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AFNS 416 > 3 - Antimicrobial Resistance 1 > Flashcards

3 - Antimicrobial Resistance 1 Flashcards

1
Q

What is an antimicrobial

A

Any substance that kills or slows the growth of bacteria but causes little or no damage to the host
Used in treatment of bacterial diseases

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2
Q

Antimicrobial vs antibiotic

A

Microbial = semi-synthetic, synthetic or natural compound
Antibiotic = naturally produced

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3
Q

Four classes of antimicrobials

A
  1. Antibacterial
  2. Antiviral
  3. Antifungal
  4. Antiparasitic
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4
Q

Antimicrobial uses in agriculture

A
  • therapy
  • prophylaxis / metaphylaxis
  • growth promotion
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5
Q

What is prophylaxis vs metaphylaxis

A

Pro = preventative use
Meta = mass medication of an entire animal population to reduce the incidence of disease in a population that already has some evidence of disease

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6
Q

How is antimicrobial use in agriculture unique?

A

Administration at the group level
Whole populations of animals and their bacteria exposed to antimicrobials

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7
Q

Three mechanisms of action of antimicrobials

A
  1. Inhibit cell wall synthesis and cell membrane synthesis/maintenance
  2. Inhibit DNA replication (novobiocin) or DNA synthesis (sulphonamides)
  3. Inhibit protein synthesis

Slides 13-15

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8
Q

What is antimicrobial resistance

A

Bacteria resist the effects of an antimicrobial
Can be intrinsic or acquired

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9
Q

Intrinsic vs acquired AMR

A

Intrinsic: always resistant (some genetic mechanism)
Acquired: become resistant with exposure by acquiring resistance genes

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10
Q

Example of intrinsic resistance

A

Gram negative e coli will not respond to penicillin bc cell walls do not have receptors

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11
Q

“Intrinsic AMR” has recently been changed to what? Why?

A

Expected resistant phenotype
where >90% considered resistant

Determination of susceptibility phenotypic breakpoints are always exposure dependent (i.e. survival changes with dosing, modes of administration)

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12
Q

Brief history of resistance biology

A

1926 = Alexander Fleming discovers penicillin
Soon noticed some bacteria were resistant
Since then, resistance has emerged to every antimicrobial, starting with random gene mutations

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13
Q

Four mechanisms of resistance

A
  1. Reduced permeability
  2. Antimicrobial agent modification
  3. Active efflux
  4. Target modification
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14
Q

Explain the mechanism of reduced permeability

A

Intrinsically resistant bacteria would have permanent cell wall differences that do not let the drug in
If not, can change their cell wall or receptors so drug can no longer enter cell

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15
Q

Explain the mechanism of antimicrobial agent modification

A

Enzyme or protein in cell (wall, cytoplasm) that changes the form of the antimicrobial compound so it can no longer bind its receptor

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16
Q

Explain the mechanism of active efflux

A

Bacterial cell membrane/wall has efflux pump, spits antimicrobial back out before it binds its receptors
Can be upregulated upon exposure to a drug, not always compound specific

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17
Q

Explain the mechanism of target modification

A

Mutation or genetic change in receptor so antimicrobial can no longer bind it therefore cannot invoke its action

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18
Q

What is antimicrobial cross-resistance

A

A physiological adaptation that increases the resistance to a number of unique agents through a single resistance mechanism (often efflux pumps that can pump out multiple antimicrobials in a drug class, different drug classes, biocides, heavy metals, etc)

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19
Q

What is triclosan

A

Antimicrobial that was present in many toothpastes, handsoaps

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20
Q

Cross resistance is, simply, …

A

a single mechanism conveying resistance to multiple different types of compounds

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21
Q

What is AMR co-selection

A

Multiple resistance mechanisms/genes to otherwise unrelated drugs/compounds of different classes are selected together as a result of genetic linkage

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22
Q

Examples of what is and is not co-selection

A

e.g. resistance to penicillin and ampicillin (both beta-lactam class)… NO! single mechanism = cross-resistance

e.g. two mechanisms (one plasmid) = ampicillin + oxytetracycline resistance genes

23
Q

Slide 38*

A

Co-selection

24
Q

Mechanisms of getting resistance genes

A
  • acquired gene mutations
  • horizontal gene transfer (mobile genetic elements)
  • recombination between genetic elements
25
Q

Horizontal gene transfer allows…

A

movement of resistance gene between different strains, species, genre

26
Q

Slide 42

A

Horizontal gene transfer, mobile genetic transfer

27
Q

What are ICE?

A

Integrative Conjugative Elements
Self-transmissible mobile genetic element
Able to take out large elements of chromosomal DNA, excise it, transmit it, insert it into new cell

28
Q

Use of one compound (antimicrobial or biocide) for one animal = AMR to…

A
  1. That compound in that animal species and that pathogenic bacterial species
  2. That compound in other bacterial species
  3. That compound and other compounds in other bacteria in that animal, the environment, other animals/humans
29
Q

What is surveillance

A

Systematic ongoing collection and analysis of data and giving the information to those who need to know so that action can be taken

30
Q

What is monitoring

A

Surveillance without action/response component

31
Q

Objectives of AMR surveillance

A
  • analysis of trends in AMR rates
  • freq of AMR infections
  • Impact of infections on human and animal health
  • data to inform antimicrobial categorization
  • data for risk assessment/analysis
32
Q

Objectives of AMU surveillance

A
  • analysis of trends in AMU rates
  • AMU oversight/regulation/education
  • data for risk assessment/analysis
  • ideally linked to AMR data
33
Q

What is integrated surveillance

A

Integrate AMR and AMU data,
Integrate data across one health sectors

34
Q

Examples of integrated surveillance in Canada

A

CIPARS, CNISP, CARSS, AMRNet

35
Q

What is integrated AMR/AMU surveillance

A

Data from multiple sources/pops are analyzed to understand how AMU affects AMR in complex system

36
Q

Sample sources for integrated AMU/AMR surveillance

A

Human specimens, food-animals, retail food, environment (crops, water, soil)

37
Q

Objective of integrated AMR/AMU surveillance

A
  • foodborne transmission
  • nosocomial infection
  • information, education, regulation
38
Q

Slide 54

A

What a national AMR/AMU surveillance system looks like

39
Q

When does integrated AMR/AMU surveillance get complicated

A

Trying to link animal AMU to human AMR?
Link individual use to population level resistance?

40
Q

Current target bacteria in Canada (2)

A
  • Clostridioides difficile
  • Mycobacterium tuberculosis
41
Q

Who is responsible for AMU/AMR surveillance?

A

Split between federal and provincial/territorial governments

42
Q

Canadian program designed specifically for one health?

A

CIPARS: Canadian Integrated Program for Antimicrobial Resistance Surveillance

43
Q

What is CARSS? What year did it start?

A

Canadian Antimicrobial Resistance Surveillance System
In 2015, created to integrate AMU/AMR data

44
Q

Examples of AMR/AMU surveillance programs run by CARSS

A
  • Canadian tuberculosis reporting system
  • Canadian integrated program for antimicrobial resistance surveillance
45
Q

What is CNISP

A

Canadian Nosocomial Infection Surveillance Program
- National surveillance system for hospital-associated infections

46
Q

Data gaps in AMR/AMU surveillance

A
  • companion animals (AMR + AMU greater than reported)
  • animal pathogens (AMR)
  • rural, northern, indigenous communities
  • long term care (AMR + AMU)
47
Q

What is AMRNet

A

Designed to harvest antimicrobial susceptibility data from diagnostic labs on human and vet sides
Data is in labs, goal is to pull it into national repository

48
Q

Two critical areas for action in AMR/AMU surveillance

A
  • Development of a complete, integrated AMR/AMU surveillance program that expands on current success
  • Investment in AMR/AMU surveillance resouces
49
Q

What antimicrobial were chickes getting? What did this lead to

A

Ceftiofur to control e coli infections
Salmonella became resistent to ceftriaxone
Industry stopped using

50
Q

What is the “attributable or etiological fraction” of AMR

A

Cases of infections that would not have occurred without use of antimicrobial

Prior antimicrobial exposure = increased vulnerability to infection
Slide 79

51
Q

Two types of attributable fraction

A

Competitive effect and selective effect

52
Q

What is competitive effect

A

Suppression of general “colonization resistance”

Wipe out good microbes, allow bad ones to take over = sickness

53
Q

What is selective effect

A

Drug exposure favours resistant pathogen

Not all populations of a pathogen are resistant or susceptible
Killing the susceptible ones allows for the resistant ones to take over, which can be more virulent

AFNS 416 (22 decks)

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