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weird conditions of antibioitcs

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3 reasons why bacterium should be suscept but patient doesnt respond
-acidic pH at infection site decreases med action.

-vascular occlusion prevents med from reaching site.

-immunological factors require bacteriocidal and you gave a STATIC DUMMY
3 REASONS WHY A PATIENT SHOULDNT RESPOND BUT DID!!
1. acid pH site increases some activity

2. kidney concentrates antibiot, high enough levl kills bug

3. host defense mechanisms just work
6 events that precipitate resistance
1. natural selection
2. overuse of antibiots
3. overuse of broadspectrum
4. poor patient compliance
5. international travel, rapid spread of resistance.
6. feeding antimicrobials to livestock
2 categories of developing resistance
a. chromosomal mutation of indiv cell


b. resistance gene trasnfer between cells
2 ways to develop chromosomal mutation of individ cell
-somatic mutation (spontaneous)

-selective pressure (exposing to antibiots pressures them to mutate)
4 ways to transfer R genes
-transduction
-conjugation
-transformation
-plasmid transfer
who does conjugation occur in?
only gram negative bugs
how is resistance transferred in transduction?
via a BACTERIOPHAGE in gram positives or negatives. a bacteriophage is a virus that only infects bacteria
transformation; what is it?
transfer of bacteria-free genetic material into bacteria; causes resistance
plasmid transfer
-non-chromosomal dna
R-plasmids
transferred by any of the other three methods of transfer, also
TRANSPOSONS - jumping from one plasmid to another - this is translocation.
4 mechanisms of resistance
-altered antimicrobial target site
-inactivate antibiotic by producing an enzyme
-change cell membrane permeability
-combine mechanisms
2 ways to alter permeability
decrease uptake - porins
efflux - pump antibact out!
2 ways to modify antimicrobial's target to resist it:
-change penicillin binding proteins (PBP) - penicillin can't bind and inhibit bug.

-alter enzyme or ribosome target - new replacement is not susceptible.
principal of therapeutic drug monitoring
when amount of drug necess for treatment is considerably high, have to monitor activity so that toxic levels aren't reached.
multidrug resistance
resistance of a bacteria to multiple drugs
how multidrug resistance is caused
plasmids can have more than one resistance gene, transfers all to bacteria. MDR GNB

multiple r-genes can accumulate on the chromosome. MDR TB
MDR TB - caused by?
multi drug resistance - accumulation of r-genes on the chromosomes
mdr gnb - caused by?
multidrug resistant gnb

transfer of conjugal plasmid with multiple resistance genes
esbl
extended spectrum betalactamase
-ß-lactamases capable of hydrolysing extended spectrum cephalosporins and penicillins and aztreonam.

-associated with E. coli or Klebsiella pneumoniae

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