Hospitals opt for gas sterilization, surveillance cultures to combat duodenoscope-caused infections

From 2013 to 2015, at least eight clusters of carbapenem-resistant enterobacteriaceae (CRE) infections were reported in different centers across the U.S. A Chicago-area outbreak involving 44 patients — one of the largest ever reported — was investigated by the Centers for Disease Control and Prevention (CDC) and traced to a contaminated endoscope used in endoscopic retrograde cholangiopancreatography (ERCP). The CDC published its findings in JAMA in October 2014. Infections in Pittsburgh, Milwaukee, Seattle and Los Angeles, which contributed to the deaths of more than 20 patients, have also been attributed to duodenoscopes.

Bret T. Petersen, M.D., a gastroenterologist at Mayo Clinic's campus in Rochester, Minnesota, says the CDC has been investigating CRE outbreaks for several years. "We now know that at each of the sites, a small number of cases of CRE or other multidrug-resistant organisms were caused by transfer of bacteria between patients on duodenoscopes. Some were confirmed by endoscope cultures and some were shown epidemiologically to be endoscope-related, despite negative cultures of the instrument itself. The evidence is fairly convincing that endoscopes were the vectors for transmission," he explains.

Unlike previous reports of bacterial transmission via duodenoscopes — some dating back to the 1980s — recent outbreaks have not resulted from lack of endoscope drying, other lapses in reprocessing procedures or defective devices. Instead, the problem seems to lie with the design of the elevator mechanism on the distal end of duodenoscopes, which provides orientation of catheters, guide wires and accessories into the endoscopic visual field. The internal channel of the mechanism is complex and particularly difficult to clean and disinfect.

A key question raised by the CDC investigations is whether current endoscope reprocessing guidelines can ensure patient-safe instruments. No additional cases of multidrug-resistant infections have occurred in hospitals where high-level disinfection was replaced by ethylene oxide (EtO) sterilization or post-reprocessing quarantine and testing.

Tracking transmission

Enterobacteriaceae, which include klebsiella, E. coli and enterobacter species, naturally exist in the gastrointestinal tract. They become carbapenem resistant when they acquire one of several plasmid-borne resistance factors from other enterobacteriaceae. The most common known resistance factor in the U.S. is Klebsiella pneumonia beta-lactamase, although others, such as New Delhi metallo-beta-lactamase, which was implicated in the Chicago outbreak, are increasingly prevalent.

The spread of multidrug-resistant organisms raises serious concerns, Dr. Petersen says. One is that many duodenoscope-caused infections may go unrecognized because they are difficult to trace. "Infections related to drug-resistant organisms can be challenging to track down. Not every patient exposed to the bacteria is affected; some become colonized and a small number develop clinical infections. Those infections may not show up for weeks to months after the initial exposure and even then, the infection often isn't found in the same organ — bacteria introduced during biliary procedures may present as pneumonia, bacteremia or urinary tract infections. So it is possible that we are transmitting common infections more often than we think but just don't know it. What we have been calling endogenous infections after ERCP may, in fact, be transmitted by endoscopes."

Regulatory issues

In 2014 and 2015, the Food and Drug Administration (FDA) began requiring device manufacturers to submit their full validation data showing that reprocessing instructions, when followed correctly, effectively clean and disinfect endoscopes. Olympus, which makes the most commonly used duodenoscope in the U.S., recently submitted updated validated cleaning and reprocessing data to the FDA for their most current 180 series instrument.

"The manufacturer's guidance for reprocessing of the 180 series duodenoscope has slight changes in the instructions for manipulation and brushing of the elevator region, where we think infections tend to reside," Dr. Petersen says. "These are modest but explicit changes, and we expect the same for other instruments and from the other industry partners. Otherwise, the FDA has not gone beyond guidance that all sites should reassess training and oversight of reprocessing procedures. They can't simply remove the technology from the market, so they're trying to ensure there are sufficient and uniform safety processes in place across the country, but it's a challenge."

ASGE Duodenoscope Infection Control Summit

On March 30, 2015, the American Society for Gastrointestinal Endoscopy (ASGE) brought together experts in epidemiology, infection control and endoscopy, FDA and CDC representatives, hospitals that experienced outbreaks, and device manufacturers. The aims were to confirm current FDA and industry guidelines for cleaning endoscopes and identify gaps in knowledge and issues to address going forward.

"The sites that have released data on their CRE outbreaks have adopted measures beyond the FDA guidelines," Dr. Petersen explains. "At least four are using ethylene oxide sterilization; one or more are culturing the instrument after each high-level reprocessing cycle and quarantining it from use until results return negative. Both methods are cumbersome and neither is perfect, but it's what centers are opting for."

He says the first step across all Mayo sites was to culture and sterilize every duodenoscope in the inventory to ensure no problems exist. Mayo Clinic's campus in Rochester, Minnesota, is using weekly EtO sterilization, with the intention of moving to per-procedure gas sterilization as capabilities are ramped up.

Douglas O. Faigel, M.D., says the current practice at Mayo Clinic's campus in Arizona is to perform CRE screening on all patients undergoing a procedure with a duodenoscope.

"That scope is not used again until the result is negative," he says. "We are double reprocessing all our duodenoscopes between uses. If a duodenoscope is used on a patient with CRE or a positive CRE screen, then we will send that scope for gas sterilization. All these steps go well beyond manufacturer and FDA recommendations."

At Mayo Clinic's campus in Florida, all duodenoscopes are double reprocessed between uses, and patients undergoing duodenoscope procedures will soon be screened for CRE, according to gastroenterologist Michael B. Wallace, M.D. As with other Mayo sites, scopes used on patients with a positive CRE screen will be sent for gas sterilization.

For more information

Epstein L, et al. New Delhi metallo-β-lactamase-producing carbapenem-resistant Escherichia coli associated with exposure to duodenoscopes. JAMA. 2014;312:1447.

ASGE Duodenoscope Infection Control Summit executive summary. American Society for Gastrointestinal Endoscopy.

Interim duodenoscope surveillance protocol. Centers for Disease Control and Prevention.