Antimicrobial Resistance (AMR) ANSC 100 PDF

Antimicrobial Resistance (AMR) ANSC 100 Simon Otto, PhD DVM BSc Associate Professor [email protected] The University of Alberta, its buildings, labs, and research stations are primarily located on the traditional territory of...

Antimicrobial Resistance (AMR) ANSC 100 Simon Otto, PhD DVM BSc Associate Professor [email protected] The University of Alberta, its buildings, labs, and research stations are primarily located on the traditional territory of Cree, Blackfoot, Métis, Nakota Sioux, Ir oquois, D ene, and Ojibway/Saulteaux/Anishinaabe nations; l a n d s t h a t a r e n o w k n o w n a s p a r t o f Tr e a t i e s 6 , 7 , a n d 8 a n d h o m e l a n d o f t h e M é t i s. T h e U n i v e r s i t y o f A l b e r t a r e s p e c t s t h e s o v e r e i g n t y, l a n d s , h i s t o r i e s , languages, knowledge systems, and cultures of and pay tribute to First Nations, Métis and Inuit nations. 1 If you are interested in Public Health: Introduction to Public Health: SPH 200 Fall / Winter Investigation of Foodborne Illness (iFBI): SPH 415/515 Fall every other year One Health SPH 416/516 Winter Applied Public Health and Epidemiologic Principles SPH 300 – New Course! Winter 2025 Health Promotion in an Unequal World SPH 303 – New Course! Winter 2025 7 Just Approved – UEC in Planetary Health! https://calenda r.ualberta.ca/p review_progra m.php?catoid= 44&poid=9356 2&returnto=13 681 8 Search SPH https://www.ualberta.ca/en/public-health/programs/search-sph.html 9 My Research One Health epidemiology of antimicrobial resistance (AMR) AMR/antimicrobial use (AMU) surveillance; diagnostic testing Antimicrobial stewardship www.heat-amr.com 10 Learning Objectives Objective 1: Explain what antimicrobials are and how they are used in animals Objective 2: Illustrate the broad mechanisms of action for antimicrobials Objective 3: Describe what antimicrobial resistance is, including intrinsic and acquired resistance Objective 4: Describe the broad mechanisms that confer AMR Objective 5: Explain the effects of AMR and the examples given in class Objective 6: Define antimicrobial stewardship 11 Common Abbreviations/Terms AMR – antimicrobial resistance AMU – antimicrobial use ERP – expected resistance phenotype (New!) ARG – antimicrobial resistance gene ARO – antimicrobial-resistant organism HGT – horizontal gene transfer ICEs – Integrative conjugative elements 12 Antimicrobials (aka Antibiotics) Antimicrobial - “Any natural, semi- synthetic or synthetic substance that kills or slows the growth of micro- organisms but causes little or no damage to the host.” 13 What do we mean when we say “antibiotic”? 1. Antibacterials 2. Antivirals Antimicrobials 3. Antifungals 4. Antiparasitics 14 Antimicrobial Use in Livestock Therapy: treatment of infection in individual animals - e.g., individual piglet, calf, cow 15 Antimicrobial Use in Livestock Therapy: treatment of groups of food animals - e.g., broilers with E. coli infection 16 Antimicrobial Use in Livestock Prophylaxis and Metaphylaxis: administered to of groups of food animals to prevent disease e.g., feedlot calves on arrival; in ovo/newborn chicks 17 Antimicrobial Use in Livestock Metaphylaxis: - Antimicrobials given to groups of animals where some individuals in that group already have a bacterial disease https://www.researchgate.net/publication/281440602_Prophylaxis_Metaphylaxis _in_Veterinary_Antimicrobial_Therapy 18 Antimicrobial Use in Livestock Growth Promotion: administered to of groups of food animals to improve performance e.g. grower phase pigs; broilers, calves 19 Antimicrobial Uses in Livestock Unique to livestock and agriculture - Treatment at the group level - Whole populations of animals and their bacteria exposed to antimicrobials 20  Mechanisms of Action Giguère et al, 2013. Antimicrobial Therapy in Vet Med, 5th Ed. 21  Mechanisms of Action Inhibit Cell Wall synthesis 22  Mechanisms of Action DNA replication (quinolones, novobiocin) DNA synthesis (sulphonamides) - folic acid 23 Mechanisms of Action Inhibit protein synthesis 24 Summary 1. The different ways that antimicrobials are used in animals and how this differs from human use 2. Mechanisms of antimicrobial action 25 Learning Objectives Objective 1: Explain what antimicrobials are and how they are used in animals Objective 2: Illustrate the broad mechanisms of action for antimicrobials Objective 3: Describe what antimicrobial resistance is, including intrinsic and acquired resistance Objective 4: Describe the broad mechanisms that confer AMR Objective 5: Explain the effects of AMR and the examples given in class Objective 6: Define antimicrobial stewardship 26 Antimicrobial Resistance (AMR) What is it? - Bacteria resist the effects of an antimicrobial - Intrinsic – always resistant (genetic) - Acquired – become resistant with exposure by acquiring resistance genes - Remember! It’s about the BUG (not the host) - Host = person or animal infected with the BUG - Bug = bacteria (or viruses, fungi, or parasites) 27 Antimicrobial Resistance (AMR) What is it? - Bacteria resist the effects of an antimicrobial - Intrinsic – always resistant (genetic) - Acquired – become resistant with exposure by acquiring resistance genes - “Expected resistant phenotype” (ERP) to replace “intrinsic” resistance - >90% are considered resistant - EUCAST (European Committee on Antimicrobial Susceptibility Testing) - Rationale: all determination of susceptibility phenotypic breakpoints are always “exposure dependent” and there was no clear definition of “intrinsic” resistance (i.e., survival may change with dosing, modes of administration) - https://www.eucast.org/expert_rules_and_expected_phenotypes/expected_phenotypes#:~:text=EUCAST%20has%20decided %20to%20replace,ampicillin%20is%20an%20example). 28 Expected Resistance Phenotype Giguère et al, 2013. Antimicrobial Therapy in Vet Med, 5th Ed. 29 Giguère et al, 2013. Antimicrobial Therapy in Vet Med, 5th Ed. 30 https://news.harvard.edu/gazett e/story/2016/09/a-cinematic- approach-to-drug-resistance/ https://www.youtu be.com/watch?v=pl Vk4NVIUh8 31 Biology of Resistance 1926 – Alexander Fleming discovers penicillin Soon noticed that some bacteria were resistant Since then, resistance has emerged to every antimicrobial Starts with random gene mutation 32  More history? Regarding Penicillin – Dec 11, 1945 Nobel Prize speech: - “There may be a danger in underdosage. It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body.” - “The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.” https://www.nobelprize.org/uploads/2018/06 /fleming-lecture.pdf Quote - Alexander Fleming in: Osterholm and Olshaker. Deadliest Enemy: Our War Against Killer Germs. 2017. Little, Brown and Company. New York. ISBN 978-0-316-34369-5. 33  Why is Resistance still an issue? Not a new problem Increasing science Natural selection – “survival of the fittest” - Inevitable with the use of antimicrobials “Bacteria change to resistance… but people are resistant to change.” (John Prescott, OVC) 34  Earth’s Geologic Clock (Adapted from Jim Hutchinson) http://en.wikipedia.org/wiki/File:Geologic_clock.jpg 35  Mechanisms of Resistance Giguère et al, 2013. Antimicrobial Therapy in Vet Med, 5th Ed. Material for your reference (4 slides) 36 Mechanisms of Resistance Fig. 3.1. Giguère et al, 2013. Antimicrobial Therapy in Vet Med, 5th Ed. 37 Mechanisms of Resistance Fig. 3.1. Giguère et al, 2013. Antimicrobial Therapy in Vet Med, 5th Ed. 38 Mechanisms of Resistance Fig. 3.1. Giguère et al, 2013. Antimicrobial Therapy in Vet Med, 5th Ed. 39 Summary 1. What AMR is and the difference between intrinsic and acquired resistance 2. Mechanisms of antimicrobial resistance 40 Learning Objectives Objective 1: Explain what antimicrobials are and how they are used in animals Objective 2: Illustrate the broad mechanisms of action for antimicrobials Objective 3: Describe what antimicrobial resistance is, including intrinsic and acquired resistance Objective 4: Describe the broad mechanisms that confer AMR Objective 5: Explain the effects of AMR and the examples given in class Objective 6: Define antimicrobial stewardship 41 42 Cumulative Impacts by 2050: https://goo.gl/bHKaHs Nov 12, 2019: https://www.cca-reports.ca/reports/the-potential-socio- economic-impacts-of-antimicrobial-resistance-in-canada/ 43  AMR Selection Bacterial acquisition of resistance is inevitable  selection by treatment - Existence of ancient genes Multiple mechanisms – resistance genes - Acquired gene mutations  NEW genes - Horizontal gene transfer  mobile genetic elements - Recombination between genetic elements 44 Horizontal Genetic Transfer Mobile Genetic Elements 45  Two Aspects for Consideration AROs ARGs Dr_Microbe: https://www.istockphoto.com/photo/biofilm-of-antibiotic-resistant-bacteria-gm615889954-106972753 Image generated using AI by www.midjourney.com (13) Bengtsson-Palme, et al., 2023, https://doi.org/10.1016/j.envint.2023.108089 46  Ecology of AMR Genes Common focus: AMU effect on pathogens More problematic: effect on resident flora - Gut, skin, soil, sewage, etc. Bacteria may act as resistance gene donors across bacterial species - Transmission between mammalian/other species Spread does not respect phylogenetic, ecologic or geographic borders - Local development  Global spread 47  49 http://www.phac-aspc.gc.ca/cipars-picra/gfx/epi-lg-eng.png AMR Quandaries AMR prevalence reductions: – Animals 10-15% – Humans 24% Lancet Planetary Health, 2017 (1): https://doi.org/10.1016/S2542-5196(17)30141-9 Lancet Planetary Health, 2018 (2): https://doi.org/10.1016/S2542-5196(18)30186-4 PLoS ONE 10(3) e0116746: https://doi.org/10.1371/journal.pone.0116746 50 AMR Quandaries https://doi.org/10.1099/mic.0.000573 51 AMR Quandaries Nature. 2018 Mar 19. doi: 10.1038/nature25979. [Epub ahead of print] https://www.nature.com/articles/nature25979 “One in four drugs with human targets inhibit the growth of bacteria in the human gut. These drugs cause antibiotic-like side-effects and may promote antibiotic resistance.” 52 https://doi.org/10.1016/j.envint.2019.105117 53 http://www.mdpi.com/2079-6382/4/4/567 54 Current AMU Policy in Canada 55 56 Antimicrobial Stewardship Shift from “prudent / judicious use” Stewardship = - Taking personal responsibility for something one does not own - Careful and responsible management of something entrusted to one’s care (Stephen Page, AVT AUS) 57 Antimicrobial Stewardship Primary goal of antimicrobial stewardship - To optimize clinical outcomes while minimizing unintended consequences of antimicrobial use - To minimise the selection and dissemination of antimicrobial resistance (Stephen Page, AVT AUS) 58  59 http://www.gazette.gc.ca/rp-pr/p1/2016/2016-07-02/html/reg2-eng.php Regulatory Changes – Food and Drugs Regulation: 1. Mandatory surveillance reporting 2. No Own Use Importation of Medically Important Antimicrobials 3. Establishment license for Active Pharmaceutical Ingredient importation 4. Alternative products approval http://www.gazette.gc.ca/rp-pr/p1/2016/2016-07-02/html/reg2-eng.php 60  Policy changes: - Removal of Growth Promotion claims - VETERINARY OVERSIGHT http://www.hc-sc.gc.ca/dhp- mps/vet/antimicrob/amr- notice-ram-avis-2017- eng.php 61 Summary 1. Broad impacts of AMR and current “challenges” 2. Antimicrobial stewardship 3. Some Canadian policy directions to improve stewardship 62 If you are interested in Public Health: Introduction to Public Health: SPH 200 Fall / Winter Investigation of Foodborne Illness (iFBI): SPH 415/515 Fall every other year One Health SPH 416/516 Winter Applied Public Health and Epidemiologic Principles SPH 300 – New Course! Winter 2025 Health Promotion in an Unequal World SPH 303 – New Course! Winter 2025 63 Thank you! Questions? 64