December 20, 2013 (updated December 23, 2015) A Chicago newspaper reported on December 27, 2013, that a hospital in Park Ridge (IL) had identified an outbreak of carbapenem-resistant Enterobacteriaceae, or “CRE” for short.

According to The Daily Herald, Advocate Lutheran General Hospital had linked this outbreak of CRE to reusable medical instrumentation routinely used in the U.S. to perform a type of (upper) gastrointestinal (GI) endoscopic procedure known as endoscopic retrograde cholangiopancreatography, or “ERCP.”

Update: At least two of this hospital’s patients who were infected with this outbreak’s strain of CRE died. For more details, read my related article “Alert: Association of GI Endoscopy with Two Patient Deaths: Illinois, 2013.

Advocate Lutheran General Hospital’s investigation of its outbreak of CRE in 2013 — along with several others reported herein, including a few in 2014 that were the focus of a USA TODAY newspaper article — linked contaminated GI endoscopes used during ERCP not only to patient infection or colonization, but to patient mortality. I recommend that healthcare staffers consider contacting their GI endoscope’s manufacturer for specific instructions for thorough reprocessing of those endoscopes in inventory featuring a forceps elevator, such as the side-viewing duodenoscope. — Lawrence F Muscarella, PhD

The specific type of reusable instrumentation that health officials linked to this CRE outbreak is a GI endoscope that may be referred to, not surprisingly, as an “ERCP endoscope” or as a side-viewing duodenoscope.

In response, hospital officials notified all 243 patients who underwent ERCP at Advocate Lutheran General Hospital between January, 2013, and September, 2013, of their potential exposure to ERCP endoscopes contaminated with the outbreak’s infectious strain of CRE.

The Centers for Disease Control and Prevention (CDC) often refers to CRE as “nightmare bacteria,” or as “superbugs,” primarily because of their resistance to most antimicrobial drugs.

For the readers convenience, this article is divided into sections:

  1. Part 1: “The largest CRE outbreak in U.S.”
  2. Part 2: “An overlooked ‘superbug’ epidemic”
  3. Part 3: “Outstanding questions”
  4. Recommendations
  5. References

PART 1 – The largest CRE outbreak in U.S. history

A report by the CDC describing its investigation of Advocate Lutheran General Hospital’s CRE outbreak — which may be the largest outbreak of this dangerous superbug ever recorded in the U.S. — was published in the January 3, 2014, issue of Morbidity and Mortality Weekly Report (MMWR).

The Food and Drug Administration (FDA) and the Illinois Department of Public Health and the Cook County Department of Public Health assisted the CDC in its investigation of this outbreak. Read Box A, below.

Box A. Tip of the iceberg?  Suggesting that Advocate Lutheran General Hospital’s CRE outbreak may be only the tip of the iceberg and reflective of a global “superbug” epidemic linked to ERCP, almost a dozen other CRE outbreaks have been confirmed in the U.S. and Europe during the past few years.

These other outbreaks linked to ERCP, which have received little attention, are discussed in the main article and in my article: “Investigation of Bacterial Outbreaks during Endoscopic Retrograde Cholangiopancreatography (ERCP).”

These outbreaks are also discussed in my peer-reviewed article “Risk of transmission of carbapenem-resistant Enterobacteriaceae and related ‘superbugs’ during gastrointestinal endoscopy.”

Update: Several of these deadly CRE outbreaks were also discussed in two newspaper articles published the same week in 2015: USA TODAY (January 21, 2015) and The Seattle Times (January 22, 2015).

A “New Delhi” strain of CRE

The specific strain of CRE responsible for Advocate Lutheran General Hospital’s outbreak in 2013 is known as “New Delhi Metallo-Beta-Lactamase–Producing Escherichia coli.

Briefly, E. coli is a species of bacteria within the genus known as Escherichia, which, in turn, is of the family of bacteria known as Enterobacteriaceae. Klebsiella pneumonia is another well-known bacterium of the Enterobacteriaceae family.

Many bacterial members of the Enterobacteriaceae family are part of the normal flora of the human GI tract, or gut. Nevertheless, these bacteria can, and do, cause opportunistic infections, with deadly consequences.

As their name indicates, CRE are resistant to carbapenems, which are an important class of antibiotics known as “beta-lactam” antibiotics.

For additional information, read my related article: “Multiple CRE Outbreaks Linked to Contaminated Endoscopes in the U.S and Europe: A Smoking Gun?” which provides a discussion of the possible cause of several recent outbreaks of CRE following ERCP.


These “nightmarish bacteria” of the Enterobacteriaceae family confer their antibiotic resistance through their production of a specific enzyme (by way of gene encoding) that renders carbapenems ineffective, allowing bacteria that the antibiotic would otherwise destroy to survive and infect patients.

Carbapenems are considered one of the last lines of defense against “hard-to-treat” bacteria, such as multidrug-resistant Enterobacteriaceae.

Two examples of these enzymes — known as carbapenemases — that confer the bacteria’s resistance to carbapenem antibiotics are:

  • K. pneumoniae carbapenamase, or “KPC,” which, not surprisingly, is produced by carbapenem-resistant K. pneumoniae (as well as by other gram-negative bacteria, such as E. coli, that may acquire the KPC-encoding gene [i.e., blaKPC] through “gene sharing”), or CRKP; and
  • New Delhi Metallo-Beta-Lactamase-1, or “NDM-1,” which (also not surprisingly) is produced by New Delhi Metallo-Beta-Lactamase–Producing E. coli (and other gram-negative bacteria that may acquire the NDM-1-encoding gene [i.e., blaNDM-1] through gene sharing.  This was the specific strain of CRE responsible for Advocate Lutheran General Hospital’s outbreak.

Quality Reviews for Hospitals, Manufacturers, and Infected Patients:  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.

The FDA’s medical-device-reporting (MDR) database

According to an FDA database, the following two regulated medical devices were linked by Advocate Lutheran General Hospital to its CRE outbreak following ERCP:

  • at least one manufacturer’s side-viewing duodenoscope (click here); and
  • at least one manufacturer’s automated endoscope reprocessor, or “AER” (click here).

According to the CDC’s report in MMWR, in addition to the outbreak’s strain of NDM-producing E. coli, another nightmarish bacteriacarbapenem-resistant K. pneumoniae (or CRKP, which may also be referred to as KPC-producing K. pneumoniae) — was recovered from Advocate Lutheran General Hospital’s contaminated GI endoscopes, specifically from the terminal section (the elevator channel) of this hospital’s side-viewing duodenoscope.

Most notably, these bacteria were recovered from the GI endoscope after it had been manually cleaned and high-level disinfected using an AER.

Although not discussed in the CDC’s MMWR report, a hospital inspection report describes two patient deaths associated with Advocate Lutheran General Hospital’s CRE outbreak.

This inspection report also provides a manufacturer’s perspective, suggesting that the hospital may not have used the correct, validated brush to clean the ERCP endoscope’s distal tip, which is where the forceps elevator is housed.


Advocate Lutheran General Hospital’s notification of its 243 “at risk” patients of their potential exposure to, and possibly infection with, CRE is proactive and may necessarily result in increased patient safety and quality, not just at Advocate Lutheran General Hospital, but also at other hospitals across the U.S. that learn of and study the potential root causes of this CRE outbreak. Read: Box B, below.

This article is a sequel to my other article about superbugs ‘infecting’ the GI endoscopic setting: ‘Investigation and Prevention of Bacterial Outbreaks during Endoscopic Retrograde Cholangiopancreatography (ERCP)’; click here to read it. — Lawrence F Muscarella, PhD

Box B: Disclosure

Whereas some U.S. hospitals might notify the public and the infected patients of the cause and source of such a nightmarish outbreak of CRE, others may not.

For instance, one hospital in Seattle (WA) linked at least 7 patient deaths — some reports suggest 11 patient deaths — in 2012 to a CRE outbreak similarly linked to contaminated GI endoscopes used during ERCP.

Nevertheless, after reportedly seeking counsel from the local department of health and the CDC, the hospital decided not to report this outbreak publicly, including not to the infected patients.

Read more about this hospital’s outbreak in The Seattle Times article (January 21, 2015): “Undisclosed superbug sickened dozens at Virginia Mason.”

Failing to disclose the cause of the outbreak even to the infected patients appears not to be unique. By way of another example, the reader is directed to The New York Times article (April 28, 2014) entitled, “A Deadly Fungus and Questions at a Hospital,” which reports that, despite 5 children dying from a fungal outbreak linked to contaminated bed linens, their families were not told of the outbreak once its cause was discovered, only to learn about it indirectly and years later.

EtO “gas” sterilization of GI endoscopes 

Advocate Lutheran General Hospital reported that — as a corrective and immediate action to stop its outbreak and prevent further instances of CRE infection — it exposed its ERCP endoscopes to a complete ethylene oxide (EtO) gas sterilization cycle.

But the “gas sterilization”of GI endoscopes raises as many questions as problems it attempts to redress.

Consider this:  According to one newspaper (The Daily Herald; December 27, 2013: “Lutheran General has permanently moved to the use of gas sterilization — the same as is used for operating room equipment. With that change, patients should have no concerns about undergoing the procedure.”

More of my comments and conclusions about this outbreak and the risk of disease transmission during GI endoscopy appear in an article by Medscape entitled “CDC Confirms Superbug Transmission via Endoscopy” (January 03, 2014).— Lawrence F Muscarella, PhD

Box C, below, discusses the notification and screening of patients of the risk of CRE infections and colonizations following ERCP.

Box C: Advocate Lutheran General’s infections – A landmark outbreak 

A likely watershed moment, Advocate Lutheran General Hospital’s landmark CRE outbreak is one of the first reported instances of a hospital notifying potentially exposed patients of the importance of their being screened for bacterial infection or colonization due to the use of a contaminated GI endoscope.

When an instrument reprocessing breach is identified and suspected of contributing to disease transmission, like Advocate Lutheran General Hospital’s confirmed outbreak, affected patients are often notified of the singular risk of transmission of a blood-borne virus, such as HIV and the hepatitis B and C viruses, but rarely of the potential for infection or colonization with a bacterium, such as the CRE superbug.

One recent article remarks that potentially exposed patients were not contacted and screened for a superbug infection following the identification of an outbreak of a multidrug-resistant bacterium linked to contaminated GI endoscopes because “neither treatment strategies nor specific precautions exist for colonization with” this superbug (Bajolet et al., 2013).

It appears, therefore, that Advocate Lutheran General Hospital’s notification of each of its 243 “at risk” patients (who underwent ERCP at Advocate Lutheran General Hospital between January, 2013, and September, 2013) establishes a new, notable, and safety precedent.

Maybe confirmed infection-control and endoscope-reprocessing breaches now warrant that affected patients be notified and screened or tested, not only for infection with a blood-borne virus (as has been the norm), but also for infection or colonization with a superbug, such as CRE. This possibility warrants further discussion.— Lawrence F Muscarella PhD

Based on the report in the MMWR discussing Advocate Lutheran General Hospital’s CRE outbreak, whether the FDA or CDC would request that patients who had been previously notified within the past year or two of an unrelated endoscope-reprocessing breach confirmed at other healthcare facilities within the U.S. — at least those treated with GI endoscopes of the same type or model as the ones that Advocate Lutheran General Hospital linked to its CRE outbreak following ERCP — would now have to be notified, too, ex post facto, of the potential (in addition to their possible exposure to a blood-borne pathogen) for their colonization or infection with CRE is unclear.

This possibility, which warrants further discussion, is explored in another of my articles: “Lessons Taught by a Recent ‘Superbug’ Outbreak: Could ‘Ex Post Facto’ Notification be Warranted?

The implications of Advocate Lutheran General Hospital’s public notification of 243 affected patients about their increased risk of CRE infection following ERCP:

  • are far-reaching;
  • may be prophylactically and wisely intended, in part, to prevent person-to-person transmission of this outbreak’s strain of CRE in the community; and
  • are not limited to public health, but would also bring into focus the FDA’s regulation of GI endoscopes and other types of medical devices.

A corrective action: Some well-crafted and -intended “mud”? 

In response to this “move,” two points are offered:

First, in truth, an adverse event such as Advocate Lutheran General Hospital’s CRE outbreak is often caused by more than one deviation, error, or contributing (and confounding) factor some of which may never be identified and published.

Indeed, the first priority of public health officials is to prevent the adverse event’s recurrence, and this objective requires prompt action and sometimes adoption of the adage that: “if you throw enough mud at the wall, some of it will stick.

An adverse event’s actual causes, and the specific corrective and preventive actions intended to prevent its recurrence, may be employed in the medical setting based on some supportive data.

But, to the risk manager’s (and design engineer’s) chagrin, the precise causes of an investigated adverse event may be surmised or presupposed, not necessarily definitively determined.

According to the CDC, Advocate Lutheran General Hospital’s CRE outbreak in 2013 was likely due to the ERCP endoscope’s complex physical design, which can “pose a particular challenge for cleaning and disinfection.”

It may be, however, that not every factor that specifically contributed to this hospital’s CRE outbreak has been published, and that some other hitherto unrecognized contributor, unrelated to the ERCP endoscope’s physical design,  may have played a significant role in causing this hospital’s CRE outbreak. Read: Box D, below.

No matter, this hospital’s corrective employment of EtO gas to sterilize the implicated ERCP endoscopes, while it may have been a case of “thrown mud,” appears to have prevented further cases of CRE infections and, at least until more information about the outbreak’s cause is known, to have been judicious.

If the precise cause of Advocate Lutheran General Hospital’s CRE outbreak has not been definitively determined, then guarantees that it is under control and patients are safe may be challenged. — Lawrence F. Muscarella, Ph.D.

Second, empirical data supporting the effectiveness of EtO gas for the “sterilization” of ERCP endoscopes are scant.  Update: A paper published in February 2016 provides additional evidence in support of the effectiveness of EtO gas sterilization for the prevention of CRE outbreaks.

Box D: An unresolved issue: CRE-contaminated rinse water?

The possibility remains that an unrecognized factor may have contributed to Advocate Lutheran General Hospital’s CRE outbreak in 2013.

To be sure, the CDC’s MMWR report (January 3, 2014) does not report whether the CDC or hospital officials microbiologically sampled the hospital’s tap water, or the rinse water used by the hospital’s automated endoscope reprocessor (AER), to exclude, or to confirm, either, along with any other suspect environmental surface, as a possible source of this hospital’s CRE outbreak.

According to the CDC, the implementation of EtO gas sterilization for processing Advocate Lutheran General Hospital’s ERCP endoscopes stopped its outbreak, but this outcome may have been due as much to EtO gas’s sterilizing effectiveness as to it being, unlike the AER’s high-level disinfecting process, an entirely “dry” process.

Interestingly, a report by Kotsanas et al. (2013) describe an investigation that identified the likely source of a CRE outbreak in an intensive care unit (ICU) to be contaminated sinks.  Three clinical isolates of the CRE’s outbreak strain (i.e., Serratia marcescens that produces carbapenemases) were indistinguishable or closely related to four environmental isolates sampled from the grates and drains of several hand-washing sinks located in the ICU.

According to Kotsanas et al. (2013), first, CRE can be “hardy” environmental organisms that develop and grow in biofilms; and, second, their findings demonstrate the key role that bacterial contamination of the environment can play in the transmission of CRE in the healthcare setting.

Similarly, Starlander and Melhus (2012) reported that during a period of seven months, four patients in a neurosurgical ICU became infected or colonized by a multidrug-resistant strain of K. pneumoniae.  The investigation revealed that the source of this outbreak was a contaminated sink. This outbreak was successfully controlled, in part, by replacing the sink and its plumbing.

And, Walsh and colleagues (2011) identified NDM-1-positive bacteria in samples of drinking water and waste seepage in Asia. In short, therefore, the type of CRE recently confirmed to be responsible for an outbreak at a hospital near Chicago, IL, in 2013 following ERCP — click here to read more about this outbreak — is not exclusively a patient-borne bacterium.

Muscarella (2004), too, has written about the contribution of the environment to outbreaks of antibiotic-resistant gram-negative bacteria.

In his paper Muscarella (2004) asked whether the cause of an outbreak of imipenem-resistant P. aeruginosa following bronchoscopy, which was investigated by Sorin et al. (2001), might have been due more to bacterial contamination of the water used to rinse the bronchoscope after its chemical reprocessing (coupled with inadequate terminal forced-air drying of the bronchoscope) than, as suggested by Sorin et al. (2001), patient-to-patient transmission due to the improper connection of an automated endoscope reprocessor to the bronchoscope.

In another paper Muscarella (2010) discusses the potential contribution of environmental surfaces to outbreaks of multidrug-resistant K. pneumoniae, emphasizing that these surfaces, including rinse water, should not be excluded as plausible sources of ERCP-related infections of ordinarily enteric bacteria, including those that are resistant to antibiotics, unless patient-to-patient transmission has been definitively confirmed.

Other instances during the past 30 years linking patient morbidity and mortality to ERCP endoscopes terminally rinsed with contaminated water during their reprocessing also have been published (Muscarella, 2004).

Whether Advocate Lutheran General Hospital’s CRE outbreak in 2013, linked to two patient fatalities, could have been due to contaminated rinse water — not inadequate cleaning or high-level disinfection of the ERCP endoscope, per se, due to the ERCP endoscope’s complex physical design as intimated by the CDC in its January 3, 2014, issue of MMWR — remains unclear, but available data, to date, do not rule out this possibility.

Indeed, rinse water contaminated with CRE being a possible “smoking gun” responsible for Advocate Lutheran General Hospital’s outbreak in 2013 would also be consistent with the recent publication of data showing (via an EPA-registration) that even intermediate-level disinfection — and therefore, certainly, high-level disinfection — destroys tested strains of CRE within 2 minutes. It could be that high-level disinfection of Advocate Lutheran General Hospital’s ERCP endoscopes was effective, but was compromised with contaminated water during endoscope-reprocessing’s subsequent water-rinse phase.

PART 2 – An overlooked ‘superbug’ epidemic? 

Advocate Lutheran General Hospital’s reported outbreak of CRE linked to ERCP endoscopes contaminated with “superbug” strains of both E. coli and of K. pneumonia — while possiby the largest ever documented in the U.S. — is only one of more than a dozen outbreaks that have occurred in the U.S. and globally within the past few years.

These several other outbreaks — which, despite being notable, first, are often overlooked in public discussions; and, second, are discussed in Box E (below) — appear now to be central to a better and more complete understanding of the precise causes of Advocate Lutheran General Hospital’s CRE outbreak.

For additional information on this topic, the reader is directed to my related article: “Investigation and Prevention of Bacterial Outbreaks during Endoscopic Retrograde Cholangiopancreatography.”

As emphasized by Gastmeier and Vonberg (2014), there has been an “enormous increase” in published endoscopy-associated CRE (namely, Klebsiella spp.) outbreaks within the past 4 years.

Box E: More than a dozen recent outbreaks of CRE following ERCP since 2008.

A number of reports of CRE following ERCP have been reported since 2008. These documented reports (which may significantly under-estimate the true incidence of these types of infections) include:

— 1.  FDA Report, dated 3/07/2014 (USA): At least eight  patients were infected or colonized with carbenepenum-resistant Enterbacteriaceae at one hospital after having undergone ERCP. (Report No. 2518897-2014-00001)

— 2.  FDA Report, dated 1/28/2014 (USA):  Five patients tested “positive” (i.e., infection or colonization)for carbenepenum-resistant Enterbacteriaceae that produced a New Delhi metallo-β-lactamase (i.e, NDM-CRE) after having undergone ERCP with the same duodeno-videoscope. (Report No. 2951238-2014-00027)

— 3.  FDA Report, dated 11/13/2013 (USA):  Four patients tested “positive” (i.e., colonization) for carbapenem-resistant Enterobacteriaceae after having undergone ERCP with the same video duodenoscope. (Report No. MW5033987)

— 4.  A hospital outside of Chicago, USA (2013): An outbreak of “CRE” following ERCP — click here to read a newspaper report discussing this outbreak at Advocate Lutheran General Hospital — which, to date, is the largest superbug outbreak in U.S. history. (FDA MAUDE Report No. 2518897-2013-00005)

Several more reports of CRE outbreaks, with associated morbidity and mortality, are documented in the FDA’s MAUDE (“Manufacturer and User Facility Device Experience“) database.

Update: Pittsburgh (PA): On October 9, 2014, the University of Pittsburgh Medical Center (UPMC) reports that after an “uptick”  of antibiotic infections (most likely, CRE infections) were identified in patients who underwent ERCP in 2012, the hospital changed its practices, switching from high-level disinfection of ERCP endoscopes to ethylene oxide gas (EtO) sterilization.

According to UPMC, the “normal process” (presumably, high-level disinfection) “failed to eliminate all bacteria” (presumably, from the ERCP endoscope’s elevator wire channel).

Whether the hospital and the manufacturer of the ERCP endoscope (as well as the manufacturer of the automated endoscope reprocessor, if one was used at UPMC) notified the FDA and filed a MAUDE report of these infections (as regulations require), and, if so, whether one of these reports is unknowingly listed above in this box article, is unclear.


I provide a number of recommendations to prevent infections of CRE and other types of bacteria following ERCP in my related article “Investigation and Prevention of Bacterial Outbreaks during Endoscopic Retrograde Cholangiopancreatography,” which provides additional insights into the possible causes of these approximately one dozen outbreaks of CRE (see above), in addition to Advocate Lutheran General Hospital’s outbreak, that were recently confirmed in the U.S. and Europe following ERCP.

The CDC published one particularly important recommendation. While EtO sterilization may prevent CRE transmission via a ERCP endoscope, the CDC states that:

At this time, CDC recommends facilities reprocess endoscopes as directed by the manufacturer; however, this is a focus of the ongoing assessments. CDC is not recommending a wholesale switch to sterilization; however, facilities should review their endoscope reprocessing practices to ensure all manufacturers’ reprocessing recommendations are followed exactly. Any reprocessing recommendations, including sterilization with ethylene oxide (if recommended), would be validated by the manufacturer.” — CDC (click here)

Provided they are performed meticulously, standard methods for reprocessing GI endoscopes — cleaning, high-level disinfection, water rinsing, and drying — therefore appear to remain intact (see: Box F, below).

Indeed, I recommend that healthcare staffers consider contacting their GI endoscope’s manufacturer for specific instructions for thorough reprocessing of those endoscopes in inventory with a forceps elevator, such that are used during ERCP.

Further, endoscope manufacturers almost universally instruct that only the specific brush that they have validated for the effective cleaning of ERCP endoscopes, particularly of the area around, near and behind the forceps elevator, should be used.

Box F: A reporting error? 

The aforementioned newspaper article discussed at the beginning of this article (“Lutheran General finds, stops bacteria source”; The Daily Heraldclick here) states that:

“The type of bacteria involved (in this outbreak) is one most people have in their digestive systems, but a strain has developed that is highly resistant to antibiotics through the misuse of antibiotics in some Third World countries, Kelly said.”

This newspaper article adds that: “While still relatively rare in the United States, this strain of bacteria is becoming an emerging problem here as it’s resistant to industry-standard methods of cleaning some types of medical equipment.”

This newspaper article’s latter quote is somewhat confusing and possibly in error, however.

While Advocate Lutheran General Hospital’s infectious strain of CRE is resistant to antibiotics (as this newspaper article correctly states), this superbug would not be expected to be resistant to the “industry-standard” method of cleaning and high-level disinfection, which this hospital was reportedly performing to process its ERCP endoscopes before and at the time of this outbreak.

This outbreak suggests that improved communications and enhanced working relationships between manufacturers of complex reusable medical equipment, such as ERCP endoscopes; the FDA and CDC; and healthcare facilities is necessary to ensure patient safety. — Lawrence F Muscarella, PhD

Non-spore forming bacteria, such as CRE, are susceptible to, and ordinarily and quickly destroyed by, high-level disinfection, provided, however, that the design of the GI endoscope or other type of reusable instrument does not hinder contact of an effective high-level disinfectant (or the cleaning detergent) with every one of its contaminated surfaces.

The CDC’s clarification of whether it now recommends (which, by the way, is most unlikely) the “gas sterilization” of all reusable GI endoscopic equipment that is both used during ERCP and is potentially contaminated with CRE or another superbug, such as the duodenoscope, is requested. — Lawrence F Muscarella PhD

Note that the EPA-registration of several currently marketed intermediate-level disinfectants are labeled to kill CRE (e.g., Enterobacter cloacae [NDM-1 positive] and K. pneumoniae [KPC-2] positive, multidrug- and carbapenem-resistant) within 2 minutes.

And, if intermediate-level disinfection so quickly kills these CRE, certainly the more robust process of high-level disinfection, if performed properly, would be expected to kill even more rapidly Advocate Lutheran General Hospital’s outbreak strain of CRE.

Public Alert: According to the Chicago Tribune (click here), “This is going to be a problem in other places,” Kelly warned. “It’s going to spread.” Therefore, a review of all available information about not only the possible causes of this “superbug” outbreak, but also the necessary corrective actions to prevent its recurrence is recommended

In response to this CRE outbreak, a hospital’s replacement of the current “industry-standard” method of cleaning and high-level disinfection with EtO gas sterilization could be premature and based on incomplete data and findings.

PART 3 – Outstanding questions

A number of questions arise from the documented outbreak at Advocate Lutheran General Hospital and its response to the outbreak. These questions include:

Quality for Consumers, 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.

  1. In addition to HIV and the hepatitis B and C viruses, do patients now have to be notified of and screened for the risk of transmission (i.e., infection or colonization) of a superbug (e.g., CRE) whenever an endoscope-reprocessing breach is confirmed?
  2. Has a root cause analysis of Advocate Lutheran General Hospital’s CRE outbreak been performed and published for the public to review?
  3. Were any of Advocate Lutheran General Hospital’s implicated ERCP endoscopes dismantled to determine whether its “sealed” elevator-wire channel or affixed plastic distal hood was internally contaminated with the outbreak’s strain of CRE?
  4. Were Advocate Lutheran General Hospital’s implicated ERCP endoscopes returned to their manufacturer(s) for repair and servicing, during which time infectious biofilms of CRE may have been unwittingly removed from inside the endoscope, causing the hospital’s subsequent EtO gas sterilization of these returned-to-service ERCP endoscopes to appear to be responsible for stopping this CRE outbreak?
  5. Were ERCP endoscopes of only one manufacturer (or of several) implicated in this hospital’s CRE outbreak?
  6. Are standard reprocessing guidelines sufficient for destroying all types of bacterial superbugs that might contaminate a GI endoscope?
  7. Or, is high-level disinfection (at least of the type, model and brand of implicated GI endoscope), at times, insufficient to destroy CRE that has contaminated an ERCP endoscope?
  8. Have automated endoscope reprocessors (AERs) that have been cleared by the FDA demonstrated their effective reprocessing of: (i) a single, specific model of an ERCP endoscope sold by one manufacturer; (ii) all manufacturers’ models, brands, and types of ERCP endoscopes; or, (iii) not necessarily any ERCP endoscope models, despite the AER likely being cleared by the FDA to reprocess “all types of flexible endoscopes”?
  9. Is every AER model on the U.S. market associated with validation data showing their effectiveness for disinfecting the ERCP endoscope as a whole (consistent with the limited “per device” paradigm), or for specifically showing sufficient mycobacterial log reductions (as seemingly required) in the exposed areas around and near the elevator forceps itself (pursuant to the more complete “per site” paradigm)? (A review of available data on-line suggests the former.)

Additional questions are raised in my related article, “GI Endoscopy: Pushed Beyond its Reprocessing Limits?” A response to each of these questions is requested of the hospital, the FDA, and/or the CDC.

This outbreak is a ‘perfect storm’ of sorts that reveals a system of many interacting components: the complex designs of gastrointestinal endoscopes; the FDA’s regulation of the quality of these devices, and a healthcare facility’s practice of infection control and endoscope reprocessing. This system and its several components appear to require that additional checks and balances be developed and implemented, to ensure quality and patient safety. — Lawrence F Muscarella, PhD


  1. Alrabaa SF, Nguyen P, Sanderson R, et al. Early identification and control of carbapenemase-producing Klebsiella pneumoniae, originating from contaminated endoscopic equipment. Am J Infect Control 2013 Jun;41(6):562-4.
  2. Aumeran C, Poincloux L, Souweine B, et al. Multidrug-resistant Klebsiella pneumoniae outbreak after endoscopic retrograde cholangiopancreatography. Endoscopy 2010 Nov;42(11):895-9.
  3. Bajolet O, Ciocan D, Vallet C. et al. Gastroscopy-associated transmission of extended-spectrum beta-lactamase-producing Pseudomonas aeruginosa. J Hosp Infect 2013 Apr;83(4):341-3.
  4. Carbonne A, Thiolet JM, Fournier S, et al. Surveillance and outbreak reports Control of a multi-hospital outbreak of KPC-producing Klebsiella pneumoniae type 2 in France, September to October 2009. Euro Surveill 2010 December 2;15(48):pii=19734 (click here).
  5. Centers for Disease Control and Prevention (CDC). Notes from the Field: New Delhi Metallo-β-Lactamase–Producing Escherichia coli associated with endoscopic retrograde cholangiopancreatography — Illinois, 2013. MMWR January 3, 2014;1051 (click here).
  6. Gastmeier P, Vonberg RP. Klebsiella spp. in endoscopy-associated infections: we may only be seeing the tip of the iceberg. Infection 2014 Feb;42(1):15-21.
  7. Kotsanas D, Wijesooriya W, Korman T, et al. “Down the drain”: carbapenem-resistant bacteria in intensive care unit patients
    and hand-washing sinks. MJA 2013; 198: 267–269.
  8. Medscape. CDC Confirms Superbug Transmission via Endoscopy. January 3, 2014
  9. Muscarella LF. Contribution of tap water and environmental surfaces to nosocomial transmission of antibiotic-resistant Pseudomonas aeruginosa. Infect Control Hosp Epidemiol 2004 Apr;25(4):342-5.
  10. Muscarella LF. Investigation and prevention of infectious outbreaks during endoscopic retrograde cholangiopancreatography. Endoscopy 2010 Nov;42(11):957-9.
  11. Naas T, Cuzon G, Babics A, et al. Endoscopy-associated transmission of carbapenem-resistant Klebsiella pneumoniae producing KPC-2 b-lactamase. J Antimicrob Chemother 2010;1305-6.
  12. Sorin M, Segal-Maurer S, Mariano N, et al. Nosocomial transmission of imipenem-resistant Pseudomonas aeruginosa following bronchoscopy associated with improper connection to the Steris System 1 processor. Infect Control Hosp Epidemiol 2001 Jul;22(7):409-13.
  13. Starlander G, Melhus A. Minor outbreak of extended-spectrum β-lactamase-producing Klebsiella pneumoniae in an intensive care unit due to a contaminated sink. J Hosp Infect 2012 Oct;82(2):122-4.
  14. Walsh TR et al. Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: An environmental point prevalence study. Lancet Infect Dis 2011;11:355.

Article by: Lawrence F Muscarella, PhD, president and owner of the think-tank quality and safety company “LFM Healthcare Solutions” — click here for a list of its services. Article posted 12/30/2013 Rev A; updated: 3/18/2016, Rev A.

6 thoughts on “Overlooked Outbreaks of “CRE” Linked to GI Endoscopy: A “Superbug” Epidemic in Our Midst?”
  1. I would focus first on the possibility that reprocessing staff was not consistently following manufacturer (not Evotech) guidelines for bedside cleaning as well as brushing properly, with emphasis on cleaning the elevator and all accessible channels and scope surfaces. I am especially interested to learn which reprocesser and LCG are used at this facility.

    1. StevenBBB: I am researching the answers to your questions. I am hopeful that I might be permitted to review a root cause analysis of this incident.

    1. Dr. Holmes, Good morning.

      Yours is an insightful suggestion, namely, that the AER (automated endoscope reprocessor) or its rinse water — remember in the 1980s these were primary contributing factors to several Pseudomonas aeruginosa outbreaks (with associated patient deaths) following ERCP — used to reprocess implicated GI endoscopes was the source of the superbugs responsible for at least some of the recently publicized outbreaks of CRE (carbapenem-resistant Enterobacteriaceae) linked to GI endoscopy.

      In my editorial — Muscarella LF: “Investigation and prevention of infectious outbreaks during endoscopic retrograde cholangiopancreatography.” Endoscopy. 2010 Nov;42(11):957-9; see: — I suggest just what you have proposed:

      — that the AER, coupled with inadequate drying of the ERCP endoscope’s several internal channels, could have been an important contributor to at least some of these recent CRE outbreaks following GI endoscopy. (I am not sure whether the CDC or FDA has considered this.)

      Please review my editorial in “Endoscopy” – I would be most appreciative if you were to respond to it, below, in this thread.

      As I wrote on another published article — Muscarella LF. “Contribution of tap water and environmental surfaces to nosocomial transmission of antibiotic-resistant Pseudomonas aeruginosa.” Infect Control Hosp Epidemiol. 2004 Apr;25(4):342-5 — it is true that antibiotic-resistant gram-negative bacteria, such as P. aeruginosa and, possibly, CRE, or carbapenem-resistant Enterobacteriaceae (as you suggest), are not only patient-borne, but may also be involved in environment-to-patient disease transmission, with associated morbidity and mortality.

      Dr. Holmes, again, yours is a good suggestion that warrants further discussion.

      Interesting, your suggestion (and my editorial’s) would explain why, as reported by the CDC in the January 3, 2014, issue of MMWR, CRE — which was linked to multiple patient infections and colonizations following ERCP performed by Advocate Lutheran General Hospital (Park Ridge, IL) in 2013 — was sampled from the ERCP endoscope’s elevator forceps area *after* cleaning and automated disinfection using an AER. Indeed, this might occur if the rinse water, which contacts the ERCP endoscope *after* disinfection, were the source of the CRE.

      Your suggestion would also explain why Advocate Lutheran General Hospital’s CRE outbreak was terminated once the hospital began sterilizing its ERCP endoscopes using ethylene oxide (EtO) gas (in lieu of high-level disinfection), a process that is “dry” and would prevent further contact of the ERCP endoscopes with the AER or with its rinse water, either of which you propose could be a source of this hospital’s CRE outbreak.

      Whether the rinse water was a contributing factor to Advocate Lutheran General Hopsital’s CRE outbreak in 2013 is important to determine, because the findings would address a current question: Is there something about CRE that causes it to be not only resistant to antibiotics, but also to high-level disinfection? The CDC’s report in MMWR intimates that sterilization may now be necessary to prevent CRE transmissions via contaminated ERCP endoscopes. At this time, I am not convinced of the inadequacy of high-level disinfection for reprocessing ERCP endoscopes contaminated with CRE during clinical use.

      Lawrence F Muscarella, PhD (President, LFM Healthcare Solutions, LLC)

      1. Dear Dr Muscarella

        Thank you for your response.

        Would it be beneficial to re-validate the decontamination of this ERCP in AER, using target organisms (e.g. CRE) with the focus on the elevator? This is to verify whether reprocessing using high level disinfection in AER is capable of removing target organisms from the endoscope satisfactorily.

        I agree with you that we should not ignore other potential causes such as final rinse water quality, the effectiveness of self disinfection AER, dryness status of the endoscope, condition of the endoscope, condition and duration of storage and transport etc.

        Have you read the article related to KPC (Klebsiella pneumoniae carbapenemase) in France 2009?(

        Perhaps, in a short term, ethylene oxide sterilization would provide greater assurance to remove all contaminants from the endoscopes following incident or outbreak.
        However, I would rather we examine all those factors first before moving towards ethylene oxide sterilization for a permanent solution. This is due to lack of availability of ethylene oxide sterilization facilities, turn around time, cost implications etc.

        Kind regards

        1. Dr. Holmes, Yes, it might prove important, and certainly would be insightful, to re-validate the automated endoscope reprocessor (AER), under worst-case testing conditions, for the cleaning, high-level disinfection, and drying of the ERCP endoscope model in question, especially if any original validation data for any of these three decontamination steps were lacking, or if an endoscope model of this physical complexity (and “age, wear and tear”) were not originally challenged during clearance testing.

          Even more so, re-validation testing, especially of the elevator forceps, the elevator wire channel (if exposed), and the area of the ERCP endoscope where the forceps is housed, would definitively demonstrate whether the “CRE” bug is easily killed (and is more readily destroyed, as would certainly be expected, than the marker bacterium for high-level disinfection, namely, Mycobacterium tuberculosis) during high-level disinfection. One would certainly expect that “CRE,” while evolving and now resistant to carbapenem and other beta-lactam antibiotics, would be quickly destroyed during exposure to any high-level disinfection process. But this conclusion warrants investigation, confirmation, and publication.

          Yes, I have read the article about KPC (Klebsiella pneumoniae carbapenemase) in France in 2009, and I agree with you that, through a root cause analysis, all possible factors (not merely the most obvious ones) that might have contributed to Advocate Lutheran General Hospital’s CRE outbreak in 2013 be investigated and studied before guidelines recommend the ethylene oxide (EtO) gas of ERCP endoscopes, although, at least in the interim, the hospital’s employment of EtO gas sterilization seems to have been most wise.

          The hospital’s (and CDC’s) finding that EtO gas sterilization, which is a “dry” process, prevented further instances of CRE transmission supports your original suggestion that the AER’s rinse water might have been a potential reservoir of the outbreak’s CRE. It would be important to learn whether the CDC cultured the AER’s and/or the hospital’s rinse water to evaluate it as a possible source of the outbreak’s CRE strain. Inadequate drying of the ERCP endoscope, more than any other shortcoming, could have been an important contributor to this CRE outbreak.

          Dr. Holmes, are you aware of any published studies that have used CRE as a target organism for the demonstration of a high-level disinfection process’s effectiveness? I know of one that performed a similar type of test on a similar organism (see: Aumeran et al., 2010; “Endoscopy”).

          Best regards, Larry (LF Muscarella PhD)

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