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Antibiotic Resistance
Describes types of resistance
34
Pharmacology
Professional
09/14/2011

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Term
Drug Modification by B-lactamase production.

Drugs affected
Definition
Causes B-lactam hydrolysis. Open the garage door.

Penicillins, cephlosporins, carbapenems, aztreonam
Term
Drug Modification of Fluoroquinolones
Definition
Acetylation
Term
Drug modification of Aminoglycosides
Definition
Hydroxylation
Term
Drug Modification by Clindamycin
Definition
Nucleotransferase
Term
Beta Lactamases can be mediated two ways..

They can be produced two ways...
Definition
Plasmid or Chromosomally.

Constitutive or Inducible
Term
The most common plasmid-mediated Beta-lactamases in Gram Negative bacteria are...

Drugs stable in the presence of these...
Definition
TEM-1, TEM-2, SHV-1

Extended-spectrum cephlosporins (2,3,4)
Beta-lactamase inhibitors
Carbapenems
Term
TEM and SHV-Beta Lactamases
Extended spectrum beta-lactamases (ESBL

How to treat ESBL
Definition
They are mutants of classical enzymes - change by 2 amino acids. And hydrolyze most extended-specturm cephlasporins and aztreonam.

Treat with Carbapenems and are inhibited by clavulanic acid.
Term
Organisms that produce ESBL
Definition
Klebsiella, E.coli, other Enterobacteriacea and non-fermenting Gram-neg bacteria (SPACE bugs)

nosacomial gram neg, pseudomonas and acintobacter
Term
ESBL is mediated by
Definition
Plasmids
Term
Laboratory Detection of ESBL
suceptability
CP
Definition
Suceptible <8mcg/ml
Intermediate 16 mcg/ml
Resistant >32 mcg/ml

you may miss the ESBL producer in the intermediate phase. but there is no marker for ESBL producing organism.
Term
Recommended ESBL detection Process
CP
Definition
If MCI >2ug/ml to ceftazidime, cefotaxime, ceftriaxone, then must do an ESBL confirmatory test.
Term
What is an ESBL confirmatory test?
CP
Definition
>3 two-fold concentration decrease in an MIC for antimicrobial tested in combo with clavulanic acid or >5mm increase in ceftaz/clavulanic zone diameter. Then it must be reported as RESISTANT to cephlasporins and PCN.
Term
AmpC B-lactamases are...
Definition
chromosomal and inducible.
Term
AmpC B-lactamses are not inhibited by
Definition
beta-lactmase inhibitors. Different form ESBL.
Term
AmpC B-lactmases are resistant to ...
Definition
1st, 2, 3 cephlaosporins
Broad-spectrum PCN assocaiated with Beta lactamases
Term
AmpC B-lactamases are produced by
CP
Definition
SPACE bugs
Seratia
Pseudomonas
Acinetobacter
Citrobacter
Enterobacter.
Term
How does the AmpC B-lactmase work?
CP
Definition
B-lactamase under the control of ampC gene (it is turned on) and the repressor gene (turn off).

The mutation is the loss of repressor gene - stably depressed.
Term
how to treat Amp-C beta-lactamase
Definition
Carbapenems, Cefepime.
Term
What are the 2 categories of Carbapenemases?

How are they encoded.
Definition
Serine B-lactamases and Metallo-B-lactamases (MBL)

Chromosomally or plasmid.
Term
Most common bug that carries transferable MBLs?
Definition
Psuedomonas
Term
What are the 2 categories of Carbapenemases?

How are they encoded.
Definition
Serine B-lactamases and Metallo-B-lactamases (MBL)

Chromosomally or plasmid.
Term
How to treat Carbapenemase?
MIC >32 mcg/ml
Definition
Polymixin B (91%)
in vitro synergy - +rifampin or + imipenem
Mix with other agents to reduce the occurance of resistance.
Tigecycline (100%)
Term
Altered Protein Target Site
MRSA works by
CP
Definition
Loss of PBP2 to PBP2a
mecA gene
Term
PBP2a is resistant to
Definition
all beta-lactams
Term
True or False:
CA-MRSA is less susceptible than HA-MRSA
CP
Definition
False.
CA-MRSA has higher virulance but has more suceptibility.
Term
Clindamycin Inducible Resitance is common in many _____ resistant strains
CP
Definition
Macrolide.
Term
Test Clindamycin inducible resitance by...
CP
Definition
D-Test
presence of erm genes and if D test posiive (erthromycin induces expression and decreases activity of clindamycin) do not use Clinda.
Term
What is altered in Vancomycin Resistant strains
Definition
D-ala-D-ala
changed to:
D-ala-D-lac (VanA, B, D)
D-ala-D-ser (Van C, E, L)
Enterococcous species (espeically E. faecium)

Van A is on a plasmid.
Term
VISA is resistance to Vanc by...
Definition
increased cell wall structure.

Not realted to VRSA - MRSA aquares VanA gene.
Term
Tetracycline has a resistance to organisms my
Definition
efflux pum.
Tet A-E: pumps drug out of cells
tetM-Tet 0 - protects ribosomes.
Term
Why does Tigecycline not get pumped out by the Tet
Definition
Because it has a D-ring side chain that gives steric hindernce.
Term
MexXY-OprM in Pseudomonas aeruginosa is a constiuative efflux pump. Which drug is susceptible to this pump?
Definition
Tigecycline - will not cover pseudomonas.
Term
When is Pseudomonas and Acinetobacter resistant to Meropenem?
CP
Combination of mechanisms.
Definition
When you have BOTH
1)Up-regulation of efflux pump genes
2) loss of porin channel protein.
Term
how do you treat ESBL producers?
Definition
Carbapenem is the drug of choice.
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