3 - Antimicrobial Resistance 1 Flashcards
What is an antimicrobial
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
Antimicrobial vs antibiotic
Microbial = semi-synthetic, synthetic or natural compound
Antibiotic = naturally produced
Four classes of antimicrobials
- Antibacterial
- Antiviral
- Antifungal
- Antiparasitic
Antimicrobial uses in agriculture
- therapy
- prophylaxis / metaphylaxis
- growth promotion
What is prophylaxis vs metaphylaxis
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
How is antimicrobial use in agriculture unique?
Administration at the group level
Whole populations of animals and their bacteria exposed to antimicrobials
Three mechanisms of action of antimicrobials
- Inhibit cell wall synthesis and cell membrane synthesis/maintenance
- Inhibit DNA replication (novobiocin) or DNA synthesis (sulphonamides)
- Inhibit protein synthesis
Slides 13-15
What is antimicrobial resistance
Bacteria resist the effects of an antimicrobial
Can be intrinsic or acquired
Intrinsic vs acquired AMR
Intrinsic: always resistant (some genetic mechanism)
Acquired: become resistant with exposure by acquiring resistance genes
Example of intrinsic resistance
Gram negative e coli will not respond to penicillin bc cell walls do not have receptors
“Intrinsic AMR” has recently been changed to what? Why?
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)
Brief history of resistance biology
1926 = Alexander Fleming discovers penicillin
Soon noticed some bacteria were resistant
Since then, resistance has emerged to every antimicrobial, starting with random gene mutations
Four mechanisms of resistance
- Reduced permeability
- Antimicrobial agent modification
- Active efflux
- Target modification
Explain the mechanism of reduced permeability
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
Explain the mechanism of antimicrobial agent modification
Enzyme or protein in cell (wall, cytoplasm) that changes the form of the antimicrobial compound so it can no longer bind its receptor
Explain the mechanism of active efflux
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
Explain the mechanism of target modification
Mutation or genetic change in receptor so antimicrobial can no longer bind it therefore cannot invoke its action
What is antimicrobial cross-resistance
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)
What is triclosan
Antimicrobial that was present in many toothpastes, handsoaps
Cross resistance is, simply, …
a single mechanism conveying resistance to multiple different types of compounds
What is AMR co-selection
Multiple resistance mechanisms/genes to otherwise unrelated drugs/compounds of different classes are selected together as a result of genetic linkage
Examples of what is and is not co-selection
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
Slide 38*
Co-selection
Mechanisms of getting resistance genes
- acquired gene mutations
- horizontal gene transfer (mobile genetic elements)
- recombination between genetic elements
Horizontal gene transfer allows…
movement of resistance gene between different strains, species, genre
Slide 42
Horizontal gene transfer, mobile genetic transfer
What are ICE?
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
Use of one compound (antimicrobial or biocide) for one animal = AMR to…
- That compound in that animal species and that pathogenic bacterial species
- That compound in other bacterial species
- That compound and other compounds in other bacteria in that animal, the environment, other animals/humans
What is surveillance
Systematic ongoing collection and analysis of data and giving the information to those who need to know so that action can be taken
What is monitoring
Surveillance without action/response component
Objectives of AMR surveillance
- 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
Objectives of AMU surveillance
- analysis of trends in AMU rates
- AMU oversight/regulation/education
- data for risk assessment/analysis
- ideally linked to AMR data
What is integrated surveillance
Integrate AMR and AMU data,
Integrate data across one health sectors
Examples of integrated surveillance in Canada
CIPARS, CNISP, CARSS, AMRNet
What is integrated AMR/AMU surveillance
Data from multiple sources/pops are analyzed to understand how AMU affects AMR in complex system
Sample sources for integrated AMU/AMR surveillance
Human specimens, food-animals, retail food, environment (crops, water, soil)
Objective of integrated AMR/AMU surveillance
- foodborne transmission
- nosocomial infection
- information, education, regulation
Slide 54
What a national AMR/AMU surveillance system looks like
When does integrated AMR/AMU surveillance get complicated
Trying to link animal AMU to human AMR?
Link individual use to population level resistance?
Current target bacteria in Canada (2)
- Clostridioides difficile
- Mycobacterium tuberculosis
Who is responsible for AMU/AMR surveillance?
Split between federal and provincial/territorial governments
Canadian program designed specifically for one health?
CIPARS: Canadian Integrated Program for Antimicrobial Resistance Surveillance
What is CARSS? What year did it start?
Canadian Antimicrobial Resistance Surveillance System
In 2015, created to integrate AMU/AMR data
Examples of AMR/AMU surveillance programs run by CARSS
- Canadian tuberculosis reporting system
- Canadian integrated program for antimicrobial resistance surveillance
What is CNISP
Canadian Nosocomial Infection Surveillance Program
- National surveillance system for hospital-associated infections
Data gaps in AMR/AMU surveillance
- companion animals (AMR + AMU greater than reported)
- animal pathogens (AMR)
- rural, northern, indigenous communities
- long term care (AMR + AMU)
What is AMRNet
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
Two critical areas for action in AMR/AMU surveillance
- Development of a complete, integrated AMR/AMU surveillance program that expands on current success
- Investment in AMR/AMU surveillance resouces
What antimicrobial were chickes getting? What did this lead to
Ceftiofur to control e coli infections
Salmonella became resistent to ceftriaxone
Industry stopped using
What is the “attributable or etiological fraction” of AMR
Cases of infections that would not have occurred without use of antimicrobial
Prior antimicrobial exposure = increased vulnerability to infection
Slide 79
Two types of attributable fraction
Competitive effect and selective effect
What is competitive effect
Suppression of general “colonization resistance”
Wipe out good microbes, allow bad ones to take over = sickness
What is selective effect
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
