The Killer Bug And The Copper Cure
The hospital shimmers out of the high-desert plain of Calama, Chile, like a mirage, an unexpected oasis in this mining village of hardscrabble houses. As I walk closer, I’m gradually able to make out the name emblazoned across the facade. The huge orange-red metal letters spell out “Hospital del Cobre”. Copper Hospital.
The elevation here is 2 750 metres and crossing the plaza towards the building leaves my sea-level lungs gulping a little. But what really makes me catch my breath is behind the hospital’s glass doors: copper. Everywhere. Long, lustrous bands span the walls like racing stripes. The lift doors glimmer as if lit from within. When I enter an empty patient room, I see a broad, satiny bedside table and gleaming IV drip stands that are as gorgeous as chapel crucifixes. Even the food trays are the colour of a shiny copper coin. I marvel at the beauty of it.
It all feels over the top, as if some eccentric billionaire philanthropist wanted to echo an Inca temple in the emergency room. But as incongruously opulent as it all appears, I know that almost every inch of copper in the hospital is evidence of form following function – in extremis. If I were to ask the doctors and nurses about it, they’d tell me that just like, say, a defibrillator or an oxygen tank, the metal is part of their arsenal of medical equipment.
It has one purpose: to save lives.
Once upon a time, our biggest fears surrounding a hospital stay involved the procedure we were about to undergo. What if the doctor is having an off day? Will I be rolled into the OR for a “routine” heart bypass only to be rolled out with a sheet over my face? What if the anaesthesiologist uses too much anaesthesia – or, oh God, too little? What if the nurse who changes my bedpan has cold hands?
In recent years, however, a more terrifying concern has begun to emerge. Healthcare associated infections – or HAIs, as they’re known – strike 1.7 million people in the US annually, killing nearly 100 000 of them, according to a US Centres for Disease Control (CDC) study. The World Health Organisation (WHO) estimates that hundreds of millions more are infected with HAIs across the globe. According to a fact sheet released by the WHO, of every 100 hospitalised patients at any given time, seven in developed and 10 in developing countries will acquire at least one healthcare-associated infection.
For a while now, the most feared of these infections has been from a Methicillin-resistant Staphylococcus Aureus (MRSA), named after a common antibiotic that used to be effective against the bacteria. But years of antibiotic overuse have morphed it from ho-hum staph bacteria into a “superbug” responsible for infections that are now extremely difficult to treat. In 2004, MRSA accounted for 64% of HAIs in intensive care units of US hospitals. By 2005, it was killing more people there than AIDS and tuberculosis combined.
Then, this past April, the tide seemed to be turning. The CDC reported that rates of MRSA infections in hospitals had fallen more than 50% between 2005 and 2011. The reason, researchers speculated, was the heightened emphasis placed on thorough hand washing, screening incoming hospital patients for MRSA and the fact that the bug still responded to a few antibiotics.
Once again, however, these same antibiotics were both the solution and the problem. Despite pleas from public health officials, the overprescribing continued, with patients demanding what they didn’t need and doctors shutting them up with a few pen strokes. As a result, the void left by MRSA has been filled over the past decade by another, even more dangerous antibiotic-resistant acronym: CRE.
Carbapenem-resistant Enterobacteriaceae – so named for its ability to fight off the last-line-of-defence carbapenem antibiotics – kills as many as half of those infected, the CDC reports. Dr Daniel Uslan, an assistant clinical professor of infectious diseases at the University of California, Los Angeles (UCLA), says that in some cases, survival will require making a choice between sacrificing an infected limb or taking an older class of antibiotics, drugs that had been abandoned because they can destroy kidney function.
“We are approaching a post-antibiotic era where we have to say to families or patients, ‘I’m sorry. We have nothing to treat your infection,’” says Uslan.
CRE is not simply a one-dimensional bacterial brute; the mayhem it inflicts is multifaceted. This superbug, which is usually spread by unwashed hands or contaminated instruments, can lurk undetected in a patient until just the right moment – say, when the person’s immune system is at its weakest. It can then transfer its resistance to other relatively innocuous bacteria, leaving new monsters in its wake.
It accomplishes this Franken-feat through plasmids – circular genetic packets that can be transmitted from one bacterium to another. When CRE spews out plasmids, they contain, among other bits of DNA, the code for drug resistance. Worst case, if a CRE-infected patient moves to a different hospital – and many hospitals have no idea who is or isn’t infected – that patient can unwittingly become a Trojan Horse filled with an invisible army of mutant microbes ready to deploy and spread.
That’s precisely what happened in July 2007 at the University of Virginia Medical Centre. A 45-year-old man with hepatitis C was transferred there for liver transplant surgery, which was completed without incident. But two weeks after his discharge, the man was readmitted with a high temperature and stomach pain. Despite being flooded with round after round of the most potent antibiotics available, his condition worsened.
CRE infections are difficult to diagnose and it took three weeks to confirm this case. Still, the infection raged on. “We were trying everything,” recalls Dr Costi Sifri, a professor of infectious diseases at the University of Virginia and the medical centre’s epidemiologist. But the bacteria ravaged the man’s liver. Three months later he was dead.
The episode was tragic, but what happened next was terrifying. Within weeks of the man’s death, similar cases surfaced at the hospital. Doctors scrambled for answers as they were forced to consider the possibility of a full-blown outbreak. By the time the bug was brought under control, it had been discovered in 14 patients, half of whom would die.
It’s unclear just how many cases of CRE currently exist in the US. From the first known case, in a North Carolina hospital, CRE has spread to more than 40 states. That was enough to prompt the CDC in March to warn healthcare providers and the public that this threat was extremely serious and warranted immediate action.
“In a sense it’s a nightmare scenario, a perfect storm, whatever metaphor you like,” says Dr Arjun Srinivasan, the CDC’s point man on the tracking, prevention and elimination of HAIs. That’s because until researchers find an effective strategy to deal with and eliminate CRE, virtually any seriously ill patient in a hospital is at risk.
In more visceral terms, the fate of a man who enters a hospital and becomes infected with CRE is bleak: “Our GIs who go to Afghanistan have a greater likelihood of coming back alive,” says Michael Schmidt, a professor of microbiology and immunology at the Medical University of South Carolina. “You never see the victims on the 6 o’clock news, because these poor souls died one at a time, with their families around their beds and everyone asking, ‘Why?’ ”
Just down the road from the Copper Hospital, yawning like a bowl-shaped Grand Canyon, is the world’s largest open-pit copper mine. Its name is Chuquicamata, but the locals call it simply Chuqui. My guide, Patricio Huerta, a representative of Codelco, the state-run copper concern, explains that the name roughly translates to “the metal-tipped wooden spear”.
Ringed with ledges that from high above give it the appearance of the ruins of a Roman amphitheatre, the mine is so deep that it could fit almost four Eiffel Towers stacked on top of one another. The surrounding desert is so dry that virtually no insects crawl there and precious few birds soar above. There is only the wind kicking up the shimmering white dust from the enormous basin.
Looking more closely, however, I see life: small black “bugs” climbing slowly up the winding ledges of packed sand. I watch for an hour or so and the bugs grow bigger. They rumble around a bend at the top, small at first, then larger, then impossibly large: dump trucks, each hauling enough rubble and rock to fill a swimming pool.
In the eyes of the miners who toil here, Chuqui is an almost sacred mother goddess that was once worked and worshipped by the Incas and that continues to provide sustenance to the men who descend into the pit each day. When Huerta peers in, he sees Chile’s economy churning. After all, copper represents 15% of the country’s GDP.
But when Schmidt looks down into the pit, as he did a few years ago when he helped launch a groundbreaking study at the Copper Hospital, he sees salvation.
The idea of copper as a medicinal wonder may not be as millennia-old as the rich deposits Chuqui yields, but to call it ancient is no exaggeration either. Since as far back as when Isis was portrayed in her copper-coated goddess glory, the metal and its many alloys have demonstrated an astonishing array of therapeutic properties. According to ancient texts, copper was used to sterilise both wounds and drinking water. Instead of aspirin, Egyptians relied on copper concoctions for headaches, burns and maladies such as “trembling of the limbs”.
The Aztecs gargled with a copper potion for sore throat relief. The ancient Greeks applied a mix of copper oxide and copper sulfate powders, or honey boiled with red copper oxide, to treat fresh wounds. And the physician Aulus Cornelius Celsus (AD14 to 37) prescribed a raisin wine-based brew of pepper, saffron, myrrh, antimony and copper to treat a common problem among randy Romans: sexually transmitted diseases.
In India, where the waters of the Ganges were holy, but also hazardous to the health of the exploding population, mothers found a way to combine the spiritual with the sanitary. “They learnt very early on that when they collected water from a well or river, stored it in a copper vessel and let it sit, it would be safe to drink by the evening,” Schmidt says.
Still, the notion of using copper in any significant way in the modern era wasn’t considered until the mid-1980s, when a group of students researching infections stumbled across a remarkable discovery: doorknobs made of brass (a copper alloy) harboured far fewer bacteria than those made from stainless steel, even though the steel knobs appeared to be much cleaner. The students’ results were reported in a 1983 paper, which in turn caught the attention of Harold Michels, a materials scientist and senior vice-president of technology and technical services for the US Copper Development Association. “I was intrigued, but I was not convinced it was repeatable,” he recalls.
In 2002, Michels secured funding to conduct tests in the laboratory of Bill Keevil, an environmental microbiologist at the University of Southampton. The results, Michels says, were “very positive” and led to additional testing.
In 2007, that quest for answers launched a four-year clinical trial funded by the US Department of Defence. “Our curiosity came out of the idea that perhaps medical and healthcare environments contributed in some way to the proliferation and persistence of pathogenic bacteria and microbes,” says Dr Joseph F. John Jr., an infectious-diseases specialist and a member of the research team. “So we started to wonder about surfaces.”
Researchers ran their tests in three ICU units at three US medical centres. “We used very modest amounts of copper,” says Schmidt, who led the study. “It didn’t look like we dipped the room in a vat of molten copper.”
Instead, scientists covered six surfaces in eight ICU rooms: bedrails, the tray tables, the arms of visitors’ chairs, IV poles, computer mouses and the nurse call button, and then sampled them for the next three-and-a-half years.
“We had no idea what to expect,” Schmidt says.
Their findings turned out to be statistically almost too good to be true: the copper surfaces retained 96.8% fewer antibiotic-resistant bacteria than did wood, plastic, painted or other metal surfaces.
As remote as it is, Calama may seem like an odd place for a world-class research project. The site looks more like a moonscape than a place scientists would tap for crucial corroborating evidence of copper’s CRE-slaying capabilities.
It made more sense when Huerta, my guide, and Dr Marco Crestto, an administrator at the Copper Hospital, reminded me that the bulk of the hospital’s patients were miners from the area. Who better to reap the potential benefits of copper than those who excavate it?
Nevertheless, Dr Crestto told me, the head of the hospital was sceptical when he was first approached. He insisted that the most effective way to reduce infections was through old-school protocols, such as hand washing and surface cleaning. When Schmidt began explaining the wonders of the early findings, the director relented. And once the hospital was in, it was all in. Working in conjunction with the University of Chile in Santiago, Codelco researchers installed nearly 1 000 copper surfaces in 100 rooms in three hospitals.
When they heard of the study, the people of Calama were thrilled, Crestto says. For obvious reasons, they had a sense of pride, he says.
The metal didn’t disappoint: results revealed that the pathogenic bacterial load was 90% lower on surfaces fitted with copper than it was in control rooms where the metal hadn’t been installed.
With the results in Chile echoing their promising findings, the scientists at the other medical centres conducted a study to tackle the next and most obvious question: if copper was so effective at killing bacteria, would that translate into fewer in-hospital patient infections? The answer: copper surfaces slashed the number of healthcare–associated infections in ICU units by nearly 60%, according to findings published last May in the journal Infection Control and Hospital Epidemiology.
“That’s a big number,” says Schmidt. “We were surprised at how big. Nothing we know of has come close to being that effective. Most importantly, it confirmed what we had hoped: that by simply reducing the number of CRE and MRSA on frequently touched surfaces, we were able to cut the number of HAIs dramatically.”
But how can a seemingly inert substance that has no obvious antibacterial properties accomplish what disinfection and drugs can’t?
Copper is believed to be a sort of Kryptonite to CRE and other pathogenic bugs – any contact the germs have with the metal spells an immediate weakening, followed by death. First, the CRE’s outer membrane ruptures. Through that rupture oozes vital nutrients and water, quickly sapping the cell’s strength. As a result, that which moments earlier was a “superbug” has turned into a mortally wounded weakling.
This initial damage occurs quickly – too quickly for the cell to recover and try to repair its damaged membrane or to multiply by transferring its resistance, researchers say. The kill shot quickly follows.
“It forces the bacterium to make free radicals, so it’s literally committing suicide when it’s exposed to copper,” says Schmidt. “The DNA is destroyed, and if there’s no DNA, there’s no life.”
I walk in the hospital of the forgotten. Chile’s Hospital Urgencia Asistencia Pública, located in downtown Santiago, is the country’s largest emergency hospital and the facility of last resort for people who are penniless and in need of urgent healthcare.
My guides are Daniel Diez, a public-health team spokesman with Codelco, and Karen Ulloa, a nurse who specialises in hospital infections. Both are wary about showing me this venerable yet crumbling facility. Diez had warned me that the scenes we’d encounter would be grim.
As we walk down a long, dim hall, I see why he’d expressed concern. Where the block walls meet the floor, small avalanches of rubble lie in piles. Fissures spread across the floor tiles and ceilings like broken capillaries. Fluorescent lights blink and buzz. In the third-floor burn unit, the scenes of agony are playing out so intimately that I feel like an unwelcome intruder. In one room, a man lies moaning, a bandaged arm hanging in traction, his torso wrapped in gauze that is mottled with brownish-yellow splotches. In another room, a patient is motionless, his face twisted into a mask of anguish. The hospital, Diez explains, is in its current state of disrepair because the healthcare workers are far too busy to accommodate contractors and renovations.
That logistical reality made the idea to install copper a long and often-frustrating process. But the Chilean government was so encouraged by the findings in Calama and other parts of the world that it insisted that the country’s largest public hospital not be deprived.
The solution: copper workers from the equipment-makers are on 24-hour call, ready to take advantage of small windows of time to install a bedrail here, a sink there. And hospital staffers are grateful, caring for the fixtures by polishing them to a high sheen. “They want it to be like new,” Ulloa says.
Chile cherishes its copper. I can’t turn a corner without catching a shiny glimpse of it. At the Santiago Bueras metro station, 400 metres of copper railing provide riders with a bacteria-free helping hand, thanks to the government. The paediatric hospital, Roberto del Rio, has outfitted 18 ICUs with copper bedrails, bed lever handles, nursery stations, doorknobs, push plates, sinks and taps – partly for another study, yes, but also to protect the city’s children from CRE.
Elsewhere, in countries from Spain to South Africa, researchers are working to broaden and deepen the body of research. Uslan, for example, is helming a study that seeks to replicate the results of previous clinical trials and also to determine whether use of the metal on a widespread basis is cost-effective. To do so, a research team is targeting the UCLA liver transplant unit and medical ICU.
“UCLA has some of the more complicated patients in the world because we have a very high-volume organ transplant programme here,” Uslan explains. “Those patients are most susceptible to infection.
“We need to see how effective copper is. But we also need to tease out what’s really important to coat and what the highest impact surfaces would be,” he says. “And what I mean by that is, do you coat everything in copper? Do you make the walls and floors copper? Or are there certain things that give you the most bang for the buck?”
Uslan and others also want to know whether other cheaper methods of limiting HAIs might do the job just as well. A number of hospitals, for instance, have found success zapping rooms with UV light or fogging them with hydrogen peroxide gas. Research has also demonstrated a reduction in the presence of CRE and other antibiotic-resistant bugs through strict cleaning and hand washing protocols.
All of those alternatives come with big downsides. Hydrogen peroxide gas and UV light, for example, can be as dangerous to patients as they are to bacteria. They require clearing people out of rooms, a huge drain of time and money. Hand washing and surface cleaning will always
be important, doctors say. “But what if after cleaning, someone else comes along with contaminated hands and touches the surface?” Schmidt asks. “With one swipe of the hand, you’re back where you started. The advantage of copper is that it continually knocks down the bacteria.”
The University of Virginia Medical Centre outbreak alerted the hospital to a bigger problem: inconsistency in cleaning regimens. In deconstructing the episode, Sifri says, the staff learnt that the same workers didn’t clean the same surfaces. “Some surfaces weren’t being cleaned at all,” he adds. “Others would be cleaned well one day and somewhat ineffectively the next.” Copper provides a “foolproof” solution, says Sifri.
The battle has only grown more urgent. Because just as quickly as researchers are coming up with answers, the bug is adapting. Other frightening examples are overseas versions of CRE called NDM-1 and OXA-48. NDM-1, which first appeared in 2009 in India, has spread to at least 15 countries, including South Africa.
I’m feeling small as I stand peering into the vast bowl that is Chuquicamata, watching the dust rise. The pit has been mined for several centuries; it has 90-plus years of life remaining. When it is spent, Mina Sur, the South Mine, less than a kilometre away, will provide the miners with work excavating the ore that will be crushed, then roasted and smelted, eventually creating the cathode sheets that will go out to the world in the reddish form we know as copper.
I gaze into the mine. The trucks head out with their payloads. Not far away the Copper Hospital already believes in their cargo. So, too, does the hospital of the forgotten. The trucks rumble slowly, inevitably, upwards.
By Brian Smith