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Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

COMBATING ANTIMICROBIAL RESISTANCE AND PROTECTING THE MIRACLE OF MODERN MEDICINE Gillian J. Buckley and Guy H. Palmer, Editors Committee on the Long-Term Health and Economic Effects of Antimicrobial Resistance in the United States Board on Population Health and Public Health Practice Health and Medicine Division A Consensus Study Report of PREPUBLICATION COPY: UNCORRECTED PROOFS

THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001 This project has been funded in whole or in part with federal funds from the Applicable Institute/Center, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN263201800029I. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project. International Standard Book Number-13: 978-0-309-XXXXX-X International Standard Book Number-10: 0-309-XXXXX-X Digital Object Identifier: https://doi.org/10.17226/26350 Library of Congress Catalog Number: XXXXXXXXXX Additional copies of this publication are available from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu. Copyright 2021 by the National Academy of Sciences. All rights reserved. Printed in the United States of America Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2021. Combating antimicrobial resistance and protecting the miracle of modern medicine. Washington, DC: The National Academies Press. https://doi.org/10.17226/26350. PREPUBLICATION COPY: UNCORRECTED PROOFS

The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president. The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contributions to engineering. Dr. John L. Anderson is president. The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president. The three Academies work together as the National Academies of Sciences, Engineering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The National Academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding in matters of science, engineering, and medicine. Learn more about the National Academies of Sciences, Engineering, and Medicine at www.nationalacademies.org. PREPUBLICATION COPY: UNCORRECTED PROOFS

Consensus Study Reports published by the National Academies of Sciences, Engineering, and Medicine document the evidence-based consensus on the study’s statement of task by an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and the committee’s deliberations. Each report has been subjected to a rigorous and independent peer-review process, and it represents the position of the National Academies on the statement of task. Proceedings published by the National Academies of Sciences, Engineering, and Medicine chronicle the presentations and discussions at a workshop, symposium, or other event convened by the National Academies. The statements and opinions contained in proceedings are those of the participants and are not endorsed by other participants, the planning committee, or the National Academies. For information about other products and activities of the National Academies, please visit www.nationalacademies.org/about/whatwedo. PREPUBLICATION COPY: UNCORRECTED PROOFS

COMMITTEE ON THE LONG-TERM HEALTH AND ECONOMIC EFFECTS OF ANTIMICROBIAL RESISTANCE IN THE UNITED STATES1 GUY H. PALMER (Chair), Regents Professor of Pathology and Infectious Diseases, The Jan and Jack Creighton Endowed Chair, Paul G. Allen School for Global Health, Washington State University; Senior Director of Global Health, Washington State University System MICHAEL BAYM, Assistant Professor, Biomedical Informatics, Harvard University CÉSAR DE LA FUENTE, Presidential Assistant Professor, Perelman School of Medicine, School of Engineering and Applied Science, University of Pennsylvania JENNIFER DIEN BARD, Director, Clinical Microbiology and Virology Laboratory, Associate Professor of Pathology (Clinical Scholar), Keck School of Medicine, University of Southern California MARTA GOMEZ-CHIARRI, Professor, Department of Fisheries, Animal, and Veterinary Sciences, College of the Environment and Life Sciences, The University of Rhode Island GUILLAUME LHERMIE, Associate Professor, Animal Health Economics and Veterinary Public Health, College of Veterinary Medicine; Director, Simpson Centre for Agricultural and Food Innovation and Education, The School of Public Policy, University of Calgary, Canada PREETI MALANI, Chief Health Officer, University of Michigan, Professor of Medicine, Division of Infectious Diseases, University of Michigan School of Medicine ELEFTHERIOS MYLONAKIS, Charles C.J. Carpenter, MD, Professor of Infectious Diseases, Professor of Medicine, Assistant Dean of Medicine, Professor of Molecular Microbiology and Immunology, Warren Alpert Medical School of Brown University; Director, Rhode Island Hospital and The Miriam Hospital IRUKA N. OKEKE, Professor, Department of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Ibadan EMMANUEL OKELLO, Assistant Specialist in Cooperative Extension, Population Health, and Reproduction, School of Veterinary Medicine, University of California, Davis AYLIN SERTKAYA, Vice President and Senior Economist, Eastern Research Group MICHELLE SOUPIR, Associate Chair for Research and Extension, Equity Advisor, College of Engineering; Professor, Department of Agriculture and Biosystems Engineering, Iowa State University ANDY STERGACHIS, Professor of Pharmacy and Global Health, Adjunct Professor of Health Metrics Sciences, Epidemiology, and Health Systems and Population Health; Associate Dean of Pharmacy; Director, Global Medicines Program & Biomedical Regulatory Affairs Program, University of Washington Schools of Pharmacy and Public Health MARY E. WILSON, Clinical Professor of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco; Adjunct Professor, Global Health and Population, Harvard T.H. Chan School of Public Health QIJING ZHANG, Clarence Hartley Covault Distinguished Professor, Associate Dean for Research and Graduate Studies, Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University Study Staff 1 See Appendix B, Disclosure of Unavoidable Conflict of Interest. PREPUBLICATION COPY: UNCORRECTED PROOFS v

GILLIAN J. BUCKLEY, Study Director KARA LANEY, Senior Program Officer ROBERTA WEDGE, Senior Program Officer (from May 2021) AASHAKA SHINDE, Research Associate (from October 2020) LEILA MEYMAND, Senior Program Assistant (from October 2020) MISRAK DABI, Finance Business Partner ROSE MARIE MARTINEZ, Senior Director, Board on Population Health and Public Health Practice JULIE PAVLIN, Senior Director, Board on Global Health ROBIN SCHOEN, Director, Board on Agriculture and Natural Resources PREPUBLICATION COPY: UNCORRECTED PROOFS vi

Reviewers This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We thank the following individuals for their review of this report: RITU BANERJEE, Vanderbilt University Medical College MARLENE BELFORT, University at Albany, State University of New York KAREN C. CARROLL, Johns Hopkins University School of Medicine REBECCA GARABED, The Ohio State University YRJÖ GRÖHN, Cornell University KENT KESTER, Sanofi MARK L. LAWRENCE, Mississippi State University MAUREEN LICHTVELD, University of Pittsburgh MARK G. PAPICH, North Carolina State University TIMOTHY M. PERSONS, United States Government Accountability Office AMY PRUDEN, Virginia Polytechnic Institute and State University TARA VIJAYAN, University of California, Los Angeles Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report nor did they see the final draft before its release. The review of this report was overseen by JIM E. RIVIERE, North Carolina State University, and ELLEN WRIGHT CLAYTON, Vanderbilt University. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies. PREPUBLICATION COPY: UNCORRECTED PROOFS vii

Acknowledgments This report is a product of the cooperation and contributions of many people. The committee and staff are grateful for the support of the National Academies of Sciences, Engineering, and Medicine’s Health and Medicine Division (HMD) staff who contributed to producing this report. The committee and staff thank Tina Seliber, Lauren Shern, Leslie Sim, and Taryn Young in the HMD Executive Office; Anne Marie Houppert, Christopher Lao-Scott, Rebecca Morgan, in the National Academies Research Center; Sadaf Faraz, Devona Overton, Esther Pak, and Marguerite Romatelli in the Office of the Chief Communications Officer; Stephanie Miceli in the Office of News and Public Information; Julie Eubank in the Office of Congressional and Government Affairs; and Mandy Enriquez, Dempsey Price, Alejandro Velazquez, and in the Office of Conference Management. We extend particular thanks to Roberta Wedge for joining the project and providing invaluable analysis and Rebekah Hutton for her work on the cover design. The committee’s work was enhanced by the systematic analysis of Kristine Moore and Anje Mehr whose commissioned paper informed this report. We also thank Yunxin Joy Jiao for graciously sharing her graphic designs for reprint in Chapter 1. The committee thanks all the speakers and moderators who participated in committee meetings, as well as others who provided information, input, and assistance. They include the following: Frank Møller Aarestrup, Mark Albrecht, Neena Anadaraman, Anand Balachandran, Manica Balasegaram, Helen Boucher, Susan Bright, Felipe C. Cabello, Angela Caliendo, Amanda Cash, Clare Chandler, Ryan Cirz, Michael Craig, Chris Crnich, Peter Panduro Damborg, Gautam Dantas, Mary Denigan-Macauley, Lynn Filpi, William Flynn, Heather Fowler, Jay Garland, Cyril Gay, Claire Gordon, Luca Guardabassi, Tim Jinks, Bill Keleher, Wes Kim, Jane Knisely, Kevin Krause, Ramanan Laxminarayan, Brian Lubbers, John Lynch, Marc Mendelson, Mark Miller, Chris Murray, Kevin Outterson, Mark Papich, Timothy Persons, Carmem L. Pessoa-Silva, Jessica Petrillo, Tom Pilcher, John Rex, Jennifer Schneider, Anand Shah, Gunnar Skov Simonsen, Brad Spellberg, Padmini Srikantiah, Bruce Stewart-Brown, Fred C. Tenover, Paige Waterman, Craig Wilson, Barbara Zimmer. To Dr. Christopher Murray, Institute for Health Metrics and Evaluation, University of Washington, and the Global Research PREPUBLICATION COPY: UNCORRECTED PROOFS ix

on Antimicrobial Resistance team, we extend particular thanks for sharing key findings from their Lancet paper in review. Finally, we have special thanks to the National Institute of Allergy and Infectious Diseases of the National Institutes of Health for generously funding this project. PREPUBLICATION COPY: UNCORRECTED PROOFS x

Preface I was in the lobby of the Fred Hutchinson Cancer Research Center in Seattle, waiting to meet with a colleague, when a wall display of the timeline of successful hematopoietic bone marrow transplants caught my attention. The timeline, in the form of a spiral, starts slowly in the 1970s—successes were few and failures many as scientists strove to understand the basic immunology underlying transplantation and clinicians to establish the optimal procedures and patient care. The successes slowly and then suddenly accelerate, providing life-saving transplants where previously no hope existed. Today, bone marrow transplants are performed in hospitals worldwide. Indeed, it is paradoxical that one of the highest accolades for the incredible achievements in modern medicine over recent decades is that we can take them for granted. The same is true for numerous medical procedures: organ transplants, joint replacements, improved cancer treatment, even safe childbirth. All of us know someone whose lives have been touched by these advances. Underlying this remarkable progress is the reliance on effective antibiotics to prevent and treat infections in patients at their most vulnerable moments. Addressing the challenges of the emergence and spread of resistant microbes; improving laboratory diagnostics and surveillance; and catalyzing the development of new classes of medicines is highly complex, cutting across scientific disciplines, medical specialties, institutions, and agencies. However, the goal is clear: preserve the medical advances of the past and allow continued progress, all afforded by and dependent on the availability of effective antibiotics. Given the complexity of antibiotic resistance and the inherent multidisciplinary and interdisciplinary approaches required to address resistance, and to ensure a robust pipeline of effective medicines, the committee brought together expertise from across human, animal, and environmental health sectors. The committee has endeavored to examine the full range of initiatives and programs incorporated into the National Strategy and Action Plan for Combating PREPUBLICATION COPY: UNCORRECTED PROOFS xi

Antibiotic-Resistant Bacteria and the progress in meeting the goals of the plan. The responsiveness of the multiple U.S. government agencies engaged in carrying out the plan was deeply appreciated as was the evaluation conducted by the Center for Infectious Disease Research and Policy at the University of Minnesota. Equally, given the need for global solutions to a challenge that knows no borders, the committee benefited from the multiple international organizations engaged in preserving antibiotic effectiveness and appreciates their willingness to share their expertise and perspectives. The committee was respectful of prior reports on antibiotic resistance and endeavored to assess their recommendations in the context of the committee’s statement of task. On behalf of the committee, I want to express my appreciation for the openness of these organizations and agencies and their efforts in working to ensure access to effective antibiotics. A study of this magnitude requires a tremendous commitment from the committee members. All have sacrificed evenings, weekends, and holidays—without financial compensation—in this commitment and in their desire to bring the best possible science to bear on a challenging issue. Their commitment was all the more impressive as the study took place during the COVID-19 pandemic. Several of our committee members had front-line clinical care responsibilities, others increased commitments in laboratory testing, surveillance, and modeling—all were impacted by the pandemic by increased responsibilities at work and at home. Despite these increased responsibilities and the ability to only meet and work together virtually, the committee, individually and collectively, brought their expertise, experience, and knowledge to the task. I cannot thank them enough. On behalf of the committee, I would like to express our thanks and appreciation to the National Academies leadership and staff: Rose Marie Martinez, Senior Director of the Board on Population Health and Public Health Practice; Kara Laney, Senior Program Officer; Roberta Wedge, Senior Program Officer; Aashaka Shinde, Research Associate; and Leila Meymand, Senior Program Assistant. A special thank you and deep appreciation to the Study Director, Gillian Buckley, who provided exceptional leadership throughout the study. Without her leadership and the work of the staff in planning, organization, and editing, this report would not have been possible. The evolutionary basis of antimicrobial resistance dictates that there will be no magic bullets or simple solutions. Ensuring that modern medicine can continue to rely on effective antibiotics will require continual innovation and process improvement. Minimizing the need for antibiotics through preventive health care and improved sanitation, housing, and access to clean water is achievable as is ensuring that the right antibiotic is available and given at the appropriate dose for the appropriate duration. Achieving those goals is fundamental to meeting the National Academy of Medicine’s vision of “a healthier future for everyone.” Guy H. Palmer, Chair Committee on the Long-Term Health and Economic Effects of Antimicrobial Resistance in the United States PREPUBLICATION COPY: UNCORRECTED PROOFS xii

Contents ACRONYMS AND ABBREVIATIONS xvi SUMMARY S-1 The Scope of the Problem, S-2 The Health and Economic Burden of Resistance, S-2 Strengthening Surveillance, S-3 Stewardship and Infection Prevention, S-4 Bringing New Products to Market and Ensuring Their Reach, S-7 The National Action Plan for Combating Antibiotic-Resistant Bacteria, S-10 A Role for the United States in Coordinated Global Action, S-11 1 INTRODUCTION 1-1 The Charge to the Committee 1-6 References, 1-10 2 THE SCOPE OF THE PROBLEM 2-1 Human Action Exacerbates Resistance, 2-2 Antimicrobial Resistance Is a Global Problem, 2-14 Antimicrobial Resistance Is a Complex Adaptive Problem, 2-21 One Health Is a Complex Adaptive Response, 2-24 References, 2-25 3 THE HEALTH AND ECONOMIC BURDEN OF RESISTANCE 3-1 Review of Recent Reports, 3-1 Challenges of Quantifying the Burden of Resistance, 3-11 Developing More Precise Estimates of the Burden of Antimicrobial Resistance, 3-26 References, 3-31 4 STRENGTHENING SURVEILLANCE 4-1 Surveillance Systems, 4-2 Data Collection and Analysis, 4-10 Monitoring Antimicrobial Resistance in Water, 4-25 References, 4-33 5 STEWARDSHIP AND INFECTION PREVENTION 5-1 Stewardship in Human Medicine in the United States, 5-2 Stewardship in Animal Medicine in the United States, 5-12 Diagnostic Stewardship in the United States, 5-20 Strategies to Prevent the Emergence of Resistance, Especially in Low- and Middle-Income Countries, 5-25 References, 5-32 PREPUBLICATION COPY: UNCORRECTED PROOFS xiii

6 BRINGING NEW PRODUCTS TO THE MARKET AND ENSURING THEIR REACH 6-1 Medicines, 6-1 Diagnostics, 6-29 Investing in One Health Solutions, 6-38 References, 6-48 7 THE NATIONAL ACTION PLAN FOR COMABTING ANTIBIOTIC-RESISTANT BACTERIA 7-1 The 2015 National Action Plan, 7-1 GAO Reports, 7-5 Federal Government Implementation of the National Action Plan, 7-8 National Action Plan for Combating Antibiotic-Resistant Bacteria, 2020–2025, 7-14 References, 7-18 8 A ROLE FOR THE UNITED STATES IN COORDINATED GLOBAL ACTION 8-1 Strengthening Surveillance, 8-4 Reducing Need, 8-6 Ensuring Sustained Leadership, 8-10 References, 8-12 APPENDIXES A COMMITTEE MEMBER BIOGRAPHIES B DISCLOSURE OF UNAVOIDABLE CONFLICT OF INTEREST C OPEN SESSION AGENDAS PREPUBLICATION COPY: UNCORRECTED PROOFS xiv

Acronyms and Abbreviations 3GC third-generation cephalosporin AACTING Network on quantification of veterinary Antimicrobial usage at herd level and Analysis Communication and benchmarking to improve responsible usage ABSSSI acute bacterial skin and skin structure infections ACTIV Accelerating COVID-19 Therapeutic Interventions and Vaccines AIDS acquired immunodeficiency syndrome AMR antimicrobial resistance AMU antimicrobial use AR antibiotic resistance ARG Argentina ARLG Antibacterial Resistance Leadership Group ARLN Antibiotic Resistance Laboratory Network ASPR HHS Office of the Assistant Secretary for Preparedness and Response AUS Australia AUT Austria AVMA American Veterinary Medical Association AWaRe WHO’s Access, Watch, Reserve classification of antibiotics BARDA Biomedical Advanced Research and Development Authority BGR Republic of Bulgaria BL beta-lactam BLI beta-lactamase inhibitor BSI bloodstream infection C. auris Candida auris C. difficile Clostridioides difficile CABP community-acquired bacterial pneumonia CARB National Action Plan for Combating Antibiotic-Resistant Bacteria CARB-X Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator CDC Centers for Disease Control and Prevention CDI Clostridioides difficile infection CHE Switzerland CHL Chile CI confidence interval cIAI complicated intra-abdominal infection CLIA Clinical Laboratory Improvement Amendments of 1988 CLSI Clinical and Laboratory Standards Institute PREPUBLICATION COPY: UNCORRECTED PROOFS xv

CLSI-VAST veterinary antimicrobial susceptibility testing CMS Centers for Medicare & Medicaid Services CO-ADD Community for Open Antimicrobial Drug Discovery COVID-19 coronavirus disease, 2019 CR carbapenem-resistant CRAB carbapenem-resistant Acinetobacter baumannii CRE carbapenem-resistant Enterobacterales cUTI complicated urinary tract infection CYP Cyprus CZE Czech Republic DALY disability-adjusted life year DARPA Defense Advanced Research Projects Agency DFUI diabetic foot ulcer infections DISARM Act Developing an Innovative Strategy for Antimicrobial-Resistant Microorganisms Act DNA deoxyribonucleic acid DNDi Drugs for Neglected Diseases Initiative ECU Ecuador EMA European Medicine Agency EPA U.S. Environmental Protection Agency EQS Environmental Quality Standard ESBL extended-spectrum beta-lactamase ESP Spain EST Estonia EUCAST European Committee on Antimicrobial Susceptibility Testing FAO Food and Agriculture Organization of the United Nations FDA U.S. Food and Drug Administration GAIN Act Generating Antibiotic Incentives Now Act GARDP Global Antibiotic Research and Development Partnership GBR United Kingdom GCI gonococcal infection GCOA Global Coalition on Aging GDP gross domestic product GHA Ghana GLASS Global Antimicrobial Resistance and Use Surveillance System GLASS-EAR Emerging Antimicrobial Resistance Reporting GN gram-negative GRC Greece HABP/VABP Hospital-associated bacterial pneumonia/ventilator-associated bacterial pneumonia HHS U.S. Department of Health and Human Services PREPUBLICATION COPY: UNCORRECTED PROOFS xvi

Hib Haemophilus influenzae type b HIC high-income country HIV human immunodeficiency virus HRV Croatia HUN Hungary hVISA heterogeneous vancomycin-intermediate Staphylococcus aureus ICU intensive care unit IDSA Infectious Diseases Society of America IHME Institute for Health Metrics and Evaluation IMF International Monetary Fund IMI imipenem-hydrolyzing β-lactamases IMP imipenemase metallo-β-lactamase IND India IPPS inpatient prospective payment system ISL Iceland ITA Italy KPC Klebsiella pneumoniae carbapenemases LIMS Laboratory Information Management System LMIC low- and middle-income country LTU Lithuania LUX Luxembourg LVA Latvia MDR multidrug-resistant MDR G- multidrug-resistant Gram negative bacteria MIC minimal inhibitory concentration MKD Republic of North Macedonia MLST multilocus sequence MRSA methicillin-resistant Staphylococcus aureus NAHMS National Animal Health Monitoring System NARMS National Antimicrobial Resistance Monitoring System NCATS National Center for Advancing Translational Sciences NCBI National Center for Biotechnology Information NDARO National Database of Antibiotic Resistant Organisms NDM New Delhi metallo-β-lactamase NGO nongovernmental organization NIAID National Institute of Allergy and Infectious Diseases NIDDK National Institute of Diabetes and Digestive and Kidney Diseases NIH National Institutes of Health NITAG National Immunization Technical Advisory Group NLM National Library of Medicine NOR Norway PREPUBLICATION COPY: UNCORRECTED PROOFS xvii

NZL New Zealand OECD Organisation for Economic Co-operation and Development OIE World Organisation for Animal Health (formerly Office International des Epizooties) OXA-48 Oxacillinase-48 PACCARB Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria PCAST President’s Council of Advisors on Science and Technology PCORI Patient-Centered Outcomes Research Institute PCR polymerase chain reaction PCV pneumococcal conjugate vaccine PEPFAR U.S. President’s Emergency Plan for AIDS Relief POCIS polar organic chemical integrative sampler POL Poland PPE personal protective equipment QIDP qualified infectious disease product qPCR quantitative polymerase chain reaction R&D research and development rCDI recurrent Clostridioides difficile infection REVAMP Act Re-Valuing Anti-Microbial Products Act RNA ribonucleic acid ROM Romania rUTI recurrent urinary tract infection S. pneumonia Streptococcus pneumonia SAB Staphylococcus aureus bacteremia SfAM Society for Applied Microbiology SRB Serbia SVK Slovakia SVN Slovenia SWE Sweden TCV typhoid conjugate vaccine THA Thailand TUR Turkey UN United Nations U.S. United States USAID U.S. Agency for International Development USD United States dollars USDA U.S. Department of Agriculture UTI urinary tract infection UW University of Washington PREPUBLICATION COPY: UNCORRECTED PROOFS xviii

UW tele-ASP University of Washington Tele-Antimicrobial Stewardship Program VA Department of Veterans Affairs VEN Venezuela VetCAST EUCAST subcommittee for Veterinary Antimicrobial Susceptibility Testing VIM Verona integron-encoded metallo-β-lactamases VNM Vietnam VRE vancomycin-resistant Enterococci WASH water, sanitation, and hygiene WFD Water Framework Directive WHO World Health Organization WWTP wastewater treatment plant ZAF South Africa PREPUBLICATION COPY: UNCORRECTED PROOFS xix

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Antimicrobial resistance is a health problem that threatens to undermine almost a century of medical progress. Moreover, it is a global problem that requires action both in the United States and internationally.

Combating Antimicrobial Resistance and Protecting the Miracle of Modern Medicine discusses ways to improve detection of resistant infections in the United States and abroad, including monitoring environmental reservoirs of resistance. This report sets out a strategy for improving stewardship and preventing infections in humans and animals. The report also discusses the strength of the pipeline for new antimicrobial medicines and steps that could be taken to bring a range of preventive and therapeutic products for humans and animals to the market.

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