Widening superbug outbreak raises questions for FDA, manufacturers
By the time 18-year-old Aaron Young wound up at Ronald Reagan UCLA Medical Center in Los Angeles last October, he’d been wrestling for months with excruciating stomach pain and vomiting that repeatedly sent him to the emergency room.
Diagnosed with acute pancreatitis, he underwent what is typically a low-risk procedure in which doctors inserted a special device down his throat to treat his digestive system.
But instead of recovering, Young developed a raging bacterial infection and a relentless 104-degree fever. He recovered after nearly three months in the hospital but had to return for another procedure in late January. The infection flared anew, and he is now likely to be in the hospital for at least another month, his family says.
Young is among seven patients at UCLA who were infected with a hard-to-treat “superbug” that hospital officials traced to two specialized scopes that they said were contaminated despite being thoroughly cleaned. Two of the patients later died, and scores more were potentially exposed.
After the incident became public, the Food and Drug Administration warned that the devices, called duodenoscopes, can be difficult to sanitize and “may facilitate the spread of deadly bacteria.”
Now medical experts and lawmakers want to know why the FDA and the manufacturers of the devices — all of which have been aware of the potential problem for years — didn’t move more quickly and aggressively to ensure patient safety.
The urgency around the issue intensified Wednesday after Cedars-Sinai Medical Center in Los Angeles disclosed that four patients who underwent endoscopic procedures had been infected by the same germ as at UCLA: a drug-resistant form of carbapenem-resistant Enterobacteriaceae, or CRE.
Hartford Hospital in Connecticut said Wednesday that 281 patients were possibly exposed during the same type of procedure to a strain of E. coli.
Young’s family, meanwhile, has sued Olympus Corp., the manufacturer of the device involved in the UCLA case, on his behalf, alleging fraud and negligence. The suit claims the company didn’t provide updated cleaning protocols to hospitals when it introduced a newer version of the device in 2010.
“The lawsuit is almost beside the point,” said Lori Smith, Aaron’s adoptive mother and herself a registered nurse, in her first interview on the matter. “We’d just like them to do something so that people are better informed. Nobody said Aaron could get something from these scopes that could kill him. . . . We just had no idea.”
The family of Antonia Torres Cerda, a 48-year-old woman who died in November after apparently being exposed to a contaminated duodenoscope at the hospital, has sued the company for wrongful death. Cerda underwent the endoscopy procedure before receiving a liver transplant.
An Olympus spokesman said the company “does not comment on active legal matters or speculation” but added that it “continuously strives to improve our products for safe and effective use.”
‘Why did it take so long?’
For years, the FDA has received warnings — from hospitals, from clinicians, and from the Centers for Disease Control and Prevention — about possible links between the duodenoscopes and the spread of deadly infections. The devices are used in a procedure known as ERCP, or endoscopic retrograde cholangiopancreatography, on roughly 500,000 patients annually in the United States. They are considered a critical tool in diagnosing and treating cancers, gallstones and other ailments of the digestive system in a minimally invasive way.
The general public may not have known about the small but serious risks associated with bacteria harbored in duodenoscopes, but some medical experts have been flagging the problem for decades.
“We have known about this even as early as 1983 or 1984,” said John Allen, a professor at the Yale School of Medicine who is president of the American Gastroenterological Association. In 1987, Allen wrote in an academic journal about 10 of his patients in Minnesota mysteriously becoming infected with a bacteria known as Pseudomonas. He and his colleagues traced the infections to a single duodenoscope, whose small crevices harbored bacteria despite repeated cleanings.
In 2009, after a dozen patients in France were infected with drug-resistant bacteria linked to a contaminated duodenoscope, the FDA, the CDC and the Department of Veterans Affairs warned hospitals and other medical facilities about the risk of cross-contamination if scopes weren’t properly cleaned and sterilized. That warning applied to all medical scopes, not just duodenoscopes.
But since 2012, infections linked to duodenoscopes have occurred at Advocate Lutheran General Hospital near Chicago, where 44 people were infected, and at the Virginia Mason Medical Center in Seattle, where at least 32 patients became ill and 11 died. It’s unclear how significant a role the CRE bacteria played in those deaths.
Over the years, Allen said, experts responded to outbreaks by adding another cleaning step, such as flushing the devices with alcohol. The latest outbreak “reemphasizes the fact that we haven’t solved the fundamental problem,” which he said ultimately could boil down to a design flaw.
During the past two years, the FDA has received at least 75 reports about the devices, involving at least 135 patients, and those numbers may be low given that many such events don’t get reported. In 2013, the agency said, it received notice from the CDC about a possible association between the complex devices and multi-drug-resistant bacteria. Sen. Patty Murray (D-Wash.) last month wrote to FDA Commissioner Margaret Hamburg, urging the agency to publicly address the issue.
“The big question is, why did it take so long?” said John Greene, an infectious-disease doctor at Moffitt Cancer Center in Florida, who in 2013 co-authored an article about an outbreak involving duodenoscopes in Tampa. “It’s a very fair question. . . . Unfortunately, things don’t happen until bad outcomes occur.”
Ten House members are asking similar questions. In a letter Wednesday to the FDA, they wrote, “The alarming spread of superbug outbreaks across the country demands a forceful, substantive response from the federal government.” One of the letter’s authors, Rep. Ted Lieu (D-Calif.), represents the district where Ronald Reagan Medical Center is located and has called for a congressional hearing.
Stephen Ostroff, the FDA’s chief scientist and soon to be its acting commissioner, said in an interview that the agency had indeed been closely studying the problem before the most recent outbreak. He said agency officials had become especially concerned about the 2013 Illinois infections because there were no obvious sterilization lapses and because the devastating CRE bacteria was becoming more common across the country.
The agency redoubled its efforts, scouring medical research and adverse events reports to try to answer several critical questions: Are existing disinfection procedures sufficient? If not, what are the alternatives? Is the problem unique to one model or manufacturer? Does the intricate design of duodenoscopes make them especially hard to sterilize?
Last year, Ostroff said, the FDA requested more data from the three manufacturers marketing duodenoscopes in the United States — Fujifilm, Pentax and Olympus — to prove that their cleaning instructions actually work. It asked for more data after deciding the first batch was insufficient and began conducting its own tests to see if specific features make the devices hard to sanitize.
“These are not things you do overnight,” Ostroff said.
Olympus began selling its TJF-Q180V duodenoscope in 2010. The company had altered its previous design, sealing up a part of the scope known as the “elevator” mechanism in an effort to help prevent infections. But the company never notified regulators, despite rules that require FDA clearance if changes can “significantly” affect a device’s safety or effectiveness.
Olympus said in a statement that it had determined the changes were minor enough not to warrant a new application. The FDA disagreed. After it learned of the changes, the agency last year asked the company to apply for approval of its updated duodenoscope.That application is pending. But the FDA has continued to allow Olympus to sell the device, in part, it said this week, because removing it from the market could lead to a harmful shortage of duodenoscopes in the United States.
“They are absolutely essential devices,” Ostroff said. “We know that there’s approximately half a million of these procedures that are done every year, and the overwhelming majority of them are done safely and without complications. That needs to be kept in mind. Our job is to see what we can do to make this procedure even safer than it currently is.”
That effort is well underway. Bret Petersen, a Mayo Clinic doctor who serves on the board of the American Society for Gastrointestinal Endoscopy, said the group will meet on the issue this month with federal officials, hospital officials and device makers. Allen, the American Gastroenterological Association president, said his group will focus on the issue at a conference in San Francisco. He said federal officials and device makers, as well as venture capitalists, are planning to attend.
“We’re putting them all in a closed room,” he said, “and saying, ‘What do we have to do to innovate our way out of this and drive the infection rate to zero?’ ”
‘It’s just complete fear’
Lori Smith and her husband, Glenn, don’t blame Ronald Reagan Medical Center for the hellish months their son has endured since becoming infected last fall. The hospital has said it closely followed national guidelines and instructions from Olympus in sterilizing its scopes, and now is using even stricter protocols.
“We don’t believe UCLA did anything wrong,” Glenn Smith said. “Aaron is alive today because of UCLA.”
Their anger is aimed at the FDA and the manufacturer, which they say should have done more to ensure the device’s safety.
But on many days, their anger is trumped by sadness and worry.
Young, who also suffers from sickle cell disease, had the first endoscopic procedure last fall to check for gallstones and to place a stent in his bile duct. The second procedure was to remove the stent. Separately, he also had his gallbladder removed. What followed should have been a relatively quick and smooth recovery, but has been neither. At times, he has been on six different antibiotics.
Lori and Glenn, who spent months at his bedside, take turns visiting each day but have jobs they can’t afford to quit. Young’s siblings come by as often as they can. But he spends a lot of lonely hours in his third-floor room, sleeping and texting on his iPhone, his TV almost always muted but tuned to Nickelodeon.
Even when Young does return home, he won’t be in the clear. The CRE bacteria is no longer infecting his bloodstream, but doctors have said that the bug remains colonized in his body, meaning he faces an elevated risk of another infection.
“Is the next time it flares up the time the antibiotic won’t work? Or the time he’ll be so sick he won’t come out of it? It’s just complete fear for his future, and it takes a toll on his whole family,” his mother said. “It’s just something that’s going to be there for the rest of his life.”