Discovery research: The scientific challenge of finding new antibiotics

David Livermore*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

194 Citations (Scopus)

Abstract

The dwindling supply of new antibiotics largely reflects regulatory and commercial challenges, but also a failure of discovery. In the 1990s the pharmaceutical industry abandoned its classical ways of seeking antibiotics and instead adopted a strategy that combined genomics with high-throughput screening of existing compound libraries. Too much emphasis was placed on identifying targets and molecules that bound to them, and too little emphasis was placed on the ability of these molecules to permeate bacteria, evade efflux and avoid mutational resistance; moreover, the compound libraries were systematically biased against antibiotics. The sorry result is that no antibiotic found by this strategy has yet entered clinical use and many major pharmaceutical companies have abandoned antibiotic discovery. Although a raft of start-up companies-variously financed by venture capital, charity or public money-are now finding new antibiotic compounds (some of them very promising in vitro or in early trials), their development through Phase III depends on financial commitments from large pharmaceutical companies, where the discouraging regulatory environment and the poor likely return on investment remain paramount issues.

Original languageEnglish
Article numberdkr262
Pages (from-to)1941-1944
Number of pages4
JournalJournal of Antimicrobial Chemotherapy
Volume66
Issue number9
DOIs
Publication statusPublished - Sep 2011

Bibliographical note

Funding Information:
D. L. has received conference, speaking and research support from numerous pharmaceutical companies. He holds shares in AstraZeneca, Merck, Pfizer, Dechra, and GSK, and, as executor, manages further holdings in GSK and Eco Animal Health. He is an employee of the UK HPA and is a UK taxpayer. R. B. is currently a senior partner at Transcrip partners LLP and works with several large and small pharmaceutical companies in the area of antibiotic development. He is also a non-executive director of Helperby Therapeutics Ltd. R. F. has provided consultative advice to Destiny Pharma, GSK, Menarini Recherche and Novartis. F. B. is an employee of Eli Lilly and Company Ltd. I. C. is a member of the Scientific Advisory Board of Destiny Pharma Ltd and has recently received research funding from Cubist, Destiny, Galapagos, Leo, Pfizer, Novartis and Novacta. T. W. is an independent consultant, a retired employee and shareholder of GSK, and in the past 5 years has received financial remuneration for consultancy or presentations from GSK and Chiron/Novartis. The remaining members of the Working Party have none to declare.

Keywords

  • Antibacterial discovery
  • Antibiotic discovery
  • Antimicrobial discovery
  • Genomics
  • High-throughput screening

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