After 85 years, antibiotics are growing impotent. So what will medicine, agriculture and everyday life look like if we lose these drugs entirely?
Predictions that we might sacrifice the antibiotic miracle have been around almost as long as the drugs themselves. Penicillin was first discovered in 1928 and battlefield casualties got the first non-experimental doses in 1943, quickly saving soldiers who had been close to death. But just two years later, the drug’s discoverer Sir Alexander Fleming warned that its benefit might not last. Accepting the 1945 Nobel Prize in Medicine, he said:
“It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them… 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.”
As a biologist, Fleming knew that evolution was inevitable: sooner or later, bacteria would develop defenses against the compounds the nascent pharmaceutical industry was aiming at them. But what worried him was the possibility that misuse would speed the process up. Every inappropriate prescription and insufficient dose given in medicine would kill weak bacteria but let the strong survive. (As would the micro-dose “growth promoters” given in agriculture, which were invented a few years after Fleming spoke.) Bacteria can produce another generation in as little as twenty minutes; with tens of thousands of generations a year working out survival strategies, the organisms would soon overwhelm the potent new drugs.
Fleming’s prediction was correct. Penicillin-resistant staph emerged in 1940, while the drug was still being given to only a few patients. Tetracycline was introduced in 1950, and tetracycline-resistant Shigella emerged in 1959; erythromycin came on the market in 1953, and erythromycin-resistant strep appeared in 1968. As antibiotics became more affordable and their use increased, bacteria developed defenses more quickly. Methicillin arrived in 1960 and methicillin resistance in 1962; levofloxacin in 1996 and the first resistant cases the same year; linezolid in 2000 and resistance to it in 2001; daptomycin in 2003 and the first signs of resistance in 2004.With antibiotics losing usefulness so quickly — and thus not making back the estimated $1 billion per drug it costs to create them — the pharmaceutical industry lost enthusiasm for making more. In 2004, there were only five new antibiotics in development, compared to more than 500 chronic-disease drugs for which resistance is not an issue — and which, unlike antibiotics, are taken for years, not days. Since then, resistant bugs have grown more numerous and by sharing DNA with each other, have become even tougher to treat with the few drugs that remain. In 2009, and again this year, researchers in Europe and the United States sounded the alarm over an ominous form of resistance known as CRE, for which only one antibiotic still works.
Health authorities have struggled to convince the public that this is a crisis. In September, Dr. Thomas Frieden, the director of the U.S. Centers for Disease Control and Prevention, issued a blunt warning: “If we’re not careful, we will soon be in a post-antibiotic era. For some patients and some microbes, we are already there.” The chief medical officer of the United Kingdom, Dame Sally Davies — who calls antibiotic resistance as serious a threat as terrorism — recently published a book in which she imagines what might come next. She sketches a world where infection is so dangerous that anyone with even minor symptoms would be locked in confinement until they recover or die. It is a dark vision, meant to disturb. But it may actually underplay what the loss of antibiotics would mean.
In 2009, three New York physicians cared for a sixty-seven-year-old man who had major surgery and then picked up a hospital infection that was “pan-resistant” — that is, responsive to no antibiotics at all. He died fourteen days later. When his doctors related his case in a medical journal months afterward, they still sounded stunned. “It is a rarity for a physician in the developed world to have a patient die of an overwhelming infection for which there are no therapeutic options,” they said, calling the man’s death “the first instance in our clinical experience in which we had no effective treatment to offer.”
They are not the only doctors to endure that lack of options. Dr. Brad Spellberg of UCLA’s David Geffen School of Medicine became so enraged by the ineffectiveness of antibiotics that he wrote a book about it.
“Sitting with a family, trying to explain that you have nothing left to treat their dying relative — that leaves an indelible mark on you,” he says. “This is not cancer; it’s infectious disease, treatable for decades.”
As grim as they are, in-hospital deaths from resistant infections are easy to rationalize: perhaps these people were just old, already ill, different somehow from the rest of us. But deaths like this are changing medicine. To protect their own facilities, hospitals already flag incoming patients who might carry untreatable bacteria. Most of those patients come from nursing homes and “long-term acute care” (an intensive-care alternative where someone who needs a ventilator for weeks or months might stay). So many patients in those institutions carry highly resistant bacteria that hospital workers isolate them when they arrive, and fret about the danger they pose to others. As infections become yet more dangerous, the healthcare industry will be even less willing to take such risks.
Those calculations of risk extend far beyond admitting possibly contaminated patients from a nursing home. Without the protection offered by antibiotics, entire categories of medical practice would be rethought.
Many treatments require suppressing the immune system, to help destroy cancer or to keep a transplanted organ viable. That suppression makes people unusually vulnerable to infection. Antibiotics reduce the threat; without them, chemotherapy or radiation treatment would be as dangerous as the cancers they seek to cure. Dr. Michael Bell, who leads an infection-prevention division at the CDC, told me: “We deal with that risk now by loading people up with broad-spectrum antibiotics, sometimes for weeks at a stretch. But if you can’t do that, the decision to treat somebody takes on a different ethical tone. Similarly with transplantation. And severe burns are hugely susceptible to infection. Burn units would have a very, very difficult task keeping people alive.”
Doctors routinely perform procedures that carry an extraordinary infection risk unless antibiotics are used. Chief among them: any treatment that requires the construction of portals into the bloodstream and gives bacteria a direct route to the heart or brain. That rules out intensive-care medicine, with its ventilators, catheters, and ports—but also something as prosaic as kidney dialysis, which mechanically filters the blood.
Next to go: surgery, especially on sites that harbor large populations of bacteria such as the intestines and the urinary tract. Those bacteria are benign in their regular homes in the body, but introduce them into the blood, as surgery can, and infections are practically guaranteed. And then implantable devices, because bacteria can form sticky films of infection on the devices’ surfaces that can be broken down only by antibiotics
Dr. Donald Fry, a member of the American College of Surgeons who finished medical school in 1972, says: “In my professional life, it has been breathtaking to watch what can be done with synthetic prosthetic materials: joints, vessels, heart valves. But in these operations, infection is a catastrophe.” British health economists with similar concerns recently calculated the costs of antibiotic resistance. To examine how it would affect surgery, they picked hip replacements, a common procedure in once-athletic Baby Boomers. They estimated that without antibiotics, one out of every six recipients of new hip joints would die.
Antibiotics are administered prophylactically before operations as major as open-heart surgery and as routine as Caesarean sections and prostate biopsies. Without the drugs, the risks posed by those operations, and the likelihood that physicians would perform them, will change.
“In our current malpractice environment, is a doctor going to want to do a bone marrow transplant, knowing there’s a very high rate of infection that you won’t be able to treat?” asks Dr. Louis Rice, chair of the department of medicine at Brown University’s medical school. “Plus, right now healthcare is a reasonably free-market, fee-for-service system; people are interested in doing procedures because they make money. But five or ten years from now, we’ll probably be in an environment where we get a flat sum of money to take care of patients. And we may decide that some of these procedures aren’t worth the risk.”