1. Professor Barry Cookson Division of Infection and Immunity, Division of Infection and Immunity, Univ. College London Univ. College London Antimicrobial Stewardship Reflections on International Efforts

2. Antimicrobial Stewardship Infection Prevention & Control ECDC AMR Strategy New Diagnostics, Antibiotics and Treatments Prioritisation of R&D & Interventions: Organisational & Behavioural Training/ Education: Professio- nals & Public AMR & AB Usage Surveillance International Collaboration

3. Seven Key Areas 7) strengthened international collaboration with a wide range of governmental and non-governmental organisations, international regulatory bodies and others to influence opinion, galvanise support, and mobilise action to deliver the scale of change needed globally.

4. 8 components of WHO Regional Strategy Combined strategy on HAI and AMR and link to patient safety Strengthen surveillance of HAI and combine AMR Improve use of standardized surveillance methods and indicators, and process & progress indicators Standardize guidelines and tools for infection control and prevention in health care settings, including AM drug use. Move from individual projects to national programmes Foster partnership with professional groups Review research agenda, training needs and gaps Political commitment, advocacy, resources Pittet et al, Considerations for a WHO European strategy…. The Lancet Infectious Diseases 2005; 5: 242-250.

5. Kenneth Calman Clinical Governance & Total Quality Management Liam Donaldson WHO Patient Safety Sally Davies UK Representative WHO Executive 2014 AMR Strategy Champion?

6. The Healthcare Associated Infection and related AMR paradox: high burden but little action Complex issue: with no immediate, easy solution Requires multi disciplinary approaches: never easy Control and Prevention seen as costly Diffuse issue: Individual or Institutional or “Public Health” problem?

7. Why the increased profile in the “00”s? A Patient Safety Issue at last –WHO Global Patient Safety Alliance Hand Hygiene Surgical Site Infection Antimicrobial Resistance (never progressed!) –DG SANCO funded European project Improving Patient Safety in Europe (IPSE) International community & media views changed as a result of SARS & the Pandemic Flu threat Crying wolf no longer: Armageddon organisms are evident globally

8. “EUROPE” 17 Old Member States (MS) 10 New MS EEA:European Economic Area adds Iceland, Liechtenstein and Norway EFTA: European Free Trade Association Switzerland, Iceland, Liechtenstein and Norway EU acceding countries: Croatia April 2013 See European Economic Area http://en.wikipedia.org/wiki/European_Free_Trade_Associa tion#Current_members http://en.wikipedia.org/wiki/European_Free_Trade_Associa tion#Current_members

9. “In England (~2005) we make hospital acquired infection (HAI) rates publically available by named hospital” After the initial shock around Europe: in 2012 6/28 European countries are doing this!

10. Publication of hospital specific HAI infection rates Cookson et al, J Hosp Infect 2011: 79; 260-264 EU Directorate (SANCO) group suggested possibility of different systems: Confidential within the health care institution, not public health authorities e.g. individual surgical team infection rates. Confidential benchmarking within surveillance networks with publication of anonymised or aggregated results e.g. surveillance of surgical site infections. Disclosure to public health authorities e.g. early warning of notifiable nosocomial events. Public reporting of agreed indicators e.g. composite structure and process indicators or HAI rates e.g. France, England Vive la Différence

11. Consensus standards and performance indicators for healthcare associated infection in Europe Cookson et al, J Hosp Infect 2011: 79; 260-264 Topic AgreeModifyNeutralDisagree Organisation85%9%4%1% Control79%7%2% Surveillance79%11%1%2% Education79%14%1%3% Resources79%15%2%5% Overall Averages 80% 11% 2% 3% Overall Averages 80% 11% 2% 3%

12. Seven Key Areas 2) optimising prescribing practice through implementation of antimicrobial stewardship programmes that promote rational prescribing and better use of existing and new rapid diagnostics Behaviours of patients and doctors (Agricultural, Aquaculture, Vets use: science, politics and economic hurdles: overwhelmingly important!)

13. ECDC Activities (Council Recommendation 2002/77/EC) 2013 !!! Exploring misuse of antimicrobial agents in human medicine across whole chain of stakeholders : prescribers, pharmacists and patients. Sales of antimicrobial agents without a prescription (SCORE 2002-03) 2014: Antibiotic Prescribing & Resistance in European Children (ARPEC) 2014-15: Follow up review of EC Recommendations

14. Seven Key Areas 1)improving infection prevention and control practices in human (and animal health), both through enhanced dissemination & implementation of best practice & better use of data and diagnostics 5) better access to and use of surveillance data..facilitate greater data consistency & standardisation across the system & encourage improved data linkage

15. Relevant DG SANCO EU Networks EARSS: European Antimicrobial Resistance Surveillance Scheme ESAC: European ESAC: European Surveillance of Surveillance of Antimicrobial Consumption Antimicrobial Consumption HELICS HELICS Hospitals in Europe Link for Infection Control through Surveillance ECDC unofficial1993 2000 HELICS 2008 Embedded in Improving Patient Safety in Europe (IPSE) 2005 2002

16. C section (n= 12 124) HELICS-associated national networks (2000-2003) SSIrateper100op. Anonymised Countries

17. Large differences are found between countries in rates of HAIs, in distribution of rates in the characteristics of the infections This is attributable to:  Differences in definition interpretation/data collection?  Differences in recruitment?  Difference in Antibiotic Rx & other medical policies?  Difference in the quality of care?

18. Healthcare-Associated Infections surveillance Network (HAI-Net) Coordination Groups (European experts) and contact points in participating countries Modules:  Surgical site infections: 16 countries  HAI in intensive care units: 14 countries  Point prevalence survey: 30 countries  HAI in long-term care (HALT-2, outsourced): 24 countries  Surveillance of C. difficile infections, pilot: 14 countries  Concordance of definitions, Validation studies Need post discharge

19. Five Countries Reporting Hip Prosthesis Infections to ECDC have shown reduced infection rate trends between 2004-06 Source: HELICS-SSI, ECDC Annual Epidemiological Report 2008

20. Methicillin-resistant Staphylococcus aureus EU 2005- 2007  2 Countries with a significant increase (2005–2007)  8 Countries with a significant decrease (2005 – 2007) MRSA (%) No. of countries 0 10 20 30 40 50 EARSS-ECDC

21. Alcohol hand rub consumption in acute care hospitals, ECDC PPS 2011-2012

22. Structure and process indicators: percentage of single room beds Single room beds in participating hospitals (%): median = 11.1% Source: ECDC, 2012 (ECDC PPS data as of 23/11/2012) Source: ECDC, 2012 (ECDC PPS data as of 23/11/2012) *Poor data representativeness

23. Prevalence of antimicrobial use in acute care hospitals, ECDC PPS 2011-2012 *Poor PPS data representativeness

24. Seven Key Areas 3) improving professional education, training and public engagement

25. COMPETENCY 1: Infection Prevention &Control COMPETENCY 2: Antimicrobial resistance & antimicrobials COMPETENCY 3: Prescribing antimicrobials COMPETENCY 4: Antimicrobial Stewardship COMPETENCY 5: Monitoring and learning https://www.gov.uk/government/publications/antimicrobial-prescribing-and- stewardship-competencies https://www.gov.uk/government/publications/antimicrobial-prescribing-and- stewardship-competencies 2013

26. Training HALT eBug

27. Seven Key Areas 4) developing new drugs, treatments and diagnostics (and infection prevention and control interventions) 6) better identification and prioritisation of AMR research needs e.g. new drugs, improved rapid or point-of- care diagnostic tests for humans (& animals).

28. Relevant DG R&D Projects HARMONY (1999-2001) incl MRSA typing network Harmonisation of Antibiotic Resistance measurement, Methods of typing Organisms and ways of using these and other tools to increase the effectiveness of Nosocomial infection control ARPAC (2002-2005) Very useful papers Antibiotic Resistance Prevention and Control ARMed (2002-2006) Antibiotic Resistance in Mediterranean Countries MOSAR (2007-2012) Mastering hOSpital Antimicrobial Resistance in Europe        

29. BURDEN 2008-2013 Very useful data Burden of Resistance and Disease in Europe IMPLEMENT 2008-2013 (www site?) Implementing Strategic Bundles for Infection Prevention & Management. PROHIBIT 2008-2013 Analyses existing guidelines and IPC practices SATURN 2010-2015 Impact of Specific Antibiotic Therapies on the prevalence of hUman host ResistaNt bacteria R-GNOSIS 2011-2016 Studies in Multidrug-resistant GNRs

30. Other Ongoing Projects " Routine diagnostic tool for urinary tract infections caused by extended spectrum beta lactamase and carbapenamase producing bacteria" (ROUTINE) "Rapid identification of respiratory tract infections (RID-RTI) "Development of a handheld antibacterial drug resistance diagnostic device using nanowire technology" (NANOMAL) "Automated next generation sequencing for diagnostic microbiology“ (PATHSEEK),

31. HORIZON 2020 HEALTH.2013.2.3.1-1: Drugs and vaccines for infections that have developed or are at the risk of developing significant anti-microbial resistance. HEALTH.2013.2.3.1-2: Stratified approaches to antibacterial and/or antifungal treatment

32. A “Perfect Storm” Companies withdrawing from antimicrobial market as: New drug development expensiveNew drug development expensive Resistance, not just side effects, a huge challengeResistance, not just side effects, a huge challenge Patient numbers often relatively small & regimens shortPatient numbers often relatively small & regimens short Patents short-livedPatents short-lived

33. Founded in 2007 Spreading the costs of R&D

34. IMI New Drugs for Bad Bugs (ND4BB) initiative COMbatting BACterial resistance in Europe (COMBACTE) €194.6m “CLIN-Net”: large clinical trials “LAB-Net”: microbial surveillance for trial site selection –Studies : Novel antibiotic vs skin and respiratory infections New human immunoglobulin monoclonal antibody against S. aureus alpha toxin Molecular basis of the bacterial cell wall permeability (TRANSLOCATION) €29.3m –Explore how to stop the Gram negative bacteria ejecting antimicrobials

35. Trans Atlantic Task Force Recommendations Future Collaborations (1)

36. Trans Atlantic Task Force Recommendations Future Collaborations (2)