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Transcript
Antimicrobial Resistance (no superbugs but dumb people) @healthfromenvir Martin Cormican, Centre for Health from Environment Ryan Institute, National University of Ireland, Galway Antimicrobial Resistance and Microbial Ecology Group School of Medicine, NUI Galway What Is the Cause of the Problem ? In A Tweet Microbial world is a gene cloud • Genes drift • Bacteria transform • Some transform to resistance • Our choices make resistance a winner • What Are the Solutions ? Tweet 2 • Surveillance • Targets • Incentives • Penalties • Education & Training & Guidelines are only of value in preparing stakeholders to accept controls The Talk in In Pictures: Antimicrobial Resistance 4 One Health • OIE endorses the “One Health” approach as a collaborative and all-encompassing way to address, when relevant, animal and public health globally People • Animals PrGWS K – N. Galway Groundwater/Stream PrGWS C – E. Galway Spring Well ~ 115 Houses ~ 277 Houses PrGWS M – N.E. Galway Spring Well ~ 354 Houses Rural Water Supplies Antimicrobial Resistance: We Are Not Always Blaming Vets Charles Darwin Antimicrobial-Resistance & Theory of Evolution 8 Finches Darwins work based on form of the animal (phenotype) in the days before DNA analysis (genotype) 9 What is a Species ? The Orderly World of Zoology •Male & Female Can Mate and Produce Fertile Offspring •DNA (genotype) is transmitted vertically from parent to offspring •DNA sequences don’t generally wander about between species •Gradual step-wise changes in genotype & associated change in phenotype (evolutionay time scale is centuries /millenia) 10 What is a Species ? The Chaotic World of Bacteria • Bacteria that group together as relatively similar to each other in terms of pehnotype & genotype (DNA sequence) are called a species • The boundary between one species & anohter is somewhat arbitrary • DNA is transmitted vertically from mother to daughter cell • DNA sequences also wander about all over the place 11 The Microbial Gene Cloud 12 The Microbial Gene Information Cloud 13 What is a Species ? The Chaotic World of Bacteria • Major changes in genotype may happen rarely in terms of per number of organisms (e.g. 10-20) but this may still be frequently in time (because there are so many) • Most major changes in genotype are lethal but that does not matter as the loss is almost immediately replaced (1 cell becomes 2 in 20 minutes) • Some major genotype changes by chance will make a bacteria that is wholly or partly resistant to some family of antimicrobial agent 14 Antimicrobial Agents : Flemings Mould • Antimicrobial agents have always existed in the environment e.g. soil & water • Bacteria that could survive in presence of these tend to take over in that setting • Natural Selection: Many Environmental Bacteria Tend to Be Antibiotic Resistant • Intrinsic Resistance 15 Intrinsic Resistance • Pseudomonas aeruginosa • When Fleming discovered penicillin Pseudomonas aeruginosa was already resistant • Also resistant to many other antibiotics • Rarely cause infection (unless already sick) • Similar issues with Acinetobacter species. 16 Pathogens Were Generally Susceptible to Antimicrobial Agents. Why ? • Penicillium mould does not grow in living people or animsals 17 Pathogens Were Generally Susceptible to Antimicrobial Agents. Why ? • Obligate commensals and pathogens grow in animal /human host • Little exposure to antimicrobial agents • Little selection pressure to favor bacteria with resistance genes • If a E. coli picked up a resistance it would not do it any and may be a dead weight gene 18 Acquired Resistance in Originally Susceptible Bacteria • The era of therapeutic antimicrobial use • Intense selection pressure on bacteria of animals /humans • The regular E. coli die • E. coli variants with resistance gene surive multiply & spread 19 What Makes a Good Therapeutic Antimicrobial ? • A useful therapeutic antimicrobial • A) stop/kill bacteria • B) not harme the host (people & animals) • Act at specific biological targets that are present and important in target bacteria but absent or not important in host 20 The Antimicrobial Class Concept • Similar chemical compounds usually act at the same target or targets • e.g. all penicillins & all cephalosporins have common chemical motif & all act on enzymes that are important in buidling the bacterial cell wall 21 The Antimicrobial Class Concept • Changes in the specific target that reduce vulnerability to any member of a class tends to result in loss of vulnerability to many or all antimicrobials in that class (e.g. Penicillins) • Enzymes that inactivate one member of the class often inactivate several/many or all members of the class. 22 The Class Concept & Regulatory Pharmaceutical Guff • Licensing & Promotion of one fluoroquinolone in animals and a different one in human 23 We Understand Acquired Antimicrobial Resistance • Well understood, entirely predictable and probably inevitable consequence of antibiotic use • A consequence of inappropriate use and of appropriate use • A consequence of use no matter who prescribes/consumes them or for whatever purpose • But overuse and irrational use makes it happen faster and for no corresponding benefit 24 Acquired Antibiotic Resistance: No Superbugs Just Human Folly 25 Acquired Antibiotic Resistance: No Superbugs Just Human Folly •We pretty know how & why it happens •We have a very good idea how to slow it down •Nationally & Globally we can not organize ourselves to act •“Wicked Problem” 26 Intermission • End of Part One 27 Part 2 • 1. How bad is the situation now ? • 2. Is it likely to get better or worse ? • 3. Does what happens in one species matter for others (and vice versa) • 4. What can be done ? • 5. What is likely to be done ? 28 How Bad is the Situation Now ? Pretty bad ? 1. Increasing Levels of Resistance 2. Very Few New Antibiotics (even fewer that matter-Why ?) 29 EARS-NET S. aureus EARS-NET Enterococcus faecium EARS-NET E. coli EARS-NET ESBL E. coli EARS-NET Klebsiella pneumoniae EARS-NET ESBL K. pneumoniae EARS-NET Carbapenem Resistant K. pneumoniae Spreading Faeces & Eating Faeces Clonal Spread of Bacteria and a Scattering Gene Cloud E. coli K. pneumoniae Enterocooccus faecium (Clostridium difficile & Norovirus) All Enteric Bacteria 37 Global Inequity in a Global Village 38 Cancun Airport 2013 39 The Global Nature of the Problem Travel & Trade 40 Why So Few New Antibiotics ? Under investment ? More public funding for research More tax breaks for industry Less rigorous licensing for new antimicrobials 41 Why So Few New Antibiotics ? Less rigorous licensing for new antimicrobials Current Requirement “not noticeably worse that some existing comparator treatment (not always the best comparator in my view) 42 Why So Few New Antibiotics ? Conservative Evolution The Number of Easy Biochemical Targets Was Probably Quite Limited BMJ: Cormican and Vellinga 43 Is It Likely to Get Better or Worse ? The Situation is almost certain to get Worse 44 Animals & Humans Links Overview • All Use Drives Resistance • Bacteria transfer between species • (For Proof See Salmonella & Campylobacter & VTEC) • Resistance genes transfer between species of bacteria 45 Animals & Humans Links • The Challenges of Linking Animal & Human Data • What is “Resistant” • Is resistant for a cow resistant in a chicken or a person ? 46 A Common Frame For Interpretation ECOF • Wild Type (Original Shape - Sensitive) • Non- Wild Type (New Shape - Not really sensitive even if not outright resistant) 47 What Could Be Done ? • Awareness & Education • Guidelines • Whistling in the Wind • Powerful Social, Professional and Economic Factors Sustain Current Practice (Wicked) 48 What Could Be Done ? • Awareness & Education • Guidelines • Preparation to Accept Regulation • Surveillance & Targets • Incentives & Penalties 49 What Else Could Be Done ? • Reducing Diagnostic Uncertainty • Reducing Fear (of complaint & litigation) • Accepting Death (humans & animals) 50 What is Likely to Be Done – More Hand Wringing • Far Too Little & Far Too Late • The Tragedy of the Commons • The “Wicked Problem” 51 HAND DISINFECTION WITH ALCOHOL BASED HAND RUB IS EFFECTIVE FOR MOST BACTERIA IF YOUR HANDS ARE ALREADY CLEAN 52 Acknowledgments • Dearbhaile Morris, Niall DeLappe, Catherine Ludden, Akke Velliinga, Sandra Galvin, Aoife Callanan, Sinead Duane, Andrew Murphy, Christine Domegan, Eamon O’Shea and others • Environmental Protection Agency • Health Research Board • & You 53 Jimmy Buffet Connection • Margaritaville (adapted lyric) • Some people claim there’s a superbug to blame • But I know its our own damn fault 54