) *if conc. below MIC, can promote resistance!

Question 37

preferred dosing regimen for a time-dependent drug

Answer 37

lower and more frequent doses

Question 38

why is time-dependent killing difficult with penicillins?

Answer 38

have short half-life, so have to re-dose often

Question 39

What things cause antimicrobial resistance?

Answer 39

- misuse/overuse - prior exposure - zoonotic pathogens: using abx in food animal feed? - veterinary abx use, esp. in food animals

Question 40

Reasons NOT to eliminate abx use in food-prod. animals?

Answer 40

- impacts on animal health/well-being - impacts on productivity - impact on feed use, food prices, etc. - "Danish Experience": even though "non-therapeutic" use of abx in food animals were eliminated, net abx use still increasing increasing for "production" use

Question 41

Which classes of abx are considered by WHO to be Class II: "Highly important"?

Answer 41

aminoglycosides cephalosporins phenicols *all others that you have to know are Class I: "Critically Important"

Question 42

How to avoid antimicrobial resistance

Answer 42

- appropriate drug choice - treat to clear the infection completely - know the "likely" pathogens using a body system approach

Question 43

resistance mechs. for aminoglycosides

Answer 43

inactivation extrusion reduced target affinity

Question 44

resistance mechs. for cephalosporins

Answer 44

inactivation extrusion reduced target affinity

Question 45

resistance mechs. for fluoroquinolones

Answer 45

altered target binding

Question 46

resistance mechs. for macrolides

Answer 46

membrane impermeability

Question 47

resistance mechs. for penicillins

Answer 47

inactivation exclusion reduced target affinity

Question 48

resistance mechs. for sulfonamides

Answer 48

substrate competition alternate pathways reduced target affinity

Question 49

resistance mechs. for tetracyclines

Answer 49

membrane impermeability

Question 50

Post-antibiotic effect (PAE)

Answer 50

persistent suppression of bacterial growth after drug is "gone"

Question 51

PAE in vitro

Answer 51

time for innoculum to increase 10 fold following drug removal

Question 52

PAE in vivo

Answer 52

time for colony forming units to increase 10-fold after PDC drops below MIC

Question 53

PAE is proportional to:

Answer 53

Cpmax

Question 54

PAE is longer in what type of microbes?

Answer 54

Gram +

Question 55

PAE is longer with use of which agents?

Answer 55

conc-dependent agents

Question 56

Steps for proper clinical use of antibiotics

Answer 56

1) select appropriate antimicrobial agent 2) choose suitable dosing regimen 3) provide supportive therapy (anti-inflamm/diarrhea, bronchodilators, fluids, etc. but beware of drug interactions!!)

Question 57

considerations for choosing an antimicrobial

Answer 57

``` patient status host toxicity drug interactions sampling and sensitivity testing location/identity of pathogen(s) drug lvls needed govt. regulations ```

Question 58

Acronym for choosing an abx

Answer 58

``` "SPACED": Species Pharm. considerations Adverse rxns Compatibility/Compliance Economics Duration of Therapy/Dose Regimen ```

Question 59

what is microbiological (true) resistance?

Answer 59

condition wherein high conc. of antimicrobials are required to kill (arrest growth) of a microorganism - MIC increased to a lvl that can't be safely achieved - can impact multiple classes of drug simultaneously