Superbug: The Fatal Menace of MRSA

Unusual book

  CHAPTER 1

THE FIRST ALERT

Tony Love’s knee ached.

The rangy, round-headed thirteen-year-old had banged into a friend a week ago while they were playing volleyball in the school gym. They crashed to the floor together, arms and untied shoelaces flying, and Tony scraped his elbow. After school, he and his mother and his grandmother had bandaged the cut and shrugged it off. He was a teenager, after all; Clarissa Love, his mother, expected her son to be rambunctious. It was mid-September 2007. The weather was still hot south of Chicago and Tony was still in summer mode, twitching behind his desk at school until the bell rang and he could burst out and work it off. The scratch was no big deal, and Tony was tough; he was the second child of six, and the only boy until his baby brother, the youngest, had come along. Tony saw himself as the man of the family, keeping his sisters in line while Clarissa, who was thirty, worked as an aide for the disabled.

The elbow had healed up after a few days, but then his left knee started to hurt. Now it was hot and so swollen he couldn’t bend his leg. When he tried to put his weight on it, it throbbed like his heart had gone down behind his kneecap. Clarissa had gone away for a few days, so her mother Sandra put the oldest sister in charge of the other children, hooked Tony’s arm around her shoulder, and steered him out to the car. He leaned on her heavily, hopping on his good leg and wincing when the other foot hit the ground.

At the little local hospital, the emergency room doctor listened to Tony’s story and shrugged. It was probably a sprain, he said; take the boy home, give him Motrin, wrap the knee in hot towels, and it would be better in a few days. They staggered home.

It did not get better. Four days later, Tony’s left knee still hurt, and his left foot and both of his hands did too. His hip joints ached so much he didn’t want to walk, not even to the bathroom. He didn’t want to eat, either. A thirteen-year-old boy with no appetite; to his grandmother, that was the biggest warning sign of all. She checked his temperature and found it was 104. Frightened, she hauled him out to the car and took him to the next-biggest local hospital, a few miles further south. The ER staff there checked his vital signs and listened to his story: the scrape, the fever, the lethargy, the joint pain for more than a week, the not wanting to eat or pee.

They were a little worried, they told his grandmother. Tony’s pulse and blood pressure looked normal and his breathing was fine, but the fever indicated an infection, and his kidneys weren’t working as well as they should. The hospital was willing to admit him, but to be safe, the ER staff thought they ought to take him to a children’s hospital. There was a very good one, they said, back toward the city, at the University of Chicago, and they called an ambulance.1

It was the end of the workday, and Clarissa met Tony and her mother at Comer Children’s Hospital, a gleaming new glass pile just off the university’s park-like main boulevard. The ambulance crew that brought them rolled Tony straight up to the medical floor, and the nursing staff began admitting him, checking his vital signs again and going over his paperwork from the smaller hospital. The ER staff there had suspected that Tony had osteomyelitis, a bone infection that could be caused by several kinds of bacteria. It was a serious condition, but not rare, and it was treatable, requiring that he get the right drugs for whichever bacteria were infecting him and be monitored by someone who understood the disease in children.

But while they were talking, Tony’s condition abruptly got worse. He became agitated and confused; then he began breathing fast and deep. His skin had been radiating heat from the fever, but it turned cold as quickly as if someone had parked him in front of an air conditioner. The medical staff around him recognized the signs: the bacterial infection was spilling over into his bloodstream, and his immune system’s spiraling reaction was slowing his pulse and crashing his blood pressure. In half an hour, he had gone from a sick kid to a kid in crisis.

A nurse phoned urgently upstairs to the pediatric intensive care unit, checking for an open bed that had all the monitoring equipment they would need. The technicians kicked the gurney’s brake locks and got him rolling, skidding past the curvy computer stations and the kid-friendly bright red columns. Tony was sliding into septic shock, and that was an emergency. Inside his body, chemicals released by his immune system were triggering a cascade like dominos falling. They were stretching the firm walls of his blood vessels, making them porous, and fluid was leaking out into his tissues. Blood cells were clumping and clogging his capillaries, and his oxygen-starved organs were beginning to fail. Clarissa felt her stomach cramp in fear. In front of her eyes, her son was dying.

In the ICU, the staff sedated Tony and slid a tube down his throat, turning the hard work of breathing over to a ventilator. They threaded IVs into his veins and hooked him to bags of fluids, plugging in four drugs to bring back his blood pressure and stimulate and stabilize his heart rate, and four more drugs to contain whatever bacteria were revving his immune system into overdrive.

To his bewildered mother and grandmother, the swirl of controlled chaos around Tony was as inexplicable as his sudden collapse; the ICU staff seemed to be trying everything, hoping it would bring him back from the brink. No diagnosis was possible yet. They had been in the hospital barely an hour, not long enough for test results to make it down to the lab and back. But the medical staff had a strong suspicion of what could bring a healthy boy down so quickly, and the clue lay in one of the drugs they ordered pushed into his veins. It was called vancomycin, and it was famous in hospitals as a drug of last resort. They used it against a bacterium that had learned to protect itself against most of the other drugs thrown at it, a particularly dangerous variety of staph called methicillin-resistant Staphylococcus aureus—MRSA, for short.

Staph, the short form of the family name Staphylococcus, is an ancient organism with a vast arsenal of tricks and defenses, some of them newly learned, others as old as man. It is unpredictable, dynamic, potentially deadly—and for more than a decade, it had been the obsession of a small group of University of Chicago researchers. Geographic accident had brought Tony to a place that understood how to help him, but it was far too soon to know whether he had arrived in time.

Orthopedic surgeons and plastic surgeons converged on the room Tony had been hastily stashed in. The fever, the septic shock, the pain in his legs and joints—all the symptoms indicated the infection was making abscesses that would need to be opened and drained immediately. The teams ran him quickly through radiology for a CT scan, peering at the screen for the bright white spots that indicate infection, and then to the operating room to get him prepped and anesthetized.

Plastic surgeons are the watchmakers of medicine, practiced at maneuvering in tight areas packed with crucial interconnected parts. They went to work on Tony’s left hand, cutting carefully through ligaments and tendons to preserve as much function as possible. Inside his fingers, they found pockets of pus the size of nickels. There was one in the center of his hand; it was the size of a golf ball. There were others in his right hand, too, and more hidden beneath the bones of his right foot. Orthopedic surgeons are cabinetmakers, trusted to protect the strength of the body’s scaffolding and the smooth function of its joints. They probed Tony’s hips and shoulders with a long wide-bore needle, looking for infection trapped behind the joints’ cartilaginous sheaths. His left knee, the one he couldn’t bend, was rigid and swollen. When they slid the needle in, pus pushed out under pressure, forcing back the base of the syringe. They got out enough to fill a baseball.

One of the orthopedic surgeons sliced into Tony’s left thigh and eased apart the muscles. There was pus underneath them, creamy and dull. There was too much to evacuate through the small incision they had cut, so they kept cutting, looking for the end of the pocket. They laid his thigh open from his knee almost to his hip joint; wherever they cut, they found a dense deposit of pus wrapped around the bone. They used a tool like a dentist’s jet to work it free, rinsing the cavity between bone and muscle with high-pressure water and sucking the slurry away. The abscess was so deep that they could not trust they had cleaned out all the infection, and so they left the gash open. They wrapped it in dressings that would let the mess drain, and rolled him back to the ICU.

They brought Tony back to a room at the center of the unit, as close as they could put him to the nurses who would monitor his every moment. He was still sedated and intubated and teetering on the verge of shock. He had pneumonia, and his liver was not clearing waste products from his blood. The intensive-care team pumped him with drugs and fluids: antibiotics to kill the still-unidentified bacteria, immune globulin to neutralize toxins, vasopressors to keep his blood pressure up. The drug doses had to be maintained in a delicate, shifting balance. Too much or too little could send his heart into an off-kilter rhythm, or scatter small clots through his bloodstream, or clamp down the small vessels in his extremities and kill a finger or toe.

Not long after Tony came back to the ICU, the unit’s computer pinged with the first report from the hospital’s microbiology lab. The results validated the intuition of the health care workers who had ordered him onto vancomycin many hours earlier. Tony did have MRSA.

“They told me he was the sickest child on that ICU,” Clarissa recalled. “They didn’t expect him to live.”

The Chicago group’s long journey with MRSA began in 1996, eleven years before Tony rolled through their emergency room doors. It started with a casual hallway conversation between Dr. Robert Daum, the chief of pediatric infectious diseases, and Dr. Betsy Herold, a faculty physician. They had both noticed that they were suddenly seeing a lot more kids with staph.2

That staph infections were occurring was not, in itself, remarkable. Staphylococcus is a large genus of bacteria, and S. aureus—the strain that is most common in humans, and that most people mean when they say “staph”—is probably one of mankind’s oldest evolutionary companions. Over millions of years, it has learned to live benignly on human skin and in human nostrils, in a microscopic intimacy that biologists call “commensal,” from the Latin words for “being at table together.” At any moment, one out of every three of us is carrying S. aureus without being made sick by it.3 But when that mutual balance is disrupted, S. aureus can attack with ferocity, causing infections that range from simple skin boils and rashes to muscle and bone abscesses, pneumonia, toxic shock, even infestations of the valves of the heart.4 The countless generations of close contact have given the bacterium an unmatched familiarity with the human immune system, and out of that long acquaintance it has evolved a huge range of microbiological weapons called virulence factors—more than seventy cell-destroying enzymes and toxins, many more than any other bacterium can produce.5

Staph is a fearsome aggressor when the body’s protective mechanisms are disrupted, both the first-line defense of our skin and the complex chemical weaponry of the immune system. It is notorious for invading not only large surgical wounds, but the small incisions made to accommodate IV lines and dialysis catheters; it enters the body through the smallest gap, and it forms sticky, infectious films on the tubes passing through those gaps. It is a grave danger to anyone whose immune defenses have been reduced by age, illness, or treatment for disease: newborn infants, chemotherapy recipients, people whose poor kidney function forces them into regular dialysis. It is by far the most common cause of infections in hospital patients, causing almost a half-million serious illnesses every year.6

And in addition to its virulence, staph possesses another potent weapon: it has been developing successful defenses against antibiotics for as long as antibiotics have existed. That is not a long time, since penicillin only went into wide use at the end of World War II. But staph is so adept at evading threats to its existence that it learned to protect itself against penicillin almost as soon as the earliest experimental doses of the drug were deployed, and long before it was placed on the open market.7 Ever since, bug and drugs had been locked in a lethal game of leapfrog, with staph always one leap ahead. After penicillin, pharmaceutical chemists created a new drug, methicillin, with a chemical structure that had never before existed in nature—a strategy they thought would provide decades of protection against staph’s adaptive brilliance. But methicillin, launched in 1960, was not even on the market a year before staph developed resistance against it as well.8 For decades, pharmacologists spun new compounds out of methicillin’s structure, hoping to find the perfect molecular shape to penetrate staph’s defenses, but they had never been successful for long.*

By the time Daum and Herold paused in the hallway of Wyler Children’s Hospital in 1996, methicillin resistance was so widespread that almost every large hospital in the United States had detected at least one MRSA infection, and a third of all the staph cases that occurred during hospital stays were caused by MRSA instead of common drug-sensitive staph.9 Almost all those MRSA infections had a common history: they began after the victim was admitted to a hospital. The victims were nursing-home residents or cancer patients or had long-term medical problems. They were vulnerable because they were diabetic and took dialysis three times a week, or because they had cystic fibrosis and their lungs were full of sticky mucus that made a great breeding ground for germs.

The cases that Daum and Herold were noticing were not like those patients. They were not old people or babies or anyone who had been sick for a long time. Instead, they were children who had not been in any hospital for as long as their families could remember, but who nevertheless had been felled by an inexplicable bacterial attack.

In twenty-four years in medicine, Daum had seen a lot of staph, and he had developed a rueful respect for the bug’s persistence and resilience. He knew better than to assign human qualities to a bacterium, and yet he would slip and speak as if it knew what it was doing. “It knows how to live on inanimate objects, in our noses, in our skin, in our genitals,” he would say. “It’s virulent, it’s adaptive, and it is able to circumvent almost everything we throw at it. It is a perfect pathogen.”

By 1996, Daum had been at University of Chicago for eight years. He was a Boston native, but he had stepped aside from the straight-to-Harvard path expected of aspiring doctors in Boston and gone to Montreal for college instead. He stayed for medical school and stayed again for residency—and then succumbed to tribal custom and headed to Harvard at last for a postgraduate fellowship. He still spoke good French, and at home he often listened to old Edith Piaf recordings. Her defiant, luxuriant melancholy was a paradoxical comfort after long days confronting the terrible damage that childhood diseases could do.