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How will history judge our current response to antimicrobial resistance?

I’m interested in considering how a scientist or historian might judge current responses to antimicrobial resistance in 30, 100 or 300 years and whether looking through that lens offers any insights into what we could do differently now!


Now is a truly remarkable time to be engaged in antimicrobial resistance. The decades long perceived threat is now a reality with an estimated >1m deaths per year (The Lancet). The urgency is obvious. The last two-decades has seen a remarkable transition from a major Pharma led-antibiotic industry to a biotech/academic led-response. In parallel, awesome organisations have developed to nurture the field including CARB-X, BARDA, GARDP, Novo Repair Impact Fund, AMR Action Fund, WHO and others. Alternative financial models e.g. subscription models, to encourage antibacterial R&D are an emerging reality. There is more enthusiasm and momentum in this space than there has been for the last 20-years. World-wide interest in infectious diseases, driven by the pandemic, may make microbiology and antibiotic R&D sexy again.


I do worry that, in the short term, in the search for new antibacterials to treat patients, we are overly attracted to innovation rather than pragmatism.


I have two key questions for you:

What if there were no good new antibiotic chemical classes?

What if there were no good new antibiotic targets?


A scientist or historian reviewing our current activities, with the benefit of 30, 100 or 300 years hindsight, would almost certainly conclude that it would have made sense to completely exhaust any opportunities in the known antibiotic chemical classes and clinically validated antibiotic targets as soon as possible. It does not make any sense to wait for decades before doing so.


But the antimicrobial resistance community, scientists, and funders, largely ignore the known, in search of innovation and novelty.


Acquiring funding to explore traditional antibiotic chemical classes such as the beta-lactams, macrolides, aminoglycosides, tetracyclines or their targets can be exceptionally challenging, perhaps because of a perception that they have been mined to death.


In this blog I am going to explore some of these options and will encourage the community to engage with this discussion so that we might perhaps identify some areas that merit investigation.

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silverly
Jan 25, 2022

I agree that “innovation” has been seductive. But there are no new targets. , or at least they are not limiting. I’ve said it for many years that single-target inhibitors are prone to rapid resistance. This became obvious in virology and to me at that time, that the way out was use of combinations to prevent resistance. This evolved for TB and for HIV, HCV. But not for resistant bacterial pathogens. There are many examples of single target inhibitors that have not been developed. As I’ve been saying for 30 years, we need to try combinations. And if we don’t, then your historians of science will look back and chide us for not doing multitargeting sooner and more purposefully.


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