Widening the War on Drug-Resistant Bacteria

By Kathleen Yount

The horror stories aren't new, but they're still shocking and often tragic. A small child comes to the emergency room for a scraped elbow and ends up in intensive care with multiple organ failure. Antibiotic-resistant bacteria carve holes in the brain of a man admitted to the hospital for simple shoulder surgery. Doctors watch in horror as a teen changes from cheerleader to corpse in a matter of hours, her flesh literally eaten away by a virulent form of common bacteria.

It is estimated that each year two million patients develop infections while hospitalized, and 100,000 of those patients die. With development of new antibiotics at an all-time low in most pharmaceutical companies, physicians can now describe a dozen doomsday scenarios in which multi-drug-resistant bacteria, immune to all of our antibiotic weapons, could sweep through the population, killing thousands. So are we on the brink of a new epidemic, or is the “superbug” threat a whole lot of hype? The truth is that we’re locked in a never-ending battle with enemies inside us, and it’s probably a war without end.

Lousy With Microbes

Each square centimeter of our skin is home to about 100,000 bacteria; in fact, there are more bacterial cells in our bodies than human cells. From the moment a new baby enters the birth canal, he or she is colonized with millions of bacteria. We also consume bacteria in our food, breathe them in our air, and share them with every person and surface we touch. No amount of hand sanitizer can keep us germ-free, but that’s okay because all of these microbes typically live in balance, and our immune systems usually know when and how to kill off the ones that can make us sick. Sometimes, though, the microbial balance is disrupted and invaders are allowed to slip past the body’s defenses. The system might break down because of an infection by an overpowering virus, or perhaps as a result of a wound, burn, or other trauma. Or the culprit could be an illness such as cancer, lupus, or rheumatoid arthritis that requires chemotherapy or some other immune-compromising drug. In these circumstances, the bacterial population inside can mutate with unnerving speed from silent sojourners to deadly attackers.

Battling the Bad Bugs See a rogue's gallery of antibiotic-resistant germs.

Bacteria seem like simple organisms when compared with the vast complexities of human beings, but they’re tough cookies. They’re older than we are—three billion years, give or take a million. They’re also tougher than we are: One species, Deinococcus radiodurans, can withstand radiation blasts that would kill a human thousands of times over. And, try as we might, bacteria end up outsmarting every antibiotic we design to kill them.

Alan Stamm, M.D., who is in charge of infection control at UAB Hospital, says that the growing survivability of bacteria is actually a testament to improved health care: Bugs are getting harder to kill because we are, too. “Very ill patients live longer now than ever before,” Stamm says. “They can survive more chemotherapy, more invasive surgery—and as a result they develop more complications, including bacterial infections.” In other words, the longer we live, the more exposure we have to bacteria. And as the microbes in our bodies encounter more environmental stresses and antibacterial potions, they figure out ways to survive them. In this respect, improved health care is speeding up natural selection among bacteria.

It's a Bird, It's a Plane, It's... A Superbug?

Today, about 75 percent of antibiotic prescriptions in the United States are written for upper respiratory tract infections. By and large, such infections are caused by viruses—which means that antibiotics do absolutely nothing to cure them. But this widespread prescribing of antibiotics—coupled with people’s tendency to take pills until their symptoms go away, then toss the bottle—leaves our insides riddled with mutant bacteria and us blithely unaware of how we’re stacking the odds against ourselves.

“Thanks to the Internet, patients nowadays are very educated—or at least they think they are,” says UAB infectious disease specialist Craig Hoesley, M.D. “They go into their doctors’ offices with problems, and they feel much better walking out with something in their hands than being told that they don’t need antibiotics. That’s probably most true of parents with sick kids—when you’ve got a screaming child with a painful ear, you don’t want to hear ‘it’ll go away’; you want somebody to do something to make your child stop hurting.

“I think most doctors want to do the right thing for the health of their patients and the community, but not prescribing antibiotics can be bad for business,” Hoesley adds. “If parents can choose between a pediatrician who will prescribe an antibiotic and one who is just going to talk about viruses, which one are they going to see?”

The problem is compounded by agribusiness, which for years has been giving animals antibiotics to promote growth—because the heavier they are, the more money they’ll fetch when sold. “Chickens are loaded with bacteria,” says Hoesley, “so by giving them antibiotics willy-nilly you can end up with birds that are colonized by drug-resistant bacteria, and people who eat infected chickens can become infected if the meat isn’t cooked properly.”

Spreading It Around

“When people in the community receive antibiotics for most any reason, the microbes in their bodies are more likely to develop resistance to many different families of antibiotics,” says Stamm. “If you take penicillin, the bugs in your body become resistant to penicillin; but oddly enough, they also become more resistant to other antibiotics.”

Treating patients who become ill from these bacteria can be a challenge, because it’s hard for doctors to choose the right antimicrobial therapy. “We might start treating a patient with three antibiotics, only to find that the bacteria causing the problem are resistant to all three,” says Stamm. “Once we finally find out what the organism is and what drug the patient needs, we sometimes have to use drugs that are more toxic.” Stamm stresses that antibiotics aren’t always benign; allergic reactions, blood toxicity, gastrointestinal distress, and other complications can always result from antibiotics, and the more powerful the antibiotic, the more likely such side effects become.

And sometimes none of the drugs work at all. “We can say there’s a drug for everything, but we also realize that none of the drugs work 100 percent of the time,” Stamm continues. “Some infections caused by Staphylococcus aureus can be cured by a penicillin 80 percent of the time. For more drug-resistant staph aureus, we have to use vancomycin, which works 70 percent of the time. But out of every 10 patients there’s going to be at least one we just can’t help.”

Doctor's Dilemma

Even in hospitals, patients sometimes receive antibiotics when they don’t really need them. “If a patient develops a little bit of fever,” says Stamm, “her doctor might give her two or three antibiotics instead of waiting a day or two to figure out whether the fever represents an infection. And if she does have an infection, it may become clear that there’s one drug that can treat it, but she might still be kept on all three drugs. So the patient receives three drugs for two weeks when she should have gotten one drug for 10 days.” The result? More resistant microbes.

Why would any hospital concerned about antibiotic resistance continue such a practice? Because a lot of mystery still remains in the art and science of medicine. “Say I gave my patient three antibiotics and now she’s better,” Stamm says. “Even though there might be good evidence that only one of the drugs affected the bacteria, if this course of action got my patient through her crisis, do I really want to stop the other two and risk a relapse? Or the opposite can happen: It’s three days later and the patient isn’t any better, but she’s also not any worse. And I might think, ‘I don’t know what this is, but at least I’ve stabilized it. Now I’ll take more time to figure out what it is, but I’m not going to stop any of the drugs because I’m afraid if I do, things will get worse.’”

Can't Stop the Flow

Is the growing problem of microbial resistance starting to slip out of our control? According to Stamm, the rate of infection among hospital patients nationally has not increased. “If you look at the infection rates now versus 10 or 20 years ago for many procedures, the overall rate of infection has actually decreased,” he says. “What’s different is that, of the infections that do occur, the percentage caused by resistant organisms has increased.”

So our hospitals aren’t being swept by a rash of infections, but drug resistance is a growing problem, and it’s nearly impossible to avoid. Even if one department or one hospital does everything absolutely right in terms of sterilization and patient isolation, no health-care center can operate in isolation, and microbes will always find their way in.

“All hospitals have patients who’ve been in other hospitals locally and sometimes elsewhere in the world,” Stamm says. “So even if a hospital maintains the most scrupulous infection control, it’s only going to minimally delay the appearance of drug-resistant pathogens in our population.”

Because not everyone who is contaminated becomes sick, there’s no lock-solid way to detect the microbes and prevent them from traveling—patients and hospital staff alike can become colonized with bacteria and never know it. “Perhaps only 10 percent of the people who get colonized with vancomycin-resistant enterococci—a cause of bloodstream infections—get sick,” says Stamm. “So it’s not as though everyone who has one of these bugs has a red light going off over their heads. These people can spread multi-drug-resistant organisms to others on their units, and it might be a week or two before any of those people get sick, if they ever do.”

Even when a person is perceptibly ill and treated with appropriate antibiotics, physicians can’t be certain that the disease-causing pathogens have been eliminated. “We can get them well again, but that doesn’t necessarily mean the organism is cleared from their bodies,” says Hoesley. “Curing a patient is not the same as sterilizing him.”

Hoesley says that while it’s not feasible to screen every person in a hospital for bacterial contamination, right now all patients in certain units of the hospital—such as surgical and medical intensive-care units—are regularly and repeatedly screened for infection so that staff will be able to isolate patients who become contaminated. Beyond that, he says, it’s hard to know what to do. “Should we try something different in terms of screening and washing patients before surgery? Or should we implement different infection-control precautions? There are a lot of questions, but not a lot of answers—it’s a problem we’re really trying hard to solve.”

Which Side Is Winning?

“I can recall seeing people 30 years ago who were facing the same crises,” says Stamm. “So it’s not a burgeoning epidemic. But if you look at it from the perspective of one of the unlucky patients who has germs that are resistant to everything we ordinarily use, it’s a life-and-death issue.”

This battle of drug resistance is still a relatively new one—for both sides. “We’re not even 100 years into the antibiotic era,” says Hoesley, pointing out that Alexander Fleming first spotted penicillin in a tray of mold in 1928. “When penicillin was discovered, it worked for basically everything. But when it started being used on a broader scale, by the mid-1940s, some strains of bacteria had already become resistant to it. And now most strains of staph aureus—the bacteria Fleming was studying when he discovered penicillin—are totally immune.” On the other hand, antibiotics have become infinitely more sophisticated since penicillin, so it’s too early to say who’s got the advantage.

And so the seesaw continues; man builds drugs to kill bacteria, and the bacteria figure out a way around the drugs. “That’s just the expectation for every drug: If we use it, and we expose the bacteria to it, bacteria will change and find a way to escape it every time,” Hoesley says. “This is a problem that hospitals are always going to have. The only way to combat it is to use antibiotics. We need to be proactive managing the drugs we use and also be steadfast about infection control.

“We’ll make better and better antibiotics, and we’ll survive—we’re not going to get killed off by these guys. But they won’t go away either. Bacteria may be primitive, but they’re survivors as much as we are.”

This article originally appeared in the Fall 2006 issue of UAB Magazine