Antibiotics 1,2,3,4 Flashcards
3 classes of antimicrobial agents
- natural
- synthetic (chemotherapeutic)
- semi-synthetic
3 reason to make semi-synthetic drugs
- reduce toxicity
- change kinetics
- modify spectrum
2 effects of antimicrobials
- bacteriostatic
2. bacteriocidal
Tetracycline down sides:
had to take 4x/day, short half life
Describe B-lactam ring:
house (5 ring) and garage(4 ring): S for chimney, N for door, O for car near garage
MRSA is resistant to what?
ALL the Beta-lactams
5 targets of antimicrobials:
- cell wall
- cytoplasmic membrane
- ribosomes
- nucleic acid
- folic acid
structure of peptidoglycan has 2 main blocks M and G, they are:
N-acetyl glucosamine
N-acetyl muramic acid
Both disaccharides
how are peptidoglycan connected?
4 peptide chain pentapeptide bridge (gly)
T/F Humans can only use L-Glu?
Yep, only bacteria can use the D form
Where does vancomysin bind?
binds to precursor: D-ala D-ala
what do you treat MRSA with?
Vancomycin
Does Vancomycin work on Gram -ve?
Nope. Only gram +ve
How did enterococci become resistant to Vanco?
found a new ways to make cell wall: put a D-Lac instead of D-ala D-ala
What is VISA?
Vanco intermediate staph aureus: makes thicker peptidoglycan
VSSA?
Vanco sensitive staph aureus:
how does penicillin work?
blocks the enzymes needed to catalyze Gly - D-ala D-ala reaction
What’s beta lactamase?
bacterial enzyme that hydrolyzes and deactivates penicillin
Altered penicillin-binding proteins
form of beta lactam resistance
What’s so special about clavulanic acid?
inhibits beta-lactamase, irreversibly binds to it. then allows amoxycillin to do it’s work. Amoxyclav
Amoxyclav gets around plasmid or chromosomal? which bug?
Plasmid. can treat staph aureus
amoxyvclav won’t work on Pseudomonas. why?
has chromosomal resistance
Ticarcillin is used for?
treating pseudomonas cause it’s not affected by chromosomal resistance
How would you treat pseudomonas aeruginosum that acquired a plasmid encoded resistance gene?
Ticarcillin plus clavulanic acid = Timentin
tetracylcines and amino glycosides act on what?
bacterial protein synthesis
Aminoglycosides treat gram what?
negative
how does amino glycosides interfere with protein synthesis?
bind to 30S and messes with codons, mutating the protein, low concentration initially, then becomes leaky and then high concentration and stops protein synthesis
Resistance to aminoglycosides: 4 ways
- modify outer membrane
- ribosomal mutation
- Efflux (tetracycline)
- enzymatic mod in the periplasm
What is the story behind metronidazole?
only works on strict anaerobes, is a prodrug which is activated by bacteria’s own metabolism
difference between multi-drug resistant and extensively drug-resistant TB?
MDR-TB: resists 2 our of the 4 drugs
XDR-TB: resists 4 our of the 4 drugs
I have ecoli, can I use metronidozal? why?
Nope. cause ecoli is not a strict anaerobe.
Which drug can’t get through gram -ve cell wall?
vancomycin
What is resistant to all Beta lactams?
Pseudomonas cause of chromosomal resistance
3 ways for gene transfer in bacteria
- transformation
- phage-mediated
- plasmid-mediated
bacteria just sucks up some fragment DNA in the environment, what’s that called?
transformation
What’s the source of antibiotic resistance in horizontal gene transfer?
Your own damn commensals…
What’s the two phases in bacteriophage cycle?
lysogenic (chillin’)
lytic (bursting)
How can you tell that a bacteria got new DNA in the genome?
change in phenotype. eg. Germany group got ecoli that made shiga toxin
What’s transduction
gene transfer through a bacteriophage
Plasmid-mediated conjugation sucks: why?
one bacteria can transfer mutilresistance plasmid and knock out 5 classes of antibiotics we can use
what are sex-pili? (besides being an awesome band name.)
cytoplasmic bridges between bacteria where plasmid transfer occurs
is typhoid fever caused by one pathogen?
No, multiple
What does S, R, I, mean wrt in vitro susceptibility
susceptible
resistant
intermediate
What are some host factors to consider when choosing antibiotics?
pregnancy? allergies?
streptomycin kills salmonella typhae in vitro, so LOAD up the patient now right?
Nope. It doesn’t work in vivo
Do newer quinilones work in chest infections?
Yes. older ones couldn’t reach the lungs
Why do antimicrobial susceptibility testing?
may have acquired resistance
Dilution methods involve what?
test tubes and two-fold dilutions to see the MIC (minimum inhibitory concentration)
Why do you need a control for the MIC determination?
cause it may be bacteriostatic
why disc susceptibility test?
multiple drugs get tested and can related to MIC via disc diameter
What’s an E-test strip?
one strip, one antibiotic, many many many concentrations for reading disc edge to determine MIC
When would you treat TB with only one drug.
When dont’ have active TB or symptoms
3 effects of antibiotic combinations:
- indifference
- antagonism
- synergy
Penicillin G and streptomycin did what to endocarditis?
synergized and killed all the bacteria within 30 hours of injection!
Mechanisms of synergy:
- block sequential steps (eg. synthesis of folic acid)
- inhibit enzymatic degradation
- enhance antimicrobial uptake by baterial cell
example of inhibition of enzymatic degradation
co-amoxyclav (clav knocks out plasmid resistance, amoxycillin goes in for the kill
Example of enhance antimicrobial uptake by baterial cell
penicillin to start poking holes in the cell wall and let the aminoglycosides rush in to inhibit protein synthesis
How does tetracylcine and penicillin G antagonize each other?
the bactericidal activity is inhibited by a bacteriostatic agent
what’s an example of enzymatic degradation induction re: antibiotic antagonism?
Ampicillin induces more beta lactamase and then piperacillin get inhibited and can’t do work when normally piperacillin wouldn’t induce it as much
How else does antibiotic antagonism happen?
1. inhibition of bacteriocidal via static
2. induction of degradation
3.
4.
competition for binding sites
inhibition of target
What’s Jawetz’s Laws?
Bacteriostaticx2 = additive/indifferent
bacteriostatic + bacteriocidal = antagonistic
bactericidal x 2 = synergistic
With grid formation of antibiotic combinations in vitro, what does it mean when you draw a line between the MIC of both antibiotics? What does the line tell you?
If there are vials below the line: you have synergism
If there are vials at the line: additive
If vials above the line then it’s antagonistic
