1. ANTIMICROBIAL RESISTANCE Edith Blondel-Hill MD,FRCP Medical Microbiologist/Infectious Diseases Specialist Medical Director Interior Health Antimicrobial Stewardship Program Do Bugs Need Drugs? Program 1

2. ACKNOWLEDGEMENTS Dr. Titus Wong - UBC Dr. Miguel Imperial- LifeLabs 2

3. OBJECTIVES Discuss problem of antimicrobial resistance Discuss mechanisms of antibiotic resistance Discuss strategies to prevent or delay antimicrobial resistance 3

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5. INTRODUCTION OF ANTIBIOTIC RESISTANCE JAMA Nov 22, 1947

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8. ANTIMICROBIAL RESISTANCE Major Public Health Crisis increasing prevalence of resistant organisms multiple causes for antimicrobial resistance decline in development of antibiotics Urgent need to develop and implement programs to preserve existing antibiotics ANTIMICROBIAL STEWARDSHIP

9. ANTIMICROBIAL RESISTANCE Multiple Causes for Antimicrobial Resistance inappropriate use in humans antibiotic use in food animals/agriculture antimicrobials in consumer products/environment

10. ANTIMICROBIAL RESISTANCE Antibiotics DO NOT CAUSE resistance to develop in a single bacterium. Antibiotics SELECT for resistant organisms which arise from mutations and/or acquire genetic material from other organisms.

11. Resistant Strains Rare x x Resistant Strains Dominant Antimicrobial Exposure x x x x x x x x x x SELECTION OF ANTIMICROBIAL RESISTANCE

12. SURVIVAL OF THE FITTEST

14. SUPERBUGS MRSA VRE ESBL Carbapenemase Producing Organisms (CPO)

15. EMERGENCE OF RESISTANCE Loss or Gain of Genetic Material and/or Mutation

16. HOW ANTIMICROBIAL RESISTANCE IS GENERATED 16

17. HOW ANTIMICROBIAL RESISTANCE IS GENERATED 17

18. HOW BACTERIA ACQUIRE NEW GENETIC MATERIAL 18

19. CLARIFYING POINTS Some mechanisms of resistance are innate in bacteria Some mechanisms of resistance are acquired in bacteria Antibiotics do not cause resistance. They select for resistant bacterial populations. 19

20. IMPACT OF ANTIMICROBIAL RESISTANCE 20

21. ANTIBIOTIC RESISTANCE THREATS IN THE UNITED STATES CDC 2013 Healthcare implications 2 million people infected 23,000 deaths $20 billion – direct healthcare costs $35 billion- additional cost Prioritization of bacteria into 3 categories of threat Urgent / Serious / Concerning

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23. TARGETS FOR ANTIMICROBIAL ACTION 23 1. folate metabolism 2. nucleic acid synthesis 3. protein synthesis, 4. cell membrane 5. cell wall synthesis

24. MECHANISMS OF ANTIMICROBIAL ACTION 24 1. inhibit folate metabolism 2. inhibit nucleic acid synthesis 3. inhibit protein synthesis 4. disrupt cell membrane 5. inhibit cell wall synthesis

25. ANTIBIOTICS AND MECHANISMS OF ACTION Inhibit Folate Metabolism sulfonamides trimethoprim Inhibit Folate Metabolism sulfonamides trimethoprim Inhibit Nucleic Acid Synthesis quinolones metronidazole Inhibit Nucleic Acid Synthesis quinolones metronidazole Inhibit protein synthesis aminoglycosides tetracyclines erythromycin clindamycin linezolid Inhibit protein synthesis aminoglycosides tetracyclines erythromycin clindamycin linezolid Disrupt cell membrane polymixins colistin daptomycin Disrupt cell membrane polymixins colistin daptomycin Inhibit cell wall synthesis beta-lactams (penicillins, cephalosporins, carbapenems) vancomycin Inhibit cell wall synthesis beta-lactams (penicillins, cephalosporins, carbapenems) vancomycin

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27. CLARIFYING POINTS Each antibiotic (generally) has ONE mechanism of action Each antibiotic action can be countered by ONE or MORE mechanism of resistance Each bacteria can have ONE or MORE mechanism of resistance to antibiotics 27

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29. DIFFERENT WAYS TO STUDY RESISTANCE MECHANISMS Mechanism of action perspective Mechanism of resistance perspective 29

30. MECHANISMS OF RESISTANCE 30 A.altered target (drug cannot bind to target) B.bypass inhibited pathway (bacteria no longer needs inhibited pathway) C.antibiotic inactivation (destruction or enzyme modification) D.decreased influx (decreased drug entry into bacteria) E.increased efflux (drug enters, but is pushed out)

31. MINIMUM INHIBITORY CONCENTRATION (MIC) MINIMUM BACTERIOCIDAL CONCENTRATION (MBC)

32. TESTING FOR ANTIMICROBIAL RESISTANCE Phenotype Genotype 32

33. OVERCOMING ANTIMICROBIAL RESISTANCE Patient Treatment Perspective novel antibiotics (10 by 20 campaign) combination therapy alternatives to antibiotics Public Health Perspective Surveillance [laboratory detection, monitoring, characterization] Prevention and Control [infection control, antimicrobial stewardship] Research [basic, translation, clinical, epidemiologic] Product Development [novel agents, rapid diagnostics] 33

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38. ANTIBIOTICS 80% of antibiotics are used in the community 75% of antibiotics used respiratory infections 50% of antibiotics are inappropriate

39. Pamphlet Parent Guide Project poster Handwashing signs Stickers Activity placemat 9 PRINT RESOURCES

40. GRADE TWO KIT Bugsy puppet Overheads Dark light and gel Book

41. Bugs and Drugs