Lecture 11: Antimicrobial Drugs and Drug Resistance Flashcards
______: Used when immunization has not occurred and the immune system has
difficulty to eliminate infection
antimicrobial drugs
______: are useful against bacterial infection, when very few antivirals are available
antimicrobial drugs
T/F: antimicrobial drugs must display selective toxicity or they will cause damage to the host
true!
what are the two broad categories of antimicrobial drugs?
synthetic and natural
T/F: synthetic antimicrobials are better than natural
false! natural are always better at what they do
T/F: Large number of naturally occurring antibiotics with no clinical use
true! there are so many antibiotic producing organisms
antimicrobial drugs can be… Bacteriostatic or bacteriocidal, what is the difference?
Bacteriostatic- stops growth
bacteriocidal- kills
antimicrobial drugs can be… Broad spectrum or narrow spectrum, what is the difference?
Broad spectrum- covers all bases but destroys everything with thing it targets
narrow spectrum- specific and tailored to specific microbe
T/F: Cell wall active agents offer excellent selective toxicity
true! most widely used class of antibiotics… because eukaryotic cells dont have cell walls! doesn’t target us!
largest class of cell wall active antimicrobial drugs are _____
beta lactam antibiotics
_______ antibiotics:
Common feature is the b-lactam ring
* Naturally occurring: produced by Penicillium and Cephalosporium fungi
* Example: penicillins and cephalosporins
* Can be modified in the lab to produce semi-synthetic drugs that have a
modified spectrum of activity
* Susceptible to beta-lactamases
* Enzyme produced by some bugs to cut and inactivate beta-lactams
beta lactam antibiotics
who produces beta lactam antibiotics?
Penicillium and Cephalosporium fungi
T/F: shape of beta lactam ring will affect where it works/functions
true!
what are semi-synthetic antibiotics?
how are beta lactam antibiotics altered?
naturally occuring antibiotics that have been altered to resist the things that destroy them…
by adding a big blocker to beta lactam ring, can prevent beta lactamase from cutting its cut site and destroying antibiotic!
T/F: Penicillins have a narrow spectrum of
activity
true!
______: Characterized by a five membered ring
attached to the beta-lactam component
penicillins
what do penicillins target?
transpeptidation in gram positive bacteria
T/F: penicillins Cannot penetrate outer membrane of gram negative bacteria
what has been done to combat this?
true!
Semi-synthetic penicillin are modified
to provide some activity against gram
negative bugs
_____: Structurally distinct from penicillins
* Six membered ring is attached to the beta-lactam component
cephalosporins
what do cephalosporins target?
also target transpeptidation of peptidoglycan, like penicillin!
doesn’t allow peptidoglycan to be cross-linked, alters strength
T/F: Better resistance against beta lactamases than penicillin
true!
T/F: Broader spectrum of activity than penicillin
true!
which antibiotic is grouped into generations?
cephalosporins
1st gen, 2nd gen, etc.
cephalosporins are _____, they can’t kill fully formed cells because they can only target cell wall while its actively being built… meaning number of bacteria will stay the same
bacteriostatic
Growth factor analogs are structurally similar to growth factors but do not
_________
function in the cell
_______: Inhibit growth of bacteria by inhibiting folic acid synthesis and thus nucleic acid synthesis
sulfa drugs
screws over their replication! can’t make proteins or nucleotides!
why is the selectivity of sulfa drugs so good?
they target things we don’t have… so they’re great at what they do!
sulfa drugs are fully _______
synthetic
sulfa drugs are often used in combination with another analog… why?
Combination therapy minimizes the likelihood of resistance, overwhelming bug so that chance it avoids everything is almost non-existant
_______: Extremely narrow spectrum cell wall active agent
* Analog of mycolic acid component needed by Mycobacterium spp
isoniazid
________:
* Synthetic antimicrobials
inhibit DNA gyrase
Quinolones
quinolones inhibit DNA gyrase, what does DNA gyrase do? why is it such a perfect target?
Prevents supercoiling of DNA, enzyme is only used in DNA replication in bacteria… doesn’t target us at all!
quinolones are active against both…. bacteria
gram negative and gram-positive
making it broad spectrum!
ciprofloxacin is a _______ that is useful against life threatening infections
fluorinated quinolone (fluoroquinolone)
Protein synthesis inhibitors target _____ ribosomes
70S
why are there some risks with using protein synthesis inhibitors?
they target 70S ribosomes, which we have in our mitochondrial matrix.. but its pretty hard to get that far in the cell so we can still use PSI
_______: Bind to the 30S subunit of 70S ribosomes
* Block translation
* Narrow spectrum
* Useful against gram negative bugs
* Often used as a last resort drug
* Damaging to the kidneys and ears
* Examples include streptomycin,
gentamycin and neomycin
aminoglycosides
examples of aminoglycosides include… (three)
streptomycin,
gentamycin and neomycin
why are aminoglycosides used as a last resort drug?
damaging to kidneys and ears… only used if patient has no other option
what are the three types of protein synthesis inhibitors?
aminoglycosides, tetracycline, macrolides
_______: Broad spectrum
* Produced by species of the Streptomyces genus
* Bind to the 30S subunit
* Consist of both natural and modified semisynthetic
drugs
* Binds to calcium damaging teeth and bone
* Shouldn’t be used in children and pregnant
women
* Used in veterinary medicine and to promote
animal growth
* Creates problems with resistance
tetracycline
who produces tetracycline?
species of Streptomyces
why are tetracycline drugs used to promote animal growth?
competitive bacteria are removed, animals can grow more since they arent competing for nutrients
______: Broad spectrum of activity
* Bind to the 50S ribosomal subunit
* Only inhibits translation of some proteins
* Some proteins are preferential translated and others are not
* Creates a detrimental protein imbalance inside of the cell
* Useful to treat infection in patients with allergies to beta lactam
antibiotics
* Example: erythromycin and azithromycin
* Produced by Streptomyces spp.
macrolides
how do macrolides work?
they create detrimental protein imbalances by binding to 50S ribosomal subunit
puts cell in trouble!!
when are macrolides used to treat infection in place of another antibiotic? (allergies!)
Useful to treat infection in patients with allergies to beta lactam antibiotics (ex: penicillin)
what are two examples of macrolides
erythromycin and azithromycin
Daptomycin is a _____
novel antibiotic
who produces Daptomycin
streptomyces
Daptomycin is a cyclic lipopeptide, and is active against ____
gram-positives
how do Daptomycin work?
Forms pores in the plasma membrane causing
depolarization
* Cell cannot synthesize necessary biomolecules
* Cell death occurs
are daptomycin bacteriostatic or bacteriocidal
bacteriostatic, they poke holes.. don’t lyse… so they’re not outright killing bacteria
when does daptomycin resistance occur? how?
Resistance can occur when bacteria alter plasma
membrane composition… since bacteria can change their composition so much easier than us (we pretty much can’t!)
Platensimycin is a _____
novel antibiotic
______: Inhibits fatty acid biosynthesis
* Produced by Streptomyces platensis
* Broad spectrum of activity against gram positive bacteria
* Useful against important resistant gram positive pathogens
* MRSA and VRE
* Does not cause toxicity in the host
platensimycin
who produces Platensimycin
streptomyces Platensis
T/F: Platensimycin does not cause toxicity in the host
true!
useful against important resistant gram positive pathogens
______ occurs when an organism develops a mechanism
to elude the activity of an antimicrobial drug that it should otherwise
be susceptible to
Antibiotic resistance
T/F: Genes for antibiotic resistance can either be encoded on a plasmid or directly
within the genome
true!
how does antibiotic resistance occur?
through random mutation
Resistance is prevalent because of widespread and sometimes
incorrect use of antibiotics… in what three sectors?
medicine (handed out to humans too often, not taken properly)
veterinary med (given too much to animals)
agriculture (antibiotic runoff into drinking water)
what five mechanisms can bacteria use to become resistant to antibiotics?
reduce permeability (shut out antibiotic)
inactivation of antibiotic
alternation of taregt (change binding site through randome mutation)
development of resistant biochemical pathway
efflux (let in antibiotic, then kick it out)
T/F: Emergence of antibiotic resistance in gram negatives is super prevalant (more than gram positive)
true! many types of bacteria are becoming increasingly resistant but lots of them are gram negative !!
what four ways can we prevent antibiotic resistance?
Infection prevention
Rapid and conclusive diagnosis
Appropriate/prudent use of antibiotics
Prevention of transmission
how do we use patterns of antimicrobial resistance to our advantage?
we try to anticipate the next big breakout! stay on top of mutations best we can (pretty much impossible)
