A Philosopher Looks at Antibiotic Resistance

The antibiotic crisis and its cascading impact is a well-characterized seemingly insoluble infectious disease problem. There is a large context of factors that impact antibiotic and exacerbate the problem which include: the ever present threat of evolved resistance and consequent antibiotic stewardship concerns, the low relative price of antibiotics (versus more lucrative pharmaceutical products), the outrage that accompanies any attempt to raise the price of an antimicrobial, the fact that one individual’s (or animal’s) use of an antibiotic can impact another individual’s future use, and the general societal undervaluing of infectious disease control, prevention, and treatment.

In recent years, one of the biggest legislative effort to incentivize antibiotic development has been The GAIN Act, which is “pull” incentive that provides an additional 5 years of market exclusivity for certain qualified infectious disease products (QIDPs) that is stacked upon other market exclusivity that may exist because of its novel chemical nature, its applicability to pediatric patients, or its niche in treating a rare (orphan) disease. Importantly this market exclusivity is not intellectual property based, but instead results from the FDA not allowing any generic versions to be marketed for that period of time. Other pull initiatives include special technology payments to hospitals that use certain “breakthrough” antibiotics that use them as well as proposals to reimburse hospitals higher for drug-resistant infections and to carve antibiotics out of bundled payments for hospitalization (removing the incentive to use cheaper antibiotics when more expensive and more effective ones may be indicated). There are also “push” initiatives that fund early development such as CARB-X.

Given this context, it is clear that there is a real problem to solve — one that is often blamed on markets. Gregory Salmieri — a philosopher and friend of mine dating back to when he was a graduate student at the University of Pittsburgh’s philosophy program — has recently published an innovative and creative solution in the George Mason University Law Review.

In his piece, Salmieri first presents the current situation in a very comprehensive manner addressing legislation and new proposed business models (such as decoupling/delinking revenues from sales volume). Next, he makes a convincing case that antibiotics suffer from a “tragedy of the commons” in which “a resource of immense value” is “being used myopically in a way that destroys existing stocks of the resource” with little “being done to find or develop new stocks of it.”

The proposal Salmieri advances is one premised upon enabling “creators of drugs to profitably exercise their rights over the drugs in a manner that preserves the drugs’ effectiveness over time—ideally into the indefinite future.” By tying patent life explicitly to resistance rates of target organisms to a predetermined threshold (e.g. remaining below 20%), a patent could exist in perpetuity (like a trademark). Such a mechanism incentives the judicious use of the antibiotic in order to preserve its profitability at higher patent-protected prices that could also reflect a premium placed on drugs-of-last resort, increasing return on investment over a longer term horizon.

Salmieri also addresses certain complications including cross resistance to drugs developing and issues related to how other countries steward antibiotics.

I think that this is an excellent paper to read — irrespective of whether you agree with the solution —because it offers a clearly reasoned solution that looks at this problem through a different lens and allows one to better conceptualize a problem that has been looming since the time of Alexander Fleming’s prescient warning. I hope it finds a large audience and sparks the debate it merits.

What do Legionnaire's, Parrots, and Sharks Have in Common: A Review of The Pandemic Century

The latest book on pandemics and infectious disease that I’ve made my way through is Mark Honigsbaum’s The Pandemic Century: 100 Years of Panic, Hysteria, and Hubris, “a book about these events and processes, and the reasons why, despite our best efforts to predict and prepare for them, they continue to take us by surprise.” That theme is an important one that deserves attention as time and again, a new infectious disease threat appears and calamity ensues. This cycle repeats over and over.

True to the panic and calamity aspect, Honigsbaum begins his book discussing shark attacks occurring in the North Atlantic, a supposed venue in which such attacks were not known to occur. Sound familiar? We’ve heard that a lot: Ebola doesn’t occur in West Africa, Zika doesn’t occur in the Western Hemisphere, Chikungunya is restricted in its geographic spread, etc etc

Infectious diseases — though we try to find strict laws of nature to confine them — are fluid physical phenomena whose dynamics are influenced by countless factors that are very hard to account for in models and cannot be dogmatized. It is not a foregone conclusion that each pandemic threat can be easily beaten back as we have seen with malaria, tuberculosis, influenza, and HIV (to name a few prominent ones). As New York Times science journalist Carl Zimmer notes in his review of the book: “What made this past century unusual was not pandemics per se, but our expectations about beating them. The germ theory of disease and other scientific advances in the 19th century fostered a sense of mastery over the microbial world.”

Honigsbaum’s book is divided into several chapters recounting various outbreaks and pandemics. Some of these are familiar such as the 1918 influenza pandemic, the 1976 Legionnaire’s Disease outbreak, SARS, and HIV. However, some are less familiar such as the parrot fever (psittacosis) outbreak that occurred in 1930s America. Of this outbreak, Honigsbaum colorfully writes:

Perhaps the most important factor of all, however, had been the popularity of lovebirds with American consumers and the lucrative interstate trade that saw itinerant peddlers going door-to-door offering parakeets to widows and housewives. In 1930, the idea that these cute American-bred birds might be the avian equivalent of Trojan horses was too disturbing to contemplate.

I recommend this book to those who want an easily digestible account of pandemics and outbreaks that are not only headline-grabbing but reveal holes in our preparedness and knowledge regarding infectious disease and microbiology. When each outbreak occurs, it is invariably followed by conspiracy theories, fake news, panic, sometimes disregard, and a whole host of other human responses that are driven by the uncertainty that characterizes the early days of a response. This is nothing new and is something that will continue but will hamper response and containment activities. The value of learning the history contained in this book is as Carl Zimmer notes in his review, “Surely the value of understanding history is that it gives us a chance to stop repeating our mistakes.”