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Antibacterial resistance
IDIT3 - Pumeranz
23
Medical
Professional
02/07/2011

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Term
What are some mechanisms of bacterial resistance?
Definition
1. Target changes
2. Decrease permeability
3. bind -up antibiotic
4. Efflux pumps
5. Bypass inhibited process
6. overproduction of target
7. Enzymatic inactivation
Term
Bacteriodes fragilis is resistant to gentamicin having acquired a plasmid carrying a gene producing aminoglycoside-hydrolyzing enzymes. T or F?
Definition
False. It's bc amino glycosides can't get into the cytoplasm of anaerobic bac bc there's no ETC
Term
What is the difference between intrinsic and acquired resistance?
Definition
Intrinsic - something that's there already... ex) aminoglycoside resistance due to lack of ETC
Aquired - from outside sources
Term
Where are the Penecillin Binding Proteins?
Definition
Inside the cell wall on the inner membrane
Term
What is the target of gentamicin?
Definition
targets the ribosomes!
Cidal! bc it causes membrane protein problems! -> leakage
Term
How does gentamicin reach its target in GNR's (Gram negative rods)?
Definition
1. Through outer membrane via porins (originally there to regulate osmolarity)... drawn into the (-) charge in the periplasmic space
2. Uses the ETC to cross the cytoplasmic space
2.
Term
50 yo female w. prolonged hospitalization due to complications from cholecystectomy. Has ventilator associated pnum due to PSUEDOMONAS AERUGINOS and is started on CEFTAZIDIME.

7 d later, recurrent fever prompts blood cultures which grow PSEUDOMONAS AERUGINOSA now resistant to CEFTAZIDIME.

DNA fingerprinting shows they're the same bug.
Intrinsic or aquired?
Definition
Aquired
Term
How does Ceftazidime reach it's target?
Definition
Target : PCN binding Protein (PBP)
Goes through porins to get to the inner membrane
Term
How can different organisms become resistant to Ceftazidime?
Definition
1. create beta-lactamase
2. efflux pump
3. ...etc
Term
How can resistance genes be passes?
Definition
1. conjugation
2. Transduction (via bacteriophage)
3. Transformation (naked free DNA)
Term
Selection pressure
Definition
proportional to how much of that antibiotic is around the area...
Term
Selection pressure
Definition
proportional to how much of that antibiotic is around the area...
Term
Vancomycin (mech)
Definition
bind to D-ala Terminus and prevent cell wall formation
Term
How does S. aureus develop resistance to penecillin?
Definition
Penicillinase (beta-lactamase)
Term
How do PCNase resistant PCN's work?
Definition
modify the PCN with aromatic ring to block where the PCNase is binding. (PCNase resistant PCN)
2.
Term
What change will make bugs resistant to all beta-lactams?
Definition
Change in the PDP2 (normal) -> PBP2A
***Carried on MecA mobile operon in plasmid
Term
How can methicillin resistance be overcome?
Definition
Use non PDP targets!
ex) Ribosomes: Macrolides, Aminoglycosides, tetracyclines, Vancomycin, Daptomycin
Term
D- test
Definition
Term
What is the mainstay Tx for MRSA?
Definition
Vancomycin
*big!! hydrophilic
Term
Why are G(-) rods resistant to Vancomycin?
Definition
Vancomycin is too big to get in through the porins on the outer membrane.
Term
How can MRSA develop vancomycin resistance?
Definition
1. Modify the D-ala terminus -> D-ala D-Lac
** carried on vanA gene
2. Making more peptidoglycan! Increases targets to soak up drugs till the assault it over. low grade resistance but much more common!
Term
What does the plasmid-mediated vanA gene carry?
Definition
Vancomycin resistance by changing D-ala D-ala -> D-ala D-lac
Term
What is a sensitive MIC?
Definition
<2 microgram/mL ...<1 is better
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