This issue marks the first anniversary of The Lancet Microbe. This has been a year of profound change during which the world has experienced the most consequential infectious disease outbreak of the past 100 years. However, although COVID-19 continues to dominate the headlines, progress addressing one of the most significant infectious disease concerns, antimicrobial resistance, remains glacial. The status of antibacterial pipelines was summarised by WHO on April 15 in their report 2020 Antibacterial Agents in Clinical and Preclinical Development: an overview and analysis.
The report emphasises the seriousness of the situation with the bottom line that “the clinical pipeline and recently approved antibiotics are insufficient to tackle the challenge of increasing emergence and spread of antimicrobial resistance”. However, the activity within the preclinical pipeline offers some hope, and if a fraction of the energy and investment directed against COVID-19 were to be diverted here, it is easy to imagine that the future of antimicrobials would be reinvigorated. As the report outlines, “the preclinical and clinical pipeline continues to be driven by small- and medium-sized companies, which in general are struggling to find investors to finance late-stage clinical development up to regulatory approval”.
Given that genuinely new types of traditional antibacterials are in increasingly short supply as new agents are mainly derivatives of existing classes, the report, for the first time, expands its scope to encompass non-traditional products, such as monoclonal antibodies, bacteriophages, antimicrobial peptides, and antibacterial enhancers. That these products tackle infection in novel ways provides further hope that they can reduce the pressures on microbial populations that drive the selection of resistance against conventional drugs. Nevertheless, it is likely that even the most novel non-traditional antibacterial product will at some point select for resistance if used at scale. As for the traditional antibacterial drugs, the guiding principle will still need to be stewardship.
As noted above, the report highlights that a lack of financial impetus is the underlying problem when it comes to encouraging and supporting the development of new antimicrobial products. This issue also has a bearing on COVID-19. Although not directly relevant to antimicrobial development, a recent preprint explored the sources of investment that fed into one of the SARS-CoV-2 vaccines, offering some lessons that counter the prevailing dogma of the importance of private enterprise. The study investigators scoured records to uncover the source of funding for the Oxford-AstraZeneca COVID-19 vaccine. They found that at least 97% of the research and development funding for both the vaccine and the underlying technology came from public and charitable funds. Despite the assertion in WHO's report that “small- and medium-sized companies” drive the antimicrobial pipeline, it is not unusual for private enterprise to be absent at this early stage, with discovery and development costs borne by universities and public funding bodies. Maybe we need to be brave enough to admit that sometimes the commercial model is not the answer to all questions.
This statement is not intended as a criticism of commercial enterprise per se, it is just a recognition that conventional models of antimicrobial drug development have not succeeded. And tweaks that build on the current commercial system have not shown signs of delivering the results the world needs. Furthermore, finding better ways to fund pharmaceutical manufacturers does not seem to be the most efficient way to get support to researchers who drive the development process.
Increasingly it is pointed out that the COVID-19 pandemic has shown what can be achieved with the appropriate political will. Such statements are closely followed by bemusement that other issues approaching similar scales of impact are not looked upon with the same urgency. This question is even more pertinent with regard to antimicrobial resistance, which more so than other problems has the genuine potential to be existential in its impact. Over the second year of The Lancet Microbe, we hope to see the COVID-19 pandemic significantly diminished. Unfortunately, we are less optimistic about progress in tackling antimicrobial resistance. In fact, it will come as little surprise if a similar report in a year's time will be almost indistinguishable from the current version. Maybe the only way tangible progress can be made is if policy makers and the electorates that motivate them recognise, admittedly very late in the day, that we are in an antimicrobial resistance crisis?
