When it comes to antibiotics, resistance is anything but futile!

If there's one constant that we can rely on in the never-ending hunt for better, safer drugs it is that a drug that lowers cholesterol or blood sugar today, will still do so decades from now. Thus, the massive investment that was required to develop that drug pays off not just in staggering short-term rewards for the investor (typically big pharma), but also in considerable long-term rewards for future generations who can benefit from discoveries made perhaps before they were even born. 

However, there is one class of drugs that we cannot say that about, the efficacy (or lack thereof) of which is becoming a bigger and bigger problem - antibiotics. We are in somewhat of an evolving crisis with this class of drugs, and "evolving" is the appropriate word because this class of drug, unlike one for say dyslipidemia, diabetes or depression, is working against a living organism; the drug-target interaction in this case is far from a static one, and just like many bacteria have learnt to evolve and live with us over eons of evolution, so can/do they learn to live with us in the presence of antibiotics. 

Antibiotic resistance is often discussed in terms of being a contemporary issue, but you know, we have known of resistance as far back as the early 1940s, when penicillin resistance was first identified. Ditto tetracycline, from which a resistant strain of Shigella evolved on the cusp of the sixties, and it only took two years after the launch of methicillin in 1960 for a resistant strain of Staphylococcus aureus (MRSA) to evolve. Millions of people have had their lives saved by antibiotics since their introduction, but ironically today those bacteria are back and threatening lives due to inappropriate use (as well as abuse) of those antibiotics.

Experts have been banging the table for years about the problem, and how rampant prescribing and overuse of antibiotics is going to come back to haunt us, as well as pointing out that modern agriculture is also at fault in terms of farmers putting antibiotic-fueled growth of livestock (and profits) above the nation's health.  Today it seems that at least one prominent personality has had enough, and that person is President Barack Obama, who tabled an executive order last Thursday demanding that his administration do something about it. 

"This is an urgent health threat, and a threat to our economic stability as well," stated Dr. Thomas Frieden, director of the U.S. Centers for Disease Control and Prevention.

Obama's executive order bypasses Congress completely, and immediately requires the setting up of a joint task force led by the Secretaries of Health & Human Services, Defense and Agriculture, whose role is to prepare a report and outline a five-year action plan by no later than next February. The task force also has to pore through a report produced by Obama's own Council of Advisors on Science and Technology, and recommend which action items to execute in the near term. 

The take-home message is clear - doctors need a go-to test that confirms that a patient has a bacterial (and not viral) infection, so that inappropriate (and useless) prescription of antibiotics is eliminated, as well as a test that can determine that a patient has an antibiotic-resistant infection. The executive order puts $20M on the table as a prize for anyone who invents such a test(s) that will have far-reaching impact on the careful, correct and conscientious use of antibiotics, as well as newly improving incentives for big pharma to return to the barren battlefields of the (seemingly forgotten) war against superbugs.

Additionally, current federal spending on that war is to be doubled - from its current investment of $450M a year - to $900M, and it is expected that antibiotic discovery research in government-funded labs will see significant improvements as a result. Of course, Obama wants the biggest weapons brought back out onto the battlefield to help, and that means persuading big pharma to unlock their doors - something which is estimated to require another $800M to persuade and facilitate big pharma to discover just one new antibiotic. 

It's an aggressive move, but one totally justified by the developing crisis and the future health and economic costs of widespread antibiotic resistance; not least because antibiotic resistance just hasn't seemed a "sexy" challenge of late, and we need to change that fact - and fast. The burgeoning gram-negative bacteria are the masters of such resistance, capable of invoking it in mere days when conditions threaten them, and turning a patient from recovery back into illness again during the same course of antibiotics. But you know, their very existence has centered on their capacity to survive disadvantageous environments, and that's been going on for millions and probably billions of years, so of course they are damn good at their job!

While big pharma as a collective abandoned antibiotic discovery due to a combination of extremely challenging science, unfavourable economics and a brutal regulatory environment, there was one pharma that proudly retained its interest in the segment - Pfizer. They were no newcomer to the field either, having been extremely successful in producing and marketing penicillin as far back as the forties, and Pfizer was widely believed to have had one of the top antibacterial pipelines and divisions in the world. But these days it's less about competition from other pharma (who have exited the space) and more about R&D competition from within - do we develop a novel antibiotic or a PCSK9 inhibitor?

The economics of classical big pharma force the choice of the latter. The very nature of antibiotics makes them less attractive as drugs - we only take them for 7-10 days (or less, and that is also part of the problem) and we may never have to take them again, whereas a cholesterol-lowering drug or a blood sugar-reducing drug may be taken for life. Rather ironically, we also tend to regard the latter two as life-saving drugs yet take antibiotics somewhat for granted. Even if it is truly the antibiotic class that has had the biggest impact on saving lives and extending lifespan, historically and currently, in various crisis situations.

But seemingly, a problem that gets eradicated in a week with some cheap antibiotic seems to garner a lot less respect than seeing one's cholesterol numbers go down with an extremely expensive regimen. It might be truly some kind of inverse financials that's at the root of the problem, and only if antibiotics are significantly raised in price will any form of sustainable economics arise for the discovery of new ones. We expect to swallow penicillin for the price of some salt and sugar, but are okay with companies charging tens of thousands per year for a cancer drug?!

What's the difference? They are both life-saving treatments. Flesh-eating bacteria are not that much different from a metastatic cancer, in that both develop resistance to drugs designed to kill them, and both of them are hell-bent on killing you via the resistance they develop. But one major difference is that cancer is not an infectious disease while bacteria are all around us and in us, and bacterial resistance is a community issue, a population issue, a global issue. Antibiotics (and resistance to them) must not be taken for granted. 

We have got to introduce a new model that includes economic opportunity for big pharma to return to antibiotic R&D because resistance is on the rise, and the overuse of antibiotics continues recklessly. Education of the public, doctors and healthcare professionals, and even of the government itself (by scientists) is needed in order to raise awareness and reverse the trend ongoing due to the widespread misuse of antibiotics. Barack Obama is clearly intending to get this issue firmly onto the evening news and dinner table while simultaneously pushing too readily-prescribed pills off our bedside tables, and I think that can only be a very good thing. 

Whether illicit drugs or antibiotics - the more you use, the more you lose!