By Seán Finan

And scattered about it, some in their overturned war-machines, some in the now rigid handling-machines, and a dozen of them stark and silent and laid in a row, were the Martians–dead!–slain by the putrefactive and disease bacteria against which their systems were unprepared; slain as the red weed was being slain; slain, after all man’s devices had failed…

H.G. Wells, The War of the Worlds  

The WHO World Antibiotic Awareness Week ran from 15-22 November. It coincided with similar European and American initiatives. So, in the interests of raising awareness, I thought I would highlight a few figures.

Antimicrobial resistance currently causes an estimated 70,000 deaths annually. If current practices continue, the death toll is expected to hit to ten million per year by 2050. That works out at about one death every three seconds.

The threat isn’t limited to increased mortality. Anti-microbial resistance could cast medical practice back to turn-of-the-century standards. Turn of the 20^th century, that is. Without antibiotics, the chance of infection turns chemotherapy and invasive surgeries into mortal gambles. During these procedures, the body’s immune system is subject to massive exposure and needs antibiotic support. Even ordinary nicks and scratches can lead to fatal infections without effective antibiotics.

So what is antimicrobial resistance? How does it come about? What can we do to combat it and prevent the “antibiotic apocalypse”?

Antibiotics and Evolution

Bacteria are among the oldest life forms on the planet. They spread and evolve quickly and constantly, adapting to meet new challenges and environments. Some are harmless. Others are beneficial or even essential to human life. Others, such as the bacteria thought to have caused the Black Death, have caused us some problems. Since Alexander Fleming discovered antibiotics, hundreds of variations and classes have been invented. However, bacteria quickly adapted. The first strains of penicillin-resistant bacteria had been documented in labs before penicillin hit the mass market. Antimicrobial resistance describes the ability of bacteria to combat antibiotics that would have previously overwhelmed them.

Much of this resistance is an unavoidable product of evolution. Bacteria can develop this antimicrobial resistance at astonishing speeds, partly because they can pass their adaptive mutations laterally to other bacteria: they are not confined to passing evolutionary adaptions to their direct descendants.

Accelerating Evolution

The spread of resistance has been dramatically accelerated by the use and misuse of antibiotics by humans. There are three main factors at play.

First, the extended use of antibiotics. Bacteria that are exposed to an antibiotic for long enough without succumbing will likely develop resistance. Second, the indiscriminate or inappropriate use of antibiotics. In many cases, antibiotics are prescribed for minor illnesses, dulling humanity’s blade for the sake of avoiding a day in bed. In other cases, antibiotics are prescribed to treat viruses. Not only is this completely ineffective, but it gives whatever bacteria lie dormant in a patient the chance to develop resistance. Today, self-medication is a major driving factor in antimicrobial resistance. People experience certain symptoms, remember that they were prescribed antibiotics for similar symptoms in the past and self-prescribe. India has seen a dramatic rise in this practice and a corresponding rise in resistant bacteria.

Third, and perhaps most troubling, is the use of antibiotics in agriculture. It was discovered that administering certain antibiotics to livestock could dramatically accelerate their growth. Factory farms the world over immediately began flushing their cattle with antibiotics. Plenty of strains of resistant bacteria resulted and plenty of those are capable of infecting humans. Furthermore, the antibiotics are often still present in the meat we consume and capable of promoting antimicrobial resistance within us.

Losing the Arms Race

These problems seemed fairly minor in the heyday of antibiotic invention. Between 1980 and 1984, for example, 19 new antibiotics were approved by the FDA. Even if we weren’t winning the arms race, we were at least keeping up. However, that rate of development has stalled. Only 13 new antibiotics were approved between 2000 and 2014. We have largely relied on private industry to innovate in medicine but here, the traditional incentive structures are failing. Three problems underlie the lack of development.

1. Pharmaceutical companies rely on patents to bring profits. The patent model relies on selling as much as possible of a product within the period of protected monopoly. However, we need to actively restrict the use and sale of antibiotics to minimize resistance.
2. Antibiotics are taken for a handful of short periods over the life of the average patient. As such, they bring in much less revenue per patient than, for example, a cancer medication.
3. Antibiotics are easily reproduced by generics manufacturers and patients are generally unwilling to pay premium prices for them.

The result is that 15 of the world’s top 18 pharmaceutical companies have stopped researching new antibiotics.

An Existential Threat?

The bottom line is that the number of ineffective antibiotics is growing and the number of new antibiotics being produced is falling. Factor in a superbug or two and the phrase “existential threat” doesn’t seem particularly hyperbolic. So what can we do to address the threat?

The Battle Plan

In 2014, a British report recommended ten steps that should be taken by world governments

Step one is to combat the spread of disease by improving sanitation, both in hospitals and outside. Antibiotics are often used extensively in undeveloped nations to combat the diseases that result from poor hygiene and water quality.

Steps two, three and four address health practices. The report recommends improving diagnostic tools to reduce inappropriate prescriptions, promoting effective alternatives (such as vaccines) to reduce use and raising public awareness of the appropriate use of antibiotics and the consequences of continued inappropriate use. Recent experiments have targeted doctors by asking them to mount a pledge to use less antibiotics on their office wall, sending them monthly reports on their rate of prescription compared to their peers and training them to better deflect patients who demand a prescription. The measures seem to dramatically reduce the rate of prescription.

Step five is to reduce the use of antibiotics in agriculture. Europe has banned their use for promoting animal growth. However, though the efficacy of the ban has been questioned. Furthermore, America and the BRIC nations are the worst culprits and their use is growing.

Step six addresses the development problem by “delinking” reward from sales. The idea is to promote research by granting large monetary awards for the development of new antibiotics. These rewards could be made conditional on the new antibiotics being kept off the market until absolutely necessary. Pharmaceutical companies (somewhat predictably) liked the idea of “delinkage” and many jointly issued the Davos Declaration in 2016, calling for rewards of up to $1.3bn for each new and effective antibiotic. Profits prevail, even in the face of the apocalypse, it seems. Moralizing aside, the British report found that re-purposing just 0.05% of the G20’s combined health budget could address most of the problems.

Steps seven, eight, nine and ten involve global coordination, including launching a global surveillance network to track the spread of resistance, improving the pay and recognition for scientists researching infectious diseases and creating a global innovation fund for antibiotic research. The fight against antimicrobial resistance depends ultimately on the success of the tenth step: building a global coalition and presenting a united front against bacteria. The WHO has recommended that this framework be made legally binding.

Recent weeks have raised many questions about the future of healthcare in America. Without wanting to downplay the importance of insurance and access within the country, I can’t help but feel that we’re taking our eyes off the long game. The Obama Administration made strong commitments to funding antibiotic research and promoting better practices. I can only hope that this won’t change with the new administration.