Mechanisms of Antimicrobial Action and Resistance 1 Flashcards

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0
Q

PBP 1a and 1b, what is their activity and function?

A

Transpeptidase activity

Peptidoglycan synthesis and cell wall elongation

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1
Q

Molecular weight of Penicillin Binding Proteins goes ______ as the number increases (i.e. PBP 1a vs PBP 6)

A

Molecular weight is inversely proportional to the PBP #

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2
Q

PBP 2 activity and function?

A

Transpeptidase activity

Maintains rod shape

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3
Q

PBP 3 activity and function?

A

Transpeptidase activity

Peptidoglycan synthesis and septum formation

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4
Q

PBP 4, 5, and 6 activity and function

A

D-alanine carboxypeptidase activity

Control extent of cross-links

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5
Q

Are beta-lactams toxic to humans?

A

Targets of beta-lactams are uniquely bacterial so they are selectively toxic

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6
Q

What is superinfection and why does it occur?

A

Overgrowth in large intestine with clostridium difficile (pseudomembranous colitits)
Its a nonspecific side effect of beta-lactams

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7
Q

Hypersensitivity is a serious problem in response to what?

A

Beta-lactams

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8
Q

When does haptene formation occur?

A

Reaction of beta-lactams with serum proteins

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9
Q

Which group of bacteria are still highly sensitive to beta-lactams/penicillin G?

A

Group A streptococcus (beta-hemolytic)

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10
Q

What is the largest mechanism of resistance to beta-lactams/penicillin G?

A

beta-lactamases

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11
Q

Beta-lactamases of staphylococci act primarily as what?

A

Penicillinases

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12
Q

The inoculum size has a large effect on what?

A

The MIC

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13
Q

What are 3 limitations of early penicillins?

A

No oral administration
Resistant important groups of pathogens
Narrow antibacterial spectrum

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14
Q

What happens if penicillin G is taken orally? What have we done to compensate for this?

A

Hydrolyzed by acid in the stomach

Give a much larger dose

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15
Q

Which penicillin is acid-stable? How is it made?

A

Penicillin V

Made by adding phenoxyacetic acid to medium of mold producing penicillin

20
Q

Methicillin is _________ to beta-lactamase hydrolysis

A

refractory/resistant (?)

21
Q

Penicillin G can’t pass through what of which gram bacteria?

A

Outer membrane of gram negative bacteria

22
Q

What can pass through the outer membrane of gram negative bacteria due to its charged amino group? Is it acid-stable?

A

Ampicillin

Yes, ampicillin is acid stable

23
Q

Are there broad spectrum beta-lactamase refractory penicillins? What is the solution

A

No, so we add a broad spectrum penicillin with a beta-lactamase inhibitor

24
Q

Is methicillin refractory to beta-lactamases?

A

Yes, because if its large side chains… but that means that it also can’t cross the outer membrane of gram negative bacteria

25
Q

What are two active site directed inhibitors of beta-lactamases?

A

Clavulanic acid Sulbactam

26
Q

Methicillin resistant staph aureus: what is the resistance carried on? Is it intrinsic?

A

Yes, it is intrinsically carried on a transposon, meaning it is easily transmitted to other bacteria

27
Q

What is a haptene?

A

Antibiotic + serum protein that can cause formation of antibodies

28
Q

1st generation cephalosporin?

A

Cefazolin - antibacterial spectra and potency like penicillins

29
Q

2nd generation cephalosporin?

A

Cefoxitin - more potent and better against gram negatives (than cefazolin, 1st gen)

30
Q

What percent of people that are hypersensitive to penicillins are also hypersensitive to cephalosporins?

A

8%

31
Q

Are haptenes more commonly formed by penicillins or cephalosporins?

A

Penicillins (drug plus serum protein)

32
Q

Can bacteria have more than one beta-lactamase? Can they be effective against penicillins or cephalosporins?

A

Yes they can have more than one

Beta-lactamases can be effective against both penicillins and cephalosporins

33
Q

What is an advantage of carbapenems?

A

Resistant to many beta-lactamases

34
Q

Which bacteria can produce carbapenemases?

A

Enterobacteria

35
Q

What are 2 bacterial mechanism of resistance against carbapenems?

A

Active transport out of cell

Porin mutations preventing influx

36
Q

3rd generation cephalosporins?

A

Cefotaxime, Ceftazidime - even more potent (than 1st and 2nd gen) and highly effective against gram negatives but at the expense of being less effective against gram positives

37
Q

4th generation cephalosporins?

A

Cefepime - enhanced activity against gram negatives without loss of potency for gram positives

38
Q

5th generation cephalosporins?

A

Ceftaroline, Ceftobiprole - effective against MRSA and psuedomonas

39
Q

What percent of the population are hypersensitive to cephalosporins?

A

2%