Antimicrobial Resistance and Human Health

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1 Antimicrobial Resistance and Human Health Dearbháile Morris, Discipline of Bacteriology, School of Medicine, National University of Ireland, Galway

2 The microbial world The is a gene Talk cloud in a The Tweet... genes take new shapes...with pictures We make resistance the winning shape Working together for change 2

3 1930 s to present ANTIMICROBIAL RESISTANCE IS NOW A MAJOR PUBLIC HEALTH PROBLEM

4 Global Antimicrobial Consumption TO TONS ANNUALLY Humans Animals Plants

5 IMB: Report of Consumption of Veterinary Antimicrobials in Ireland, tonnes of antibiotics used in veterinary medicine in Ireland, 2012

6 Antimicrobial Resistance: We Are Not Always Blaming Vets

7 Human Consumption Ireland: 23 DDD per 1000 inhabitants per day 1 EU/EEA Mean: 21.5 DDD per 1000 inhabitants per day Antimicrobial consumption increase by 36% between European Surveillance of Antimicrobial consumption Surveillance of Antimicrobial Consumption in Europe, van Boeckel et al (2014). The Lancet Infectious Diseases. 14(8):

8 Charles Darwin Antimicrobial-Resistance & Theory of Evolution

9 What is a Species? The Orderly World of Zoology Male & Female Can Mate and Produce Fertile Offspring DNA is transmitted vertically from parent to offspring Gradual step-wise change DNA sequences don t wander about between species 9

10 What is a Species? The Chaotic World of Bacteria Bacteria with similar DNA sequence compared with all other bacteria are called a species The boundary between one species & another is fairly arbitrary DNA is transmitted vertically from mother to daughter cell But DNA sequences wander about all over the place Major changes happen all the time

11 The Microbial Gene Cloud

12 The Microbial Gene Information Cloud

13 Selection Pressure Any environment with Antimicrobial Agents & Microbial Populations Gut (Human & Animal) Bacteria (Sensitive and Resistant) Sewage/Septic Tank/Slurry

14 Antimicrobial Resistance Intrinsic (Natural) resistance Acquired resistance Mobile genetic element(s) conferring resistance to antibiotics can transfer between bacteria with ease.

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)

16 Why they were originally susceptible Little exposure to antimicrobial agents in human/animal associated bacteria Little selection pressure to favor bacteria with resistance genes A rare S. aureus or E. coli with a resistance gene has no advantage and may have excess baggage

17 Acquired Resistance in Originally Susceptible Bacteria The era of therapeutic antimicrobial use Intense selection pressure on bacteria of animals /humans S. aureus and E. coli without the extra baggage die Variants with the baggage surive multiply & spread 17

18 Acquired Antibiotic Resistance Well understood, entirely predictable and possibly 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

19 Acquired Antibiotic Resistance: No Superbugs Just Human Folly We pretty know much how & why it happens We have a very good idea how to slow it down Nationally & Globally we can not organize ourselves to act

20 The Pace of Change 1961 About 98% of E. coli from humans rapidly killed by Ampicillin Quarter 1-2, % 1 of E. coli from Blood Stream Infection in Ireland completely resistant to ampicillin 26.6% 1 E. coli from Blood Stream Infection in Ireland completely resistant to ciprofloxacin 1

21 How Bad is the Situation Now? Pretty bad 1. Increasing Levels of Resistance 2. Very Few New Antibiotics (even fewer that matter)

22 Intersectoral global action to mitigate AMR

23 Urgent

24

25 EARS-Net Data Q1-Q2, 2014: MRSA 113 cases 2013: Proportion MRSA = 20.3% Upward trend in % to end Q2, 2014

26 EARS-Net Data Q1-Q2, 2014: Vancomycin resistant E. faecium 102 cases % VRE fm = 45.9% - highest since surveillance began in 2002 Ireland has the highest % VREfm in Europe

27 EARS-Net Data Q1-Q2, 2014: ESBL-producing E. coli 139 ESBL positive cases cases % ESBL-positive E.coli = 10.6% - highest since surveillance began in 2002

28 EARS-Net Data Q1-Q2, 2014: MDR E. coli Resistance to: Flouroquinolones 26.8%; Aminoglycosides = 14.7% ; MDR = 15.1% highest annual proportions reported

29 EARS-Net Data Q1-Q2, 2014: ESBL-producing K. pneumoniae 18 ESBL positive cases cases In 2013, 18.4% invasive K. pneumoniae were ESBL positive - highest since surveillance began in 2006 For Q1-Q2, 2014, % has decreased to 10.8%.

30 EARS-Net Data Q1-Q2, 2014: MDR K. pneumoniae MDRKP ESBL-producing + non-susceptible to ciprofloxacin + resistant to gentamicin 2013: 12.3%. Two major clonal groups circulating Q1-Q2, % 1

31 111 pulsed field profiles (PFPs) 15 clusters (A-P; based on > 85% similarity) Two clusters comprised 47% of collection: A (n = 43) O (n = 21)

32 EARS-Net Data Q1-Q2, 2014: K. pneumoniae MDRKP ESBL-producing + non-susceptible to ciprofloxacin + resistant to gentamicin 2013: 12.3%. Two major clonal groups circulating Q1-Q2, % 1

33 EARS-Net Data Q1-Q2, 2014: Carbapenem Resistant Enterobacteriaceae 3 carbapenem resistant: 1 K. pneumoniae (KPC), 1 E.coli, 1 Other

34 EARS-Net Data Q1-Q2, 2014: Carbapenem Resistant Enterobacteriaceae 3 carbapenem resistant: 1 K. pneumoniae (KPC), 1 E.coli, 1 Other 48 confirmed CPE Annual Report National Carbapenemase-producing Enterobacteriaceae Reference Laboratory Service Species OXA- KPC NDM1 IMP OXA23 IMI GES 48 E. coli Klebsiella spp Enterobacter spp Citrobacter spp

35 Spreading Faeces & Eating Faeces Clonal Spread of Bacteria and a Scattering Gene Cloud E. coli K. pneumoniae Enterococcus faecium All Enteric Bacteria

36 ESBL-producing E. coli

37 The Global Nature of the Problem- Global Inequity in a Global Village

38 Cancun Airport 2013

39 The Global Nature of the Problem - Travel & Trade

40 Very Few New Antibiotics Why?... Under investment? Conservative Evolution.The Number of Easy Biochemical Targets Was Probably Quite Limited

41 Is It Likely to Get Better or Worse? The Situation is almost certain to get Worse

42 Animal & Human Links All Use Drives Resistance Bacteria transfer between species (For Proof See Salmonella & Campylobacter & VTEC) Resistance genes transfer between species of bacteria

43 Adapted from Guidance for Laboratory Diagnosis of Human VTEC infection HPSC September 27 th, 2014

44 Animal & Human Links The Challenges of Linking Animal & Human Data What is Resistant Is resistant for a cow, resistant for a chicken or resistance for a person?

45 A Common Frame For Interpretation ECOF Wild Type (Original Shape - Sensitive) Non- Wild Type (New Shape - Not really sensitive even if not outright resistant)

46 What Could Be Done? Awareness & Education Motivation & Incentives Regulation Reducing Uncertainty Reducing Fear (of complaint & litigation) Accepting Death (humans & animals)

47 Prevent infection and spread of disease

48 Prevent infection and spread of disease Track antibiotic resistant bacteria

49 Prevent infection and spread of disease Improve use of antibiotics Track antibiotic resistant bacteria

50 Find new antibiotics and diagnostic tests Prevent infection and spread of disease Improve use of antibiotics Track antibiotic resistant bacteria

51 One Health OIE - World Organisation for Animal Health Endorse the One Health approach - a collaborative and all-encompassing way to address, when relevant, animal and public health globally

52 One Health

53 Acknowledgments Prof. Martin Cormican Staff of ARME, NUIG, NSSRL, CPEaRLS Environmental Protection Agency Health Research Board Safefood & You

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