The phage approach
Dr Heather Fairhead, CEO, Phico Therapeutics
Mining biosynthetic pathways for new antibiotics
Professor Gerard Wright, DeGroote Institute for Infectious Disease Research, McMaster University
One of the impediments to returning to microbial natural products as sources for leads for new antimicrobials is the rediscovery of known compounds when using traditional phenotypic extract screens. With the availability of thousands of microbial genome sequences, we now understand that such an approach does not comprehensively sample the potential of most microbes to produce new compounds. By directly exploring microbial genomes and identifying biosynthetic programs that have not yet been fully explored for their antibiotic potential, it is possible to select organisms and pathways that are likely to yield novel chemistry and antimicrobial activity. Coupled with synthetic biology tools to focus on these pathways, new antibiotics can be discovered. An example of our recent work using this genomes fist strategy coupled with a phylogenomic filter will be presented with a focus on new inhibitors of the ClpP protease.
How can novel clinical trial designs address challenges in evaluating antimicrobials for multi-drug resistant organisms?
Professor Ann Sarah Walker FMedSci, Professor of Medical Statistics & Epidemiology, University College London
The paradigm of evidence-based medicine has been to optimise outcomes by iteratively improving a "standard-of-care" (SOC) regimen, which forms the basis for comparison with new interventions. Platform trials generally still follow this paradigm, comparing multiple new interventions to SOC, but speed up drug development by doing this simultaneously. However, this paradigm poses multiple challenges for antimicrobials, in particular the absence of a clear SOC, with large numbers of antimicrobials with a week evidence base supporting their use. A single SOC will drive resistance, supporting diversity in prescribing – but comparisons vs different "SOC" require multiple large non-inferiority trials which are simply infeasible. I will review two recent developments in trial design which could be exploited to address these challenges, and highlight the considerable challenges that still remain.
Innovation in Point of Care Diagnostics
Dr Tina Joshi, Lecturer in Molecular Microbiology, Faculty of Health, University of Plymouth
AntiMicrobial resistance is a serious healthcare challenge, and it is estimated that drug resistant microbes will kill 10 million people worldwide per year by 2050. This has led researchers and governments to accelerate AMR research globally, primarily focusing on antimicrobial drug discovery to increase our arsenal of antimicrobials and preserve our working antimicrobials. Diagnostics have been highlighted in several reports as a key way of reducing overuse of antimicrobials in practice and encouraging rationalisation of antimicrobial prescribing. However, despite this, development of innovative diagnostic solutions has been overlooked and underfunded, likely due to the "blue sky" nature of this type of research. Dr Joshi’s research focusses on innovative, interdisciplinary solutions for diagnosis of AMR infections at point of care. This talk will focus on AMR, links to Climate change and the importance of encouraging and investing in new, feasible, long term approaches to tackle AMR.
New methods of evaluating antimicrobials
Professor Colm Leonard, Consultant Clinical Advisor, NICE