title: Alternatives to antibiotics-a pipeline portfolio review.
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.
authors.affiliation: Chemical Biology Ventures, Abingdon, Oxfordshire, UK; Abgentis, Edgbaston, Birmingham, UK; Persica Pharmaceuticals, Canterbury, Kent, UK. Electronic address: lloyd.czaplewski@chembioventures.com.
authors.forename: Lloyd
authors.initials: L
authors.lastname: Czaplewski
authors.affiliation: Transcrip Partners Reading, Berkshire, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Bax
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: Martha
authors.initials: M
authors.lastname: Clokie
authors.affiliation: Novacta Biosystems, Welwyn Garden City, Hertfordshire, UK; Cantab Anti-infectives, Welwyn Garden City, Hertfordshire, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Dawson
authors.affiliation: Phico Therapeutics, Babraham, Cambridge, UK.
authors.forename: Heather
authors.initials: H
authors.lastname: Fairhead
authors.affiliation: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY, USA.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Fischetti
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK; Absynth Biologics, Liverpool, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Foster
authors.affiliation: School of Pharmacy, Queen's University, Belfast, UK.
authors.forename: Brendan F
authors.initials: BF
authors.lastname: Gilmore
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
authors.affiliation: Evolution Biotechnologies, Ampthill, Bedfordshire, UK.
authors.forename: David
authors.initials: D
authors.lastname: Harper
authors.affiliation: Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Henderson
authors.affiliation: Institute of Infection and Immunity, St George's, University of London, London, UK; TiKa Diagnostics, London, UK.
authors.forename: Kai
authors.initials: K
authors.lastname: Hilpert
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, UK; Queen Victoria Hospital NHS Foundation Trust, East Grinstead, West Sussex, UK.
authors.forename: Brian V
authors.initials: BV
authors.lastname: Jones
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Aras
authors.initials: A
authors.lastname: Kadioglu
authors.affiliation: Absynth Biologics, Liverpool, UK; Procarta Biosystems, Norwich, UK.
authors.forename: David
authors.initials: D
authors.lastname: Knowles
authors.affiliation: Icelandic Medicines Agency, Reykjavik, Iceland.
authors.forename: Sigríður
authors.initials: S
authors.lastname: Ólafsdóttir
authors.affiliation: GlaxoSmithKline, Collegeville, Pennsylvania, PA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Payne
authors.affiliation: MedImmune, Gaithersburg, MD, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Projan
authors.affiliation: Department of Medicine, Imperial College London, London, UK.
authors.forename: Sunil
authors.initials: S
authors.lastname: Shaunak
authors.affiliation: Kaleido Biosciences, Cambridge, MA, USA.
authors.forename: Jared
authors.initials: J
authors.lastname: Silverman
authors.affiliation: Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, UK; Plasgene, Edgbaston, Birmingham, UK.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Thomas
authors.affiliation: Pan-Provincial Vaccine Enterprise, Saskatoon, SK, Canada.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Trust
authors.affiliation: Evotec, Manchester, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Warn
authors.affiliation: AstraZeneca, Boston, MA, USA; F2G, Manchester, UK.
authors.forename: John H
authors.initials: JH
authors.lastname: Rex
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000517:prevention & control*; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D015507:Drugs, Investigational / Q000627:therapeutic use*; D006801:Humans; D014612:Vaccines / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D015507:Drugs, Investigational; D014612:Vaccines