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Suggested Citation:"Front Matter." National Research Council. 2014. Technological Challenges in Antibiotic Discovery and Development: A Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18616.
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TECHNOLOGICAL CHALLENGES
IN ANTIBIOTIC DISCOVERY AND
DEVELOPMENT

A WORKSHOP SUMMARY

Douglas Friedman and Joe Alper, Rapporteurs

Chemical Sciences Roundtable

Board on Chemical Sciences and Technology

Division on Earth and Life Studies

NATIONAL RESEARCH COUNCIL
              OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS

Washington, D.C.

www.nap.edu

Suggested Citation:"Front Matter." National Research Council. 2014. Technological Challenges in Antibiotic Discovery and Development: A Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18616.
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THE NATIONAL ACADEMIES PRESS    500 Fifth Street, NW    Washington, DC 20001

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.

This study was supported by the U.S. Department of Energy under Grant DE-FG02-07ER15872, the National Institutes of Health under Contract HHSN263201200074I (Task Order 25), and the National Science Foundation under Grant CHE-1231459.

This report was prepared as an account of work sponsored by an agency of the United States Government. Neither the United States Government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, completeness or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to an specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Government or agency thereof.

International Standard Book Number-13: 978-0-309-29814-8
International Standard Book Number-10: 0-309-29814-8

Additional copies of this report are available from the National Academies Press, 500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu.

Cover Art: Image of Clostridium Difficule. Courtesy of the Centers for Disease Control and Prevention.

Copyright 2014 by the National Academy of Sciences. All rights reserved.

Printed in the United States of America

Suggested Citation:"Front Matter." National Research Council. 2014. Technological Challenges in Antibiotic Discovery and Development: A Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18616.
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THE NATIONAL ACADEMIES

Advisers to the Nation on Science, Engineering, and Medicine

The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences.

The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. C. D. Mote, Jr., is president of the National Academy of Engineering.

The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine.

The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. C. D. Mote, Jr., are chair and vice chair, respectively, of the National Research Council.

www.national-academies.org

Suggested Citation:"Front Matter." National Research Council. 2014. Technological Challenges in Antibiotic Discovery and Development: A Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18616.
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Suggested Citation:"Front Matter." National Research Council. 2014. Technological Challenges in Antibiotic Discovery and Development: A Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18616.
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CHEMICAL SCIENCES ROUNDTABLE

CO-CHAIRS

WILLIAM F. CARROLL JR., Occidental Chemical Corporation, Dallas, Texas

JENNIFER S. CURTIS, University of Florida

MEMBERS

MICHAEL R. BERMAN, Air Force Office of Scientific Research

CAROLE BEWLEY,* National Institute of Diabetes and Digestive and Kidney Diseases

DONNA G. BLACKMOND, Scripps Research Institute

PAUL BRYAN, University of California, Berkeley

EMILIO BUNEL, Argonne National Laboratory

ALLISON CAMPBELL, Pacific Northwest National Laboratory

A.WELFORD CASTLEMAN, JR., Pennsylvania State University

RICHARD R. CAVANAGH, National Institute of Standards and Technology

MIGUEL GARCIA-GARIBAY, University of California, Los Angeles

JACQUELYN GERVAY-HAGUE, National Science Foundation

JACK KAYE, National Aeronautics and Space Administration

JOHN KOZARICH,* ActivX Biosciences, Inc.

LUIS E. MARTINEZ,* Trinity University

JOHN MILLER, U.S. Department of Energy

KENNETH G. MOLOY,* DuPont Central Research and Development

ROBERT PEOPLES, American Carpet Institute

MICHAEL E. ROGERS, National Institute of General Medical Sciences

JAMES M. SOLYST, Enviro International, Inc.

KATHLEEN J. STEBE, University of Pennsylvania

PATRICIA A. THIEL, Ames Laboratory and Iowa State University

NATIONAL RESEARCH COUNCIL STAFF

TERESA FRYBERGER, Director

INDIA HOOK-BARNARD, Senior Program Officer

KATHRYN HUGHES, Senior Program Officer

DOUGLAS FRIEDMAN, Program Officer

ELIZABETH FINKELMAN, Administrative Assistant

NAWINA MATSHONA, Senior Program Assistant

JOE ALPER, Consulting Science Writer

____________________________________

* These members of the Chemical Sciences Roundtable oversaw the planning of the Workshop on Technological Challenges in Antibiotic Discovery and Development, but were not involved in the writing of this workshop summary.

Suggested Citation:"Front Matter." National Research Council. 2014. Technological Challenges in Antibiotic Discovery and Development: A Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18616.
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BOARD ON CHEMICAL SCIENCES AND TECHNOLOGY

CO-CHAIRS

TIMOTHY SWAGER, Massachusetts Institute of Technology

DAVID WALT, Tufts University

MEMBERS

MARK A. BARTEAU, University of Michigan

DAVID BEM, Dow Chemical Company

JOAN BRENNECKE, Notre Dame University

ROBERT BERGMAN, University of California, Berkeley

HENRY BRYNDZA, E. I. du Pont de Nemours & Company

DAVID CHRISTIANSON, University of Pennsylvania

RICHARD EISENBERG, University of Rochester

MARY JANE HAGENSON, Chevron Phillips Chemical Company LLC (retired)

CAROL J. HENRY, Independent Consultant

JILL HRUBY, Sandia National Laboratories

CHARLES E. KOLB, Aerodyne Research, Inc.

SANDER G. MILLS, Merck, Sharp, & Dohme Corporation

DAVID MORSE, Corning Inc.

ROBERT E. ROBERTS, Institute for Defense Analyses

DARLENE J. S. SOLOMON, Agilent Technologies

JEAN TOM, Bristol-Myers Squibb

NATIONAL RESEARCH COUNCIL STAFF

TERESA FRYBERGER, Director

KATHRYN HUGHES, Senior Program Officer

DOUGLAS FRIEDMAN, Program Officer

ELIZABETH FINKELMAN, Administrative Assistant

NAWINA MATSHONA, Senior Program Assistant

Suggested Citation:"Front Matter." National Research Council. 2014. Technological Challenges in Antibiotic Discovery and Development: A Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18616.
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Preface

The Chemical Sciences Roundtable (CSR) was established in 1997 by the National Research Council. It provides a science-oriented apolitical forum for leaders in the chemical sciences to discuss chemistry-related issues affecting government, industry, and universities. Organized by the National Research Council’s Board on Chemical Sciences and Technology, the CSR aims to strengthen the chemical sciences by fostering communication among the people and organizations—spanning industry, government, universities, and professional associations—involved with the chemical enterprise. One way it does this is by organizing workshops that address issues in chemical science and technology that require national or more widespread attention.

On September 23, 2013, the CSR held a one-day workshop on the technical challenges in antibiotic discovery and development that explored the current state of antibiotic discovery, examined the technology available to facilitate development, discussed the technical challenges present, identified novel approaches to antibiotic discovery, and discussed the incentives and disincentives industry faces in antibiotic development. The workshop featured both formal presentations and panel discussions among participants from academia, industry, and federal research agencies. The workshop program consisted of three themes:

  • The challenges and approaches in overcoming antibiotic resistance;
  • The challenges and approaches in screening for new chemical entities with antibiotic properties; and
  • The challenges and approaches in delivering antibiotics to their intended site of action, particularly with regard to surmounting biophysical barriers.

This document summarizes the presentations and discussions that took place at the workshop. In accordance with the policies of the NRC, the workshop did not attempt to establish any conclusions or recommendations about needs and future directions, focusing instead on issues identified by the speakers and workshop participants. In addition, the organizing committee’s role was limited to planning the workshop. The workshop summary has been prepared by workshop rapporteurs Douglas Friedman and Joe Alper as a factual summary of what occurred at the workshop.

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Suggested Citation:"Front Matter." National Research Council. 2014. Technological Challenges in Antibiotic Discovery and Development: A Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18616.
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Acknowledgment of Reviewers

This workshop summary has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making the published workshop summary as sound as possible and to ensure that it meets institutional standards of objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this summary:

Carole Bewley, National Institute of Diabetes and Digestive and Kidney Diseases
Nicole Mahoney, The Pew Charitable Trusts
Melinda Moore, RAND Corporation
Douglas Weibel, University of Wisconsin, Madison

Although the reviewers listed above provided many constructive comments and suggestions, they did not see the final draft of the workshop summary before its release. The review of this summary was overseen by Douglas Lauffenburger, Massachusetts Institute of Technology. Appointed by the National Research Council, he was responsible for making certain that an independent examination of this workshop summary was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this workshop summary rests entirely with the authors and the institution.

Suggested Citation:"Front Matter." National Research Council. 2014. Technological Challenges in Antibiotic Discovery and Development: A Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18616.
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Suggested Citation:"Front Matter." National Research Council. 2014. Technological Challenges in Antibiotic Discovery and Development: A Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18616.
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Acronyms

BARDA   Biomedical Advanced Research and Development Authority
 
CDC   Centers for Disease Control and Prevention
CRE   carbapenem-resistant Enterobacteriaceae
CSR   Chemical Sciences Roundtable
 
FDA   U.S. Food and Drug Administration
 
GyrB   DNA gyrase B
 
KPC   Klebsiella pneumoniae carbapenemase
 
MIC   minimum inhibitory concentration
MRSA   methicillin-resistant Staphylococcus aureus
 
NDM   New Delhi metallo-β-lactamase
NIAID   National Institute of Allergy and Infectious Diseases
NIH   National Institutes of Health
NRC   National Research Council
NSF   National Science Foundation
 
PBP2a   penicillin-binding protein 2A
PMMA   poly(methyl methacrylate)
 
TTSS   type three secretion system
 
VRE   vancomycin-resistant Enterococcus
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Technological Challenges in Antibiotic Discovery and Development is the summary of a workshop convened by the Chemical Sciences Roundtable in September 2013 to explore the current state of antibiotic discovery and examine the technology available to facilitate development. Through formal presentations and panel discussions, participants from academia, industry, federal research agencies discussed the technical challenges present and the incentives and disincentives industry faces in antibiotic development, and identified novel approaches to antibiotic discovery.

Antibiotic resistance is a serious and growing problem in modern medicine and it is emerging as a pre-eminent public health threat. Each year in the United States alone, at least two million acquire serious infections with bacteria that are resistant to one or more antibiotics, and at least 23,000 people die annually as a direct result of these antibiotic-resistant infections. In addition to the toll on human life, antibiotic-resistant infections add considerable and avoidable costs to the already overburdened U.S. health care system. This report explores the challenges in overcoming antibiotic resistance, screening for new antibiotics, and delivering them to the sites of infection in the body. The report also discusses a path forward to develop the next generation of potent antimicrobial compounds capable of once again tilting the battle against microbial pathogens in favor of humans. Technological Challenges in Antibiotic Discovery and Development gives a broad view of the landscape of antibiotic development and the technological challenges and barriers to be overcome.

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