IDEAS | THOMAS LEVENSON
The TV hospital drama scene plays out in familiar fashion: A scrub nurse picks out a curved-bladed scalpel from the instrument tray, then places it, handle flat, onto the surgeon’s palm. The doctor lays the blade onto a patch of exposed skin, and pulls. A red line appears; blood wells. With that, another life-changing operation, has begun.
In real life, the action starts hours before any surgeon begins to cut. Parts of the process are obvious to the patient: being asked to repeat your name and date of birth; the brief meet-and-greet with your anesthesiologist; getting stuck with an IV; and, as necessary, having a pre-op staffer mark, carefully, after asking you about it again and again, which side or body part is up for grabs.
But one of the most significant steps to ensure patient safety during and after an impending trip under the knife passes mostly unnoticed: The dose of antibiotics that many surgical patients receive shortly before moving from a staging area into the operating room itself. This isn’t a treatment for a pre-existing illness. The drug is purely prophylactic, a shield to protect patients from becoming infected as a complication of surgery.
Over the last century or so, medicine in general and surgery in particular has been transformed, to the point where we all, medical professionals and the rest of us, share a basic assumption: When we are ill or in need of repair — a fractured hip, a misbehaving appendix, a distressed heart in need of a pacemaker, the range of ills and accidents that humans encounter — doctors, and specifically surgeons, can do something about it. Hidden within that assumption is the belief that the ordinary risks of surgery are slight enough to make a trip under the knife safe. In large measure, that infections associated with surgery are under control.
That’s where the antibiotics come in. There are almost 50 million surgeries performed each year in the United States. As of 2011, there were an estimated 157,500 surgical site infections . Pre-operative antibiotics are a key to keeping those numbers — and the harm infections can do — in check. A recent review reported that surgical infection for the 10 most common procedures drops from over 11 percent for patients who do not receive pre-operative antibiotics to just 4.2 percent with the drugs.
There is only one problem: We may not be able count on such gifts for much longer. Modern medicine depends not just on the skill and integrity of its practitioners, but also on a web of interconnected discoveries, techniques, and approaches to care, developed and refined over years. Because we’ve been able to rely on the certainty that the infections once associated with surgery are largely under control, doctors confidently perform the now-routine procedures — from Caesarean sections to prostate biopsies to appendectomies and more — that permit us to live and age with greater security than ever before.
But as more and more bacteria show resistance to antibiotics, the risks change — to the point that doctors and patients alike may soon face agonizing choices about whether or when to take a chance on many of the surgeries we now accept as a matter of course.
Antibiotic-resistant infections, illnesses caused by microbes that have grown invulnerable to drugs that used to kill them, are already a terrifying scourge. In 2013, the Centers for Disease Control and Prevention estimated that Americans suffer 2 million resistant infections per year leading to at least 23,000 deaths — twice the number of gun murders. Worldwide the statistics are yet more grim. Resistant disease kills at least 700,000 per year, and a study commissioned by the British government estimates that by 2050 resistant disease will kill 10 million people per year and will cost from $60 trillion to $100 trillion in lost GDP.
Humankind has always confronted microbial infections. But, beginning in the 1940s, we were released from that curse, it seemed. Ubiquitous, cheap compounds could quash amortal threat altogether. Now, that’s less and less true, and we (reasonably) focus on the renewed threat of diseases so recently believed to be vanquished, from staph infections throat to salmonella, gonorrhea, tuberculosis and many, many more.
But behind that overt (and genuine) peril, there are the more subtle dangers that emerge from the way antibiotics have woven themselves into medical practice, everywhere they are used not to cure infections but to prevent them: operating rooms, chemotherapy clinics and beyond.
Joint-replacement surgery, for example, is one of the truly liberating surgical advances of the last several decades. Knees, shoulders, and more are all replaceable, with immeasurable gains in mobility and freedom from pain. The first hip replacement came in 1947; as of 2015, 332,000 Americans a year now undergo that operation, and over 7 million of us have received one or more joint implants. As standard practice, the operation to place each new implant begins with a dose of a broad-spectrum antibiotic.
Resistance has already appeared in the operating room, of course. Forty-eight percent of the estimated 15,000 infections or more associated with hip replacements each year are resistant to standard antibiotic prophylaxis. To see what would happen as such resistance intensifies, a team of researchers led by Dr. Aude Teillant, then at the Center for Disease Dynamics, Economics and Policy (CDDEP), surveyed the ten most common surgeries and cancer chemotherapies to analyze what would happen as such resistance grows — changing the risk benefit calculation for everything from appendectomies to pacemaker implants.
Modeling a 30 percent drop in the effectiveness of pre-operative antibiotics, the researchers found that another 120,000 Americans would suffer surgical site or chemotherapy-associated infections, and at least 6,000 of those patients would die. (The toll could well be worse, the study’s authors write, given that mortality data wasn’t available for several procedures.)
Dr. Sumanth Gandra, one of the co-authors on this study, notes that, from the start of the antibiotic era, “we’ve known resistance will come.” Now, says Gandra, an infectious disease physician and CDDEP scholar, “We don’t want to end up in again in the situation” in which a procedure intended to save a patient carries with it too great a risk of killing them.
That’s what scares Dr. James Maguire, an infectious disease specialist at Brigham and Women’s Hospital. “I think some of the worst feelings we have are when we have a problem with a patient and there’s nothing we can do.” Infections following joint replacements are bad enough. They are, Maguire says, “catastrophic in terms of what happens to the patient.” Were the risk of infection to go up enough, he adds, “having seen what an infected joint replacement is all about I would think twice.”
Surgery isn’t in that predicament yet. Even though “some of the organisms we’ve heard about are really frightening,” Maguire says, “we are just by the skin of our teeth staying ahead” of them. But that will change should more antibiotics become less effective in preventing surgical complications. “I remember how terrifying it was to be in a situation where you just had nothing to offer,” he says.
Such nightmares — Maguire’s word — roil through medical practice. A San Francisco obstetrician-gynecologist notes that when there is both a mother and a baby involved the calculation gets even more complex. Even if it makes medical sense for the mother to receive a bigger dose or a targeted, more potent antibiotic before a Caesarean section, such drugs can affect the baby in ways that are not yet well understood. Even if the rates of C-sections don’t change, the risks will.
Similarly, Maguire says that, while someone contemplating a joint replacement can choose to forgo the risk, if they need a new heart valve or a ventricular assist device, “that’s potentially life and death.” In such circumstances, “if your life depending on having the device, even with great risk you’d do it. But more would die.”
As long as resistance to more drugs spreads across more microbes, that’s the future of medicine. Ordinary interventions will become more dangerous, some perhaps greatly so. Patients — all of us fortunate to live long enough to require help — will have to make harder and harder choices, whether to live with the pain of a ruined hip or to take a chance on an increasingly fraught surgery. And when there is no choice, we will have to confront odds that have shifted against us.
That’s not inevitable, of course. Medicine and basic science aren’t helpless in the face of microbial resistance. A first essential step, Ganda says, is to deploy available drugs carefully, and above all, not misuse them. “The big message is that antibiotics are finite resources.” That means, he says, “we have to use more caution” as we spend such treasure.
The misuse of antibiotics ranges from applications in agriculture — as the journalist Maryn McKenna has recently dissected in her new book “Big Chicken” — to the prescription of antibiotics for viral diseases on which they have no effect. Each time antibiotics appear in settings where they don’t actually knock out an infection, more microbes learn how to resist their effects, and the risk to humans grows.
To combat this, researchers and practitioners have come up with the concept of antibiotic stewardship. In practice this includes measures like curtailing all non-essential uses of antibiotics (like fattening a chicken); making changes in hospital practice to make sure that physicians are prescribing the right drug for a given infection; agreeing that the so called “drugs of last resort” for multi-drug resistant infections are used only when absolutely necessary; and ensuring that hospitals do everything they can to prevent infections from occurring in the first place.
That’s the second key, according to Maguire. “Hospitals are the big amplifiers of antibiotic resistance.” Right now, he says, “We have to go back to some of the basics of transmission and epidemiology. Right now we’re not winning that battle.” What’s required isn’t high tech or breakthrough discoveries, but changes in hospital habits and practices across the country and around the world.
More and better science will help too. New drugs and new biomedical approaches could tackle infections that are currently on a path towards total resistance. There are signs of progress. As of March, 39 new antibiotics were undergoing clinical trials in the United States, with 11 in phase three, the closest to approval. But that number is deceptive. Most of those new compounds were variations on existing drugs. Many of those in trials will not survive that process. No more than a third show promise of being effective against highly resistant pathogens.
More adventurous approaches — using viruses that infect bacteria to combat infections, for example, or developing new vaccines for specific microbial pathogens — are being studied, as are immunological approaches seeking to stimulate a patient’s own defense system to crush infections on its own. Basic, curiosity-driven research may lead to approaches as yet unimagined. The 20th century was marked by a series of triumphs in the fight against infectious disease. There is no reason inherent in nature or the limits of human intelligence why similar advances won’t come again.
But such advances do require a willingness to support the education of the next generation of scientists and the commitment to underwrite a broad range of scientific research — including investigations that may, in the end, turn up nothing.
Lately, political support for research funding has ebbed in the United States. But bacteria aren’t partisan. They don’t care if they exist in Donald Trump’s gut or Elizabeth Warren’s. They travel around the globe, develop and exchange resistance, exist within and move between human hosts. Microbial infection is an inherently social disease.
Modern medicine mirrors that interconnected system. It forms its own ecology, just as much as any bacterial habitat. A vast range of surgeries, therapies, and entire medical specialties are all affected when the relationship between humans and infectious agents shifts.
If antibiotic resistance keeps intensifying, and if the needed research doesn’t happen, then at least some of the medical care that we now assume will be available to us won’t be. Our joints may fail, and the choice may be between pain and increasingly acute risk of infection. Our hearts may break, and the operations that could fix them may become more and more of a gamble. A complicated childbirth could pose ever more impossible collisions between the needs of mother and infant.
A bad cut, a scraped knee, an ankle broken on a slide into second base — for three-quarters of a century these have been painful, annoying, a hassle. And nothing more. In the worst cases, that could change too.
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