December 2, 2014 — Two superbug outbreaks of carbapenem-resistant Enterobacteriaceae were recently linked to contaminated gastrointestinal (GI) endoscopes. These “nightmarish” bacteria are often abbreviated as CRE.
These two outbreaks were publicized earlier this year (2014), and both were associated with significant patient morbidity and least one to patient death.
Other documented reports of the transmission of superbugs during GI endoscopy have been reported, too, in the U.S. and globally, but these two instances of CRE outbreaks are the focus of this article primarily because of the unique publicity each received.
The first “superbug” outbreak: Chicago (IL), 2013
A well-publicized CRE outbreak occurred in 2013 at a hospital located near Chicago (IL) following GI endoscopy.
The investigation of this outbreak by the Centers for Disease Control and Prevention (CDC) was reported in the October 8th, 2014, issue of the Journal of the American Medical Association (JAMA) — click here to read the CDC’s article entitled, “New Delhi metallo-β-lactamase-producing carbapenem-resistant Escherichia coli associated with exposure to duodenoscopes.”
(Note: Dr. Muscarella may write a review of the CDC’s article in JAMA, providing his own perspectives about this CRE outbreak’s possible causes, contributing factors and required corrective and preventive actions.)
The local media in Illinois publicized this CRE outbreak last January, identifying the hospital where it occurred by name. By way of an example, click here to read the newspaper article: “Lutheran General upgrades scope cleaning after ‘superbug’ outbreak” (January 3, 2014).
The investigation of this outbreak in Illinois linked patient morbidity and mortality to the bacterial contamination of a type of GI endoscope known as a side-viewing duodenoscope. Because physicians use it to perform a medical procedure called endoscopic retrograde cholangiopancreatography, or “ERCP,” this GI endoscope may also be referred to as an ERCP endoscope.
This outbreak is discussed further in Dr. Muscarella’ related article: “Alert: Association of GI Endoscopy with Two Patient Deaths: Illinois, 2013” — click here.
The second “superbug” outbreak: Pittsburgh (PA), 2012
The second particularly salient outbreak that also recently linked transmission of CRE to contaminated GI endoscopes occurred at a hospital in Pittsburgh (PA).
Although the first infected patient was identified in 2012, the details of this CRE outbreak were only recently released, in October, 2014, approximately two years later.
A local newspaper article entitled, “Scope disinfection failure suspected in superbug cluster, leads UPMC to alter methods” — click here — provides some important information about this superbug outbreak, identifying the Pittsburgh hospital by name.
More of the details of this CRE outbreak in Pittsburgh (PA) are provided in Dr. Muscarella’s related article: “A ‘Superbug’ Outbreak Linked to Two Types of Gastrointestinal Endoscopes: Pennsylvania, 2012″ — click here.
Other CRE outbreaks linked to GI endoscopy
These two CRE outbreaks in 2012 and 2013 at a hospital in Illinois and in Pennsylvania are anything but isolated and unique.
The Food and Drug Administration’s (FDA) MAUDE database lists a number of other outbreaks of CRE (and their related superbugs, such as carbapenem-resistant Pseudomonas aeruginosa) following GI endoscopy. (“MAUDE” is an acronym for the FDA’s Manufacturer and User Facility Device Experience database.)
Several of these MAUDE reports are discussed in:
- Dr. Muscarella’s comprehensive peer-reviewed article: “Risk of transmission of carbapenem-resistant Enterobacteriaceae and related ‘superbugs’ during gastrointestinal endoscopy” (October, 2014) — click here; and
- in another related article of Dr. Muscarella’s: “Investigation and Prevention of Bacterial Outbreaks following Endoscopic Retrograde Cholangiopancreatography, or ERCP” — click here.
Both of these articles provides a number of important recommendations to prevent the transmission of CRE during GI endoscopy, and the reader’s review of it is encouraged.
UPDATE: A third CRE outbreak linked in Washington state to 7 patient deaths is also discussed, for the first time in detail, in Dr. Muscarella’s related article: “BREAKING: 7 More Deaths Linked to GI Endoscopes in Washington: Part of a National Epidemic?” — click here.
This outbreak of CRE in at least one Washington hospital may be the most significant case of disease transmission linked to a contaminated GI endoscope in U.S. history.
Sidebar #1: Patient notification, public disclosure — A commentator reported during a weekly medical news broadcast aired earlier this year, on January 15, 2014, the following about the aforementioned CRE outbreak at the hospital near Chicago (IL):
“The good news is, this is only a ‘pocket” infection in Chicago and has not yet become a systemic problem across the nation” — click here to read Dr. Muscarella’s related article discussing this remark in more detail.
As is now well documented, this statement provided an inaccurate assessment. At the time this commentator made this remark, a similar CRE outbreak had been confirmed at the aforementioned hospital in Pittsburgh (PA), as well as at other medical facilities across the U.S. and globally.
But this commentator is not entirely to blame for his incorrect statement: This Pittsburgh hospital’s CRE outbreak only became public several months later, in October, 2014.
This incident raises a number of questions about the adequacy of transparency in health care. Whether the FDA might have acted months ago providing important yet-to-be-published recommendations, had this Pittsburgh hospital released the news once its CRE outbreak was confirmed (not two years later in 2014), possibly preventing additional CRE infections in other hospitals in the U.S., is unclear, but an issue that has been previously discussed.
The Washington Post published an article in its click here. This article discussed a different superbug outbreak identified in 2011 at a hospital in Maryland., issue entitled, “‘Superbug’ stalked NIH hospital last year, killing six” —
Although 11 infected patients died, six of them from bloodstream infections, officials did not inform the public of this superbug outbreak until several months later, in 2012.
A published FDA advisory: Is one imminent?
The FDA is reputed to be publishing soon a health alert or advisory discussing this Pittsburgh hospital’s CRE outbreak, as well as several of the other CRE outbreaks linked to contaminated GI endoscopes. While not mentioning the hospital by name, several of these outbreaks are listed in the FDA’s MAUDE database.
This federal advisory, which may be co-authored by the CDC, is likely to provide a number of recommendations for the prevention of CRE transmissions during GI endoscopy. (Article continues below the sidebar.)
Sidebar #2: The risk of CRE transmissions during flexible endoscopy — As Dr. Muscarella discusses in this peer-reviewed article entitled, “Risk of transmission of carbapenem-resistant Enterobacteriaceae and related ‘superbugs’ during gastrointestinal endoscopy” — click here, transmissions of CRE and/or related superbugs are not limited to GI endoscopy and have also been reported, albeit less frequently, following bronchoscopy and cystoscopy. (Refer to Sidebar #3, below, entitled “CRE-contaminated bronchoscopes, too.”)
This FDA advisory is also likely to conclude that the complexity of the forceps elevator mechanism featured in both ERCP endoscopes and EUS endoscopes may be particularly challenging to clean and high-level disinfect.
(Briefly, the distal end of these endoscopes feature an elevator forceps mechanism that connects to a knob on the endoscope’s control head via a housed wire. Using this knob, the physician can adjust the angle of this forceps elevator mechanism as required, for example, to manipulate an accessory or to improve the injection performance of the puncture needle.)
While its contents are, of course, unknown at this time, the FDA’s forthcoming advisory may suggest, too, that hospitals (and other types of healthcare facilities) consider using EtO gas sterilization (if it’s available and at least for the time being) to process GI endoscopes, in additional to cleaning, but in lieu of high-level disinfection.
The use of EtO gas sterilization for this purpose is somewhat controversial, although it is at least indirectly evidence-based, and is to prevent additional instances of CRE infection.
As previously noted, the two previously discussed CRE outbreaks identified in 2012 and 2013 at a hospital in Pittsburgh (PA) and one near Chicago (IL), respectively, were both reportedly stopped by the use of EtO sterilization.
Note, however, that no EtO gas sterilization processes have been cleared by the FDA for processing GI endoscopes, the FDA’s likely forthcoming recommendation to consider using it notwithstanding.
No matter, it is my opinion that provided the detergent and brush during cleaning and the high-level disinfectant during chemical immersion contacts all of the GI endoscope’s potentially contaminated surfaces, there is virtually no risk of the GI endoscope transmitting any patient-borne infectious agent. — Lawrence F Muscarella, PhD
Sidebar #3: CRE- contaminated bronchoscopes, too — A recent report confirms that the transmission of CRE is not limited to GI endoscopes and can be transmitted via contaminated bronchoscopes, too.(1)
According to this report, eight patients of a hospital in Germany were infected or colonized in 2013 with CRE (namely, with carbapenem-resistant Klebsiella pneumoniae, or CRKP). The infections included pneumonia and sepsis.
As other outbreak investigations have similarly found,(2) this report concluded that: “a review of the compete reprocessing operation in (the) endoscopy unit did not identify any deviations.”(1)
(Note: Whether any undetected deviations contributing to disease transmission occurred at the time of the outbreak, but no longer at the time of the investigation’s subsequent review of the department’s infection-control practices, is unclear and cannot be ruled out.)
Risk factors were assessed, and it was confirmed that the majority of these eight affected patients had been in contact with one of two bronchoscopes. As a consequence, these suspect bronchoscopes were microbiologically sampled, with one being found to be contaminated with the outbreak strain of CRE, and the other with high levels of other bacteria.
Both bronchoscopes were removed from service and returned to their one manufacturer for inspection. This manufacturer identified “defects of the internal channel surfaces in both instruments,”(2) requiring that each bronchoscope be repaired.
Both bronchoscopes were returned to service. Yet, during surveillance sampling one was found again to be contaminated with bacteria, although not with the outbreak strain of CRE. this bronchoscope was taken out of use.
This report highlighting contaminated bronchoscopes as a risk factor for transmission of CRE suggests that as much as GI endoscope models that feature a complex forceps elevator mechanism (namely, ERCP endoscopes and EUS endoscopes — refer to the main article) that has been the focus of recent investigations into the causes of some CRE outbreaks,(2) those flexible endoscopes, too, including bronchoscopes that do not feature such a mechanism, but instead that are (unknowingly) damaged similarly pose an increased risk of CRE transmission.
Indeed, according to this report,(1) poorly serviced flexible endoscopes with one or more internal channels that might become worn or torn during routine use are prone to CRE transmissions. Because these endoscopes cannot be easily inspected for these tears into which infectious bacteria may become deposited and transmitted to patient, an important question (not discussed in this German report) arises:
As it has been suggested for GI endoscopes(1,3), is EtO gas sterilization recommended for bronchoscopes and other types of flexible endoscopes, too, to prevent outbreaks of CRE?
It is recommended that the forthcoming FDA alert or the statements of one or more task forces will address this important question.
The incidence of CRE transmissions during GI endoscopy is increasing.
Therefore, prompt and enhanced measures, including discussions focusing on corrective and preventive actions validated for the prevention of CRE infections via GI endoscopes, are necessary to prevent additional superbug outbreaks in the U.S. and globally.
Legal Reviews for Patients, Hospitals, Manufacturers: Click here to read about Dr. Muscarella’s expertise and legal assessments of the causes of healthcare-associated infections, including “superbug” outbreaks linked to contaminated GI endoscopes and other reusable medical equipment.
Also encouraged are efforts designed to improved transparency and accountability in health care, not solely by healthcare facilities, whose prompt public notification of outbreaks of CRE and related superbugs (linked to contaminated reusable medical equipment) would necessarily and self-evidently improve quality and patient safety, but also by manufacturers, whose prompt filing of MAUDE reports is expected by the FDA.
Other important recommendations to prevent disease transmission during flexible endoscopy are provided in Dr. Muscarella’s peer-reviewed article, “Risk of transmission of carbapenem-resistant Enterobacteriaceae and related ‘superbugs’ during gastrointestinal endoscopy” (October, 2014).
Sidebar #4: Dr. Muscarella’s related articles — Featured in his blog (“Discussions in Infection Control“) — click here — is a list of several of Dr. Muscarella’s other related articles that discuss several CRE outbreaks identified during the past few years, both in the U.S. and globally.
Included in this list are Dr. Muscarella’s articles:
- “Alert: Association of GI Endoscopy with Two Patient Deaths: Illinois, 2013” — click here.
- “Overlooked Outbreaks of “CRE” Following GI Endoscopy: A ‘Superbug’ Epidemic in Our Midst?” (which was posted a year ago, in 2013) — click here.
- “Lessons Taught by a Recent “Superbug” Outbreak: Could Ex Post Facto Notification be Warranted?” — click here.
- “Investigation and Prevention of Bacterial Outbreaks during Endoscopic Retrograde Cholangiopancreatography (or, ERCP)” — click here.
Closing remarks: A few important final points
A few final points: Some of which the FDA’s forthcoming health advisory or alert is likely to address, include the following:
First, the finding by the aforementioned Pittsburgh hospital that not just ERCP endoscopes, but also EUS endoscopes are apparent fomites or vehicles for the transmission of CRE warrants discussion and appropriate action, as endoscopic ultrasound has not been previously identified as a significant risk factor for CRE infections.
Second, ERCP endoscopes feature two type of designs: those models designed with a sealed elevator wire channel (that houses the wire connecting the control knob to the forceps elevator mechanism) and those featuring an open, exposed channel, requiring its manual reprocessing.
Whether the sealed elevator-wire-channel design (not requiring reprocessing) is less prone to CRE transmissions (or can become contaminated with infectious biofilms and ironically become more prone to infection) — and whether manual reprocessing of these types of endoscopes is safer than automated reprocessing — are both unclear at this time, but warrants investigation and clarification, ideally by the FDA in its forthcoming advisory.
To date, no one manufacturer’s model of ERCP (or EUS) endoscope, the automated vs. manual reprocessing of the endoscope, or the sealed elevator-wire-channel design vs. the open, exposed design has been been distinguished from the other and determined to be less prone to CRE infection.
Third, unlike some newer models of ERCP endoscopes, EUS endoscopes feature an exposed (not sealed) elevator wire channel that requires reprocessing. Refer to the model’s operator’s manual for information about the specific steps that are necessary to perform to prevent disease transmission.
Fourth, it is recommended that one or more of the professional GI endoscopy organizations (if they have not already done so) convene a task force with the responsibility of developing a policy and providing recommendations for healthcare practitioners, along with a course of action.
Such a task force’s efforts could significantly reduce current confusion and the risk of patient injury during GI endoscopy by helping to rid the waters into which both the manual and automated the reprocessing of ERCP and EUS endoscopes now wades of its current murkiness.
On infrequent occasions the FDA has released a public health advisory alerting the public to the risk associated with the faulty reprocessing of GI endoscopes. The growing number of reports of ‘superbug’ infections linked to contaminated GI endoscopes argues for the release of another such alert. — Lawrence F Muscarella, PhD
Fifth, the FDA has previously released health advisories discussing the faulty reprocessing of GI endoscopes, although these types of reports issued by the Agency are infrequent.
These alerts include:
Preventing Cross-Contamination in Endoscope Processing Safety Communication from FDA, CDC, and the VA (Issued: November 19, 2009) — click here;
- FDA and CDC Public Health Advisory: Infections from Endoscopes Inadequately Reprocessed by an Automated Endoscope Reprocessing System (September 10, 1999) — click here;
Any forthcoming guidance by the FDA that would stem the current tide and reduce the incidence of superbug transmissions during GI endoscopy would provide an important contribution to public health.
And, sixth, the CDC has not in the past recommended that healthcare practitioners routinely monitor (i.e., microbiologically sample) the internal channels and other potentially contaminated surfaces of GI endoscopes for bacterial contamination, save for its practice possibly during a bacterial outbreak’s investigation.
This practice is controversial primarily because there is currently no published standardized protocol addressing, among other questions:
- the necessary steps to perform to sample and recover any surviving microorganisms;
- how often this practice is to be performed;
- which of the instrument’s surfaces and channels are to be sampled;
- whether the presence of viruses and fungi, in addition to bacteria, is to be evaluated, too; and
- how the results are to be interpreted (e.g., what levels of one type of bacteria, compared to another, might be permissible and not pose an infection risk?).
Whether performing this proactive practice, preemptively and routinely, using a validated method demonstrated not to be prone to “false- negative” results would be feasible, improve quality, and reduce the risk of disease transmissions during flexible endoscopy is unclear, but warrants discussion, in general, and possibly in either the forthcoming FDA advisory or a statement that may be released by a professional GI endoscopy organization’s task force investigating the causes of recent outbreaks of CRE during GI endoscopy.
Article by: Lawrence F Muscarella, PhD; posted: 12/2/2014; revised: 1/21/2015, Rev A.
1. Zweigner J, et al. A carbapenem-resistant Klebsiella pneumoniae outbreak following bronchoscopy. Am J Infect Control 2014;42:936-7.
2. Epstein L, 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.
3. McCool S, et al. High Level Disinfection (HLD) Failure in Gastrointestinal Scopes with Elevator Channels – Is it Time to Switch to Ethylene Oxide (ETO) Sterilization? [Abstract] Present by the University of Pittsburgh Medical Center (or, “UPMC”) at Infectious Disease Week, 2014. (Philadelphia, PA)
4. Muscarella LF. Risk of transmission of carbapenem-resistant Enterobacteriaceae and related ‘superbugs’ during gastrointestinal endoscopy. W Journal Gastrointest Endosc 2014 October 16; 6(10): 457-474 — click here.