Hardwiring antimicrobial resistance mitigation into global policy

This is the final version. Available on open access from Oxford University Press via the DOI in this recordIn the wake of COVID-19, antimicrobial resistance (AMR) has become termed the 'silent pandemic', with a growing number of editorials warning that international momentum for AMR mitigation is being lost amidst the global turmoil of COVID-19, economic crises and the climate emergency. Yet, is it sufficient to now simply turn the volume of the pre-existing AMR policy discourse back up? Although existing AMR initiatives have previously achieved high levels of international attention, their impact remains limited. We believe it is time to critically reflect on the achievements of the past 7 years and adapt our AMR policies based on the substantial literature and evidence base that exists on the socioecological drivers of AMR. We argue that developing a more sustainable and impactful response requires a shift away from framing AMR as a unique threat in competition with other global challenges. Instead, we need to move towards an approach that emphasizes AMR as inherently interlinked and consciously hardwires upstream interventions into broader global developmental agendas.University of ExeterWellcome TrustNorwegian Research Counci

Universal Methods for Transgene Induction Using the Dexamethasone-Inducible Transcription Activation System pOp6/LhGR in Arabidopsis and Other Plant Species

The use of chemically inducible systems for transgenes expression is a crucial requirement for modern plant biology research, as it allows (1) expression of transgenes that compromise plant viability or fertility when constitutively expressed and (2) spatio-temporal control of transgene expression levels. We describe the stringently regulated and highly responsive dexamethasone-inducible gene expression system pOp6/LhGR, which comprises of a chimeric transcription activator LhGR and a corresponding pOp6 promoter. Upon induction, the LhGR activator binds to the pOp6 promotor and induces expression of the target gene of interest. We provide detailed protocols for inducing transgene expression at different developmental stages and in different plant species and discuss dexamethasone stability and the use of its analogues. We also introduce new, versatile, GATEWAYTM compatible binary vectors that are now available for the pOp6/LhGR system

Reinventing the antimicrobial pipeline in response to the global crisis of antimicrobial-resistant infections

Opinion article. The pipeline for new antibiotics is dry. Despite the creation of public/private initiatives like Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (Carb-X) and the Antimicrobial Resistance (AMR) Centre, the current focus on ‘push-pull’ incentives for the pharmaceutical industry still relies on economic return. We propose a joint, internationally-funded antimicrobial development institute that would fund permanent staff to take on roles previously assigned to pharmaceutical companies. This institute would receive ring-fenced, long-term, core funding from participating countries as well as charities, with the aim to focus on transforming the largely dormant antimicrobial pipeline. Resulting drugs would be sold globally and according to a principle of shared burdens. Our proposed model for antimicrobial development aims to maximise society’s investment, through open science, investment in people, and the sharing of intellectual property

There is no market for new antibiotics: This allows an open approach to research and development

There is an increasingly urgent need for new antibiotics, yet there is a significant and persistent economic problem when it comes to developing such medicines. The problem stems from the perceived need for a 'market' to drive commercial antibiotic development. In this article, we explore abandoning the market as a prerequisite for successful antibiotic research and development. Once one stops trying to fix a market model that has stopped functioning, one is free to carry out research and development (R&D) in ways that are more openly collaborative, a mechanism that has been demonstrably effective for the R&D underpinning the response to the COVID pandemic. New 'open source' research models have great potential for the development of medicines for areas of public health where the traditional profit-driven model struggles to deliver. New financial initiatives, including major push/pull incentives, aimed at fixing the broken antibiotics market provide one possible means for funding an openly collaborative approach to drug development. We argue that now is therefore the time to evaluate, at scale, whether such methods can deliver new medicines through to patients, in a timely manner

NIMble innovation — a networked model for public antibiotic trials

Antibiotic research and development is at an inflection point. Faced with ongoing problems with commercial innovation, we argue for a networked public approach to support and coordinate existing research and development initiatives by sustainably moving promising compounds through clinical trials. We propose a global public infrastructure of institutes tasked with (1) conducting all trial stages up to market authorisation, including small-scale compound production; (2) negotiating licensing agreements for global production and distribution by industry partners; and (3) using public purchasing agreements or subscription models to ensure commercially viable drug production at equitable prices. We invite stakeholders to consider our Networked Institute Model's benefits for unblocking the public and private antibiotic pipeline

There is no market for new antibiotics: this allows an open approach to research and development

There is an increasingly urgent need for new antibiotics, yet there is a significant and persistent economic problem when it comes to developing such medicines. The problem stems from the perceived need for a “market” to drive commercial antibiotic development. In this article, we explore abandoning the market as a prerequisite for successful antibiotic research and development. Once one stops trying to fix a market model that has stopped functioning, one is free to carry out research and development (R&D) in ways that are more openly collaborative, a mechanism that has been demonstrably effective for the R&D underpinning the response to the COVID pandemic. New “open source” research models have great potential for the development of medicines for areas of public health where the traditional profit-driven model struggles to deliver. New financial initiatives, including major push/pull incentives, aimed at fixing the broken antibiotics market provide one possible means for funding an openly collaborative approach to drug development. We argue that now is therefore the time to evaluate, at scale, whether such methods can deliver new medicines through to patients, in a timely manner

Setting the standard: multidisciplinary hallmarks for structural, equitable and tracked antibiotic policy

There is increasing concern globally about the enormity of the threats posed by antimicrobial resistance (AMR) to human, animal, plant and environmental health. A proliferation of international, national and institutional reports on the problems posed by AMR and the need for antibiotic stewardship have galvanised attention on the global stage. However, the AMR community increasingly laments a lack of action, often identified as an ‘implementation gap’. At a policy level, the design of internationally salient solutions that are able to address AMR’s interconnected biological and social (historical, political, economic and cultural) dimensions is not straightforward. This multidisciplinary paper responds by asking two basic questions: (A) Is a universal approach to AMR policy and antibiotic stewardship possible? (B) If yes, what hallmarks characterise ‘good’ antibiotic policy? Our multistage analysis revealed four central challenges facing current international antibiotic policy: metrics, prioritisation, implementation and inequality. In response to this diagnosis, we propose three hallmarks that can support robust international antibiotic policy. Emerging hallmarks for good antibiotic policies are: Structural, Equitable and Tracked. We describe these hallmarks and propose their consideration should aid the design and evaluation of international antibiotic policies with maximal benefit at both local and international scale

Setting the standard: Multidisciplinary hallmarks for structural, equitable and tracked antibiotic policy

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordThere is increasing concern globally about the enormity of the threats posed by antimicrobial resistance (AMR) to human, animal, plant and environmental health. A proliferation of international, national and institutional reports on the problems posed by AMR and the need for antibiotic stewardship have galvanised attention on the global stage. However, the AMR community increasingly laments a lack of action, often identified as an â € implementation gap'. At a policy level, the design of internationally salient solutions that are able to address AMR's interconnected biological and social (historical, political, economic and cultural) dimensions is not straightforward. This multidisciplinary paper responds by asking two basic questions: (A) Is a universal approach to AMR policy and antibiotic stewardship possible? (B) If yes, what hallmarks characterise â € good' antibiotic policy? Our multistage analysis revealed four central challenges facing current international antibiotic policy: metrics, prioritisation, implementation and inequality. In response to this diagnosis, we propose three hallmarks that can support robust international antibiotic policy. Emerging hallmarks for good antibiotic policies are: Structural, Equitable and Tracked. We describe these hallmarks and propose their consideration should aid the design and evaluation of international antibiotic policies with maximal benefit at both local and international scales.Antimicrobial Resistance Cross Council InitiativeEconomic and Social Research Council (ESRC)Department of HealthArts and Humanities Research Council (AHRC)Wellcome TrustINRAECDDEPUK Fleming FundMedical Research Council (MRC