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Background Paper 6.1 Antimicrobial Resistance Priority Medicines for Europe and the World "A Public Health Approach to Innovation" Update on 2004 Background Paper Written by Per Nordberg, Dominique L. Monnet, Otto Cars Background Paper 6.1 Antimicrobial resistance By Emma M. Lodato, Boston University and Warren Kaplan, PhD, JD, MPH, Boston University April 2013 Update on 2004 Background Paper, BP 6.1 Antimicrobial resistance Table of Contents Acknowledgements ............................................................................................................................................ 3 Acronyms .............................................................................................................................................................. 4 1. Introduction ................................................................................................................................................. 5 2. Why does the problem persist? ................................................................................................................ 6 2.1 New variants of resistance have continued to emerge .................................................................. 7 2.2 Transmission of antibiotic-resistant bacteria .................................................................................. 8 2.3 Antibiotic misuse continues to be a challenge ................................................................................ 9 3. Epidemiological trends ........................................................................................................................... 10 3.1 Increasing levels of Gram negative resistant bacteria in Europe ............................................... 10 3.1.1 Escherichia coli ............................................................................................................................. 11 3.1.2 Multidrug-resistant Klebsiella pneumoniae ............................................................................. 12 3.1.3 Carbapenem resistance in Pseudomonas aeruginosa ............................................................. 12 3.1.4 Staphylococcus aureus................................................................................................................. 13 3.1.5 Emerging carbapenemase-producing bacteria in Europe. ..................................................... 14 3.2 Antibiotic resistance in other regions ............................................................................................ 15 3.2.1 The Americas ................................................................................................................................ 15 3.2.2 Asia and the World ...................................................................................................................... 15 4. The disease and economic burdens of antibiotic resistance ............................................................ 16 5. What are the current policy initiatives regarding AMR control? .................................................... 17 5.1 European Union ................................................................................................................................ 17 5.2 World Health Organization ............................................................................................................ 19 5.3 World .................................................................................................................................................. 20 5.4 The Americas ..................................................................................................................................... 21 6. Research into the past and present pharmaceutical interventions: what can be learnt? ............. 22 6.1 Antibiotic development ................................................................................................................... 22 6.2 Are incentives insufficient for the pharmaceutical industry? .................................................... 22 6.3 Public resources for basic and applied research ........................................................................... 23 6.4 What is in the current antibiotic pipeline? .................................................................................... 23 6.5 Optimization of antibiotic dosing regimens ................................................................................. 24 7. What are the gaps between current research and potential research issues which could make a difference? .......................................................................................................................................................... 25 7.1 Need for Rapid and inexpensive diagnostics ............................................................................... 25 7.2 Identifying the most urgent needs for new antibiotics ................................................................ 25 7.3 New therapeutic approaches .......................................................................................................... 26 6.1-2 Update on 2004 Background Paper, BP 6.1 Antimicrobial resistance 7.3.1 Alternatives to antimicrobials: Antivirulence medicines ....................................................... 26 7.3.2 Host-pathogen interactions ......................................................................................................... 27 7.3.3 Non-antibiotics ............................................................................................................................. 27 7.3.4 Use of Phage and Phage Therapy .............................................................................................. 27 7.3.5 Vaccines: Primary prevention of resistance .............................................................................. 28 8. Conclusion ................................................................................................................................................. 29 References ........................................................................................................................................................... 30 Annexes ............................................................................................................................................................... 41 Annex 6.1.1: Examples of Global Activities and Publications Addressing Antimicrobial Resistance ...................................................................................................................................................................... 42 Annex 6.1.2: Correlation between Antibiotic Consumption and Resistance in Europe .................. 48 Annex 6.1.3: Correlation between Antibiotic Consumption and Resistance in the World ............. 49 Annex 6.1.4: Outpatient Antibiotic Consumption ................................................................................ 50 Annex 6.1.5: Examples of Campaigns Addressing the Issue of Antimicrobial Resistance ............. 52 Annex 6.1.6: Successful Campaigns for Prudent and Appropriate Antibiotic Use .......................... 56 Annex 6.1.7: Examples of Diagnostics for Containing Antimicrobial Resistance............................. 58 Annex 6.1.8: Antibiotic Resistant Streptococcus pneumonia trends in Europe, 2005 and 2010 ..... 65 Annex 6.1.9: Antibiotic Resistant Escherichia coli trends in Europe, 2005 and 2010 ....................... 67 Annex 6.1.10: Meticillin Resistant Staphylococcus aureus trends in Europe, 2005 and 2010 ......... 71 Annex 6.1.11: Antibiotic Resistant Enterococcus faecium trends in Europe, 2005 and 2010 .......... 74 Annex 6.1.12: Epidemiological Trends in the USA ............................................................................... 77 Annex 6.1.13: Epidemiological Trends in the World ............................................................................ 81 Annex 6.1.14: Examples of the Economic Impact of Antimicrobial Resistance ................................ 85 Annex 6.1.15: Activity Review of the European Commission on Antimicrobial Resistance .......... 90 Annex 6.1.16: Press Release of IMI's €223.7 Programme to Combat Antibiotic Resistance ............ 95 Annex 6.1.17: European Commission Funded FP7 Projects on Antimicrobial Resistance .............. 97 Annex 6.1.18: Activity Review of the WHO and Antimicrobial Resistance .................................... 102 Annex 6.1.19: Examples of Concerted Action Addressing Antimicrobial Resistance in Europe . 106 Annex 6.1.20: Examples of Public Private Partnerships Concerning Antimicrobial Resistance .. 109 Annex 6.1.21: FDA Approved New Molecular Entity Antibiotics, 2004 – 2012 ............................. 113 Annex 6.1.22: Incentives to Encourage Antimicrobial Research and Development ...................... 114 Annex 6.1.23: Antibiotic Development Pipeline, 2011 ....................................................................... 117 Annex 6.1.24: Bacterial Vaccines Licensed for Distribution in the USA, 2005 – 2012 .................... 121 Acknowledgements We wish to thank all of those who have helped me to complete this update: Anita Korinsek–Porta, Eric Georget, Drs. Louis Kazis, David Rosenbloom:, Dr. Sean Devlin 6.1-3 Update on 2004 Background Paper, BP 6.1 Antimicrobial resistance Acronyms AMR Antimicrobial resistance CGD Centre for Global Development CDC US Centers for Disease Control and Prevention CHMP Committee for Medicinal Products for Human Use EARS-NET-Net European Antimicrobial Resistance Surveillance System Network
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