Review

.2016 Feb;16(2):239-51.

doi: 10.1016/S1473-3099(15)00466-1. Epub 2016 Jan 13.

Alternatives to antibiotics-a pipeline portfolio review

Lloyd Czaplewski¹, Richard Bax², Martha Clokie³, Mike Dawson⁴, Heather Fairhead⁵, Vincent A Fischetti⁶, Simon Foster⁷, Brendan F Gilmore⁸, Robert E W Hancock⁹, David Harper¹⁰, Ian R Henderson¹¹, Kai Hilpert¹², Brian V Jones¹³, Aras Kadioglu¹⁴, David Knowles¹⁵, Sigríður Ólafsdóttir¹⁶, David Payne¹⁷, Steve Projan¹⁸, Sunil Shaunak¹⁹, Jared Silverman²⁰, Christopher M Thomas²¹, Trevor J Trust²², Peter Warn²³, John H Rex²⁴

Affiliations

¹ Chemical Biology Ventures, Abingdon, Oxfordshire, UK; Abgentis, Edgbaston, Birmingham, UK; Persica Pharmaceuticals, Canterbury, Kent, UK. Electronic address: lloyd.czaplewski@chembioventures.com.
² Transcrip Partners Reading, Berkshire, UK.
³ Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
⁴ Novacta Biosystems, Welwyn Garden City, Hertfordshire, UK; Cantab Anti-infectives, Welwyn Garden City, Hertfordshire, UK.
⁵ Phico Therapeutics, Babraham, Cambridge, UK.
⁶ Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY, USA.
⁷ Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK; Absynth Biologics, Liverpool, UK.
⁸ School of Pharmacy, Queen's University, Belfast, UK.
⁹ Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
¹⁰ Evolution Biotechnologies, Ampthill, Bedfordshire, UK.
¹¹ Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, UK.
¹² Institute of Infection and Immunity, St George's, University of London, London, UK; TiKa Diagnostics, London, UK.
¹³ School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, UK; Queen Victoria Hospital NHS Foundation Trust, East Grinstead, West Sussex, UK.
¹⁴ Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
¹⁵ Absynth Biologics, Liverpool, UK; Procarta Biosystems, Norwich, UK.
¹⁶ Icelandic Medicines Agency, Reykjavik, Iceland.
¹⁷ GlaxoSmithKline, Collegeville, Pennsylvania, PA, USA.
¹⁸ MedImmune, Gaithersburg, MD, USA.
¹⁹ Department of Medicine, Imperial College London, London, UK.
²⁰ Kaleido Biosciences, Cambridge, MA, USA.
²¹ Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, UK; Plasgene, Edgbaston, Birmingham, UK.
²² Pan-Provincial Vaccine Enterprise, Saskatoon, SK, Canada.
²³ Evotec, Manchester, UK.
²⁴ AstraZeneca, Boston, MA, USA; F2G, Manchester, UK.

PMID:26795692
DOI: 10.1016/S1473-3099(15)00466-1

Free article

Review

Alternatives to antibiotics-a pipeline portfolio review

Lloyd Czaplewski et al. Lancet Infect Dis.2016 Feb.

Free article

.2016 Feb;16(2):239-51.

doi: 10.1016/S1473-3099(15)00466-1. Epub 2016 Jan 13.

Authors

Affiliations

¹ Chemical Biology Ventures, Abingdon, Oxfordshire, UK; Abgentis, Edgbaston, Birmingham, UK; Persica Pharmaceuticals, Canterbury, Kent, UK. Electronic address: lloyd.czaplewski@chembioventures.com.
² Transcrip Partners Reading, Berkshire, UK.
³ Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
⁴ Novacta Biosystems, Welwyn Garden City, Hertfordshire, UK; Cantab Anti-infectives, Welwyn Garden City, Hertfordshire, UK.
⁵ Phico Therapeutics, Babraham, Cambridge, UK.
⁶ Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY, USA.
⁷ Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK; Absynth Biologics, Liverpool, UK.
⁸ School of Pharmacy, Queen's University, Belfast, UK.
⁹ Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
¹⁰ Evolution Biotechnologies, Ampthill, Bedfordshire, UK.
¹¹ Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, UK.
¹² Institute of Infection and Immunity, St George's, University of London, London, UK; TiKa Diagnostics, London, UK.
¹³ School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, UK; Queen Victoria Hospital NHS Foundation Trust, East Grinstead, West Sussex, UK.
¹⁴ Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
¹⁵ Absynth Biologics, Liverpool, UK; Procarta Biosystems, Norwich, UK.
¹⁶ Icelandic Medicines Agency, Reykjavik, Iceland.
¹⁷ GlaxoSmithKline, Collegeville, Pennsylvania, PA, USA.
¹⁸ MedImmune, Gaithersburg, MD, USA.
¹⁹ Department of Medicine, Imperial College London, London, UK.
²⁰ Kaleido Biosciences, Cambridge, MA, USA.
²¹ Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, UK; Plasgene, Edgbaston, Birmingham, UK.
²² Pan-Provincial Vaccine Enterprise, Saskatoon, SK, Canada.
²³ Evotec, Manchester, UK.
²⁴ AstraZeneca, Boston, MA, USA; F2G, Manchester, UK.

PMID:26795692
DOI: 10.1016/S1473-3099(15)00466-1

Abstract

Antibiotics have saved countless lives and enabled the development of modern medicine over the past 70 years. However, it is clear that the success of antibiotics might only have been temporary and we now expect a long-term and perhaps never-ending challenge to find new therapies to combat antibiotic-resistant bacteria. A broader approach to address bacterial infection is needed. In this Review, we discuss alternatives to antibiotics, which we defined as non-compound approaches (products other than classic antibacterial agents) that target bacteria or any approaches that target the host. The most advanced approaches are antibodies, probiotics, and vaccines in phase 2 and phase 3 trials. This first wave of alternatives to antibiotics will probably best serve as adjunctive or preventive therapies, which suggests that conventional antibiotics are still needed. Funding of more than £1·5 billion is needed over 10 years to test and develop these alternatives to antibiotics. Investment needs to be partnered with translational expertise and targeted to support the validation of these approaches in phase 2 trials, which would be a catalyst for active engagement and investment by the pharmaceutical and biotechnology industry. Only a sustained, concerted, and coordinated international effort will provide the solutions needed for the future.

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