"A little less conversation, a little more action please
All this aggravation ain't satisfactioning me
A little more bite and a little less bark
A little less fight and a little more spark
Close your mouth and open up your heart and baby satisfy me
Satisfy me baby"
- Elvis Presley, 'A Little Less Conversation', 1968
It's World Antimicrobial Resistance Week (WAAW) and there has been a flurry of articles, reports and events around the world designed to draw attention to the worldwide problem of antimicrobial resistance (AMR) and the need for change.
I'm not sure what 'The King' knew about AMR in 1968, but the lyrics of his song sum up the commentary from more than a few people about the need for more action and less talking in the global push to address AMR.
What is the problem?
Put simply, AMR is when microbes, such as bacteria, viruses, fungi and parasites, no longer respond to the drugs designed to kill them.
It occurs because the antimicrobial medicines we have to fight diseases like MSRA, tuberculosis and typhoid are losing their effectiveness as these microbes evolve.
And, already, AMR kills 700,000 people each year.
Often, however, this happens below the radar, as it were, out of sight in what's been called the 'silent tsunami'.
To put it into context, at the time of writing the COVID-19 pandemic, which the world has thrown literally trillions of dollars to fight in less than 12 months, has killed 1,356,000 people this year.
However, the predictions are that by 2050 - a mere 30 years away - AMR will kill 10 million people each year.
The economic impacts will be substantial as well, costing the global economy an estimated US$100 trillion and pushing 28 million people into poverty.
Whether it's not being able to treat infections, the high number of deaths, or preventing health care options like surgery and hospitalisation due to greater risk of infection, AMR is a major global health and economic issue for rich and poor countries alike.
Source: World Bank. 2017. Drug Resistant Infections: a Threat to Our Economic Future: Key Findings, http://pubdocs.worldbank.org/en/440641493730169238/1708276-AMR-Report-Summary-Web.pdf, accessed 21/11/2020.
More action needed
While there is a lot of good work that has already been done in the fight against AMR, there is an urgent need to do more.
The attention given to the issue has grown dramatically over the last two decades. Twenty years ago few were talking about it, whereas today many are.
There have been many good initiatives in response launched by a wide range of stakeholders and organisations. For example, there is the UN General Assembly's 2016 Political Declaration on Antimicrobial Resistance, a Global Action Plan on AMR under the auspices of the World Health Organization, the private sector-led AMR Industry Alliance, the ground breaking O'Neill Review on AMR in 2016, various efforts by national government initiatives and extraordinary advocacy by global health experts like Dame Sally Davies and others to draw attention to the issue.
However, the Wellcome Trust has just released its new report The Global Response to AMR, which argues that while the world has achieved notable successes, we are at a critical point in the trajectory of tackling AMR and risk irreparably weakening the future global response to AMR.
The Wellcome Trust argues that the world has already made great progress so far by:
putting AMR on the global political agenda - international political forums are now regularly talking about it
getting a broad, multi-sectoral coalition of actors working together willing to tackle the problem, and
substantially funding the initial discovery phase and next translational stage of developing new antimicrobials.
But the Trust also points out that the global response to AMR is at a critical juncture because ambitions have not always translated into meaningful action.
Prioritising what to do first has proven difficult and the Wellcome Trust says the AMR agenda was losing momentum even before COVID-19 hit.
There has been a lot of conversation about AMR but not enough action, to paraphrase the 'King'.
In many cases the problems have been identified, but it's in identifying and implementing the solutions that the issue has been.
There are many facets to fighting AMR, whether it's trying to develop new antimicrobials, better managing the use of the antimicrobials we still have, looking at environmental pollution or better using data and surveillance, there are many actions that need attention.
And perhaps that's part of the problem.
A case study: developing new antibiotics
One example is in the problems in developing new antibiotics.
There have been some excellent initiatives developed in the last few years to support the early stage development of new antibiotics. These include the Global Antibiotic Research and Development Partnership (GARDP) created by the World Health Organization and the Drugs for Neglected Diseases initiative, the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) - a not-for-profit led by Boston University and funded by a consortium of governments and foundations, and the US$1 billion AMR Action Fund initiated by the pharmaceutical industry through the International Federation of Pharmaceutical Manufacturers and Associations.
A key problem, however, is that the market is not sufficiently commercially attractive enough to encourage the development of new antibiotics.
Basically, no one is prepared to pay enough for the new antibiotics once they get to market.
That's pretty incredible for a global health problem that is going to kill 10 million people a year and cost US$100 trillion.
And the problem is not new, it's been around for decades.
Over the last few decades large pharmaceutical companies have withdrawn from the antibiotics market because the returns just aren't there. Smaller start-up biotech companies have similarly found the commercial environment very tough.
The recent bankruptcies of emerging biotech companies, like Achaogen and Melinta Therapeutics, that have tried to commercialise new antibiotics demonstrates that more work needs to be done to make the market for new antibiotics commercially viable.
In spite of the good 'push' initiatives to encourage early stage drug development, there hasn't been enough 'pull' incentives at the other end of the development chain to make taking such antibiotics to market sufficiently attractive.
There are a number of pilots under way at the moment to trial subscription style purchasing models that reward companies based more on the value of the antibiotic and less on the volume of antibiotics sold, such as those initiated by the UK and Swedish Governments and proposals like the Pasteur Act in the US.
Hopefully these sorts of initiatives will drive more action to redress the fundamental commercial problems of developing new antibiotics.
Renewed momentum needed
There are, however, many other issues in that need to be addressed in the AMR space, such as managing existing antibiotics better, environmental protection, infection control, vaccine development and anti use in farming.
There is a debate going on right now about whether the COVID-19 outbreak will be a blessing or a curse in the cause of fighting AMR.
On one hand, COVID-19 could distract attention from other areas of global health like AMR. Once the dust settles and COVID is dealt with, everyone may just forget about AMR and infectious diseases altogether and go back to normal business. This wouldn't be the first time future pandemic preparedness has been forgotten soon after a pandemic.
Or the outbreak could be the catalyst to put more priority on dealing with global health threats like AMR. COVID-19 has shown what can happen if the world doesn't take the threat of infectious diseases seriously.
Maybe the chance has come to build on all the important and worthwhile talking about AMR that has happened to date and drive more action to fix one of the world's great global threats.