Patient infections linked to endoscopes, particularly duodenoscopes, are not a new phenomenon. Past outbreaks have helped shape our current infection prevention and control strategies, but the level of risk for the future remains uncertain.
Several years ago, multiple infectious outbreaks related to duodenoscopes used for endoscopic retrograde cholangiopancreatography (ERCP) were reported in medical journals and the news media. These drew significant attention to the issue of contaminated duodenoscopes, and endoscopes in general, and led to a variety of innovations in patient screening, endoscope reprocessing, and scope design. However, infections related to endoscopes are not a new phenomenon.1 In the 1970s and 80s, there were nearly 50 reports of Salmonella spp. infections linked to endoscopes.2 Over 200 cases of Pseudomonas infection (in straight-viewing devices and duodenoscopes) and several cases of Hepatitis B virus cross-infection were also reported during and after this time.2, 3 In the late 80s into the mid-90s, even Helicobacter pylori cross-infection was found to readily occur after endoscopic examination of positive patients.4, 5 One report estimated a transmission frequency of ~4 per 1000 endoscopies when the population infection rate was ~60%.5 In the late 90s there were several reports of Hepatitis C (HCV) cross-infection, and in 2001 there was another scare in New York which was ultimately linked to contaminated medication vials rather than endoscopes.2, 3 However, although rare, these HCV outbreaks were accompanied by significant media and public sensationalism, not unlike the recent scares about “superbugs.”
These superbugs, or more accurately multi-drug-resistant organisms (MDRO), emerged primarily in the 21st century when multiple outbreaks of duodenoscope-related were uncovered. The MDRO outbreaks included multidrug-resistant Pseudomonas aeruginosa at prominent centers in the USA, the Netherlands, and India and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in France and the USA in the 2000s.1, 6 The most recent and perhaps well-known outbreaks of carbapenem-resistant Enterobacteriacea (CRE) appeared initially in 2012 in Europe and then in the United States (U.S.).1 A subsequent U.S. Senate investigation noted that while manufacturer safety alerts about a potential contamination issue were sent to select institutions in Europe in 2013 and 2014, U.S. institutions were unaware of these other outbreaks even when experiencing their own.7 By the time the US Food and Drug Administration (FDA) began to examine the issue more closely in 2014, there had already been 12 known outbreaks involving 166 patients. By Spring 2015, there were at least 25 outbreaks linked to closed-channel duodenoscopes from three manufacturers and involving at least 250 patients between Europe and the USA. Ultimately, between January 2000 and December 2017, there were at least 32 known outbreaks involving over 45 sites and at least 400 patients.7 These numbers are likely significantly underreported given the likelihood of subclinical infections as well as undetected or unreported outbreaks.
Three patterns emerge when looking back at each of these outbreaks. First, the cause of endoscope-linked infections was often attributed to a breach in cleaning and reprocessing protocols. This included failure to properly follow the recommended reprocessing step, which can be complicated and tedious. Second, somewhat dishearteningly, outbreaks also occurred despite following the reprocessing steps correctly, thereby revealing systematic flaws in the methods or materials themselves. For example, the Salmonella infections exposed variability in cleaning and disinfectants among institutions.3 Interestingly, almost no further outbreaks have been reported since several medical societies jointly published standardized cleaning recommendations in 1988.2 Pseudomonas, which forms biofilms and thrives in moist environments, highlighted the inadequacy of low and intermediate level disinfectants, underscored the need to perform a 70% ethanol flush of all the channels followed by appropriate forced-air drying. Even at this early stage, the difficulty in disrupting biofilm at the elevator channel of duodenoscopes was demonstated, over a decade before the recent CRE outbreaks.3, 8, 9 The pseudomonas outbreak also revealed contamination of the automated-endoscope-reprocessors of the time, with the discovery of biofilm deposits on the internal plumbing and detergent tanks which then seeded the endoscopes.3 With H. pylori it was the discovery of inadequate exposure time to disinfectants, with viral hepatitis it was poor manual brushing/cleaning, and with ESBL Klebsiella, inadequate drying and storage (although whether this was truly the cause was never confirmed).1, 2 Some of the CRE outbreaks were halted by ethylene oxide gas sterilization or a culture-and-quarantine program after each device use, and these methods were subsequently included in the FDA recommended supplemental reprocessing measures for duodenoscopes.10, 11 Each of these outbreaks therefore iteratively helped shape the currently recommended reprocessing steps, which include a pre-rinse, meticulous manual cleaning, high-level disinfection, in some cases liquid or gas sterilization, in some cases surveillance culturing of the endoscope, proper drying, and proper storage.12 Lastly, the outbreaks were often reported and studied well after they began, sometimes by years.1, 7 This highlights the limitations the of the existing reporting systems and the difficulty in detecting and tracing these infections.
The recent attention to this topic, changes in reprocessing, enhanced surveillance and auditing, and device modifications may have contributed to a reduction (but not elimination) of device-related patient infections. In 2017 there were fewer than 100 reported infections, and in 2018 the 45 infections and 3 deaths related to duodenoscope contamination.13 It remains unknown whether the issue of endoscope-related infection had largely been overcome, or whether this is a tenuous calm before the next flurry of outbreaks, perhaps from a different organism. While earlier infections were largely driven by breaches in reprocessing, CRE in particular highlighted the dangers of drug resistance, increasing virulence, the complex design of duodenoscopes, and the lack of standardized transparent reporting. Despite increased vigilance, another MDRO transmitted via duodenoscope was recently reported (mobile colistin resistance (mcr-1) positive Klebsiella pneumoniae).14
The parallel debate happening is regarding the magnitude of this problem overall. On one hand, these are still rare events, especially considering the thousands of endoscopies safely performed every day. The primary culprit of persistent contamination appears to have been pinpointed to the complex elevator mechanism of duodenoscopes, and has led to design updates. On the other hand, many patients were harmed, public perception about the safety of endoscopy was diminished, institutional reputations were damaged, there remain the threats of litigation, and postmarket surveillance studies ordered by the FDA have still shown a 5.4% or more rate of duodenoscope contamination with high-concern organisms.13 Furthermore, many of the reprocessing changes and device redesigns have largely been in reaction to outbreaks. What have we learned from the most recent experiences? Could proactive steps be taken to avoid history repeating itself? If so, at what cost would these measures be deemed acceptable for widespread adoption? These complex issues will be explored in more detail as part of a forthcoming educational series on Innovations in Duodenoscope Design from the AGA Center for GI Innovation and Technology (CGIT).
Disclosures
Dr. Thaker has received consulting and speaking fees from Boston Scientific.