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.

The cases he and Herold had noticed stood out not just because they were mysterious but because they were severe. One fourteen-year-old had a raging infection that filled the spongy bone of his heel with pus. Another, only six, had a painful, walled-off abscess, hard with clotted blood, buried deep in the muscle of his butt.10 The illnesses were as serious as the infections that people contracted if they had been in the hospital, and taken major antibiotics, long enough to undermine their immune systems. But these children had not been in any hospital; nor did they suffer from any of the chronic conditions such as diabetes that could have made them vulnerable. If they had staph at all, it should have been only a rash or an eyelid stye, a minor problem that a kid might pick up in everyday life.

And incontrovertibly, they did have staph. Again and again when the team sucked tiny samples of pus out of the infections and sent them to the hospital’s lab, the samples grew into S. aureus’s streaky yellow colonies. (Aureus comes from the Latin for “golden.”) Even more troubling, this staph was drug-resistant. When the lab technicians dropped minuscule dots of drug-impregnated paper onto the staph colonies and watched for the ring-shaped dead zone that would indicate the bug was susceptible to the drug, again and again no ring formed. The children had MRSA—and they had acquired it out in the community, a setting where MRSA was not supposed to be.

A virulent, drug-resistant hospital bug in children who had never been in a hospital? It made no sense. Herold and Daum responded in the classic manner of scientists. They performed a study. Delving into the hospital’s archives, they pulled the medical charts of every child hospitalized with S. aureus from mid-1993 to mid-1995, and for comparison’s sake pulled charts from five years earlier. They sorted through the sets from the 1980s and the 1990s, dividing them into progressively smaller subsets. First they separated out children with methicillin-susceptible staph, leaving only children with MRSA. Then they separated out children who developed MRSA while they were hospitalized, leaving only children who would have come into the hospital from the community already infected. Finally, they took a second look at the records of the children with those community infections, and separated out any child who had been hospitalized in the six months before the infection, had been intubated or catheterized even as an outpatient, had undergone surgery, or had anyone in their household to which the same conditions applied—anyone, in other words, who had some intimate health care contact that might have passed the bacterium along.

That left them, in each cohort, with some number of children who had developed MRSA despite having had no contact with the health care institutions where MRSA was known to flourish. The researchers compared the two time groups and were shocked: In the past two years, there had been twenty-five cases of MRSA infection that had no link at all to health care. Five years earlier, there had been one.

The medical records revealed that these infections were different from the norm in several striking ways. Over more than three decades, bit by bit, the MRSA that patients contracted in hospitals had developed resistance to an enormous range of drugs. It could disarm not only methicillin, but a vast class of similar drugs, called beta-lactams for a feature of their chemical structure. It had accumulated additional defenses against other drug classes, so many of them that the bacterium was protected against most of the antibiotics that physicians use every day.11 It could reliably be treated only by one drug, vancomycin. By 1996, when doctors diagnosed MRSA they expected it to be multidrug-resistant. But the MRSA in the Chicago children did not possess multiple resistance. It had defenses against methicillin and the other beta-lactams, but that was all.

In another oddity, the bug in the children with the community infections seemed to have a different genetic structure than the MRSA norm. Because they had seen the children so recently, the Daum team still had samples of their blood stashed in the hospital’s laboratory freezers. And because biomedical researchers are pack-rats who never throw away anything that might one day be useful, they also had in the freezer some samples from children who had developed MRSA infections in the hospital sometime in the 1990s. The lab technicians isolated the bacterial DNA in the samples and used a technique called pulsed-field gel electrophoresis—PFGE, for short—to generate a bar code–like pattern that served as each bacterium’s molecular fingerprint. When the test was done, the researchers noticed something striking. The bar codes representing the fourteen-year-old and the six-year-old boys—who were not related to each other, and who came to the hospital 6 months apart—were identical to each other, and different from all the rest.

The study confirmed what Herold and Daum had suspected: this strain of MRSA that had walked in from the surrounding neighborhood was different from the MRSA they were used to in perplexing and potentially alarming ways. They wrote an article describing their findings and submitted it to the Journal of the American Medical Association. The journal kicked it back.

“They said we didn’t know what MRSA strains looked like,” Daum said. “So I called up the editor and said, ‘You know, I think that’s wrong. I think we do know.’ And in the end we had to send the genetic evidence that showed incontrovertibly they were MRSA.”

The journal eventually published the paper, on February 25, 1998, almost two years after Daum and Herold first discussed their worries. But just a few pages away, it also ran an editorial that suggested the team had just not done their homework.12 Somewhere in the patients’ past, it said, there must be a link to health care—a hospital admission, a clinic visit, a grandparent in a nursing home, or an uncle who was a janitor—that the researchers had simply missed.

For Daum, the medical journal’s implicit dismissal of their work was doubly frustrating. The University of Chicago is a private institution where faculty fund their research by means of the grants they attract. The journal had published the work, but did not endorse it; and without the blessing of the medical establishment, funding would be hard to come by. It was exasperating to have caught the scent of something and not have the resources to pursue it.

In the months that followed the paper’s publication, other researchers—including disease detectives at the Centers for Disease Control—quietly called and wrote Daum to express similar doubts. That a virulent staph strain could be flourishing outside hospitals, attacking healthy children with no immune-system deficits, challenged everything medicine had discovered about the behavior of drug-resistant organisms. Common opinion agreed with the JAMA editorial: the Chicago group had mistakenly latched onto a hospital strain of MRSA that had leaked into the community and persisted there for a while before dying out.

The questioners had some justification for their doubts because something like what they imagined had happened once before. In 1980, a strain of MRSA had spread among heroin addicts in Detroit. There was no MRSA in the community yet, and very little in the city’s hospitals; it caused about 7 percent of the infections that occurred in Henry Ford Hospital, the major public institution. Then, over a year and a half, 100 drug addicts living in the city developed MRSA, most with minor problems but about a third with potentially fatal infections of the bloodstream and heart. None of them were being treated in the hospital when the outbreak started, but they were nevertheless almost as medically fragile as hospital patients: undernourished, underexercised, with immune systems already overtaxed. And like hospital patients, they were also multimedicated—not only with heroin or whatever else they could afford, but with black-market antibiotics that they took on the sly to prevent skin infections when they shot up. Many of them had been in and out of Henry Ford’s emergency room in the past with minor illnesses, and twelve of them had been admitted to the hospital some time in the previous year. No one else outside the hospital picked up MRSA from the addicts—but one of them carried the strain back into the hospital, where it caused sixty-five more cases, including two nurses and a surgeon who picked it up but were never made sick by it, and fifteen hospital patients to whom the nurses and surgeon unwittingly passed the bug.13

Most of the infections in the outbreak began outside the hospital, yet in the view of epidemiologists, it was still a hospital outbreak. The assumption was that one of the addicts (no one could ever say who) had been treated at Henry Ford, picked up MRSA there, carried it outside, and passed it on. Limited lab evidence supported that view. PFGE, the molecular-fingerprint technique, had not been invented yet,14 but the MRSA strains in the addicts and in the Henry Ford patients were resistant to exactly the same medications: methicillin and all the beta- lactams, and two additional classes of drugs.

By the time the Chicago group’s paper was published sixteen years later, most MRSA researchers in the United States were aware of the Detroit outbreak and in agreement about what they thought it represented: the bug could briefly escape from hospitals via discharged patients, but it could not survive long on the outside because healthy people’s immune systems defended against it too well. To people who wanted to believe the Chicago team had made a mistake, the Detroit outbreak made a perfect counterargument. They did not consider that over those sixteen years, enough time for millions of bacterial generations to be born, breed, and die, staph had been doing what it does best: evolving.

There were a few clues, buried deep in the medical literature, that something about MRSA’s behavior was changing. In 1986, New York City physicians reported at a conference that they had found a group of drug users in Harlem infected with a MRSA strain that did not match the strain in local hospitals because it was resistant to fewer drugs.15 Then, in 1993, one of those physicians wrote a letter to a medical journal about another strange MRSA case. He had seen a sixty-five-year-old woman from the Bronx who had a staph infection of the heart so severe that it caused a stroke, leaving her paralyzed, deaf, and unable to speak.16 Her case was a tragedy, but it was also a puzzle. She had had zero contact with health care: no hospitalization in the past fifteen years, no visits to friends in nursing homes, no family members working in medicine, no drug use. And her strain of MRSA—like the Harlem addicts, but unlike anything known in hospitals—was also resistant only to the methicillin family of drugs. Finally, in 1995, a physician in Jackson, Mississippi, wrote in a letter to a different medical journal that he had treated a six-year-old boy for a MRSA bone infection.17 The boy lived a life in which he was surrounded by MRSA: his aunt worked in a local hospital as a clerk, and a second local hospital was in the midst of a MRSA outbreak. But the boy’s strain of MRSA was not hospital MRSA. The MRSA strain in the Mississippi hospitals was resistant to many classes of drugs, just like MRSA strains in hospitals across the rest of the United States. But the strain of MRSA infecting the boy was resistant only to methicillin and its close relatives, just like the MRSA strains in the Harlem addicts, the Bronx grandmother, and the Chicago children who were starting to roll through Daum’s hospital doors.

“The epidemiology of MRSA may be changing,” the Mississippi doctor wrote. “Studies are urgently needed to define the true scope of this problem.”

His plea was ignored. The medical establishment persisted in believing that MRSA was purely a hospital problem.

Tony struggled for weeks. Clarissa, camped out on the couch in his room, watched uneasily as the ICU nurses repeatedly checked his vital signs. Persistent fever indicates persistent infection, and his fever remained high. Once his belly ballooned hard and tight, and the staff feared his intestines might be dying. There was no time to get him to an operating room. The surgeons shooed out his mother, covered him with sterile drapes, and opened him up right there. “He was too unstable to move,” said Dr. Robert Bielski, an orthopedic surgeon who began treating Tony within hours of his arrival. “He was really, really, really sick.”

The belly problem turned out to be an accumulation of fluid, but it was another surgical insult to his slight, ravaged body. And there were more to come. Twice the orthopedic surgeons came back, peeled open the gaping wound in his thigh and washed it out again. In between, they plugged it with a “wound vac,” a humming contraption that sucked blood and fluids out of the incision through a layer of sterile foam.

Tony had been taking vancomycin, one of the strongest drugs for MRSA, from the hour he arrived in the hospital. But the drug wasn’t working. The continuing fever was one sign. Another was the constant presence in his blood of bacteria and other compounds that indicate inflammation. Day after day, they were there.

Vancomycin is an old drug, on the market for more than fifty years, and problematic in many ways. It has to be given intravenously. Its earliest formulations made recipients deaf, and its modern version can still be toxic to the kidneys at high doses. It kills bacteria slowly, and it does not penetrate equally well into all the body’s tissues; it has an especially hard time killing bacteria in the lungs and bones. Vancomycin’s patent protection expired in the 1980s, so no pharma company is likely to spend research money to improve it.18 Still, none of the drugs that have come on the market to replace it work significantly better. It is an old, blunt tool, but the new ones in the toolbox are no sharper.19

Vancomycin is still effective against MRSA, despite decades of use. That is partly because it is a glycopeptide, a separate class of drug from penicillin and methicillin. It has a different chemical structure from the earlier drugs and attacks the bacterium in a different manner, and MRSA needed many years to evolve protections against those differences. But the drug’s long record of reliability is also due to many years of sparing use. At first, that was because physicians had many alternative drugs to use. Later, it was because they had none. Vancomycin became a drug of last resort, doled out with extreme care for fear that widespread use would encourage resistance to develop.20

And resistance was developing. By the time Tony got sick, researchers worldwide were nervously tracking an uncommon strain of MRSA that they called VRSA because it was becoming so resistant to vancomycin.21 There was a second bacterial opponent as well, a strain with an insidiously different adaptation that researchers called VISA, for vancomycin-intermediate S. aureus. VISA’s adjustments to vancomycin’s attack were subtle. Under the tests used in hospital labs, the bacteria appeared susceptible to normal doses, but hidden within the bacterial colonies were small groupings of staph that could resist that amount of drug.22 That posed a double danger: When the usual dose was given, it would kill off the susceptible bacteria, but not the more resistant ones. And when the more-susceptible staph died, it left living space for the more-resistant staph to reproduce.

Tony had VISA. After seven straight days of vancomycin, his blood cultures still grew staph. Among the dozens of people working on him was Dr. Christopher Montgomery, an intensive care specialist who had done his residency at University of Chicago and stayed to join the faculty. He split his time between pediatric critical care and—as a break—the animal lab, trying to create a way to study MRSA in rats or mice. Tall and lanky, he was science-minded and precise, describing himself as “not good at feelings.” Despite that reserve, Tony’s lab results worried him. They seemed to say the MRSA strain infecting the boy would be vulnerable to the standard vancomycin dose, and yet the bug was manifestly not responding.

The surgeons had left Tony’s leg open, but they had closed the incisions they used to tap his infected joints, because if it is left open to the air, a joint could dry out and freeze up. Montgomery thought that one of the infected joints might be harboring a more-resistant population of staph. He fretted about another possibility too. Tony was getting antibiotics through a central line, a catheter threaded into a vein below his collarbone. If the catheter had become contaminated with MRSA, it could conduct the bug straight to his heart. In the pre-antibiotic era, infections on the valves of the heart were almost uniformly fatal. So if Tony’s strain was not responding to one of the strongest drugs, the outlook could be grim.

They took the line out—and for good measure, they switched him to a different new drug, linezolid, and added an old drug called rifampin as well. The choice of drugs suggested how few options there are for MRSA treatment. Linezolid, also called Zyvox, was the first of a new type of antibiotics called oxazolidinones that had only been approved by the U.S. Food and Drug Administration in 2000.23 They were the first new class of antibiotics put on the market in thirty-two years. That newness had a downside: as a patent-protected drug, a course of linezolid could cost thousands of dollars.24 And bacteria were already adapting to it. A year after linezolid’s approval, researchers had already begun finding bacteria that were becoming resistant to it.25 Rifampin, on the other hand, was a forty-year-old drug that could not be used on its own because staph develops resistance to it very quickly. It was one of many older drugs whose effectiveness against MRSA had never actually been studied. Physicians gave it, always in combination with other drugs, to gain whatever edge they could.26

Finally, after eight days, the team weaned Tony from the ventilator. Clarissa had been present the whole time, wrapped in the paper gown, gloves, and mask required for isolation precautions, napping on the couch or sitting by the head of the gurney. She was there when they woke him up. “I couldn’t touch him, and at first he couldn’t talk,” she recalled. “But he saw me right away. I could see him trying to tell me to come and give him a hug.”

Tony was still extremely sick. He was feverish and always sweating, but the worst problem was his left thigh. The surgeons had never closed the gash that reached from his hip to his knee because the long bone, the femur, wept infection into the muscles of his leg. Bone infections are usually concentrated in one section of a bone, but this one had spread throughout the shaft. The orthopedic surgery team kept bringing Tony back to the OR, where they washed out the wound with pulsing water jets. Then they drilled into the dead bone and ground it away from the inside. Bielski, the orthopedic surgeon, had never seen an osteomyelitis so bad. He tried not to think of what a weakened, reamed-out thigh bone would mean to a kid who loved sports.

The team changed the mix of drugs yet again to daptomycin and clindamycin, another new-old drug combination that they hoped might chase the last of the infection from Tony’s blood. The switch precipitated a crisis: his fever soared, he broke out in a rash, and his blood pressure crashed. He was sedated and put back on the ventilator for a day, and then eased off it again while Clarissa watched anxiously. Over days and weeks, infections kept flaring, and it took twenty more surgeries to clean them out and repair the damage that staph toxins had strewn through his system.

The final surgery was a skin graft, to close the gaping wound in his thigh. On December 6, seventy days after arriving at Comer, Tony was finally well enough to be transferred out of the ICU.

*  *  *

After Daum’s sentinel paper in 1998, researchers told themselves that his cases were an anomaly, some strange microbiological accident that was unlikely to happen anywhere else. But then physicians around the country began reporting clusters of illnesses that resembled the ones in the Chicago children. The new victims had not contracted their infections in a health care facility, and their bacteria had resistance patterns that were not like the health care strain.

An Army hospital in Honolulu reported cases in fourteen children and adults. There were fifty-nine sick prison inmates in Mississippi; fifty-three children in Corpus Christi, Texas; fifty-three other children living on a Native American reservation near the Canadian border; and several HIV-positive men in Los Angeles who were only identified because they were cared for by the same doctors.27–31 The outbreak that got the most attention, though, was the smallest: four children in the upper Midwest who died of overwhelming infections between July 1997 and February 1999.32

The victims were a seven-year-old girl from Minneapolis, a sixteen-month-old girl from a North Dakota Indian reservation, a thirteen-year-old girl from a southern Minnesota town, and a year-old baby boy from North Dakota farm country. They had never met. None of them had been hospitalized before, and their families had no contact with health care facilities either. They had nothing in common but the MRSA that caused their deaths. It was resistant only to methicillin and the other beta-lactams. The fingerprints of two of the strains were identical, and the other two were very close matches—but all four were very unlike local hospital strains.

The children lived hundreds of miles apart, and investigators recognized their similarities almost by chance. Thanks to the cultural attitudes of several generations of Scandinavian immigrants, Minnesota has one of the best-funded public health systems in the country, with a crack microbiology laboratory, a medical complex that is the referral destination for the whole upper Midwest, and a corps of investigators who regularly lend a hand to less fortunate departments in surrounding states. Those consultations had created an informal network of lab scientists, physicians, and epidemiologists who shared stories back and forth about interesting cases. Some of them talked idly about the first case, who lingered in a Minneapolis hospital’s ICU for five weeks with MRSA infections of the bones of both hips before she died. So when the second child was carried into a small North Dakota hospital with a 105-degree fever and died within two hours—and was discovered on autopsy to have MRSA abscesses in her brain, heart, liver, and kidneys—some of them remembered the first child as well.

Months passed, and then in January and February 1999, a third and fourth child died, both of them with lungs destroyed by abscesses and hemorrhage. By then a new member had joined the network. He was Dr. Timothy Naimi, an internist and pediatrician who had arrived in Minneapolis the previous August for a two-year posting with the CDC’s Epidemic Intelligence Service, its frontline disease detectives. He heard about the first two cases from his new colleagues, and he was so struck by what they seemed to represent that he launched an investigation of his own, recruiting twenty-nine other physicians and scientists to help him. Almost exactly eighteen months after the Daum group’s paper, they published details of the four children’s cases in the CDC’s weekly journal.

In the children’s deaths, Naimi saw a warning—two warnings, in fact. The cause of their illness made it clear that the Daum group’s cases in Chicago were not a one-time anomaly. And the fact of their deaths made it equally clear that the news of a new MRSA causing illnesses outside hospitals had not reached everyday physicians. All four of the children in Naimi’s paper were taken to doctors by their families when they first fell ill. And all four had been given antibiotics—but because their doctors did not imagine that MRSA was out in the community, the children got beta-lactam antibiotics that would have had no effect on any MRSA strain.

“If you were a pediatrician or a family physician and a child came in with pneumonia or sepsis, you would not even have considered that MRSA could have been the source of infection,” Naimi said. “We understood that we were seeing the very dramatic tip of a far larger iceberg.”33

In Chicago, the iceberg was revealing itself much faster than elsewhere. There were so many cases that, when members of the Daum team spoke at medical meetings, listeners joked about “the Chicago disease.” Even with the evidence from Minnesota and North Dakota, it was tempting to say that MRSA was simply different in Chicago. But it was much more likely that the University of Chicago researchers, knowing how the bug behaved, were better at identifying its unsuspected attack. About once every two months, they found the bug in children who were gravely ill with syndromes that had never occurred in hospital MRSA cases.

Among them were two unrelated infants, a one-month-old girl and a two-month-old boy, who were brought in one week apart in August 2000 with plunging blood pressure and lungs full of fluid, so septic the emergency room assumed they had meningococcal disease.34 The boy recovered completely, but the girl was left with long-lasting neurological problems. There was a nine-month-old girl, sick at home for two days in April 2003 with what sounded like a cold, who died on her sixth day in the hospital despite being placed on a heart-lung machine. In 2004, there was a seventeen-month-old boy who arrived suffering from the same inflamed lungs and adrenal hemorrhage and died within twenty-four hours.35 And in 2005 there was an eight-year-old boy, brought to the ER in shock after scraping his leg riding his bike, who spent more than two months on a ventilator, healing the five hundred holes that MRSA toxins had melted in his lungs.36

“With some of these kids, we have every supportive care at our disposal, all our resources, and we still can’t do anything,” Montgomery said. “We recognize it is staph very quickly. We treat with the appropriate antibiotics. And still we can’t affect it.” He paused. “I guess you could call that fear.” What was especially troubling was that their numbers seemed to be increasing. In 2007, in the months that Tony was at Comer, four other children with severe MRSA disease came and went from the ICU.

Over years of study, the Chicago group began to understand why the new MRSA strain was behaving so differently. As their first PFGE results suggested, and later studies confirmed, the community-associated MRSA they found in their child patients was truly genetically different from the hospital variety.37 It was a major research finding, but it only confirmed what they were already seeing in their patients: serious illnesses unlike anything that had been reported for hospital staph.

Tony was still the sickest they had seen. Even after he was discharged on December 9, 2007, he had to endure eight weeks in a rehab hospital on the shore of Lake Michigan. He had weeks of antibiotics still to take, and months of therapy. Finally, in March 2008, he put aside his crutches and for the first time in seven months put his full weight on his leg.

“Will the leg ever be completely normal? No,” Bielski, the orthopedic surgeon, said. “Will he be able to play contact sports? Probably not. He has made a lot of progress, but I am sure we’ll be following him for years to come.”

Tony and his mother did not know, and likely would not have appreciated, that the many months of their ordeal had been just one tiny skirmish in a decades-long war between MRSA and the drugs that were developed to control it. Neither side gained the advantage for long. For every new pharmaceutical compound, the microbe developed a new defense, sometimes so quickly that the bacterium evolved resistance to a new drug even before the drug reached the market. Slowly, though, the bug was gaining the upper hand. Pharmaceutical research was running out of ideas and investment, while MRSA was finding new victims and causing illness in surprising new ways. It was a pattern that had been set almost fifty years earlier, with the first epidemic of drug-resistant staph.