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Understanding Antimicrobial Resistance: A Global Perspective

Delve into the world of antimicrobial resistance (AMR) with a focus on Norway and global challenges. Learn about the One Health approach connecting human, animal, and environmental health. Explore the history of antibiotics, AMR transmission, and solutions to combat this pressing issue. Discover the impact of antibiotic usage in agriculture, AMR development, and spread worldwide.

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Understanding Antimicrobial Resistance: A Global Perspective

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  1. Antimicrobial resistanceOne world – One Health Ernst Kristian Rødland, MD PhD e.k.rodland@medisin.uio.no

  2. Topics • What is antimicrobial resistance (AMR) • AMR in Norway • AMR globally • Futureperspectives

  3. One Health • Initiative to forgecollaborationbetweenphysicians, veterinarians and otherscientific, health and environmentallyrelateddisciplines • One Health recognizesthatthehealthofpeople is connected to thehealthofanimals and theenvironment

  4. Microbial biosphere • Bacteria • Environmental • Pathogen • Natural antibiotics • Reservoirofantibioticresistance genes Resistome

  5. How do bacteriabecomeresistant? • Vertical • Spontaneousmutations • Transferred to thebacteria`sprogeny • Horizontal • Exchange ofgenetic elements/plasmids • Packagesofresistance genes

  6. Historyofsomeantibiotics • Penicillin – 1928, regularuse in human medicine from the 1940s • Chlortetracyclin (Aureomycin) – 1945, used as a growth promotor in meatproduction • Fluoroquinolones (Nalidixic acid) – 1962

  7. Exposureroutesofantibiotics to theenvironment • Discharge from manufacturing • Urine and feces from usersofantibiotics • Antibiotics used in agriculture and aquaculture • Discardedmedicines – lackoftake-back programs

  8. Usageofantibiotics • 65% increase in human consumption (2000-2015) globally(1) • Approximately 80% ofa.b. consumption is in the animal sector(2) • Globally: 80000 (??) tonnes in agriculture (1) Klein et al. PNAS 2018 (2) WHO, 2017

  9. Antibioticselectionpressure Significantimpactontheresistome in the microbial biosphere

  10. AMR is omnipresent • E.coli from arcticbirds • Siberia, Alaska, Greenland • AMR detected in 8/97 isolates • 17 antimicrobials weretested, resistance to 14 weredetected Sjølund-Karlsson et. al. EmergingInfectiousDiseases www.cdc.gov/eid • Vol. 14, No. 1, January 2008

  11. Antibiotics in agricultureAMR transmission • «Drugresistance in Salmonella typhimurium and itsimplications»(1) • «Changes in intestinal flora of farm personnelafterintroductionof a tetracycline-supplementedfeedon a farm»(2) (1) ES Anderson, Br Med J., 1968 (2) Levy et al. N Eng J Med. 1976

  12. Ny Powerpoint mal 2011

  13. AMR, a global challenge • AMR is a global challenge(1) • Compromisestreatmentofcommoninfections • Undermines advances in modernmedicine and health • Estimation by 2050(2) • 10 million deaths/yr globally • Costs: 100 trillion USD/yr (1) WHO, 2015 (2) Jim O`Neill et.al 2016

  14. Whatcan be done?

  15. WHO Global action plan Strenghtenknowledgethroughsurveillanceand research

  16. AMR in Norway

  17. Microbiological Laboratories • Norway • 22 clinicallaboratories in total • 11 referancelaboratories • Different (several, 5-7) platforms to register microbiological data

  18. NORM/NORM-VET • Established in 1999/2000 • Surveillance program for AMR in humans, animals, food and feed • Publish data on the usage of antimicrobial agents in humans and animals • Annual reports

  19. Human clinicalisolates • All positive bloodcultures • A patientwith a given bacterialisolate is excluded from registrationwith a newisolateofthe same species within a month from the first entry • Bacteriawhichcommonlyinfecttheskinareexcluded • Other samples for selectedbacteria • Urine (E.coli, Klebsiella, Proteus) • Respiratorytractspecimen (HaemophilusInfl., S. Pneumonia) • CSF (N. Meningitidis) • Wounds (Staph. Aureus)

  20. Notifiablediseases in the Norwegian Surveillance System for CommunicableDiseases (MSIS) MRSA, VRE, ESBL-carba

  21. Challenges, computational • «Old» technology • Different laboratoriesoftenuse different laboratoryinformation systems • Investment in one system -> costly to change • Oslo University Hospital (OUS):

  22. Challenges, registrationof data • Manual work • Not possible to send data directly to NORM • Strictprivacypolicies • Avoid double registration in the system • Qualitycheck • Demanding and work intense for laboratory staff

  23. Useofantibiotics in Norway NORM NORM-VET 2016

  24. ESBL – NorwayExtended-spectrum beta-lactamases

  25. MRSA – NorwayMethicillin-resistantstaphylococcusaureus

  26. AMR Globally

  27. Global antibioticconsumption Klein et al. PNAS, 2018

  28. Results • AMR data from 22 surveillance systems • 67 countries • HICs 57%, 38 countries • UMICs 24%, 16 countries • LMICs 16%, 11 countries • LICs 3%, 2 countries

  29. AMRDevelopement and spread • Improperuseof antimicrobials • Lackofmicrobiologicaldiagnostic services • Poorsanitation and shortageofclean water • Crowding– interpersonal spread • Migration Resource limitedcountries (RLCs)

  30. AMR in the WHO African region • High prevalenceof AMR in clinical relevant bacteria • 2011: WHO publishes a policy package to combat AMR • Top priority: strenghtensurveillance and laboratorycapacity • No reliable data available from 42,6% ofAfricancountries(1) (2) (1) Tadesse, B.T., et al., BMC Infect Dis, 2017 (2) Essack, S.Y., et al.J Public Health (Oxf), 2017

  31. Availablereference labs in Africa Barbe`et. al, ClinicalMicrobiology and Infection, 2017

  32. China • Antibioticconsumptionincreased from 2,3 to 4,2 (79%) billion DDDs from 2000-2015 • 92700 tonnesofa.b. was used in China in 2013(1) • 48 % was used in human medicine • 46% wasreleasedintotheenvironment • Antibioticsaccount for approx. half thedrugs used in hospitals(1) (1) M Qiao et al., Environment International, 2018

  33. China • Colistin. «Last resort» antibiotic • 2015 – Plasmid mediatedcolistinresistance (mcr-1) wasdiscovered in pigs and humans in China Wang et al. Nature 2018

  34. India • Antibioticconsumptionincreased from 3,2 to 6,5 (103%) billion DDDs from 2000-2015

  35. AMR migration • Approx. 2 billion peoplemoveacrosslargedistances/year and 1 billion cross international borders • 20–60% ofasylumseekersarecolonizedwithresistantmicrobes(1,2) • 50-90% oftouristsvisitingthetropicsgetcolonizedwith MDR enterobacteriacea New Dehli Metallo-beta-lactamase-1 (NDM-1) (1) de Smalen, A.W., et al., Travel Med Infect Dis, 2017 (2) Heudorf, U., et al.,GMSHygInfect Control, 2016

  36. ”....If walls have proveninsufficient to stop migratingpeople, it willcertainly be so for multi-resistantmicrobes and theirconsequences.....”

  37. Future perspectives

  38. InterpretationReductionofantibioticconsumptionwill not be sufficient to control antimicrobial resistancebecausecontagion—thespreadofresistantstrains and resistance genes—seems to be the dominant contributingfactor. Improvingsanitation, increasingaccess to clean water, and ensuringgoodgovernance, as well as increasingpublic health-careexpenditure and betterregulatingthe private healthsectorare all necessary to reduce global antimicrobial resistance. My answer has to be fighting poverty

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