Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues (10 page)

The idea that other potent antibiotics also could have side effects beyond those immediately apparent wasn’t part of the conventional wisdom; it was not even a consideration. If there were no allergies manifested in the days and weeks after receiving the drugs, they were considered safe.

Almost all the great advances in medicine from the second half of the twentieth century continuing through to today were catalyzed by the deployment of antibiotics. No harm could come from their use, or so it seemed. The fallout appeared only later.

6.

THE OVERUSE OF ANTIBIOTICS

How to capture the euphoria of those early days? It was 1945. World War II had ended. We had beaten the forces of great evil; a more just society had prevailed. Americans were awash with optimism. It was a time to have lots of babies, and I was one of them. In the five years after the war, Americans bought 20 million refrigerators, 21.4 million cars, and 5.5 million stoves. It was an era for all kinds of beginnings: Tupperware, the first fins on cars, sprawling suburbs, fast-food restaurants, television, and, of course, antibiotics—the wonder drugs.

Because they were so effective and so apparently free of obvious risk, doctors and patients alike began to ask: Can’t we solve this problem with antibiotics? Like urinary tract infections? Can’t we alleviate the discomfort of sinus or dental infections, or the disfigurement of serious acne? Can’t we treat this condition with antibiotics? Like cystic fibrosis? The answer, very often, was yes.

Sometimes the benefits were dramatic, such as using antibiotics before certain surgeries as prophylaxis to prevent infections. Other times the benefits were small, but since the recognized cost, in terms of toxicity, was extremely low, even a marginal benefit seemed worth it. For example, for decades dentists routinely gave antibiotics to people with minor heart murmurs to prevent an exceedingly remote risk of heart valve infections.

I’m not questioning the efficacy of antibiotics on the small minority hospitalized with pneumonias, puerperal sepsis, meningitis, and other severe infectious diseases but rather their use on millions of healthy people with less serious infections and relatively minor complaints, such as runny noses and skin infections. Tens of millions of these people, year after year, are prescribed antibiotics in the United States alone.

The problem, as coming chapters will show, is particularly perilous for our children. They are vulnerable in ways we never foresaw.

The most obvious example of the extravagant use of antibiotics is for the common disorders known as upper respiratory tract infections. Parents of young children know the symptoms all too well: sore throats, runny noses, sniffles, earaches, sinus pain, and just plain misery. Sometimes their child has a fever, sometimes not. Most children get several upper respiratory infections every year until they are two or three years old. By age three, up to 80 percent of children have suffered at least one acute infection of the middle ear. More than 40 percent of kids experience at least six such ear infections by age seven.

Indeed, everyone—adults and children alike—develops upper respiratory infections with some regularity. We can’t escape them. They are a product of our elaborate social networks. We are exposed constantly to plumes of microbes emitted from people coughing, sneezing, and just breathing all around us. These infections will be with us as long as we live in close proximity to one another, which is how most of us want to be: near our loved ones, our friends, our schoolmates. When scientists went off to spend winters in isolated colonies in Antarctica, upper respiratory tract infections would circulate for a month or two and then die out. As with the hunter-gatherers, everyone who was susceptible got sick, and then the infectious agent had nowhere to go. There were no new hosts to infect. Only when the next plane or next ship brought in new people with their communicable microbes would the cycle begin anew.

But guess what? Upper respiratory tract infections are mainly caused by viruses. More than 80 percent of them can be traced to microbes with exotic names like rhinovirus, astrovirus, metapneumovirus, and parainfluenza. (The term
computer virus
derives from these ultracontagious human viruses.) When we get infected with one of these pathogens, we say we have come down with a cold or the flu. But after a few days of feeling somewhere from “under the weather” to dreadful, nearly everyone gradually gets better. The condition is “self-limited.” Even stubborn lingering coughs almost always fade naturally after a couple of weeks. But if you’ve been coughing for a week with no end in sight, you just might call your doctor and say, “Enough already. Give me an antibiotic.” But in fact, antibiotic treatment has no effect on the outcome of these viral infections.

When it comes to infectious diseases, a central distinction is made between bacteria and viruses. Bacteria are cells. They eat, move, breathe, and reproduce. Give bacteria their preferred nutrients and a nice home—which could be a warm nook, glacier, or volcano—and they will multiply.

In contrast, viruses are much smaller and simpler. They require a host. They can only live within a cell, be it from a human or other animal, plant, or bacterium. They hijack host cell machinery for their purposes, which includes reproduction. They cannot reproduce on their own. Sometimes they stay dormant in host cells for decades, and at other times they kill their host cells—or do both.

Since viruses don’t have cell walls the way bacteria do, antibiotics like penicillin don’t work on them. Since their protein synthesis is dependent on their host’s protein synthesis, you would have to inhibit the latter to suppress the virus. When viruses parasitize human cells—as they do with the common cold, herpes, flu, and many other infections—we cannot suppress host protein synthesis because the host is we humans. We would be poisoning our own bodies. A few drugs do interfere with the ability of some viruses to enter and exit cells or reproduce, such as acyclovir, used to treat herpes viruses, and drugs that interfere with the life cycle of HIV. Although viruses can be suppressed, there are few cures. Antibiotics, in contrast, can cure almost all bacterial infections.

But fewer than 20 percent of upper respiratory tract infections are caused by bacteria. Here, the situation gets more complex. Bacteria that occupy your throat and nose can be permanent residents, or they can be transients, or they are in-between occupants, akin to long-term tenants. Some of the most important include
Streptococcus pneumoniae
or the pneumococcus, the number-one pathogen in the upper respiratory tract and in the lungs that causes ear infections and pneumonia, respectively;
Streptococcus pyogenes
or Group A strep, which causes “strep throat”;
Staphylococcus aureus,
the bacterium found in most serious
Staph
infections; and
Haemophilus influenzae
, which used to cause ear infections with regularity and occasionally childhood meningitis before we had a vaccine.

These four bacterial species are frequently identified in upper respiratory tract infections. But not so fast. Sometimes they cause the infection, but most of the time they do not. This apparent contradiction can be explained by the fact that these microbes, whose names sound ominous, may have actually arrived in you or your child quite some time ago. You have not been infected, but instead colonized, a generally harmless event. This is an extremely important distinction that often gets overlooked.

Colonization means that these bacteria are merely living in and on you. They are not doing you any harm. While colonization is a prerequisite for most disease, by itself it is not sufficient. Most colonized people are perfectly healthy. For instance,
Staph aureus
can colonize your nose for life, and you’ll never know it. For most people, it is a part of our microbiome, as discussed previously. The bottom line: our noses and throats are hosts to vast communities of bacteria, including the friendly ones and those that are potentially pathogenic.

Moreover, certain of these bacteria have been shown to keep you healthy by inhibiting potential pathogens and modulating your immune system. One of the most interesting examples of this is the “viridans” streptococci, a group of bacteria that live peacefully in everyone’s mouth. They were initially labeled as pathogens because they were a leading cause of heart valve infections. But it gradually became clear that they are normal residents of the mouth, only occasionally entering the bloodstream and landing on a previously damaged valve. We now know that if we mix harmless viridans with pathogenic Group A strep, viridans always win out. They knock back the strep. So a bacterium that is an occasional pathogen turns out to be a significant protector of our health. This dichotomy is an important model for how to think of many other bacteria that commonly live in us.

But getting back to the main point, when do potential respiratory pathogens cause trouble in children? When should they be treated with antibiotics? One answer is another question: How healthy are your children? If they have another infection, like the “stomach flu,” or stresses on their immune system, like an allergy that blocks their Eustachian tubes, they are more vulnerable to developing more serious ear or chest infections. In rare instances, these can lead to serious complications such as pneumonia or mastoiditis, an infection of the air spaces adjacent to the ear canals.

Infections can also linger in apparently healthy children. If a thousand kids in your town have been exposed to the same respiratory virus or bacteria—not an unlikely occurrence during winter—we see a range in outcomes. Some kids have no symptoms whatsoever; they are simply carriers. Others have symptoms for one day, others still for two or three days. After four or five days, the numbers drop, but a few will always have prolonged infections. The distribution falls along a familiar bell-shaped curve: some not sick, most sick in the normal pattern, a few very sick.

A doctor can recognize a severe infection but cannot easily predict who will have trouble recovering. Thus while the numbers of the very sick are low, maybe 5–10 percent of those affected, 60 or 80 percent of kids who currently are taken to the doctor by their parents complaining of bad sore throats or ear pain walk out with an antibiotic. And most of the time the doctors have no idea if the illness is caused by bacteria or a virus.

Doctors have one very good reason to reflexively prescribe antibiotics for many upper respiratory tract infections: fear of rheumatic fever. It is a very serious inflammatory disease, resembling rheumatism, which typically occurs two to three weeks after an untreated strep infection (
Streptococcus
pharyngitis). Antibodies raised against the strep infection “cross-react” with and attack the child’s heart muscle, joints, skin, and brain—a tragic case of mistaken identity.

Before antibiotics, about one child in three hundred with a strep infection developed rheumatic fever or, if the strep strains were very “hot,” one in thirty. Nowadays doctors prescribe an antibiotic for strep throat not to shorten the duration of the infection, because it doesn’t much, but to ward off rheumatic fever. Most people and even some doctors don’t understand that the antibiotic is being prescribed for prevention and not treatment.

But here’s the problem. Kids get colonized with Group A strep in their throats all the time, especially in winter. The condition may persist for a couple of months, as they are just healthy carriers. But imagine your child acquires an ordinary cold virus during this same time and gets a sore throat. You take him or her to the doctor, who does a throat culture, and voilà: Group A strep shows up. The doctor, being reasonable, prescribes antibiotics to prevent rheumatic fever when the infection is actually caused by a virus.

Even if the strep throat is caused by bacteria, the illness is usually brief, and nearly all kids get better in the next day or two. But if your child receives antibiotics and gets better, you will inevitably think the drug made them better. It’s a classic example of the adage that correlation is not causation. The fact that your child improves after several doses of amoxicillin seems clearly correlated, but that does not prove the drug led to the improvement.

How, then, can physicians tell the difference between a mild, self-limiting bacterial or viral infection and a more serious one? Or how can they differentiate colonization from infection? This is a critically important question because the answer, which unfortunately is not clear at this time, holds the power to help curtail the overuse of antibiotics. An astute clinician knows that in most, but not all, cases, children who are at risk for developing serious complications show certain warning signs. They have higher fevers, their symptoms have been going on longer, their white blood counts are more abnormal, and they look worse. But many cases fall into a gray area.

This gray area is important. Until doctors can readily distinguish viral from bacterial throat infections, they will always follow the safer course. And they are pressed for time. They may have to see five sick children every hour of their working day and complete all of the paperwork. The conjunction of lack of practical, rapid, inexpensive, and accurate diagnostics and the incessant time crunch effectively conspire on the side of overtreatment. New diagnostics that can improve the situation are coming along, but they are hardly ever deployed; in the current climate, no one wants to pay.

And then there is always the fear of the lawyer looking over the doctor’s shoulder. What if the physician doesn’t treat a child and there is a catastrophic outcome? What if an attorney asks: “Why didn’t you give this child an antibiotic for his ear infection that turned into meningitis and left him paralyzed?”

The complicated dynamic just described has been playing out on an unprecedented scale, involving all of our children all over the world for generations. The cycle is repeating, perhaps amplifying. When millions of children are treated for bacterial infections they never had, it’s not hard to imagine that trouble could follow.