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.

Contents

• THE NATIONAL ACADEMIES
• CHEMICAL SCIENCES ROUNDTABLE
• BOARD ON CHEMICAL SCIENCES AND TECHNOLOGY
• Preface
• Acknowledgment of Reviewers
• Acronyms
• 1. Introduction and Overview
  • ORGANIZATION OF THE WORKSHOP SUMMARY
  • A VIEW FROM THE ANTIBIO TIC RESIS TANCE BATTLEFIELD
  • BIBLIOGRAPHY
• 2. Challenges In Overcoming Antibiotic Resistance
  • SELECTING ANTIBACTERIAL TARGETS TO AVOID RESISTANCE SELECTION
  • THE COMPLEX RESISTANCE MACHINERIES FOR β-LACTAM ANTIBIOTICS IN GRAM-NEGATIVE AND GRAM-POSITIVE BACTERIA
  • DISCUSSION
  • BIBLIOGRAPHY
• 3. Challenges in Screening
  • CHALLENGES IN DISCOVERING NEW ANTIBIOTICS THROUGH SCREENING
  • NEW WAYS OF LOOKING AT OLD ANTIBIOTICS AND THEIR TARGETS
  • DISCUSSION
  • BIBLIOGRAPHY
• 4. Challenges In Drug Delivery
  • NOVEL APPROACHES TO ANTIMICROBIAL THERAPEUTICS DESIGN
  • OVERCOMING ANTIBIOTIC CHALLENGES IN BIOFILM-ASSOCIATED INFECTIONS
  • DISCUSSION
  • BIBLIOGRAPHY
• 5. General Observations
• APPENDIXES
  • Appendix A Statement of Task
  • Appendix B Agenda
  • Appendix C Biographical Information
  • Appendix D Workshop Attendees

Rapporteurs: Douglas Friedman and Joe Alper.

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.

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 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.