From General Surgery News:

Nashville, Tenn.—It started with a chance discovery, a lucky break that revealed an unlucky situation.

In October 2012, the Washington State Department of Health launched a program asking all health care providers, facilities and laboratories to submit isolates that appeared to be carbapenem-resistant Enterobacteriaceae (CRE) to the state’s public health laboratories for further testing. A little more than a year after the first isolates were delivered, a state researcher noticed a trend in samples sent from Seattle’s Virginia Mason Medical Center. All came from clonal bacteria, demonstrating an outbreak of Escherichia coli that had become resistant to carbapenem.

In time, a review found that 32 patients from the hospital were sickened by an AmpC-hyperproducing E. coli between November 2012 and January 2014; all had complicated pancreatic and biliary disease, and all underwent endoscopic retrograde cholangiopancreatography (ERCP) or duodenoscopy at the hospital. Eleven of the infected patients died, but it is unclear whether the infections caused their deaths. The patients were in poor health at the time of exposure. All patients had complicated disease; some had cancer; and all had been on antibiotics multiple times.

Christopher Baliga, MD, medical director of infection prevention at Virginia Mason Medical Center, speaking at this spring’s annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), described the hospital’s response.

“We really launched a massive and thorough investigation into what was going on,” and hospital staff met with representatives of the county and state departments of health, as well as the Centers for Disease Control and Prevention (CDC).

“When we started, the scope was not really what we were looking at. We were looking at all sorts of other possibilities. We looked at doctors; we looked at hand hygiene. We looked at the room, room turnover, cleaning of the rooms. We cultured the rooms, the water,” Dr. Baliga said.

Nothing showed up. Looking at other possible causes, the hospital’s infection prevention team turned to the scopes. National guidelines did not advise culturing scopes. However, the hospital’s infection prevention team decided to go ahead with it. “We started culturing essentially every single duodenoscope that we have.”

Ultimately, the cultures revealed growth in several duodenoscopes, some the same organism implicated in the outbreak. “That, to us, was a pretty conclusive argument that the duodenoscope was probably the vehicle for transmission,” Dr. Baliga said.

It was a distressing finding because there was no identifiable cause for scopes to be harboring infectious bacteria. Virginia Mason was meeting and exceeding the reprocessing recommendations from the manufacturer, a fact that was independently validated by the manufacturer, the CDC and local public health authorities.

“What we’re left with is our belief that there was no breach in processing. We weren’t doing anything wrong that we knew of. We’re left with the belief that the recommendations for how to process duodenoscopes are not adequate.”

(Since Dr. Baliga’s talk at the SAGES meeting, the hospital has joined a patient-launched lawsuit against Olympus America Inc., the manufacturer of endoscopic medical scopes.)

The Virginia Mason experience highlights major failings in the design and manufacturer’s recommendations for cleaning and disinfecting duodenoscopes, used in more than 650,000 ERCP procedures in the United States annually.

What happened at the Seattle hospital was unusual and unfortunate, but it is not an isolated incident. Similar, although less severe, outbreaks associated with CRE- or other multidrug-resistant organism-contaminated duodenoscopes have been reported at hospitals in Chicago, Los Angeles and Pittsburgh, with at least six known outbreaks. From January 2013 until December 2014, the FDA received 75 medical device reports encompassing 135 patients in the United States related to possible microbial transmission from reprocessed duodenoscopes. Over a five-year period, 142 duodenoscope-related infections, exposures or device contaminations were reported to the FDA.

Today in the United States, there are three manufacturers of duodenoscopes: Fujifilm, Olympus and Pentax. Of these, Olympus holds the largest market share: approximately 85% of specialty endoscopes. Infections and outbreaks associated with duodenoscopes have been associated with all three.

Old Problem, New Consequences

Dr. Baliga argued that bacterial transfers from patient to patient via duodenoscopes may have been occurring for years.

“I would hazard that ever since we started doing ERCPs, we have been carrying out itty-bitty, little stool transplants on every patient—or at least 2% of them, because there’s a small percentage of scopes that weren’t fully cleaned.”

That is supported by published literature. As early as 1987, a paper linked Pseudonomas infections to duodenoscopes (Gastroenterology 1987;92:759-773). In 1991, Michelle Alfa, PhD, a microbiologist who has been studying hospital-acquired infections and medical devices for two decades, reported results from a prospective study that evaluated the recommended cleaning and drying processes for duodenoscopes. Twenty-one of 42 duodenoscopes tested were found to be contaminated, and visible moisture remained in the device’s suction channels despite use of the complete recommended automatic washer cycle (J Hosp Infect 1991;19:89-98).

Concerns about infectious spread ramped up in 2009, however, following reports of processing errors with flexible endoscopes. That year, the FDA, CDC and Veterans Affairs (VA) issued a joint safety communication, cautioning health care facilities of the risks to patients if flexible endoscopes and accessories are not processed properly. The organizations recommended steps to reduce risk for infection spread, including instructing staff to read and follow the endoscope manufacturer’s instructions for use. Also, they called on manufacturers to ensure their instructions were up-to-date, comprehensive and easy to understand, and to monitor problems in processing. Two years later, the FDA published a draft guidance document on processing and reprocessing medical devices, and held a public workshop that focused on factors affecting reprocessing of reusable medical devices.

Yet, in the fall of 2013, the CDC alerted the FDA to a potential association of multidrug-resistant bacteria and duodenoscopes. The FDA reported, “Upon further investigation, it became clear that these cases of infection were occurring despite confirmation that the users were following proper manufacturer clean and disinfection or sterilization instructions.”

By 2013, the consequences of these “itty-bitty stool transplants” had become more severe. As bacteria evolve to become more resistant to antibiotics, these tiny transfers of matter become more dangerous to patients.

“This is the perfect storm. It’s a difficult-to-clean instrument. We’re seeing a global increase in antibiotic resistance to the point where the type of bacteria is now irrelevant. These [bacteria transfers] likely happen with all bacteria, and the drug-resistant ones are simply the ones that grab our attention,” said Dr. Baliga.

“When you’re transmitting normal flora from one person to the next, it’s not a big deal. But as we get drug resistance, it’s a big deal.”

Design Failings

The difficulty lies in the intricate design of the duodenoscope, said Chris Lavanchy, engineering director at the ECRI Institute, a nonprofit organization, in Plymouth Meeting, Pa., that evaluates medical products and services for hospitals, health systems, and private and public payors.

The duodenoscope’s diameter must be small enough to enter the GI tract without causing injury. Within that compact space must fit the channels for air, water and biopsies. Unlike other endoscopes, duodenoscopes have a movable elevator, containing microscopic crevices that cannot always be reached with a brush.

“There are areas that are very difficult to access, areas that harbor bacteria,” Mr. Lavanchy said.

“The duodenoscope is the worst-case scenario when it comes to endoscopes and cleaning. You can see just grossly that the grooves and recesses make it difficult to clean,” he added, as his slides depicted an older version of a duodenoscope design (see photos).

The design constraints of duodenoscopes have become a major issue of concern at the FDA. Last winter, the agency issued a safety communication cautioning health care practitioners that the complex design of ERCP endoscopes may impede effective reprocessing. “Meticulously cleaning duodenoscopes prior to high-level disinfection should reduce the risk of transmitting infection, but may not entirely eliminate it,” the report warned.

The agency highlighted the difficulty of cleaning the moving parts of the elevator mechanism, noting “residual body fluids and organic debris” may remain in crevices after cleaning and disinfection. “If these fluids contain microbial contamination, subsequent patients may be exposed to serious infections.”

The FDA made a number of recommendations for health care facilities and staff, asking them to closely follow all manufacturer instructions for cleaning and reprocessing. Strict adherence to manufacturer instructions will minimize risk for infection, they noted. Also, the agency called for meticulous cleaning by hand of the elevator mechanism and surrounding mechanism, even when using an automated endoscope reprocessor. Cleaners should raise and lower the elevator throughout the process to brush both sides. Finally, the agency recommended that hospitals implement a comprehensive quality-control program for reprocessing duodenoscopes, including written procedures for monitoring training and adherence, documentation of tests, processes and quality monitors.

In May, the FDA’s Gastroenterology-Urology Devices Panel met to discuss the unique challenges associated with reprocessing ERCP endoscopes. Panel members unanimously agreed that the current generation of duodenoscopes fails to offer “reasonable assurance of safety and efficacy,” although they maintained that the benefits of the procedure for the population outweigh potential risks.

“I think the risk is incredibly small and the benefit of these procedures incredibly large in terms of the number of people whose lives are saved. So the risk of stopping this would be catastrophic,” said panel member Kenneth R. McQuaid, MD, GI at the VA Medical Center in San Francisco and president-elect of the American Society for Gastrointestinal Endoscopy.

Most of the panel believed that duodenoscopes should be reclassified as critical devices and should undergo sterilization rather than high-level disinfection, although some panelists believed that disinfection was sufficient.

Other conclusions from the panel included:

Human factors testing is important and should be part of the premarket assessment. The panel called for development of a set of best practices and means of assessing competency in cleaning.
The CDC’s interim guidance for surveillance on bacterial contamination of duodenoscopes is not sufficient to be implemented as “best practice,” although it does provide a well-documented outline for health care facilities.
Hospitals need to provide patients with information on risk for infection from ERCP, and disclose whether their health care facility has had an issue with infections. Patient selection is also critical for ensuring patient safety, they said.
At the SAGES meeting, which took place a few weeks before the FDA’s two-day panel meeting, Herbert Lerner, MD, deputy division director in the Division of Reproductive, Gastro-Renal, and Urological Devices in the FDA’s Office of Device Evaluation, told the audience that the FDA is looking into all issues surrounding reprocessing, cleaning and scope design. “All of that is on our radar, and we’re working on it. That’s the bottom line.”

He asked any facilities or users of scopes to report infections or potential infections to the FDA.

(At the time of publication, the U.S. Department of Justice was investigating manufacturers of medical scopes.)

Mr. Lavanchy said manufacturers are working on new features, such as a sealed compartment for the elevator. Olympus has released a new type of brush that is intended to better access the elevator for cleaning, he said. However, it is unknown whether these brushes could improve reprocessing and reduce infection spread.

In any case, it is going to take some time for an effective new design of duodenoscope to become available, said Mr. Lavanchy. “It’s also going to take a lot of testing to demonstrate that it’s effectively cleaned, both when a device is new and when it’s been used many times. Any claims about cleaning will have to be reviewed by the FDA before it can be put to market.”

Mr. Lavanchy, who often goes into hospitals to review medical device processing programs, stressed that there are four points of care in the care cycle for a medical device: cleaning, disinfecting, sterilizing and storage. Most hospitals focus on sterilization and disinfection. “But cleaning, I would argue, is at least as important, if not as important, as sterilization/disinfection because if you can’t clean something, there’s no assurance that you can sterilize or disinfect it.”

“In investigations we’ve done, we’ve found that often the step of precleaning, right after point of use, is overlooked. This is a critical step. If you don’t clean organic soil while it’s still moist, if you allow it to dry, it can be very difficult to clean out in subsequent steps.”

Preventing Further Outbreaks

So, the question remains: What should health care facilities, surgeons and GIs do to prevent further outbreaks?

At Virginia Mason, following their outbreak, Dr. Baliga and his colleagues believed that it was not enough to follow manufacturer guidelines. They considered ethylene oxide sterilization, but ruled it out because of the cost and time required, and concern that if the scopes were not fully cleaned, gas sterilization wouldn’t help either.

They decided is culturing “is the gold standard,” that’s what they would do, even though it necessitated an expansion of the hospital’s processing facilities. Today, the hospital cultures every scope after use, which means holding the instrument for 48 hours after cultures while results are processed.

“No scope can be used in a patient until we have cleaned it, disinfected it, cultured it and the cultures are negative. That gives us, I believe, then strongest statement that we can say that we can guarantee any scope used on a patient will not have culturable pathogenic bacteria,” said Dr. Baliga.

As a center that performs between 1,500 and 1,800 ERCPs a year, the new protocol required a substantial investment in additional scopes, storage space and staff to carry out cultures. In addition to scope culturing, Virginia Mason has modified informed consent and ramped up staff and provider education. It also regularly send scopes to the manufacturer for proactive safety inspections and maintenance. The full protocol is detailed online at Gastrointestinal Endoscopy ([Epub head of print]).

Of note, the protocol appears to be having the desired effect.

“There have been no new known cases since we implemented our new protocol. Where we would have had a smatter of cases continuing to be identified before, we haven’t seen any new cases,” said Dr. Baliga.

“This is a necessary procedure, as everyone in this room would say,” said Dr. Baliga, concluding his SAGES presentation. “This is a life-saving procedure that has dramatically altered medical care. I don’t think anyone is arguing that it should go by the wayside because we can’t guarantee that the scopes are clean. Ultimately, I think that the long-term solution is out there. It’s an engineering solution.”

Read more from General Surgery News…