What Can Be Done About Antimicrobial Resistance?

Happy Thanksgiving, my USian friends…

and…

and…

Who am I kidding? Happy Turkey Genocide Day. (No, I’m not referring to this.) I will take the time to re-assert my fake vegetarianism this week.

Dr Who….

…Turned 54 yesterday. Here’s the best Doctor, Tom Baker, telling us what’s what:

The 2nd Biggest Issue In The World Today…

While we expend much energy and time on debating the world-ending evils of using the wrong pronoun and/or the wrong bathroom, true Apocalyptic threats hasten to meet us. In my opinion, the two most impactful, predictable, and oncoming crises that will reshape our civilization for the worse  are Climate Change and its cousin, antimicrobial resistance.

The two are related in subtle ways. Climate change will alter patterns of human movement and clustering, as well as behaviours of disease vectors and even bacterial pathogens themselves, compelling shifts in who will need antibiotics, which ones they will need, and in what quantities.

But, also like Climate Change, a key barrier to people’s engagement with the issue is psychological distance, “the perception that the effects of an issue will be felt in the future, in a distant part of the world.” And yet this is a crisis that demands coordinated partnership between all participants in society, with strong leadership from above.

As the WHO says, “antimicrobial resistance can be tackled only through a concerted global effort, led by heads of state and global institutions, and through coordinated action by the health and agricultural sectors, in partnership with the food industry, campaign groups, and community organizations. ”

“Antimicrobial resistance is the new climate change.” And much like Climate Change, the solutions thus far suggested involve dramatic cultural change: reliance on basic handwashing to prevent disease, restraint on the part of hospitals and doctors to use most antimicrobial drugs except in extreme circumstances, denial of the ability of product manufacturers to include antibiotics in casual products, such as soap, and severely limiting the public’s ability to receive antibiotics on demand.

This is particularly problematic in low income countries, where the capacity for surveillance is limited, and where government controls over product content at points of sale is questionable and often nonexistent. In some countries, I’ve walked into a pharmacy off the street and purchased antibiotics over-the-counter, without a prescription or any evidence of medical need.

According to a WHO report, “a post-antibiotic era – in which common infections and minor injuries can kill – far from being an apocalyptic fantasy, is instead a very real possibility for the 21st Century.” We are rapidly approaching the point where minor elective surgery, like a nose job, is a serious life-threatening event, due mostly to the threat of nosocomial infection.

From an inter-sectoral perspective, most pressing is the need to remove antibiotics from the agricultural industry.  Here are some scary numbers:

However, “complex transmission routes within farm animals and between farm animals and humans… make it difficult to demonstrate whether a reservoir of [resistant bacteria] in farm animals poses a risk for animal or human health.” Yet, we have very poor surveillance systems for monitoring the extent and nature of resistance in agricultural products and populations.

Fighting antibiotic resistance is both a public health and national security priority.” (Climate change should be seen in the same light, but that’s a topic for another day.) In what I believe is one of Obama’s least noticed but most long term impactive actions, his 2014 Executive Order compelled US institutions to seek a solution to this impending crisis.

You can read about the US government’s major lines of research inquiry relating to this issue here. While the solutions presently discussed tend to be behavioural and procedural (changing prescription policies and product availability, for example), the truly transformative solutions must be technological.

By this I mean that we need new technologies for protecting individuals against infection. Several scholars have suggested that a greater reliance on vaccination may be a viable route forward, as “today is possible to make vaccines virtually against every pathogen.” It is both ironic and tragic that this revelation happens at the crucial historic conflux between the crisis of antimicrobial resistance and the epidemic of anti-intellectual rejection of vaccination at a societal level.

But the obvious technological solution is the innovation of new antimicrobial drugs. Are you sitting down? Would you be shocked to know that there has not been a new class of antibiotics developed since the 1980s?

So, given that there is a dramatic need for new antibiotics, why are drug companies not tripping over themselves to make new ones?  Surely, this is how the free market works, right? From a 2013 report by the World Economic Forum:

“…Drugs to treat chronic illnesses such as diabetes and hypertension increasingly offer a greater potential return on investment for pharmaceutical companies. Unlike with antibiotics, resistance is not an issue with these drugs. They have the potential to rapidly achieve wide market penetration.”

In other words, antibiotics do not represent a powerful enough profit drive to compel a drug company to invest a fortune in their discovery. In my view, then, there are three key business barriers preventing the free market to being a reliable forum for allowing drug companies to solve this technological dearth:

(1) If they develop new antibiotic drugs, rational policy would be to restrict their usage because we don’t want those new drugs to become resistant, too.  This means there will be limited market penetration, making drug development a financially low impact endeavour, and possibly a losing enterprise.

(2) Given that all antibiotics will become useless eventually (and fairly rapidly) due to resistance, then the time available for a new antibiotic to produce a return on investment is limited. Compare this to a blood pressure or diabetes drug, which renders sales many decades past its initial development.

(3) The old antibiotics still exist, though are clinging to relevance. Wise stewardship policy would see a reliance on those old classes of drugs before moving on to the theoretical new drug, again limiting sales and market uptake.

Despite these barriers, the Pew Institute has published a roadmap for antibiotic drug discovery.  One BMJ article recommends “delinking research and development costs from drug pricing and the return that drug companies receive on investment could correct misaligned economic incentives.” What that would look like is very unclear, but would necessarily have to involve creative “pull” incentives divorced from the traditional financial returns on R&D investment.

Another approach is to lighten the R&D burden.  This necessitates loosening the regulatory framework, which, to be blunt, would mean abutting some ethical barriers. Lowering the regulatory barrier means fewer protections for human test subjects, for example.

Creative financial incentives, such as tax incentives, have also been proposed. One of the more intriguing paths, in my opinion, is the call for a Manhattan Project for antibiotic resistance.  This would entail governments (frankly, the US government) making this issue a national priority, without concern for profit or sustainability.  Without question, this approach, sufficiently supported, would result in a new class of drug within half a decade.

But… but… but…. the nature of the beast is that, unerringly and eventually, every new class of antibiotic will be rendered unusable in a handful of generations.  Bacteria are just that advanced. So we would need to commission a new Manhattan Project every 2 generations or so.

Frankly, this seems to be a rational thing to spend our wealth on, much more so than weapons or any number of other unproductive but expensive items we choose to subsidize.

End of sermon.

One more reason I’m glad not to be single…

Man, comics have changed since my youth…