‘The end of antibiotics’

In this example of the Kirby-Bauer Disk Diffusion Susceptibility Test, E. coli bacteria are streaked on a dish with white paper disks containing seven separate antibiotics. The clear areas around the disks show where bacteria have been killed by the antibiotics. The E. coli at right is resistant to most of the antibiotics tested.

Many of us are familiar with the legend – in 1928, Scottish scientist Alexander Fleming noticed that mold infiltrating his petri dishes killed the bacteria in them, thus discovering penicillin. While antimicrobial substances had been used with some success by the ancient Egyptians and Greeks, Fleming’s discovery revolutionized medical treatment by allowing doctors to kill the sickening microbes that Louis Pasteur had proven to exist just 50 years before.

Now, more than 100 antibiotics exist, and they are a vital and omnipresent part of modern medicine. By one estimate, antibiotics save the lives of roughly 200,000 Americans annually and add 5-10 years life expectancy at birth.

The tragedy of the commons

The “tragedy of the commons” is one of the most famous and sobering concepts in analyzing human behavior – if enough humans behave only in their self-interest in using a resource, they could deplete or ruin that resource for their entire group. Ecologist Garrett Hardin’s famous 1968 exploration of this social dilemma focused on overpopulation and pollution, but it is a concept that applies all too well to the use of antibiotics.

“Antibiotics are a limited resource,” wrote the Centers for Disease Control and Prevention in a 2013 report on antibiotic resistance. “The more that antibiotics are used today, the less likely they will still be effective in the future.”

Antibiotics have often been deemed “magic bullets,” and their wonderfully curative properties make them seem almost unstoppable. But that unrelenting force behind all life on Earth also works against antibiotics – evolution. Just as humans have evolved to resist many diseases and toxins that once killed us, bacteria can and do evolve to resist the antibiotics that kill them. But while humanity’s relatively long gestation and maturation periods make our evolution proceed slowly, bacteria can reproduce roughly every 20 minutes, or 72 generations per day. With that kind of reproduction rate, the odds are that eventually a mutation will occur in a bacterium that allows it to survive an antibiotic treatment.

The problem results from two phenomenon – the overprescription and use of antibiotics by people, and the preventative use of antibiotics in livestock.

As much as 50 percent of the time, antibiotics are used unnecessarily in medical treatment, according to the CDC. Every exposure of an antibiotic to bacteria is another opportunity for the bacteria to develop a genetic mutation that lets it survive, and an environment free of helpful bacteria that that help control humans’ microbial populations.

Not only can people spread this drug-resistant bacteria to others, as demonstrated in the chart above, but bacteria themselves can spread their drug resistance to other bacteria they encounter through a process called gene transfer.

The chart below from the National Institutes of Health depicts one method of gene transfer – bacterial conjugation, in which a gene can pass directly from one bacterium to another. Several other methods, including transformation and transduction, also exist.

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Gene transfer is what antibiotic resistance such a persistent and fast-developing problem. It’s like someone figuring out the combination to a safe, and then giving it to everybody they met, and all those people giving the combination to everybody they met. Soon, the safe can stop nobody.

The other big issue is the use of antibiotics in livestock to help them grow more quickly and avoid potentially costly infections.

It’s estimated that 30 million pounds of antibiotics are given annually to livestock just in the U.S. That is several times the amount given to the country’s 318.9 million people, because antibiotics are routinely given to perfectly healthy animals. Bacteria in these animals are constantly exposed to antibiotics, which cull the weak bacteria while giving the strong ones more opportunities to develop mutations to resist them.

As far back as 1977, the U.S. Food and Drug Administration has tried to curtail this overuse of antibiotics by farmers, but it’s been stymied by powerful agricultural interests in the business world and Congress.

The polar opposite of the U.S. is the Netherlands, where the government and agricultural businesses collaborated to end the use of preventative antibiotics in livestock more than a decade ago. Stringent and common-sense cleaning and veterinary practices have allowed the country’s livestock industry to continue to flourish.

The timeline from the CDC report shows how quickly bacteria can develop resistance to an antibiotic – oftentimes, it can happen in just a year or two.

Fitter bacteria=deadlier bacteria

What perhaps some officials clung to as hope in the fight against antibiotic resistant bacteria was a hypothesis that the development of resistance by the bacteria to antibiotics made them less deadly and more vulnerable to other methods of killing them.

A paper published this week in Science Translational Medicine refutes this hunch, however, by finding that bacteria that have developed drug resistance actually proved to be more deadly and infectious to mice than their non-resistant brethren.

The conclusion “raises a serious concern that drug-resistant strains might be better fit to cause serious, more difficult to treat infections, beyond just the issues raised by the complexity of antibiotic treatment,” wrote the authors.

“We’re in the post-antibiotic era”

That was the grim pronouncement made by Dr. Arjun Srinivasan, an associate director of the CDC, in a 2013 PBS Frontline documentary.

“For a long time, there have been newspaper stories and covers of magazines that talked about ‘The end of antibiotics, question mark?'” Srinivasan said. “Well, now I would say you can change the title to ‘The end of antibiotics, period.'”

One of the most visible and deadly consequences of antibiotic resistance is the persistent spread of Methicillin-resistant Staphylococcus aureus, or MRSA. First seen in the 1960’s, it is a deadly bacteria that often hits hospitals, infecting the weak and healthy alike. Though the rate of MRSA infections has declined it recent years, more than 11,000 die from MRSA-related causes each year.

Things don’t look great for the future, but doctors, scientists and lawmakers are still working to stop antibiotic resistance from causing medicine and ultimately to backslide.

“In a world with few effective antibiotics, modern medical advances such as surgery, transplants, and chemotherapy may no longer be viable due to the threat of infection,” warned the White House in a 2014 report.

I personally hope that world never comes.

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