While on the East Coast March’s first Scalpel Weekly News was timely for its article on deaths from hypothermia, on the West Coast, the FDA’s announcement about infectious duodenoscopes resonated with our daily headlines. On March 4, Cedars-Sinai announced a cluster of carbapenem resistant Enterobacteriaceae (CRE) bacterial infections that were caused by endoscopic procedures that took place between August 2014 and January 2015. Specifically, CRE was transmitted to four patients undergoing procedures that used duodenoscopes—a device inserted down the throat and used in a procedure called endoscopic retrograde cholangiopancreatography (ERCP) that allows doctors to evaluate and remove blockages from the channels (bile and pancreatic ducts) that drain a patient’s liver. One of the four patients died from their underlying disease and not from CRE, as their CRE infection had cleared. Cedars-Sinai notified 71 additional patients who underwent ERCP procedures using the same duodenoscope that they may have been exposed to CRE bacteria. The duodenoscope involved in the procedures in which patients were infected was manufactured by Olympus Corporation.
The announcement from Cedars-Sinai comes on the heels of the Ronald Reagan UCLA Medical Center announcement on February 18th of a cluster of CRE bacterial infections that were caused by endoscopic procedures that took place between October 3, 2014, and January 28, 2015. The UCLA Health System notified 179 patients that they may have been exposed to CRE bacteria during an ERCP procedure involving a device manufactured by Olympus Medical Systems Group. According to the UCLA Health System, a total of seven patients were infected and the infection was a contributing factor in the death of two patients.
The UCLA and Cedars-Sinai CRE clusters are the fourth and fifth reported CRE outbreaks associated with ERCP duodenoscopes. An outbreak in 2014 affected 39 patients at Advocate Lutheran General Hospital in Park Ridge, Illinois, a tertiary care hospital. See: Epstein L, Hunter JC, Arwady MA, et al. New Delhi metallo-β-lactamase-producing carbapenem-resistant Escherichia coli associated with exposure to duodenoscopes. JAMA. 2014 Oct 8;312(14):1447-55. PMID: 25291580. See also: Medscape Pediatrics, CDC Confirms Superbug Transmission via Endoscopy (January 3, 2014). At the Virginia Mason Medical Center in Seattle, Washington, ERCP duodenoscopes manufactured by Olympus were responsible for a CRE outbreak that affected 32 people including 11 who died between 2012 and 2014. See: Virginia Mason, Endoscopes and ERCP; The Seattle Times, Undisclosed superbug sickened dozens at Virginia Mason (January 21, 2015); and ID Week, Endoscope-Associated Multidrug-Resistant Escherichia coli Outbreak — King County, Washington, 2012–2014 (October 11, 2014). In 2012, The University of Pittsburgh Medical Center (UPMC) found 18 patients were infected with the same CRE found in an ERCP duodenoscope. See: University of Pittsburg, UPMC Investigation into GI Scope-Related Infections Changes National Guidelines (October 9, 2014); TribLiveNews, Scope disinfection failure suspected in superbug cluster, leads UPMC to alter methods (October 13, 2014).
A search of the FDA’s MAUDE (Manufacturer and User Facility Device Experience) database, comprised of reports submitted to the FDA by mandatory reporters (manufacturers, importers and device user facilities) and voluntary reporters such as health care professionals, patients, and consumers, revealed 55 results for TJF-Q180V, the model number of the Olympus duodenoscope involved in the UCLA outbreak. Out of the 55 reports, 45 involved bacterial contamination of the device. Reports about problems with bacterial contamination of this device first appeared in the database in May 2012. The medical community, however, has been aware of this problem with ERCP duodenoscopes for much longer. For example, the journal Endoscopy published an article in 2010 in which the authors studied an outbreak of ERCP-related severe nosocomial infection due to Klebsiella pneumoniae from December 2008 to August 2009. See: Aumeran C, Poincloux L, Souweine B, et al. Multidrug-resistant Klebsiella pneumoniae outbreak after endoscopic retrograde cholangiopancreatography. Endoscopy. 2010 Nov;42(11):895-9. PMID: 20725887.
What is truly disturbing is that unlike some previous outbreaks of CRE related to duodenoscopes where investigators identified recognized breaches of approved cleaning protocols, in the outbreaks at Cedars-Sinai, UCLA, and the Advocate Lutheran General Hospital, investigators found no breach in duodenoscope reprocessing and no evidence of defects in the duodenoscope. This meant that even when the device was not defective and the device was cleaned according to the manufacturer’s instructions, CRE remained on the device and was transmitted to patients. The announcement from Cedars-Sinai stated, “Cedars-Sinai meticulously followed the disinfection procedure for duodenoscopes recommended in instructions provided by the manufacturer (Olympus Corporation) and the FDA.” An article published in JAMA about the Illinois outbreak noted that after Advocate Lutheran General Hospital changed its reprocessing procedure from automated high-level disinfection with ortho-phthalaldehyde to gas sterilization with ethylene oxide, no additional case patients were identified. See: Epstein L, Hunter JC, Arwady MA, et al. New Delhi metallo-β-lactamase-producing carbapenem-resistant Escherichia coli associated with exposure to duodenoscopes. JAMA. 2014 Oct 8;312(14):1447-55. PMID: 25291580. The implication is that the use of gas sterilization with ethylene oxide, which is not the method of cleaning directed by the manufacturers of the scopes, may successfully kill CRE. However, the CDC still recommends facilities reprocess endoscopes as directed by the manufacturer, typically high-level disinfection, because, although sterilization is the definitive mechanism to eradicate all microorganisms during reprocessing, several issues potentially limit its widespread use, including longer processing and aeration time than with disinfection, toxicity of some sterilizing agents, and potential incompatibility with some duodenoscope devices. See: Centers for Disease Control and Prevention, Healthcare-associated Infections (HAIs), CDC Statement: Los Angeles County/UCLA investigation of CRE transmission and duodenoscopes (February 20, 2015). The announcement from Cedars-Sinai stated, “Given the potential insufficiencies of the manufacturer’s disinfection instructions, and the current absence of updated national guidelines, Cedars-Sinai is using additional measures to protect patients who need to undergo a procedure involving a duodenoscope. These include enhanced monitoring techniques involving microscopic laboratory analysis (including cultures) of the duodenoscopes, both before and after procedures. These are in addition to the cleaning and high-level disinfection recommended by the manufacturer.” In an editorial published in JAMA last October, William A. Rutala, PhD, MPH, Professor of Medicine, University of North Carolina School of Medicine, Chapel Hill; Director, North Carolina Program for Infection Control and Epidemiology; Director, Hospital Epidemiology, Occupational Health and Safety Program Hospital Epidemiology, University of North Carolina Health Care; and David J. Weber, MD, MPH, Professor of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, noted that gas sterilization with ethylene oxide, “is not a long-term satisfactory solution as it has not been FDA-cleared for sterilizing gastrointestinal endoscopes, many hospitals no longer have ethylene oxide, and the sterilization and aeration time is long (12-15 hours).” Rutala WA, Weber DJ. Gastrointestinal endoscopes: a need to shift from disinfection to sterilization? JAMA. 2014 Oct 8;312(14):1405-6. PMID: 25291575.
Rutala and Weber noted that the margin of safety of the approved cleaning protocol for ERCP duodenoscopes is effectively zero, meaning the protocol is just good enough to clean the endoscope, assuming nothing weakens the protocol’s effectiveness or strengthens the microbe population. To put that in perspective, the authors compared the margin of safety of cleaning ERCP duodenoscopes to the margin of safety for cleaning surgical instruments and found that, at best, the margin of safety of endoscope reprocessing is 15 to 17 orders of magnitude less than the margin of safety for reprocessing of surgical instruments. Not 15 to 17 times less, 15 to 17 orders of magnitude less, that is literally over a quadrillion times less. The editorial argued that to improve the margin of safety associated with endoscope reprocessing, new reprocessing methods, practices, and technologies need to be developed that reliably result in sterilization of gastrointestinal endoscopes via an FDA-cleared sterilization process.
The approved cleaning protocol’s non-existent margin of safety leaves no room for human error. The Association for Professionals in Infection Control and Epidemiology (APIC) and the Society for Healthcare Epidemiology of America (SHEA) issued a statement regarding CRE outbreaks associated with ERCP devices. See: Infection Control Today, APIC and SHEA Issue Statement on Infections Associated with Duodenoscope Procedures (February, 2015). They noted a number of factors that could negatively impact the cleaning process including human factors, such as ensuring that the cleaning area is set up with a bright light and magnification so all sections of the scope being cleaned can be well visualized; distractions; interruptions in the process; or demands for rapid scope turn-around.
Two lawsuits regarding the UCLA outbreak were recently filed in the Los Angeles County Superior Court. See: Panish Shea & Boyle LLP Files First Law Suit Against Duodenoscope Manufacturer Olympus Relating to Superbug CRE Infections (February 26, 2015); Daily Bruin, Family files wrongful death lawsuit against medical scope manufacturer (February 25, 2015). Both named the manufacturer and distributers of the duodenoscope, Olympus America, Inc., Olympus Corporation of the Americas, and Olympus Medical System Corporation, as defendants. The complaints asserted claims for negligence, products liability, intentional misrepresentation, negligent misrepresentation, and fraud. The complaints allege that Olympus failed to provide end-users an effective protocol for cleaning the devices.
In addition to the manufacturer’s liability, the hospital responsible for cleaning the device and the physicians who order ERCP procedures may also be liable. Was the contamination caused by the approved cleaning protocol that has no margin of safety or for human error, or is it a combination of causes? The studies of the outbreaks at UCLA and Advocate Lutheran General Hospital imply that even when humans operate perfectly in following the manufacturer’s and FDA’s approved cleaning protocols, the endoscopes are not clean. The statement by APIC and SHEA lists a number of ways that human error may negatively impact the cleaning process, most notably when hospital administrators pressure cleaners to speed up cleaning so more procedures can be done with fewer ERCP duodenoscopes. But if the ERCP test was never ordered, there would be no risk of disease transmission. If physicians should have known as early as 2010 that ERCP procedures pose a risk of disease transmission, then the question is whether the physician’s decision to order an ERCP was reasonable in light of the risks. Interestingly, the Cedars-Sinai announcement stated that, “it would resume non-urgent (elective) duodenoscope procedures, which were halted starting February 19 [the day after the UCLA announcement] when Cedars-Sinai first learned of reports from other hospitals that that the manufacturer’s disinfections instructions may not be sufficient. The decision to resume was based on consultation with other academic medical centers around the nation, as well as with government agencies, about the additional monitoring techniques, including a waiting period for duodenoscopes after disinfection, to allow for an additional bacterial analysis of the duodenoscope before use.” The latest informed consent documentation for the elective duodenoscope procedures at Cedars-Sinai probably includes the risk of cross-contamination due to the nature of the device.
It will be interesting to see if the Los Angeles County Superior Court, which is in California’s Second Appellate District, admits any postprocedure regulatory actions by the FDA. In a recent case in which the manufacturer of a medical device lost a $3.31million negligence verdict, California’s Fifth Appellate District held that the trial court did not err in admitting the FDA’s postsurgery regulatory actions. The appellate court reasoned that the postsurgery regulatory actions were relevant, their admission did not violate the rule excluding evidence of subsequent remedial measures, and their probative value outweighed any risk of undue prejudice. Scott v. C.R. Bard, Inc., 231 Cal.App.4th 763 (Cal.App. 5 Dist. Nov 19, 2014), review denied (Feb 18, 2015). During its opening statement, the manufacturer caused the FDA’s postsurgery regulatory actions to become relevant when it intimated that the FDA had continued to monitor and regulate the medical device and had taken no action. Thus, the regulatory evidence became relevant to disabuse the jury of the notion introduced by the manufacturer that the FDA was closely monitoring this type of medical device and had found no cause for concern about the device’s safety. Given the FDA’s safety announcement about ERCP duodenoscopes, Olympus will have to avoid relying on FDA pre-market approval as a shield.
By Sarah Kelman, JD, and the experts and editors at Medical Law Perspectives.
For more details, see the Scalpel Weekly News, March 2, 2015.
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For more details on Scott v. C.R. Bard, Inc., 231 Cal.App.4th 763 (Cal.App. 5 Dist. Nov 19, 2014), review denied (Feb 18, 2015), see the Scalpel Weekly News, December 1, 2014.
See also Medical Law Perspectives, January 2012 Report: Hospital-Acquired Infections: Who Is Liable and Why?