Week 1: Antibiotic Resistance Flashcards

1
Q

Objectives

A
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2
Q

Mechanisms of bacterial antibiotic resistance

A
  • Point mutations (micro-evolutionary)
  • Macro-evolutionary change
  • Acquisition of foreign DNA
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3
Q

Describe point mutations as it pertains to bacterial antibiotic resistance

A
  • micro-evolutionary
  • may occur in a nucleotide base pair
  • ESBL (Extended spectrum beta lactamases) are examples of point mutation that occured on classical enzymes
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4
Q

Describe macro-evolutionary change as it pertains to bacterial antibiotic resistance

A
  • Whole-scale rearrangements of large segments of DNA as a single-event
  • May include: inversions, duplications, insertions, deletions or transposition of large sequences of DNA from one location of a bacterial chromosome or plasmid to another
  • Created by genetic elements known as ‘Transposons’
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5
Q

Describe Acquisition of foreign DNA as it pertains to bacterial antibiotic resistance

A

Carried by plasmids, bacteriophages or transposable genetic elements

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6
Q

What % of bacterial resistance arises from de novo mutations

A

small % of resistance evolution

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7
Q

What % of bacterial resistance arises from acquisition?

A

Is most common form of developing antibiotic resistance

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8
Q

How is genetic material transfered?

A

Transfer of genetic material coding for resistance is plasmid (P) or transposon (T) mediated

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9
Q

What are plasmids?

A

Plasmids are extrachromosomal pieces of DNA that replicate within bacterial cell but limited in transfer between classes

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10
Q

What are transposons?

A

Transposons are extrachromosomal pieces of DNA that are not limited but generally must be attached to chromosome, bacteriophage or plasmid for replication

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11
Q

Mechanisms of horizontal gene transfer

A
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12
Q

What is intrinsic resistance?

A
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13
Q

How does intrinsic resistance occur?

4 listed

A

Can be due to

  • Lack of affinity of the drug for the bacterial target
  • Inaccessibility of the drug into the bacterial cell
  • Extrusion of the drug by chromosomally encoded active exporters
  • Innate production of enzymes that inactivate the drug
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14
Q

Examples of intrinsic resistance

3 listec

A
  • Vancomycin against gram-negative organisms
  • Cephalosporins against Enterococci
  • Metronidaole against aerobic bacteria
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15
Q

Bacterial employed mechanisms of resistance

A
  • enzymatic degradation of the antibiotic agents
  • Alterations of the targets of antibiotic agents
  • Changes in cell wall permeability and/or production of efflux pumps
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16
Q

Examples of Resistance: Alteration to Penicillin Binding proteins

A
  • β-lactams (Enterococci, Streptococci, Staphylococci)
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17
Q

Examples of Resistance: Modified cell wall precursors (ie D-ala-D-ala to D-ala-D-lac)

A

Vancomycin (Enterococci, Staphylococci)

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18
Q

Examples of Resistance: Alteration to of ribosomal targets

A
  • Aminoglycosides
  • macrolides
  • Lincosamides
  • Linzolid
  • Tetracyclines
  • Tigecycline
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19
Q

Examples of Resistance: Alteration in target enzymes

A
  • Quinolones
  • TMP/SMX
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20
Q

Examples of Resistance: Efflux TetA gene

A
  • Tetracycline resistance in S. aureus
  • Streptococci
  • Enterobacteriaceae
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21
Q

Examples of Resistance: Cleave

A

β-lactamase destroy the β-lactam ring of PCNs, cephalosporins, Carbapenems (S. aureus, Pseudomonas, Enterobacteriaceae)

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22
Q

Examples of Resistance: Porin channel alteration

A
  • Carbapenem and quinolones in Pseudomonas
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23
Q

Describe the mechanism of Enterococcal resistance to Vancomycin

A
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24
Q

Describe VanA from VRE to S. aureus

A
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25
Q

Structure of GP vs GN bacteria

A
26
Q

Structure of GN bacteria

A
27
Q

Structure of GN bacteria

A
28
Q

Mechanisms of enzymatic degradation of β-lactams

A

β-lactams

  • β-lactamases
  • Classical enzymes
  • Extened spectrum β-lactamase
  • AmpC
  • Carbapenemases
  • Metallo-enzymes

Aminoglycosides

  • Acetylase
29
Q

ESBL AKA

A

Extended spectrum β-lactamase

30
Q

Extended spectrum β-lactamase

A
31
Q

Carbapenem-resistant Enterobacteriaceae

A
32
Q

Alterations of ribosomal targets

A
33
Q

Alterations of ribosomal targets D-tests

A
34
Q

Clindamycin D-test

A
35
Q

Alterations of ribosomal targets specifically for aminoglycosides

A

Mutation in 30S ribosomal subunit (ie streptomycin)

36
Q

Alterations of ribosomal targets specifically for Linezolid

A
  • G2576T mutation in domain V of 23S rRNA gene
  • Can possibly revert back after removal of antimicroial pressure
37
Q

Alterations of ribosomal targets specifically for DNA Gyrase

A
38
Q

Alterations of ribosomal targets specifically for Dihydropteroate synthetase

A
39
Q

Mechanisms of Quinolone Resistance

A
40
Q

Mechanisms of Aminoglycosides Resistance

A
41
Q

What is the MIC?

A
42
Q

Question

A
43
Q

How are breakpoints set?

A
44
Q

Susceptibility report

A
45
Q

Blood concentration of drugs and Staph aureus and Pseudomonas aeruginosa

A
46
Q

Antibiotic development vs Antimicrobial resistance

A
47
Q

Antibiotic drug-discovery

A
48
Q

12 steps to prevent antimicrobial resistance in hospitalized adults

A
49
Q

How to balance the antimicrobial impact

A
50
Q

Practice Antimicrobial control

A
51
Q

Antibiotic selection pressure of macrolides

A
52
Q

Inappropriate antibitoic prescribing

A
53
Q

How much antimicrobial use is either unnecessary or inappropriate

A
54
Q

PRevent transmission, isolate the pathogen

A
55
Q

U.S. restricts more antibiotics for livestock

A
56
Q

What percentage of antibiotics are given to animals vs humans?

A
57
Q

Vet antibiotics

A
58
Q

GN isolates

A
59
Q

GP isolates

A
60
Q
A