Back in the late 1960s, U.S. Surgeon General Dr. William H. Stewart allegedly made this provocative, very definitive statement: “It is time to close the book on infectious diseases, and declare the war against pestilence won.”
Fast forward 50 years and the U.K.’s Chief Medical Officer, Dame Sally Davies, has quite a different take, saying that antibiotic resistance to disease poses nothing less than an “apocalyptic” threat, reported The Guardian. The Centers for Disease Control added its voice, saying that antibiotic-resistant bacteria were a “nightmare,” and called for action.
So what happened in those 50 intervening years?
Nothing that you couldn't see coming, which may make the current state of affairs even more tragic. The truth is, antibiotic resistance goes way back. In 2012, a group of scientists from the University of Akron, Ohio, and McMaster University, in Ontario, Canada, reported in PLOS One on the discovery of antibiotic-resistant bacteria in an underground cave in New Mexico that has been isolated for about four million years.
It helps to understand a few of the basics about resistance. First, there are two types—intrinsic and acquired. If a bacterium is intrinsically (or innately) resistant to a given antibiotic, the bacterium is resistant to a certain type of antibiotic coded into its DNA. Either due to the way the bacterium is structured or the way it functions, certain antibiotics are powerless against the germ.
As we create more antibiotics and introduce them into the environment, in animals, and in humans, microbes get smarter. They evolve for survival; this is called acquired resistance. Bacteria can acquire resistance either through a genetic mutation or by receiving genetic material from other bacteria that already have resistance. In science-speak, this is referred to as “horizontal gene transfer.”
The modern era of antibiotics really started in the early 1900s with German scientist Paul Ehrlich. While looking for something that could kill specific bacteria, he produced a chemical dye, commercially known as Salvarsan; this compound (arsphenamine) became a magic bullet treatment against syphilis. Then, in 1928, English scientist Alexander Fleming noticed something odd in one of the petri dishes in which he had been culturing bacteria: Mold had begun to grow. Around the mold, all the bacteria was gone—it had been killed; this mold was Penicillum notatum, what we know today as penicillin.
A few years later, in 1935, German biochemist Gerhard Domagk created the first commercially available antibiotic, sulfonamide (or Prontosil as it was known then); these are the “sulfa drugs” we still use today and that have been used to treat infections that cause meningitis and pneumonia. By the late 1930s scientists Howard Florey and Ernst Chain had picked up on Fleming’s research and, after teaming up with an American agricultural company, they began producing penicillin as a widely available antibiotic—just in time for America’s entry into World War II. By the end of the war, penicillin was in mass production. With sulfa drugs and penicillin as huge success stories, the U.S. was beating back infectious disease.
At least that’s what we thought. In the mid-1940s, Fleming saw what might be coming and issued a warning in The New York Times: We should avoid the overuse of penicillin if we want to stem the proliferation of antibiotic resistance, he said; even then, there was already growing resistance to sulfonamides, the first antibiotics.
Even if Fleming’s message had sunk in, it’s clearly been forgotten today. According to a 2009 article in the New England Journal of Medicine, nearly three million kilograms—about 6.6 million pounds—of antibiotics were given to humans that year. A year later, twice as much—about 13 million kilograms—were given to animals. Other reports suggest that about half of the antibiotics prescribed in 2010 were not even needed. Antibiotic resistance is so worrisome to many infectious disease and other health experts that it even earned a spot in the World Economic Forum’s 2013 Global Risks Report.
Today, members of the science and medical communities plead for more attention to the issue, but as journalist Maryn McKenna writes in Wired magazine, the pleas are met with “instant alarm, followed almost immediately by apathy.”
So what, truly, is the outlook? Are we doomed? Will the bugs eventually win—or do we have a shot at doing something about the growing resistance to superbugs like MRSA, carbapenem-resistant enterobacteriacae, and malaria? The Food and Drug Administration says it has groups on the case, like its Center for Drug Evaluation and Research and the government-initiated surveillance program, the National Antimicrobial Resistance Monitoring System (NARMS).
But many say we are not doing nearly enough. The UK Health Protection Agency and Dame Davies say that the “pipeline [for antibiotics] is running dry” and that we have a broken model for antibiotic production. Drug companies favor medications for chronic diseases like diabetes and hypertension since these conditions require medications over years or decades, and are therefore much more profitable than short-term treatments like antibiotics.
The Infectious Disease Society of America (ISDA) reports that our progress toward the goal of developing 10 new antibiotics by 2020 is definitely not on track: Just two new antibiotics have been approved since 2009. And only seven more are in stages two or three of research and development—a figure ISDA calls “alarmingly low.” ISDA’s graph showing how many antibiotics have been approved over the past few decades makes this very clear: In the 1980s as many as 16 new antibiotics were approved.
But there is hope. In the same New England Journal of Medicine piece, physicians outlined five areas of focus in the fight to beat the superbugs, as well as the current status of each (meaning whether we are making progress or not). Our goals, they said, should include:
• Preventing infection and resistance
• Refilling the antibiotic pipeline by aligning economic and regulatory approaches (making it easier to develop, approve, and distribute improved antibiotics)
• Preserving the antibiotics we already have and slowing resistance to these drugs (This may mean decreasing or eliminating use of the drugs in animals for growth, for example, and better public reporting on antibiotic use to get a clear idea of who’s using antibiotics and why, partly to help stem the prescribing of unnecessary drugs.)
• Looking at treatments that attack microbes with decreased potential to drive resistance, which may mean we need to develop methods that don’t kill bacteria, but prevent them from causing disease in people.
• Developing treatments that target the host (i.e., people and animals) rather than microbes to avoid making resistance worse.
Whatever efforts we undertake, though, one message is crystal clear: We can no longer be apathetic about antibiotic resistance.
In the coming weeks we’ll be taking a look at some of the superbugs posing the biggest threat, both in the U.S. (carbapenem-resistant enterobacteriacae, MRSA, gonorrhea) and abroad (drug-resistant tuberculosis and malaria).
--By Anna Tomasulo
What do you think we should do to stop antibiotic resistance? Have you ever gotten a prescription for an antibiotic you didn’t need?