How Lethal Bacteria Evolve to Survive

The golden age of medicine began with the discovery of antibiotics. Less than 90 years later, their overuse has given rise to deadly "superbugs."

Earlier this year, Dr. Neil Fishman faced a tough decision. A 54-year-old man fell off his roof while doing housework, injuring his leg. Six months later, bacteria resistant to most antibiotics had infected the wound. Fishman, associate chief medical officer for the University of Pennsylvania Health System, saw few choices: use an old, toxic antibiotic that didn’t work well and would destroy the patient’s kidneys, or amputate his leg.

“It’s scary to me that in 2014 those are the only two options to give him,” Fishman, who is also chair of the Society of Healthcare Epidemiology of America’s Education & Research Foundation, told Healthline.

The patient had his leg amputated, thus saving his life. That case is anything but isolated. Fishman has been working on antibiotic resistance since the early 1990s, and has watched along with other infectious disease experts as deadly bacteria have grown stronger, antibiotic use has increased, and new antibiotic discovery has fallen to an all-time low.

They’re the only drug where administration to one patient can affect another person.
Dr. Neil Fishman, chair of the Society of Healthcare Epidemiology of America’s Education & Research Foundation

It has been 86 years since the first antibiotic was discovered. Experts like Fishman can cite reams of scientific evidence that show antibiotics are not as safe as they were once thought to be, and that widespread, indiscriminate antibiotic use triggers antibiotic resistance and other complications.

“They’re the only drug where administration to one patient can affect another person,” Fishman said.

But how do single-celled organisms continue to outsmart the species that put men on the moon and robots on Mars? The short answer is that they’ve been doing it since long before we learned to walk on two feet.

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An Emerging Epidemic in the 21st Century

The discovery of antibiotics made all medical procedures less risky, but they are slowly losing their effectiveness.

Bacteria are everywhere. And in most cases, that’s a good thing. Those tiny, single-celled organisms are keeping you alive by helping you digest your meals and aiding your body in fighting off infection and disease. Scientists at the National Institutes of Health are isolating and mapping the genes of all these bacteria, collectively called the human microbiome.

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They’re strong, resourceful, and plentiful. Microbes outnumber us by 10,000,000,000,000,000,000,000 to 1, they have existed 1,000 times longer than Homo sapiens, and they are capable of creating 500,000 generations in one human’s lifetime.

While humans simply can’t exist without the help of bacteria, many strains are deadly and have been the source of billions of deaths throughout history.

Humans were given a leg up when Dutch scientist Antonie van Leeuwenhoek discovered bacteria under a microscope in 1676, and one better when Alexander Fleming discovered penicillin in 1928. Those discoveries have led to the development of dozens of classes of antibiotics.

These drugs have been so crucial for so long that we’ve nearly forgotten what it’s like when common medical problems become life-or-death situations, though the signs of a reversal have been there all along.

People aren’t going to be able to have their teeth fixed, or their hip replaced, if we don’t stop this. All of the new medicine, all of the new surgeries, the basis of that being successful is antibiotic use.
Rep. Louise Slaughter (D-N.Y.)

Those who have been studying the issue, from top U.S. government infectious-disease scientists to doctors fighting to save their patients' lives, say we need to quit our old habits and get with the new science. According to the World Health Organization, we aren't far from a world where our best defenses against bacteria are rendered useless.

Rep. Louise Slaughter, D-N.Y., the only microbiologist in Congress, has repeatedly and unsuccessfully tried to change the way America uses antibiotics since 2007.

“People aren’t going to be able to have their teeth fixed, or their hip replaced, if we don’t stop this. All of the new medicine, all of the new surgeries, the basis of that being successful is antibiotic use,” she told Healthline. “We’re talking about strep throat being fatal. That’s the scariest thing.”

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The Greatest Bacterial Threats Facing the U.S.

The discovery of antibiotics made all medical procedures less risky, but they are slowly losing their effectiveness.

Bacteria have always had the ability to evolve defenses against organisms designed to kill them. In fact, microbes, including bacteria, are the most abundant and toughest forms of life on our planet.

Some of these single-celled organisms have become so tough that we now call them “superbugs” because they can outsmart our best antibiotic defenses.  And 23,000 Americans die each year because of them.

A recent study in the Journal of the Pediatric Infectious Diseases Society found that antibiotic-resistant bacteria are on the rise, especially in children ages 1 to 5. While a large number of infections occur inside the healthcare system, these children infected with drug-resistant bacteria had limited exposure to hospitals. And nearly three-quarters of the bacteria studied produced an enzyme that made them resistant to multiple classes of antibiotics.

Bacteria that had been isolated from the earth’s surface for more than four million years have been discovered in the depths of Lechuguilla Cave in New Mexico. Researchers found that those bacteria were highly resistant to as many as 14 different commercially available antibiotics.

“This supports a growing understanding that antibiotic resistance is natural, ancient, and hard wired in the microbial pangenome,” the researchers wrote in the journal PLOS One.

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Before the discovery of antibiotics, routine surgeries, cuts, and diseases caused by bacteria were often fatal. For example, tuberculosis (TB)—caused by the bacterium Mycobacterium tuberculosis—killed millions of people all over the world each year. The development of the antibiotic streptomycin in 1943 reduced the fatality rate for this common bacterial infection by 90 percent.

But TB hasn’t gone away. Multidrug-resistant TB—those strains that are resistant to the drugs isoniazid and rifampin—increased after a resurgence in 1992, are widespread in some developing countries, and still hospitalized 72 Americans in 2012.

Drug-resistant TB is only one of the threats identified by the U.S. Centers for Disease Control and Prevention (CDC). The top three are:

  • Clostridium difficile (C. diff): populates a person’s gut and can cause lethal diarrhea
  • Carbapenem-resistant Enterobacteriaceae (CRE): nicknamed the “nightmare bacteria” because this family of bacteria is fatal in half of all cases
  • Drug-resistant Neisseria gonorrhoeae: a species of bacteria responsible for the sexually transmitted infection gonorrhea, which can cause infertility in young women

While these are the biggest threats, recent research published in the journal Current Biology found that bacteria all over the world—on nearly every surface—have the ability to become antibiotic resistant. The most abundant and diverse pool of resistance was found in soil, where bacteria possessed genes resistant to vancomycin, tetracycline, or beta-lactam antibiotics.

All three are commonly used in veterinary and human medicine. The overuse of antibiotics was something Fleming warned about after discovering penicillin more than eight decades ago.

We’re dangerously close to what the world looked like before the discovery of penicillin.
Dr. Neil Fishman, chair of the Society of Healthcare Epidemiology of America’s Education & Research Foundation

“It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body,” he wrote while accepting the Nobel Prize in 1945. “The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug, make them resistant.”

While you can’t buy over-the-counter antibiotics at your neighborhood pharmacy, they are available at animal-feed stores. The widespread use of antibiotics in animals and humans has public health officials sounding the alarm that something must change.

“We are literally running out of antibiotics. We’re seeing more and more germs that our current antibiotics can’t treat,” Fishman said. “We’re dangerously close to what the world looked like before the discovery of penicillin.”

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How Bacteria Evolve to Survive

Superbugs can learn how to outsmart antibiotics, including by eating their dead.

The most common way bacteria develop drug resistance is through lateral gene transfer, in which bacteria pass information to one another like a student passing a note in class.

Dr. Karl Klose of the University of Texas at San Antonio explained this phenomenon during a TEDx talk: “This is equivalent of you going to the funeral of someone who had blue eyes, taking a piece of their body out of the casket, and eating it. And hey! You have blue eyes too. But now imagine that instead of blue eyes, you now are resistant to tetracycline.”

It’s a scary situation, and we’ve known about it for 40 to 50 years.
Dr. John Bolton, clinical professor of pediatrics, University of California, San Francisco

Bacteria can also transfer genes using viruses, direct contact, and good old-fashioned reproduction. While it can take decades to develop a new antibiotic, bacteria can evolve around one in as little as 20 minutes.

Dr. John Bolton, clinical professor of pediatrics at the University of California, San Francisco, said it’s basic biology that the easiest way to develop antibiotic resistance is to administer low doses of antibiotics over a long period of time, much like how antibiotics are used in animal feed. “It’s a scary situation, and we’ve known about it for 40 to 50 years,” he said.

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Using Antibiotics in Livestock

The animals we eat are fed a steady diet of antibiotics, in part because it fattens them up.

Agriculture accounts for 80 percent of all antibiotics used in the U.S., and there’s continued pressure from interested parties to maintain the status quo.

As of 2011, about 80 percent of all swine farms, cattle feedlots, and sheep farms reported that they use low levels of antibiotics in feed and water for growth or health purposes, according to the Department of Agriculture’s Animal and Plant Health Inspection Service.

The studies that are coming out now are really solid, concrete pieces of evidence that can really put this picture together.
Carmen Cordova, microbiologist, Natural Resources Defense Council

Carmen Cordova, a microbiologist with the Natural Resources Defense Council, said emerging science shows how antibiotic use in animals affects human health. She said studies now show how Staphylococcus aureus, one type of staph bacteria, can be present in humans, transferred through close contact to pigs, where it picks up resistance to the antibiotics in their feed, and then re-entered into the human population through pork consumption.

“The risks were acknowledged 40 years ago. What’s changed is that now you have more solid evidence. You have more sophisticated ways to show this is happening,” Cordova told Healthline. “The studies that are coming out now are really solid, concrete pieces of evidence that can really put this picture together.”

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More Antibiotics Makes Things Worse

Public health campaigns encourage doctors to use good judgment.

Antibiotics become less effective the more often they’re used, and C. diff is one example of how this occurs. While scientists once thought antibiotics were the cure for this stomach infection, experts now know they are actually the cause.

Drug-resistant C. diff infections—which account for 12 percent of all hospital-acquired infections—occur when beta-lactam antibiotics clear the gut of other bacteria, allowing C. diff to flourish and cause potentially fatal diarrhea.

More medication isn’t better. The right medications are better. It is not too late. If we’re not careful, the medicine chest will be empty.
Tom Frieden, CDC director

The way C. diff infections work is only one discovery that is leading scientists to believe antibiotics aren’t as safe as once thought. The most widespread overuse of antibiotics in humans is as a treatment for the common cold. As viruses—not bacteria—are the cause of colds, administering antibiotics does nothing but give bacteria ample experience to outsmart the drugs and potentially cause unwanted side effects such as vomiting and diarrhea.

“We’ve been trusted with these antibiotics that have been developed over decades and we need to preserve their effectiveness for the future,” Dr. Tom Frieden, CDC director, warned in September. “More medication isn’t better. The right medications are better. It is not too late. If we’re not careful, the medicine chest will be empty.”

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The CDC and other major health organizations have launched public-awareness campaigns urging patients and doctors to be judicious with using antibiotics because the CDC has presented evidence that slowing prescribing rates is directly linked to fewer drug-resistant bacteria.

Ramanan Laxminarayan, director and senior fellow at the Center for Disease Dynamics, Economics & Policy, said that we need a seismic shift in how antibiotics are handled in order to slow the oncoming epidemic.

“We need to stop thinking of antibiotics as commodities and more as resources,” he told Healthline.

The next story in this series examines how antibiotics are used in healthcare, why patients continue to demand antibiotics, and how financial incentives are beginning to reduce hospital-acquired infections.Continue to the next article  »