1. Otto Cars MD PhD Professor Infectious Diseases Uppsala University, Sweden Founder and Senior Adviser ReAct The Antibiotic Crisis: Setting the scene Adressing the challenges of AMR in the Northern Dimension Area Berlin, Germany, November 19, 2015

2. An independent international network to improve the management of antibiotic resistance www.reactgroup.org

3. ReAct: Main areas of action Increasing the visibility of antibiotic resistance in the global health dialogue Catalyzing actions for behavioural change, civil society mobilization and national coordinated policies against antibiotic resistance Promoting a needs-driven research and development model for new antibiotics

4. “It is not difficult to make microbes resistant to penicillin …. “The time may come when penicillin can be bought by anyone in the shops…. “ Alexander Fleming's Nobel Lecture 1945

5. Antibiotic use is widespread: 65% of respondents across the 12 countries included in the survey report having taken antibiotics in the past six months, including more than one third (35%) who took antibiotics within the past month.

7. 2013 2015 Spread of carbapenemase-producing Enterobacteriaceae (CPE) in the EU/EEA: assessment by national experts Sporadic occurrence Single hospital outbreaks Interregional spread No case reported Regional spread Endemic situation Sporadic hospital outbreaks Not participating or not reporting Non-EU/EEA countries Source: Albiger B, et al. Eurosurveillance 2015; 20(45) (12 November 2015).

8. A global nightmare……

10. The last resort- Colistin Increasing number of pubclications Biswas S. Expert Rev Anti Infect Ther. 2012;10(8):917-934

11. Access Conservation Innovation

12. Journal of Law, Medicine & Ethics, 2015

13. Some parts of the world have already run out of effective antibiotics About 70% of neonatal systemic infections can not be treated with the antibiotics recommended by WHO…. Lancet 2005; 365: 1175–88

14. “Across developing countries fewer than a third of children with suspected pneumonia receive antibiotics” United Nations Children’s Fund (UNICEF) June 2012 ….and some never entered the antibiotic era.

15. Ongoing Update 2015: Availability decreases, common long lasting shortages Pivmecillinam Fosfomycin oral Temocillin Available Available through special system Mecillinam iv Availability of old antibiotics C. Pulcini et al. CID 2012;54:268

16. For too long antibiotic resistance has been under the radar screen

17. ESTIMATES OF BURDEN OF ABR Source: WHO Global Report on Surveillance 2014

18. HUMAN MORTALITY BURDEN WHO Ebola Situation Report 12 August 2015 WHO/GIP, data in HQ as of 17 July 2015 http://www.cidrap.umn.edu/news-perspective/2012/06/cdc- estimate-global-h1n1-pandemic-deaths-284000 ANTIBIOTIC RESISTANCE > 500.000 AVIAN FLU H5N1 449 EBOLA 11,298 SWINE FLU H1N1 284.000 Antibiotic resistance – figure is a world-wide projection based on data from EU,US and Thailand (WHO Global Reoprt of Surveillance)

19. Orphanage in Bamako, Mali ESBL colonized 100% of the children and 63%, of the adult staff studied. Tandé et al. Emerg Infect Dis. 2009 Mar;15(3):472-4. Mumhibili hospital, Tanzania Tanzania The mortality rate from Gram-negative bloodstream infection was 43 %, more than double that of malaria.. Blomberg et al. BMC Infect Dis. 2007 May 22;7:43.

20. Sulphonamides Tetracyclines Penicillins Aminoglycosides Macrolides Glycopeptides Streptogramins Chloramphenicol Quinolones Trimetoprim Lincosamides 1930 1940 1950 1960 1970 1980 1990 2000 2010 Oxazolidinones The latest class of antibiotics was discovered in 1987 Lipopeptides

21. New antibiotics New antibiotics Marketing Over- consumtion Over- consumtion Resistance The failing machinery….

22. “The infrastructure of antibiotic discovery both in academia and in industry is at a dangerously low level and needs to be rebuilt”

23. The cell wall of Gram negative bacteria

24. 6.3 M€ 30.55 M€ 58.9 M€ 16 M€ 26.4 M€ 93 M€ All numbers are only IMI JU contribution (in- kind EFPIA contributions are in addition)

26. A leaking system New antibiotics Marketing Volume sales Misaligned financial incentives Irrational use

27. Towards a new financial model for R&D of novel antibiotics Needs driven - based on analysis of pipeline vs resistance and its burden Solving the scientific challenges Collaboration and knowledge sharing Incentives that stimulates R&D of priority antibiotics De-linking return of investment from sales Controlled use and distribution Equitable global access and affordability

28. No effective treatment for bacterial infections Inadequate prevention leading to avoidable infections Infection Inapppropriate use of antibiotics leading to development of resistance Inadequate incentives for R&D of new antibiotics Inno- vation failure Clinical failure Antibiot ic resistan ce Antibiotic resistance: A systems failure Adapted from Kevin Outterson www.chathamhouse.org/sites/files/

29. Maternal and child health Modern medicine Basic healthcare ANTIBIOTICS

30. 2015 Towards A Global RESPONSE 2001

31. Solutions require commitment from all policy areas Human medicine Veterinary medicineAgriculture EnvironmentResearch and education TradeSecurity Development aid Foreign policyFinance

33. www.reactgroup.org/toolbox

35. “We agree that attention should be given to global health risks, such as antimicrobial resistance, infectious disease threats and weak health systems. These can significantly impact growth and stability”.

36. Partnerships for global action National Govt’s Supra- National Org’s Civil Society

37. “Given these global coordination issues, there is a clear role for a binding international legal framework to encompass the issues of access, conservation and innovation “