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The Killers Within
By Michael Shnayerson Mark J. Plotkin
Little, BrownCopyright © 2002 Michael Shnayerson and Mark J. Plotkin
All right reserved.
Chapter OneThe Silent War
Most mornings for Glenn Morris started with his daughters. Only after he loaded the three of them-aged fifteen, twelve, and nine-into his old Infiniti G20 and dropped them off at the carpool did he head in to the hospital. But on the mornings of July 2001, while the girls were on summer vacation, Morris bid his wife goodbye and drove off alone to the front lines of a war none of his neighbors could see or hear.
As a doctor in his late forties who was both head of epidemiology at his hospital and chairman of the associated university department, Morris could have graduated from going on clinical rounds. Still, he made a point of doing it two months a year. You couldn't just teach and do research, he believed-you had to see what new infections patients were incurring. Also, going on rounds made him feel the same stomach-tightening anticipation of the unknown that he'd experienced as a medical resident more than two decades before. And so he headed in from his Tudor-style house in Roland Park-a leafy neighborhood of large, comfortable homes built a century ago as one of Baltimore's first suburbs-to spend his days treating half a hundred very sick patients, many of them indigent, in the general ward of Baltimore's Veterans Affairs Medical Center.
On the fifteen-minute drive into the city, Morris liked to listen to country-and-western music, its trucks and trains and broken hearts weaving through his thoughts of doxycycline or ciprofloxacin for one patient, vancomycin or Synercid for another. After parking in the hospital's underground garage and ascending, white-jacketed, to the general ward on the third floor, he started by checking his charts. Six new patients, he saw, had been admitted to the ward by way of the emergency room. One's condition looked especially bad.
Morris went from bed to bed, trailed by a note-taking team of medical students, interns, and residents. Because this was a VA hospital, most of the patients in the general ward were male, elderly, and afflicted with chronic conditions. Many also had symptoms that indicated bacterial infection. A decade ago, antibiotics would have knocked out all of these infections almost immediately. Now on average, about 20 percent of patients on Morris's clinical rounds had infections resistant to one, two, three, or more drugs. When he wrote for medical journals, Morris described this multidrug-resistance in dry, clinical terms that expressed none of the emotions he felt when he witnessed the ravages of an almost unstoppable infection. What he felt was dismay, and alarm, and a little twitching of fear.
When Morris pointed out antibiotic-resistant infections to his interns and residents, he didn't need to emphasize that these were bacterial infections. They'd had it drilled into them in medical school that most infections are either bacterial or viral, and that bacterial infections are the ones that respond to antibiotics. Viruses, they knew, were a whole other matter. A virus is a tiny squiggle of protein-covered DNA or RNA, so small it isn't even a living, cellular organism: its only function is to bore into the cells of other organisms and force those cells to produce more viruses. (AIDS is caused by a virus; so is the common cold.) Antibiotics are useless against viruses. Bacteria, on the other hand, are one-celled organisms: the smallest creatures on the planet. The cell has various parts that enable the bacterium to live and replicate. Those parts can be targets for antibiotics. Unless, that is, the bacteria figure out how to change or deflect the drugs and make themselves resistant.
A decade ago, Morris liked to remind his entourage, doctors had only to reach for penicillin, or one of the third-generation cephalosporins, or the then new, brilliantly effective fluoroquinolones. Now for empiric therapy-immediate treatment of new patients, before a lab could determine exactly what bug they had-doctors often found themselves in the dark, guessing which antibiotic would work. Often there was time to correct the therapy once cultures provided a profile of which drugs still worked against a bug. Sometimes there wasn't. Whenever a newspaper obituary listed cause of death as "complications" following surgery, chances were that a doctor had guessed wrong in terms of antibiotics-or that a bug had proved resistant to all of them. This was code that all healthcare workers, hospital staff, and HMO providers understood but few outside the medical world knew.
Most at risk were the old and the infirm, their immune systems deteriorated, especially in hospitals: at the dawn of the twenty-first century, roughly a third of all people older than sixty-five were dying from infections. Nearly as vulnerable, however, were the very young. Their immune systems were immature, not ravaged, but the result was the same. Tough, sometimes unstoppable strains of the usual suspects-especially Streptococcus pneumoniae-caused terrible, recurrent ear infections, or meningitis, or systemic bloodstream infections that shut down a child's vital organs. Every year, 1.2 million children around the world were estimated to die of S. pneumo, the leading bacterial cause of pneumonia. In the United States alone, S. pneumo was said to cause 500,000 cases of pneumonia, many of them pediatric, as well as 7 million ear infections, most of them pediatric, too. Only a decade ago, nearly all strains of S. pneumo had been susceptible to penicillin, the drug of choice for these infections. Now 45 percent of all S. pneumo strains were penicillin resistant. Some skeptics observed that with S. pneumo, a doctor could increase the dose of antibiotics and still hope to prevail in many cases. But that was cold comfort to parents who saw their children's lives imperiled. Gary Doern, Director of Clinical Microbiology at the University of Iowa Hospital in Iowa City, tracked S. pneumo on a national, ongoing basis and was staggered by its fast-rising rates of resistance. "Do the math," he said grimly. "Where will it be fifteen years from now?" S. pneumo claimed as many victims outside the hospital as it did because, unlike many bacterial pathogens, it was spread by droplets: coughing passed it from host to host. Enterococcus faecium and Staphylococcus aureus infected hospital patients for the most part. But with S. aureus, the most virulent of the three, there were signs that that was changing.
In January 2001, Bryan Alexander, eighteen, was found guilty of assault and drunken driving and sentenced to a 180-day term at a correctional boot camp in Mansfield, Texas. On January 4, he filed a written request for medical attention. According to his father, he filed two more requests; all three requested treatment at the local hospital. The camp nurse chose to refuse them. On January 9, Alexander died of pneumonia caused by a S. aureus infection: an otherwise healthy eighteen-year-old killed by microscopic organisms in just days. A few months later, talk show host Rosie O'Donnell very nearly died after cutting her finger with a fishing knife and incurring a multidrug resistant S. aureus infection. "On Tuesday night, April 3 , my hand started to hurt. A lot. It was an itchy-hot-burning-searing-what-the-hell-is-happening pain," she recalled. The pain became unbearable; by the next day, O'Donnell was in the hospital, her hand so swollen it looked "like a kid's bright-red baseball mitt." Multiple surgeries were needed to debride her finger-to cut away the dead and infected tissue-and decontaminate the site. Neither good health nor celebrity had protected these victims.
Strains of all three of these common bacterial infections-E. faecalis, S. aureus, and S. pneumo-were now multidrug-resistant and spreading into the community. Strains of other bacteria-Acinetobacter baumannii, Pseudomonas aeruginosa, and E. faecium-remained hospitalbound but had become resistant to all antibiotics. So widely and quickly were bacteria of different species trading their resistance genes that the vast, invisible world of bacteria could be thought of as a single, miasmic, multicelled organism, its trillions of parts all working together for the common goal of survival against antibiotics. What this boded for humans, the bugs' primary source of food, was in no way good.
At the bedside of the patient whose case history worried him the most, Morris offered greetings with a cheer he didn't feel. The patient, a man in his seventies, had come to the hospital some time ago for a routine knee replacement. Apparently, while his knee was cut open in surgery, he'd incurred a methicillin-resistant S. aureus infection, or MRSA. Nearly all strains of S. aureus were now resistant to penicillin; almost half the hospital strains were also resistant to methicillin, the drug once thought to be a permanent replacement for penicillin. The infection had manifested itself a month after the man was back home. In he came again to the hospital for surgery to decontaminate the joint, followed by a six-week course, also at the hospital, of vancomycin.
Vancomycin was a last resort, but that didn't make it a great drug. It often failed to penetrate deep bone infections, and it had to be administered intravenously, which meant using catheters, which became conduits for other disease-causing, or pathogenic, bugs. In this case, when vancomycin failed to stem the infection, the man's doctors removed the artificial joint altogether and fused the joint that remained. Then they hit him with another six-week course of vancomycin. Now he was back again, this time with a fever that almost certainly signaled the return, yet again, of his resistant infection. He had bedsores, a urinary catheter, a fused knee that was essentially worthless, and deep infections that just wouldn't quit. He was almost pathologically depressed, as well. His wife had remained a constant presence at his hospital bedside, but she was on the verge of a breakdown herself, unsure whether the downward spiral of complication after complication could ever be reversed.
Morris knew he had to prescribe vancomycin. He had no choice. But where to put the IV? The man had endured so many intravenous lines he was running out of veins. Reluctantly, Morris put him on vancomycin via a central line-a catheter introduced into one of his large veins-and wished him luck. Privately, Morris thought the man would be lucky to live out the year.
This was a case, Morris thought, that should never have happened: a man who'd come into the hospital in basically good health and emerged with a dire strain of MRSA. Doctors had a phrase they used among themselves to refer to such patients-the ones with infections resistant to one or more drugs and who seemed too sick to respond to any antibiotics.
Train wrecks, they called them.
Not every doctor and microbiologist at the dawn of the twenty-first century felt, as Morris did, that the golden era of antibiotics might be coming to an end. Not all felt that bacterial resistance had become, in the words of one physician, one of the greatest threats to the survival of the human species. But many did. And all agreed that resistance had become an urgent global issue. Stuart Levy, M.D., a Tufts University professor whose Cassandra-like warnings on the subject two decades before had all come to pass, saw only worse things to come. "We are clearly in a public health crisis," he said to anyone who would listen. "In fact, we're on the road to an impending public health disaster." Joshua Lederberg, Ph.D., Nobel laureate and longtime leading expert in antibiotic resistance at New York's Rockefeller University, felt that by comparison, the Ebola virus was small potatoes. "The odds of Ebola breaking out are quite low, but the stakes are very high. With antibiotic resistance, the odds are certain and the stakes are just as high. It is happening right under our noses."
The principal cause was overuse-and misuse-of antibiotics. In 1954, 2 million pounds of antibiotics had been produced in the United States. By the end of the century, the annual figure had risen, by some estimates, to more than 50 million pounds. Yet researchers at the federal Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, judged that a full third of the 150 million outpatient prescriptions for antibiotics written each year in the United States were unnecessary: either the infection turned out to be viral or the wrong drug was prescribed. Doctors prescribed the drugs partly to placate demanding patients and partly to protect themselves legally if they failed to prescribe an antibiotic for an infection that turned out to be direly bacterial. The proliferation of antibiotics killed many bacteria but gave the hardiest few some more chances to learn how the drugs worked-and how to resist them.
It was a phenomenon that biologists called selective pressure. Among the billions of bacteria in a drop of human blood, or on a pinpoint of skin, or in a minute isolate of phlegm in the throat or stomach acid, might be a few-just a few-with a chance mutation that enabled them to resist the antibiotic used against them. If the antibiotic was then removed because the patient felt better and stopped using it-or sometimes even if it wasn't-those few resistant bugs would have an ecological niche, or clear field, in which to run wild. Because bacteria replicated so quickly-some bugs created a whole new generation every twenty minutes-the mutants could soon fill the niche. The pressure of the antibiotic, rather than obliterating them, had selected them to survive.
Only a small portion of blame could be pinned on doctors in the community. Lethally resistant bacteria now resided in every hospital and nursing home in the world. Every year in U.S. medical institutions, 2 million patients contracted infections-bacterial, viral, and otherwise-and 90,000 died. Of those 90,000, many had drug-resistant bacterial infections, mostly S. aureus. The CDC estimated that 40,000 Americans died each year of those infections. That was more than half the number of servicemen who had died during the entire Vietnam War. These deaths occurred in ones and twos, in hospital beds spread across the country, not by the scores on a single battlefield, so they tended to be noticed only by the patients' family and friends; by the hospitals, which certainly did nothing to publicize deaths caused by organisms within their institutions; and by HMOs, which quietly raised their premiums to help cover the estimated $5 billion cost of treating drug-resistant infections each year in the United States. Doctors and researchers published academic papers on drug-resistant bacteria, and, every year, their concerns grew more urgent, their prognoses more bleak.
Excerpted from The Killers Within by Michael Shnayerson Mark J. Plotkin Copyright © 2002 by Michael Shnayerson and Mark J. Plotkin . Excerpted by permission.
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