Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues (11 page)

The magnitude of antibiotic use is enormous, and it has crept up year after year. In 1945 an article in the prestigious
Journal of Clinical Investigation
reported on the great efficacy of penicillin in treating sixty-four patients with pneumonia. Such treatment, on that scale, produced almost miraculous results. But by 2010, health-care providers prescribed 258 million courses of antibiotics to people in the United States. This more than a millionfold difference in scale amounts to about 833 prescriptions for every thousand people across the country. We don’t know if every course was taken, but probably most were. Family practitioners prescribed about a quarter of the antibiotics, followed by pediatricians and internists. Dentists prescribed 10 percent, about 25 million courses a year.

The highest prescription rate was for children under the age of two: 1,365 courses per 1,000 babies. This means that the average American child received nearly 3 courses of antibiotics in his or her first two years of life. They go on to receive, on average, another 8 courses in the next eight years. Extrapolating from the current Centers for Disease Control and Prevention statistics, the data suggest that on average our children receive about 17 courses of antibiotics before they are twenty years old. This is a big number, but it is in line with prior studies in the United States and other developed countries.

Young adults in their twenties and thirties receive, on average, another thirteen courses of antibiotics. This means that our young people are taking thirty courses of these potent drugs before the age of forty. This is the average. Some people take more, some less. But the implications loom large. Many of the young women will be mothers of the next generation who will be providing initial microbiomes to their children. This is a process we will explore shortly. How will all of those courses of antibiotics affect the handover?

*   *   *

The first recognized problem from the overuse of antibiotics was resistance. Very simply, the more often we put antibiotics into our bodies and our children’s bodies, the more likely we select for bacteria that are resistant to their action. Many people don’t quite understand resistance. They think that “they have become resistant to antibiotics,” when in fact it is the bacteria they encounter or they carry that have become resistant.

Here is one way it works. A child receives an antibiotic, say amoxicillin, to treat an infection. A derivative of penicillin, it is the most commonly prescribed antibiotic in young children in most countries. When amoxicillin is swallowed (usually in the form of a bubblegum-pink liquid), it is absorbed into the gut and enters the bloodstream. From there, it travels to all organs and tissues, including stomach, lungs, mouth, throat, skin, ears, and in girls the vagina, encountering and destroying bacteria wherever they hang out. So-called broad-spectrum antibiotics like amoxicillin are especially adept killers.

But here’s the crux of this problem: there are always innocent bystanders, lots and lots of them. All mixed populations of bacteria include both susceptible and resistant bacteria. The antibiotic eliminates susceptible microbes all over the body along with the pathogen that usually is present in one place. It is like carpet bombing when a laserlike strike is needed.

And now we are in trouble. When susceptible species are diminished or killed, populations of resistant bacteria expand. With fewer competitors around, resistant bacteria flourish. They’re the lucky ones that go on to have lots of baby bacteria. The resistant ones may be either the targeted pathogen or the many, many bystanders.

Antibiotic resistance spreads within bacterial communities in two general ways. First, it occurs through the growth of organisms that have already acquired resistance—what we call vertical transmission. It’s like the transfer of genes from grandparents to parents to children and so on down through the generations. When antibiotics are in the environment, bacteria that are resistant behave in a similar manner. They keep dividing and multiplying, passing on their genes, unlike susceptible bacteria, which are inhibited or killed.

Resistance genes can also spread via sex—what we call horizontal transmission. Some bacteria are reclusive, but many bacterial species are promiscuous, having sex all the time. But it’s not exactly as you might picture it—two bugs lying on a couch going at it. Instead, they may gain or swap genes like baseball cards, many of which confer resistance to antibiotics. When resistance genes are present and antibiotics are around, there is natural selection for the strains that have resistance genes to propagate. Thus, the surviving bacteria may be said to have adapted to the antibiotics designed to kill them, rendering the drugs less effective or completely useless. As long as antibiotics are around, resistance is favored in the populations of microbes.

The dynamics of how resistant bacteria emerge are instructive. For example, a small dose of amoxicillin is enough to kill nearly all the pneumococcus encountered but not quite all. In a population of a million pneumococci, there might be one with a small genetic variation—an outlier—that arose by chance and that is resistant to amoxicillin. After 999,999 of the others are killed, the variant multiplies, basking in the empty niche that the amoxicillin created. It becomes dominant. Occasionally, one of these resistant bacteria is passed to another child through a cough or sneeze. Now let’s imagine that the second child also gets a high dose of amoxicillin. Again all of the susceptible pneumococci die. And now, from among those more-resistant bacteria, a variant that is even more resistant survives and thrives, armed with its usual bacterial weaponry. And so on.

Resistance ramps up, little by little, or it can happen quickly. Sometimes, a resistant strain picks up new genes from another bacterium by having sex with them and, in a single bound, acquires high-grade resistance to a whole class of antibiotic agents. Many times that gene was acquired from a bystander organism that had been selected and enhanced by prior courses of antibiotics.

As long as amoxicillin is given to our children who have pneumococci in their noses and throats, whether harmless or not, antibiotic resistance is inevitable. It does not happen in every child or with every course of the drug. Sometimes variants don’t arise, or they do but they are less fit and are not transmitted to other kids. It is a kind of casino; in any individual child, or in any community, chance plays a big role. The resistant ones may fail and may be eliminated; this probably happens most of the time. But some may persist for years. In a later chapter, I discuss our studies showing this. But globally, in just this manner, resistance to penicillins has slowly and inexorably mushroomed in recent decades. It is but one example, since resistances to macrolides (like erythromycin, clarithromycin, and azithromycin), tetracyclines (like doxycycline), fluoroquinolones (like ciprofloxacin), and nitroimidazoles (like metronidazole) are all rising.

One issue is that parents are not aware of, or don’t much care about, antibiotic resistance as it develops in the broader community. Going back to the example of ear infections, the conversation in the doctor’s office might go something like this.

DOCTOR
: The reason that your daughter is so fussy is that she has an ear infection.

MOTHER
: I figured as much, since she’s had them before. Can we give her an antibiotic?

DOCTOR
: Well, in more than eighty percent of cases, the infection is due to a virus, so antibiotics won’t work.

MOTHER
: What about the other twenty percent?

DOCTOR
: Well, we are overusing antibiotics. The more we use them, the more resistance there is, and resistance is spreading across the community.

Mother does a quick calculation. The community means other children. But her child could be among the 20 percent: “Antibiotics won’t hurt, and I want to do whatever we can for her.”

Doctor does another quick calculation. It’s true: antibiotics might not help her, but they won’t hurt: “Okay, I’ll prescribe a course of amoxicillin for ten days.”

*   *   *

A second crisis is looming, accentuated by our overuse of antibiotics and resistance to the drugs: the failure of pharmaceutical firms to develop new antibiotics to keep up with the resistance. Some infections today are untreatable with current antibiotics, and more are likely to evolve.

Antibiotics vary from narrow spectrum, those affecting only a few types of bacteria, to broad spectrum, those that kill a wide variety of microbes. Most pharmaceutical companies favor broad-spectrum drugs because the broader their use, the greater their sales. Physicians also like them and for good reason—because it can be difficult to determine whether an infection is caused by
Strep
,
Staph
, or
E. coli
, and broad-spectrum agents cover the waterfront. But there is a significant downside: the broader the spectrum, the greater the selection for resistance.

It is clear that the more we use antibiotics, the quicker resistance will develop and the useful life span of each antibiotic will be reduced. In the early days of antibiotic discovery, scientists generally stayed ahead of this curve by regularly developing new drugs. But now the pipeline is drying up. The “easy” antibiotics have already been discovered. Like putting different colors of frosting on the same cupcakes, most drug companies have tweaked their existing antibiotic recipes without coming up with new ingredients.

It is not profitable for companies to go to the trouble and enormous expense of developing new antibiotics, especially if they don’t have broad application. Pharmaceutical companies want to develop drugs that millions of people will take for years, such as medications to treat high cholesterol, diabetes, and high blood pressure. That is where the profits are. A drug that only a few thousand people need each year and that will be used for only a few weeks can’t be developed under our current economic models.

A few years ago, when I served as an officer of the Infectious Diseases Society of America (IDSA), one of my jobs was to participate in efforts to convince the U.S. Congress to pass laws that could help us open up the stalled antibiotic pipeline. We at the IDSA were (and still are) very concerned about the lack of new drug development and knew that the process takes years. We cannot wait for a highly communicable bacterium that is resistant to all of our antibiotics to hit before taking action. I traveled to Washington repeatedly over several years to work with other IDSA team members, other organizations with the same goals, and the family members of people who had died or became very ill as a result of resistant organisms. We testified in Congress whenever we had the opportunity, in briefings or in formal committee meetings.

The stories of young, healthy people struck down by terrible, unrelenting infections were terribly sad and frightening. One day, Brandon Noble, a professional football player who played for the Washington Redskins, came to testify. He had reached the top of his field and was familiar to everyone in the room. But like many professional athletes, he had sustained a series of injuries, which in his case damaged his knee. He went to the hospital to have the torn ligaments repaired, a relatively routine operation. Thousands are done without mishap each year. But his knee became infected with antibiotic-resistant
Staph
, called MRSA (MRSA stands for methicillin-resistant
Staphylococcus aureus
). His knee had to be drained and cleaned out multiple times; despite these necessary treatments, the moving parts of his knee were permanently mangled. When his infection was finally cured, he could no longer walk normally, and his career was over. Limping up to the microphone, the extent of his loss was immediately evident. He later said: “The worst and most unexpected thing that I have come up against in my football career has been a tiny little thing that I can not see.”

The next witness was a mother from a small town in Pennsylvania who spoke about her son, Ricky Lanetti, a college senior who also was a football player. He was getting ready for the play-offs for the NCAA Division III championships when he noticed a sore area on his rear. It was a small abscess, pretty routine, only a little bigger than a pimple. No one, least of all him, was very concerned; he was preparing for the big game.

Within days, this young man died of a severe MRSA infection that spread from the abscess throughout his body. His immune system could not contain it, and no amount of antibiotic could save him. His mother’s grief resounded in the now-silent room. She showed me a beautiful picture of her standing with her son in his football uniform towering over her; now he was gone.

When Congress members consider any given issue, they sometimes invite a few interested parties to a panel convened by one of the subcommittees in the Senate or the House. The meetings are held in large rooms, impressive in their classic structure and furnishings and as symbols of the power of our democracy. The rooms are filled with people in pecking order—the congressional panel, sitting in the front on a dais, the tables before them where the speakers will testify, and then the seats in the back, where the waiting speakers sit along with congressional aides and others who want to hear the action.

A hearing often has three or four panels of speakers, organized by the staff in terms of the particular items to be discussed. Congress members and celebrities come first, then their friends, then the organizations that have an interest. I testified multiple times on this issue, and the IDSA, despite being the professional organization most concerned and most knowledgeable on the subject, was always in the last panel. By then, after hours of numbing testimony, self-congratulatory speeches by both testifiers and congressmen and -women, and breaks, the room was usually almost empty. Most of the Congress members had departed, but still the chair had to be there to preside, to conclude the nation’s business.

This exact scenario played out yet again. Finally I was seated at the table for testimony. I had readied my speech about why we needed to strengthen the pipeline and our suggestions about how to do it. The only congressman still there was the subcommittee chair, an older man with a distinctly southern accent. Before I could start, he said that he was glad to hear testimony about this. He continued: “A few weeks ago, I was with my friend. We were golfing. He was telling me how much his knee was hurting and how he was scheduled for surgery for a knee replacement. The next time I saw him was at his funeral. From the surgery, his knee became infected with the MRSA, and it killed him, just like that. There was no good way to treat him. So I know what you are talking about.”