A lab technician holds a bacteria culture. Photo by Sean Gallup/Getty Images.
CHARLOTTESVILLE, VA. — The doctors tried one antibiotic after another, racing to stop the infection as it tore through the man’s body, but nothing worked.
In a matter of days after the middle-aged patient arrived at the University of Virginia Medical Center, the stubborn bacteria in his blood had fought off even what doctors consider “drugs of last resort.”
“It was very alarming; it was the first time we’d seen that kind of resistance,” said Amy Mathers, one of the hospital’s infectious disease specialists.
The man died three months later, but the bacteria wasn’t done. In the months that followed, it struck again and again in the same hospital, in various forms, as doctors raced to decipher the secret to its spread.
The superbug that hit the Virginia hospital four years ago belongs to a family of drug-resistant bacteria that has stalked hospitals and nursing homes for a decade. Now, it’s attacking in hundreds of those institutions, a USA Today examination shows.
The bacteria, known as Carbapenem-Resistant Enterobacteriaceae (CRE) are named for their ability to fight off carbapenem antibiotics — the last line of defense. And so far, they’ve emerged mainly in health care facilities, killing the weakest of patients.
The bacteria made headlines this summer after a CRE strain battered the National Institutes of Health Clinical Center outside Washington, D.C. Seven died, including a 16-year-old boy. But that case was neither the first nor the worst of the attacks.
Thousands of cases
Research shows there have been thousands of CRE cases throughout the country in recent years.
Death rates among patients with CRE infections can be about 40 percent, far worse than infections such as MRSA or C-Diff, which have plagued hospitals and nursing homes for decades. And there are growing concerns that CRE could make its way beyond health facilities.
“From the perspective of drug-resistant organisms, (CRE) is the most serious threat, the most serious challenge we face to patient safety,” said Arjun Srinivasan of the Centers for Disease Control and Prevention.
Since the first case was reported at a North Carolina hospital in 2001, CREs have spread to at least 41 other states, according to the CDC.
USA Today interviewed dozens of health care authorities and reviewed hundreds of pages of journal articles, clinical reports, and state and federal health care data. The examination shows:
• CRE infections already are endemic in several major U.S. population centers, including New York, Los Angeles and Chicago.
Smaller pockets of cases have been reported across much of the country, including Oregon, Wisconsin, Minnesota, Pennsylvania, Maryland, Virginia and South Carolina.
• There is no reliable national data.
The CDC has urged states to track cases, but only a handful do so.
• There is little chance that an effective drug to kill CRE bacteria will be produced in the coming years. Manufacturers have no new antibiotics in development that show promise.
• Many hospitals — and an even greater percentage of nursing homes — lack the capacity to identify CRE, or the resources to effectively screen and isolate patients carrying the bacteria. Even when screening is possible, there’s a lack of consensus on whom to target.
“We’re working with state health departments to try to figure out how big a problem this is,” said the CDC’s Srinivasan, noting that his agency can pool whatever incidence data states collect. “We’re still at a point where we can stop this thing. You can never eradicate CRE, but we can prevent the spread.
Other experts are less optimistic.
“My concern is that there aren’t a lot of methods in our tool kit that are significantly effective in curbing the spread of these infections,” said Dr. Eli Perencevich of the University of Iowa’s Carver College of Medicine.
Tracking an elusive killer
The Virginia epidemiologists knew their CRE outbreak would be tough to contain, but it quickly became clear that this case would be even more difficult than most.
When the doctors began analyzing the bacteria in their first patient, who’d transferred from a hospital in Pennsylvania, they found not one, but two different strains of CRE bacteria. And as more patients turned up sick, lab tests showed that some carried yet another.
“We were really frustrated; we hadn’t seen anything like this in the literature,” said Costi Sifri, the hospital epidemiologist.
The doctors went back to the lab with even more urgency.
It was January 2008, five months after the first case turned up, and they’d identified five patients harboring three distinct species of CRE.
Three of those patients already were dead.
Mobile patients, mobile bugs
One challenge is figuring out where CRE is showing up.
Based on academic studies and data from the few states and counties that require some reporting, it’s clear that CRE is spreading fast.
In Los Angeles County alone, a year of surveillance through mid-2011 turned up 675 cases at hospitals, nursing homes and clinics.
In Maryland, a 2011 survey by the state health department identified 269 patients carrying CRE and estimated that up to 80 percent of the state’s hospitals had seen at least one case during the year.
It’s important to know where CRE is emerging because it spreads with patients who bounce between or among clinics, surgical centers, rehabilitation facilities, nursing homes and, of course, hospitals.
In the Chicago area, where scores of CRE infections have been found since 2008, studies show that about 3 percent of hospital patients in intensive care carry the bacteria, said Dr. Mary Hayden of Rush University Medical Center. Those same studies have found CREs being carried by about 30 percent of patients in long-term care facilities.
Not all of those patients are symptomatic: The bacteria can lurk, unseen, until a carrier’s immune system is compromised or until the bug finds a path into the body and infection sets in. And as those patients move from one facility to another, the bacteria move with them, often clinging to caregivers’ hands — and moving to new victims.
Stopping the untreatable
A few drugs show marginal effectiveness, including an old antibiotic shelved decades ago because of high toxicity. And there’s little incentive for drug companies to invest in developing alternatives. CREs develop new resistance quickly, so any new antibiotic isn’t likely to last.
“If you look at the current pipeline of antibiotics (in development) ... none of them really is going to be active against these bacteria,” said Gary Roselle of the Department of Veterans Affairs health care system.
CDC guidance for controlling CRE rests on traditional infection-control strategy: rigorous hand cleaning by staff and visitors; isolating infected patients and requiring gowns and gloves for anyone contacting them; cutting antibiotic use to slow the development of resistant bacteria; and limiting use of invasive medical devices that give bacteria a path into the body.
But the measure that may hold the most promise is contentious: screening patients for the bacteria so carriers can be isolated.
In New York City, Montefiore Medical Center cut prevalence rates in half across its nine intensive care units with a program that relied heavily on screening. The initiative tested all intensive-care patients using an experimental, high-speed assay for the bacteria, and carriers were isolated immediately.
Montefiore found that 40 percent of its CRE cases involved patients who had arrived with the bacteria when transferred from nursing homes and other institutions.
“So even if I had a perfect program to stop all patient-to-patient transmission in the hospital, the maximum impact I could have would be a 60 percent reduction in prevalence,” said Brian Currie, the hospital’s vice president for research.
Once the University of Virginia Medical Center doctors figured out that a single gene was driving the spread of CRE through the hospital, they still needed to figure out a way to find it — and stop it. And the clock was ticking.
By April 2008, eight months after they’d identified their first infection, 13 additional patients had been infected with related strains of the bacteria. Seven were dead.
Back in the lab, the doctors figured out that the gene was hitching a ride among bacteria on mobile pieces of DNA, called plasmids, that can move from one cell to another. With more work, they developed a genetic test that could identify those plasmids and the bacteria they’d affected.
The lessons learned in Virginia helped the doctors target CRE screening of at-risk patients across the hospital, as well as those checking in. So far, the hospital has been able to control its outbreak.
But the bacteria are there, lurking somewhere.
“We have continued to have patients with CREs that are related to this (first) event,” Sifri said. “We haven’t been able to close the door on this. … I’m not sure you ever can.”