Pharm - Antimicrobial Intro Part 2 Flashcards
explain what broad spectrum antibiotics are
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
name a major disadvantage of broad spectrum antibiotics
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!)
TRUE OR FALSE
narrow spectrum antibiotics may be discontinued once the infectious agent is identified
FALSE - this is true for broad
once you find out the agents you can switch to NARROW
narrow spectrum agents are effective against….
a single or just a few types of bacteria
narrow spectrum antibiotics are used when…..
the causative agent is KNOWN
how are narrow spectrum antibiotics able to target only a single or a few types of bacteria
because they target a SPECIFIC MOLECULE involved in bacterial metabolism (species specific)
which are more susceptible to developing resistance and why - broad spectrum or narrow spectrum
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
which has higher incidences of superinfeciton - broad or narrow spectrum
broad spectrum because they kill more commensal bacteria and the pathogenic bacteria can overgrow
why are some antibiotics “reserved”
to prevent resistance to them
reserved for specific indications or certain resistance types when nothing else is working
what is another name for “empirical” antimicrobial therapies and explain
when is this done?
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
what is “pre-emptive” antimicrobial therapy
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)
true or false
when giving empiric antimicrobial therapy, symptoms have already started showing
true
what is definitive therapy
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
TRUE OR FALSE
in definitive therapy, the drug may be the same as the empiric therapy
true - dose may just be lowered or the empiric therapy may be changed completely
explain suppressive therapy
ie: HIV and herpes
the virus stays latent and the infection never goes away. therapy to suppress and prevent reactivation
name 3 pharmacokinetic considerations
patient factors
drug conc in body fluids
monitoring the serum concentrations of the antimicrobial agnets (esp if they can cause toxicities)
name 2 categories of combination antimicrobial therapy
synergism and antagonism
give 5 potential reasons for combination antimicrobial therapy
-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
as mentioned, combination antimicrobial therapy is sometimes used to decrease the emergence of resistant strains
give example
tuberculosis, HIV
name 3 drug-drug antimicrobial interactions that are SYNERGISTISC (just in general - not specific)
-blocking sequential steps in bacterial metabolic sequence
-inhibit inactivation by bacterial enzymes
-enhance the antimicrobial agent uptake by bacteria
explain how trimethoprim-sulfamethoxazole combination is an example of synergism
they block sequential steps in the same metabolic sequence/pathway of bacteria
what is sulbactam
a beta lactamase inhibitor
results in SYNERGISM when combined with beta lactam
true or false
sulbactam does NOT kill bacteria
TRUE
does not kill the bacteria - protects the drug from enzymes that the bacteria make to try to destory the antibiotic
3 examples of synergism (general)
-blocking sequential steps in a metabolic sequence
-inhibiting enzymatic inactivation of the antibiotic
-enhancing antimicrobial agent uptake by the bacteria
give a specific example of the synergistic action of enhancing antimicrobial uptake by bacteria
penicillins (and other cell wall agents) increase the uptake of AMINOGLYCOSIDES by several bacteria like staphylococci, streptococci, enterococci, and Pseudomonas Aeruginosa
give 3 general examples of antagonism
-static agents inhibit cidal activity
-induce enzymatic inactivation
-competing for the same activation/target site
how is it that static agents can inhibit cidal activity and produce an antagonistic effect
cidals like bacteria that grow FAST - they target them the best
however, static agents slow the growth of bacteria
thus, cidal action is inhibited
explain how 1 drug can induce enzymatic inactivation of another and exhibit an antagonistic effect
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
explain what protein synthesis inhibitors cannot be used together and why
“MLS”
they all act on the same ribosome and will thus produce an antagonistic effect by competing for the same activation/target site
explain what post antibiotic effect is and the formula to calculate it
give an example of an antibiotic that exhibits this
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
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
PAE = T-C
PAE = 24 hours
name 3 general things that are contributing to resistance
evolution
clinical practices
environmental factors
how can clinical practices contribute to resistance
giving wrong doses or a combination drug when only a single is needed (much more too)
which particular bacteria is related to antibiotic use and antibiotic resistance
clostridios difficile
simply explain how antibiotic resistance happens
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
true or false
we can develop antibiotic resistance from animals
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
a mechanism of drug resistance is by enhanced export of the antibiotic by the bacteria
how do they do this?
through efflux pumps
a mechanism of resistance is by microbial enzyme release that destroys the antibiotic
give 2 examples of these enzymes
beta lactamases and acetyl transferases
true or false
bacteria altering their microbial proteins is NOT a method of drug resistance
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
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
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
which particular bacteria develops RND’s (resistance nodulation division exporters) as a mechanism of resistance?
pseudomonas
allows for efflux of the drug
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?
ATP binding cassette (APC) transporters
plasmodium falciparum multi drug resistance gene 1 (Pf mdr1)
is it possible for bacteria to devlop alternative pathways to the pathway inhibited by the antibiotic as a way of developing resistance?
yes
beta lactamases inactivate b lactam antibiotics by _______
hydrolysis
aminoglycosides can be destroyed by bacteria by……
give specific example
being altered by acetylation, phosphorylation, or adenylation
cloramphenicol can be inactivated by chloramphenicol acetyltransferases
explain the resistance mechanism of “incorporation of drug” and give an example
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
true or false
reduced affinity to the target site is a pretty rare mechanism of resistance
FALSE - used all the time
bacteria can become resistance through modifying their antibacterial target
how do macrolides and tetracyclines do this??
by protecting their ribosomes
bacteria can reduce affinity to their target site by acquiring a resistant form of the native, susceptible target
give a specific example
MRSA - caused by production of low affinity penicillin binding protein
(PBP -> PBP2a)
TARGET SLIGHTLY CHANGED
How do bacteria targeted by fluoroquinolones mutate their natural target to develop resistance
modifying topoisomerase2
can bacteria develop resistance through point mutations
YES
through point mutations in either the target or the activating enzymes
in sulfonamide resistance, resistant strains overproduce _______ as a form of altering their metabolic pathway
overproduce PABA
how can bacteria alter their metabolic pathway to develop resistance to vancomycin
produce D-Ala-D-lactate instead of D-Ala-A-Ala)
reduces affinity for vancomycin and vancomycin binding decreases
TRUE OR FALSE*
the overexpression of porin channels is NOT a method to antibiotic resistance
TRUE!
this is a way for the AB to get in.
increased porin channels would allow for better antibiotic action
true or false
overexpression of the drug target is a mechanism of antibiotic resistance
true
altering PBP to PBP2a
true or false
plasma encoded beta lactamases are not a method of antibiotic resistance
FALSE - it is
are efflux pumps good for resistance
YES
throws the drug out
