Pharm - Antimicrobial Intro Part 2

Question 1

explain what broad spectrum antibiotics are

Answer 1

they’re used to treat MANY different types of infections bc they are active against a wide range of bacterial species

they target processes/structures that are common to MANY different bacteria - that’s how they can treat wide variety of infections

Question 2

name a major disadvantage of broad spectrum antibiotics

Answer 2

commensal bacteria are much more susceptible to broad spectrum (over narrow)

not only can this cause side effects like diarrhea, but it can lead to superinfection - when all the good bacteria are killed and there’s still a few bad left -they can overgrow and infect again
(FINISH FULL COURSE!)

Question 3

TRUE OR FALSE

narrow spectrum antibiotics may be discontinued once the infectious agent is identified

Answer 3

FALSE - this is true for broad

once you find out the agents you can switch to NARROW

Question 4

narrow spectrum agents are effective against….

Answer 4

a single or just a few types of bacteria

Question 5

narrow spectrum antibiotics are used when…..

Answer 5

the causative agent is KNOWN

Question 6

how are narrow spectrum antibiotics able to target only a single or a few types of bacteria

Answer 6

because they target a SPECIFIC MOLECULE involved in bacterial metabolism (species specific)

Question 7

which are more susceptible to developing resistance and why - broad spectrum or narrow spectrum

Answer 7

narrow spectrum is less likely to develop resistance because they’re not used as often as broad spectrum

the more you use, the more chance of resistance

Question 8

which has higher incidences of superinfeciton - broad or narrow spectrum

Answer 8

broad spectrum because they kill more commensal bacteria and the pathogenic bacteria can overgrow

Question 9

why are some antibiotics “reserved”

Answer 9

to prevent resistance to them

reserved for specific indications or certain resistance types when nothing else is working

Question 10

what is another name for “empirical” antimicrobial therapies and explain

when is this done?

Answer 10

presumptive

given before the pathogen responsible for the illness OR the susceptibility to particular antimicrobial agent is known

done in cases of clinical experience - you know the signs and symptoms of certain infections, when early intervention is vital, when it’s difficult to identify the pathogen

Question 11

what is “pre-emptive” antimicrobial therapy

Answer 11

given when high chance they’re infected, but not showing any symptoms

done in the army a lot of infection is spreading - given to all soldiers even if no symptoms (yet)

Question 12

true or false

when giving empiric antimicrobial therapy, symptoms have already started showing

Answer 12

true

Question 13

what is definitive therapy

Answer 13

when the pathogenic organism responsible for the illness has been identified, and the treatment is modified accordingly

dose could be lowered, completely switched to narrow spectrum, pharmacokinetic adjustments, etc

Question 14

TRUE OR FALSE

in definitive therapy, the drug may be the same as the empiric therapy

Answer 14

true - dose may just be lowered or the empiric therapy may be changed completely

Question 15

explain suppressive therapy

Answer 15

ie: HIV and herpes

the virus stays latent and the infection never goes away. therapy to suppress and prevent reactivation

Question 16

name 3 pharmacokinetic considerations

Answer 16

patient factors

drug conc in body fluids

monitoring the serum concentrations of the antimicrobial agnets (esp if they can cause toxicities)

Question 17

name 2 categories of combination antimicrobial therapy

Answer 17

synergism and antagonism

Question 18

give 5 potential reasons for combination antimicrobial therapy

Answer 18

-broad-spectrum empiric therapy in seriously ill pts

-treat polymicrobial infections

-decrease emergence of resistant strains

-decrease dose-related toxicity bc can use lower doses of 1 or more components in regimen

-obtain enhanced inhibition/killing

Question 19

as mentioned, combination antimicrobial therapy is sometimes used to decrease the emergence of resistant strains

give example

Answer 19

tuberculosis, HIV

Question 20

name 3 drug-drug antimicrobial interactions that are SYNERGISTISC (just in general - not specific)

Answer 20

-blocking sequential steps in bacterial metabolic sequence

-inhibit inactivation by bacterial enzymes

-enhance the antimicrobial agent uptake by bacteria

Question 21

explain how trimethoprim-sulfamethoxazole combination is an example of synergism

Answer 21

they block sequential steps in the same metabolic sequence/pathway of bacteria

Question 22

what is sulbactam

Answer 22

a beta lactamase inhibitor

results in SYNERGISM when combined with beta lactam

Question 23

true or false

sulbactam does NOT kill bacteria

Answer 23

TRUE

does not kill the bacteria - protects the drug from enzymes that the bacteria make to try to destory the antibiotic

Question 24

3 examples of synergism (general)

Answer 24

-blocking sequential steps in a metabolic sequence

-inhibiting enzymatic inactivation of the antibiotic

-enhancing antimicrobial agent uptake by the bacteria

Question 25

give a specific example of the synergistic action of enhancing antimicrobial uptake by bacteria

Answer 25

penicillins (and other cell wall agents) increase the uptake of AMINOGLYCOSIDES by several bacteria like staphylococci, streptococci, enterococci, and Pseudomonas Aeruginosa

Question 26

give 3 general examples of antagonism

Answer 26

-static agents inhibit cidal activity -induce enzymatic inactivation -competing for the same activation/target site

Question 27

how is it that static agents can inhibit cidal activity and produce an antagonistic effect

Answer 27

cidals like bacteria that grow FAST - they target them the best however, static agents slow the growth of bacteria thus, cidal action is inhibited

Question 28

explain how 1 drug can induce enzymatic inactivation of another and exhibit an antagonistic effect

Answer 28

for example, if you give a beta lactam and then another drug that leads to the production of MORE BETA LACTAMASE - other drug will be broken down more

Question 29

explain what protein synthesis inhibitors cannot be used together and why

Answer 29

"MLS" they all act on the same ribosome and will thus produce an antagonistic effect by competing for the same activation/target site

Question 30

explain what post antibiotic effect is and the formula to calculate it give an example of an antibiotic that exhibits this

Answer 30

even when the drug is stopped, you still see its effects for a certain amount of time vancomycin is a common example PAE=T-C (T = time for viability count to decrease 10 fold to the count before drug removal in the test culture) C = time needed for viability count to go down 10 fold to an earlier count in the CONTROL culture

Question 31

we want 1 billion bacteria count. it takes 48 hours in the culture WITH VANCOMYCIN and 24 hours more when the drug is removed. what is PAE

Answer 31

PAE = T-C PAE = 24 hours

Question 32

name 3 general things that are contributing to resistance

Answer 32

evolution clinical practices environmental factors

Question 33

how can clinical practices contribute to resistance

Answer 33

giving wrong doses or a combination drug when only a single is needed (much more too)

Question 34

which particular bacteria is related to antibiotic use and antibiotic resistance

Answer 34

clostridios difficile

Question 35

simply explain how antibiotic resistance happens

Answer 35

there are a lot of bacteria and a few are drug resistane. antibiotics kill good and bad bacteria to fight the infection, but some bacteria with the resistance are NOT KILLED they are allowed to grow and take over, and even give their drug resistance to other bacteria, causing more problems

Question 36

true or false we can develop antibiotic resistance from animals

Answer 36

TRUE animals get antibiotics and can develop resistance in their guts, and then if we eat that food when not cooked properly -- we can get those same resistant bacteria

Question 37

a mechanism of drug resistance is by enhanced export of the antibiotic by the bacteria how do they do this?

Answer 37

through efflux pumps

Question 38

a mechanism of resistance is by microbial enzyme release that destroys the antibiotic give 2 examples of these enzymes

Answer 38

beta lactamases and acetyl transferases

Question 39

true or false bacteria altering their microbial proteins is NOT a method of drug resistance

Answer 39

FALSE - it is they can alter their TARGET PROTEINS, as well as their proteins that will transform antibiotic pro drugs into their active form 2 WAYS

Question 40

how can bacteria allow for REDUCED ENTRY of the antibiotic as a mechanism of resistance? for which particular bacteria and antibiotics is this resistance mechanism important

Answer 40

mutations, decreases, or absences in PORIN CHANNELS in their outer membrane important for gram negative bacteria and for antibiotics that have an INTRACELLULAR TARGET -- there are less or no porins for them to get in

Question 41

which particular bacteria develops RND's (resistance nodulation division exporters) as a mechanism of resistance?

Answer 41

pseudomonas allows for efflux of the drug

Question 42

aside from RND (resistance nodulation division) exporters, name another transporter that bacteria can develop to allow for efflux of the antibiotic what drug and gene encodes for it?

Answer 42

ATP binding cassette (APC) transporters plasmodium falciparum multi drug resistance gene 1 (Pf mdr1)

Question 43

is it possible for bacteria to devlop alternative pathways to the pathway inhibited by the antibiotic as a way of developing resistance?

Answer 43

yes

Question 44

beta lactamases inactivate b lactam antibiotics by _______

Answer 44

hydrolysis

Question 45

aminoglycosides can be destroyed by bacteria by...... give specific example

Answer 45

being altered by acetylation, phosphorylation, or adenylation cloramphenicol can be inactivated by chloramphenicol acetyltransferases

Question 46

explain the resistance mechanism of "incorporation of drug" and give an example

Answer 46

not only does the bacteria become resistant, but it can start to REQUIRE IT FOR GROWTH for example, enterococcus easily develops vancomycin resistance and thus, after prolonged exposure, can develop strains that REQUIRE vancomycin for growth

Question 47

true or false reduced affinity to the target site is a pretty rare mechanism of resistance

Answer 47

FALSE - used all the time

Question 48

bacteria can become resistance through modifying their antibacterial target how do macrolides and tetracyclines do this??

Answer 48

by protecting their ribosomes

Question 49

bacteria can reduce affinity to their target site by acquiring a resistant form of the native, susceptible target give a specific example

Answer 49

MRSA - caused by production of low affinity penicillin binding protein (PBP -> PBP2a) TARGET SLIGHTLY CHANGED

Question 50

How do bacteria targeted by fluoroquinolones mutate their natural target to develop resistance

Answer 50

modifying topoisomerase2

Question 51

can bacteria develop resistance through point mutations

Answer 51

YES through point mutations in either the target or the activating enzymes

Question 52

in sulfonamide resistance, resistant strains overproduce _______ as a form of altering their metabolic pathway

Answer 52

overproduce PABA

Question 53

how can bacteria alter their metabolic pathway to develop resistance to vancomycin

Answer 53

produce D-Ala-D-lactate instead of D-Ala-A-Ala) reduces affinity for vancomycin and vancomycin binding decreases

Question 54

TRUE OR FALSE* the overexpression of porin channels is NOT a method to antibiotic resistance

Answer 54

TRUE! this is a way for the AB to get in. increased porin channels would allow for better antibiotic action

Question 55

true or false overexpression of the drug target is a mechanism of antibiotic resistance

Answer 55

true altering PBP to PBP2a

Question 56

true or false plasma encoded beta lactamases are not a method of antibiotic resistance

Answer 56

FALSE - it is

Question 57

are efflux pumps good for resistance

Answer 57

YES throws the drug out