June 15, 2015 — The Mountain Xpress, a local newspaper in Asheville (NC), reported earlier this week that two patients died in February at a hospital in North Carolina “from infections linked to contaminated endoscopes.”

At that time of those infections, when news of this outbreak first broke in February, CNN reported that 18 patients of the Carolinas HealthCare System (CHS) had contracted “CRE” in 2015.  This cable news network also reported that, according to the hospital, 15 of these patients had the superbug upon admission to the hospital; three acquired it in the hospital; and one died.

Five months later, health officials in North Carolina still have not publicly confirmed the cause of a deadly superbug outbreak that infected 18 patients, two of whom died. — Lawrence F Muscarella PhD, independent expert.

Also at that time of the infections, WSOC-TV reported the hospital in this system to be Carolinas HealthCare System – Lincoln, in Lincolnton (NC).  CHS is a Charlotte-based healthcare system that manages hospitals throughout North Carolina, including in Lincolnton and Charlotte.

At that time, too, the Charlotte Observer reported that CHS had started screening “at risk” patients for CRE. While providing little insight into the outbreak’s true cause, this newspaper noted that CHS has changed how it cleans its duodenoscopes, but without specifically implicating these instruments as a contributing factor.

Reported now for the first time, health officials, to date, have not publicly announced the cause of CHS’s deadly superbug outbreak in 2015.

Duodenoscopes are a type of GI endoscope that was used about 670,000 times last year in the U.S. to perform endoscopic retrograde cholangiopancreatography, or ERCP.  Olympus America, Pentax Medical and FUJIFILM Endoscopy USA sell these specialized instruments.

CRE, or carbapenem-resistant Enterobacteriaceae, are multidrug-resistant bacteria that are resistant even to carbapenems, the “big gun” and “last defense” antibiotics.

Despite these news reports including CNN’s, health official have not, to date, publicly disclosed whether they suspect that contaminated duodenoscopes may have been responsible for this deadly superbug outbreak in North Carolina. — Lawrence F Muscarella, PhD

More “superbug” outbreaks

Many questions about this CRE outbreak in North Carolina remain unanswered.

To be sure, CHS’s infections are anything but the first publicized instance of CRE sickening patients in the U.S. For instance:

  The Centers for Disease Control and Prevention (CDC) reported that more than three dozen patients at Advocate Lutheran General Hospital (Park Ridge, IL), outside of Chicago, were infected in 2013 with CRE during ERCP.

Health officials concluded that contaminated duodenoscopes, which are complex in design and difficult to clean, were responsible for this hospital’s CRE outbreak. At the time, this outbreak was the most publicized, if not the largest, in U.S. history.

This outbreak is discussed in more detail in Dr. Muscarella’s two related articles: “Overlooked Outbreaks of “CRE” Linked to GI Endoscopy: A “Superbug” Epidemic in Our Midst?” and his peer-reviewed article, “Risk of Transmission of Superbugs during Gastrointestinal Endoscopy.”

  In early 2015, both The Seattle Times and USA TODAY reported that Virginia Mason Medical Center (Seattle, WA) had identified at least 32 patients who were infected with a multidrug-resistant superbug following ERCP performed between 2012 and 2014. Eighteen (18) of these infected patients died.

Officials linked this outbreak to contaminated duodenoscopes, and it replaced Advocate Luther General Hospital’s as the most talked about outbreak of its type.

Click the title to read Dr. Muscarella’s other popular and related article, “Investigation and Prevention of ‘Superbug’ Outbreaks Following Endoscopy.”

  But none can compare in publicity to last February’s outbreak of CRE at UCLA’s Ronald Reagan Medical Center (Los Angeles, CA), which, like these other two outbreaks, health officials linked to contaminated duodenoscopes. Seven (7) of this hospital’s patients were infected during ERCP, three (3) of whom died.

These outbreaks at UCLA and other hospitals could collectively be the most significant instance of disease transmission ever linked to a contaminated reusable medical instrument. — Lawrence F Muscarella, PhD (see: The Los Angeles Times)

According to the FDA, these three outbreaks confirmed that duodenoscopes may retain and transmit infectious, resistant bacteria to patients during ERCP, despite the endoscope being cleaned in accordance with the manufacturer’s instructions.


This article is written by Dr. Muscarella, who recently appeared on: CNNThe Today Show | NBC’s Nightly News | CBS Evening News | ABC World News Tonight | CBS News 3 (Philadelphia, PA) | Huffington Post Live | Wall Street Journal Live | WFMZ 69News (Allentown, PA) | CBS-Los Angeles | WSOC-TV (NC)


More CRE outbreaks linked to duodenoscopes

Other instances of medical facilities across the U.S. since 2008, but particularly since 2012, encountering a deadly CRE outbreak linked to duodenoscopes, including:

  • One of the Medical College of Wisconsin’s affiliated hospitals (Milwaukee, WI) – an unknown number of infected patients died, if any; and
  • An unnamed hospital in Florida (Highlands County) – at least 22 infected patients died.

USA TODAY provided a “timeline” last May of how the public learned about many of the deadly superbug outbreaks in the U.S. that have been linked to duodenoscopes.

In February, Bloomberg provided a graph in its February (2015) article “Scopes in UCLA Superbug Case Linked to Unreported Deaths in Other States” detailing the significant morbidity and mortality associated with several of these outbreaks.

But, in part, due to timing, Bloomberg’s graph, like most other reports discussing the recent spate of CRE outbreaks across the U.S. following ERCP, does not include last February’s sometimes overlooked CRE outbreak in North Carolina.

The Olympus TJF-Q180V duodenoscope

Olympus has sold the lion’s share of duodenoscopes in the U.S., despite its popular TJV-Q180V model, which Olympus has marketed since 2010, having not yet received a legal clearance (as ordinarily required to sell a medical device in the U.S.). Some reports estimate Olympus to have a 70% share of the global market for GI endoscopes.

You can get a superbug that can be transmitted from one hospital to another even to long term care facilities. — Lawrence F Muscarella (see: WSCOC-TV)

On March 26, 2015, in response to the disclosure of these several superbug outbreaks across the U.S. (and in Europe), Olympus provided its U.S. customers with a “revised” set of validated instructions for reprocessing its TJF-Q180V duodenoscope.

Two months later, in May, 2015, this manufacturer published its more complete updated reprocessing manual.


Quality Reviews for Hospitals, Manufacturers, Patients:  Click here to read about how Dr. Muscarella’s can help you reduce the risk of healthcare-associated infections, including “superbug” outbreaks linked to contaminated GI endoscopes and other reusable medical equipment.


A wife’s story

Addressing the increasing number of CRE outbreaks linked to GI endoscopes in the U.S. (and Europe), particularly since 2012, the FDA hosted an advisory panel meeting last May, in Silver Spring (MD), to discuss the effective reprocessing of duodenoscopes.

At this meeting Carla Warner of Statesville (NC) spoke about her husband, “Bill” Warner, who succumbed to a deadly CRE infection in 2013 following ERCP. She testified that, “Bill fought the infection courageously for over eight months, enduring excruciating pain and horrific injuries before ultimately losing his battle.”

Ms. Warner also testified that (click here to read her entire testimony):

  • “I believe that had proper testing taken place on the Olympus 180 before it was introduced to the market, my husband would be alive today and there would be no need for this hearing or my presence here”;
  • “Medical device manufacturers must hold themselves to and be held to a higher standard”; and
  • “Olympus knew of the risk but hid that information from the FDA and from medical providers, disregarding the safety of the people they were claiming to help while continuing to make a profit at their expense.”

They have failed me, our family, and my husband has paid the ultimate price of his life. Medical device manufacturers must hold themselves to and be held to a higher standard. — Carla Warner

In May, the  Los Angeles Times reported that Mr. Warner had three ERCP procedures between December 2012 and January 2013, with his doctors becoming aware of his CRE infection one month later, in February 2013.

One or two outbreaks in North Carolina?

This Los Angeles Times article also reported that Mr. Warner underwent these ERCP procedures at the Carolinas Medical Center, in Charlotte, N.C.

Modern Healthcare, like the aforementioned CNN report, reported last February that three of the 18 patients were infected with CRE while inpatients at Carolinas Medical Center-Mercy in Charlotte (NC).

But, The Mountain Xpress and WSOC-TV both report Carolinas HealthCare System – Lincoln, in Lincolnton (NC), as the facility where this outbreak occurred. Lincolnton is about 40 miles north-west of Charlotte.

Whether these news reports are referring to the same outbreak, possibly involving the transfer of infected patients between two hospitals, or to two distinct outbreaks of CRE in Lincolnton and Charlotte — or, possibly, even to three different CRE outbreaks, the third resulting in Mr. Warner’s death in 2013 following ERCP? — requires clarification by health officials.

Modern Healthcare quotes a spokesman for the CHS as saying that it “is aggressively addressing this issue. … In many cases, patients bring the infections with them when they are admitted.”

Were duodenoscopes responsible for the Carolina outbreak?

Like the Mountain Xpress report, this Los Angeles Times article further reported that Mr. Warner contracted this superbug infection “from a duodenoscope.”

But, there remains some confusion about the outbreak’s cause and whether contaminated duodenoscopes were responsible.

Notably, CNN‘s report discussing CHS’s outbreak of CRE, along with Ms. Warner’s testimony, strongly imply — although admittedly do not definitively conclude — that contaminated duodenoscopes were likely to blame for CHS’s outbreak of CRE in 2015.

Similarly implying that contaminated duodenoscopes were linked to CHS’s deadly superbug outbreak but without directly stating so, the Charlotte Observer report (from last February) states that:

  • “Carolinas HealthCare has changed how it cleans (duodenoscopes)”; and that
  • like UCLA’s Ronald Reagan Medical Center, among others, this healthcare system now uses ethylene oxide gas to sterilize its duodenoscopes.

Using this same style, CHS’s press release reveals that, in response to its outbreak, it:

  • “began to improve its cleaning process by … enhancing its current high-level disinfection process by using a ‘triple wash’ process to clean equipment”; and that
  • efforts to prevent CRE infections include using decontamination procedures and protocols “that go beyond industry standards.”

But, to be sure, the hospital’s press release, CNN report, Charlotte Observer report, and Ms. Warner’s testimony do not quote health officials or the hospital as concluding that contaminated duodenoscopes were responsible for CHS’s outbreak of CRE in 2015.

The aforementioned articles in Modern Healthcare and CNN may explain this discrepancy:  According to CHS, when sampled microbiologically, all of the hospital’s duodenoscopes tested “negative” for CRE, causing officials to take pause.

In fact, it is quite possible, if not likely, that health officials are not stating that contaminated duodenoscopes were necessarily the cause of this North Carolina outbreak based solely on the results of endoscope sampling.

Convincing scientific evidence either identifying duodenoscopes as the outbreak’s likely cause, or ruling them out, has not yet been published. — Lawrence F Muscarella, PhD

Endoscope sampling and “false-negative” sampling results

But, microbiological sampling has significant limitations (that have not been publicized well).

Several peer-reviewed scientific reports – some of which are discussed in Box A, appended below – document duodenoscopes contaminated with CRE that, when sampled microbiological, erroneously yielded no CRE growth during culturing – what’s known as a false-negative result. Even the CDC surprisingly acknowledged as much during its testimony during the FDA’s May, 2015, panel meeting.

And so it could be that the conclusion by the Los Angeles Times and Mountain Xpress that CHS’s outbreak of CRE was due to a contaminated duodenoscope is correct.

It is acknowledged that determination of the exact cause of a multidrug-resistant bacterial outbreak following ERCP can be difficult, especially if the results of the microbiological sampling of the duodenoscope are negative.

Health officials are cautioned not to rule out a duodenoscope as the potential cause of an outbreak of CRE based primarily on a “negative” endoscope sampling result. — Lawrence F Muscarella, PhD

But the CDC, in its recently published interim surveillance protocol, has itself advised that health officials not to exonerate what might be a contaminated duodenoscope responsible for an outbreak based primarily on a negative sampling result.

In summary, despite the CDC’s publication of this protocol, the microbiological sampling of endoscopes is inherently prone to suggesting erroneously that a bona fide CRE-contaminated duodenoscope is “sterile” or “CRE-clear.”

The reader is directed to Dr. Muscarella’s related blog article “A ‘Test-and-Hold’ Surveillance Policy to Prevent ‘Superbug’ Infections Following Endoscopy” to learn more about microbiological sampling and its limitations.

Medical Device Reports, or MDRs

Federal regulations require manufacturers to file a medical device report, or MDR, with the FDA “when they learn that any of their devices may have caused or contributed to a death or serious injury” (click here to read the FDA’s regulations).

These regulations are not limited to manufacturers. They also require healthcare facilities to “report a suspected medical device-related death to both the FDA and the manufacturer,” with “suspected” and “related” being operative words.

During Dr. Muscarella’s researching of this article, a filed MDR was identified appearing to describe CHS’s superbug outbreak. (Only a manufacturer whose duodenoscope “suspected” to have caused or otherwise to be “related” to this deadly outbreak would be required to file an MDR.)

Olympus’ filing of this MDR this past June (2015), 4 months after CHS first identified its CRE outbreak, appears to be in direct response to a press release – dated May 15, 2015 – that was issued by the law firm representing Ms. Carla Warner’s interests.

The filing of this MDR by Olympus does not mitigate the confusion surrounding this outbreak’s cause, however. If anything, it adds to the confusion, because the filed MDR on its face is not consistent with the stance of health officials, who, whether they are right or wrong, appear to have concluded that duodenoscopes were not responsible for CHS’s outbreak last February, the Mountain Xpress’ and Los Angeles Times’ reporting – along with the filing of this MDR – notwithstanding.

Informed consent: A twist

If, indeed, these health officials in North Carolina concluded that a duodenoscope did not transmit the superbug, the hospital, in addition to not having to file a MDR, would then seemingly not be required either to inform the 18 infected patients that their infection in 2015 might have be caused by a contaminated duodenoscope model whose design and safety the FDA has questioned.

As CBS News and the the Charlotte Observer reported reported last February, CHS’s claim that several of these 18 patients were already infected with CRE prior to admission would argue for the admitting hospital not having to file a MDR. (As noted above, the manufacturer, Olympus, appears to have filed an MDR documenting this outbreak in 2015.)

CHS’s infected patients would most likely have been told by officials that they had contracted an infection, pointing out that the signed ERCP consent form most certainly would have listed “infection” as a known complication of ERCP, and were promptly treated with one of the few remaining effective antibiotics.

But it is possible that these 18 patients were told little more about their infections.

Namely, one twist of health officials and the hospital not having publicly announced duodenoscopes as a possible cause of CHS’s outbreak of CRE is the possibility that these more than a dozen infected patients, along with likely dozens more patients potentially exposed to the contaminated instrumention, were not told — and many may still be unaware:

  • of this hospital’s deadly superbug outbreak;
  • that these patients were infected with “CRE” that has been linked at other hospitals to contaminated duodenoscopes; and
  • that the duodenoscope used to perform ERCP on these 18 patients — the Olympus TJF-Q180V model — even today remains without a legal clearance, though continues to be used throughout the U.S.

Whether health officials informed these 18 infected patients last February of this superbug outbreak warrants clarification, as the notification of these affected patients could prove more important than health officials may realize to prevent the superbug’s inadvertent transmission among CRE-colonized patients in the community.

Commentary: A shift in the burden of proof?

It may be in the public’s best interest for the burden of proof to shift, such that U.S. hospitals might reasonably presume and punchily acknowledge — based in part on the FDA’s conclusions that these instruments are complex in design, cannot always be cleaned thoroughly, and have been found responsible for several superbug outbreaks following ERCP — that a contaminated duodenoscope is the likely cause of an identified CRE outbreak, provided (among a few other considerations):

1.  patients who underwent ERCP were determined by the hospital to be at a significantly greater risk of CRE infection than those patients who did not undergo this procedure; and

2.  no data were obtained during the outbreak’s investigation to exclude a contaminated duodenoscope as the outbreak’s cause or a contributing factor; and

3.  no factor, source, contaminated reservoir, or mode of transmission was identified to be more likely the cause of a cluster or outbreak of the multidrug-resistant bacteria that infected or colonized the patients who underwent ERCP.

While endoscope sampling’s yielding of a “positive” result (i.e., bacterial growth) is generally a reliable and meaningful finding, as noted above, a “negative” culture result (no bacterial growth), by itself, should not be the basis for excluding the duodenoscope as a contributor to a superbug outbreak, due to endoscope sampling’s unreliability.

Conclusions

The effectiveness of diligent measures employed by GI endoscopy units to prevent the recurrence of CRE outbreaks is limited by the facts disclosed by state and federal health officials (and the hospitals’ own physicians and experts).

Only through the sharing of information and publication of the circumstances surrounding a hospital’s CRE outbreak can improvements be made, preventive actions implemented by other hospitals across the U.S., community-acquired CRE infections prevented, and the risk of CRE infection in hospitals further reduced.

If important facts about an outbreak’s potential cause are not disclosed, public health may be compromised, and lessons crucial for other hospitals to prevent CRE transmissions cannot be taught.

Summary and closing remarks

Despite the publicity it received in some press reports, much remains unknown about CHS’s outbreak of CRE – specifically, what health officials have determined was its cause.

Much of the confusion surrounding this outbreak would be resolved, with the public learning more about the circumstances of CHS’s outbreak, if health officials were to clarify publicly (for the first time) the likely or suspected cause of CHS’s deadly superbug outbreak in 2015, and whether contaminated duodenoscopes have been ruled out as a possible cause (and, if so, based on what findings and testing).

Determination of the outbreak’s true cause may require further investigation, such as dismantling suspect endoscopes and culturing their internal surfaces for CRE.

Also warranting public clarification is whether:

  • CHS experienced two (possibly even three?) superbug outbreaks at its hospitals in Lincolnton (NC) and Charlotte (NC)
  • or, these two hospitals were part of a single outbreak; and
  • the 18 infected patients were informed of this outbreak.

The answers to these questions may indicate that CHS’s superbug outbreak in 2015 is more significant than previously recognized.

Endoscope sampling’s unreliability, inherent inefficiency and inability to consistently yield a “positive” result (growth) from an endoscope known to be contaminated with CRE (or another multidrug-resistant bacteria) underscores the importance of additional data being collected before officials conclude that an endoscope was not responsible for an outbreak.

It may be in the public’s interest for the CDC to revise its published interim surveillance protocol to more clearly emphasize, if not boldly state at the top of the document, that investigators should not rule out a duodenoscope as a suspected cause of an outbreak of a multidrug-resistant bacteria based primarily, if not solely, on a negative sampling result: CRE-infected endoscopes (for a number of reasons) can yield “no growth” test results.

In closing, based on available data and no assertions by health officials to the contrary, it may be that CHS’s outbreak of CRE in 2015 was caused by a contaminated duodenoscope, the FDA-censured and uncleared Olympus TJF-Q180V model.


Box A. Endoscope sampling continued.

Many peer-reviewed scientific reports document duodenoscopes contaminated with CRE that, when sampled microbiological, yielded “negative” (no CRE growth) results.

Even the CDC surprisingly acknowledged as much during its testimony during the FDA’s May, 2015, panel meeting. Refer to Box A for a discussion of this topic.

  • Discussing another bacterial outbreak linked to contaminated bronchoscopes, researchers reported in 2003 that while “initially, cultures did not grow (the outbreak’s strain of bacteria,” re-culturing the endoscope, this time “both anterograde and retrograde sampling,” yielded the bacteria.[1]
  • Investigations of another outbreak in 2010 reported that five duodenoscopes were sampled during the outbreak period did not yield the outbreak’s bacterial strain, but a “modified sampling procedure” subsequently performed did. The researchers report that “while all previous attempts had been unsuccessful, this time the cultures” were positive for the outbreak’s strain.[2]
  • A recent publication by the CDC notes that: ” … negative surveillance cultures alone should not be used to rule out duodenoscopes as a source of cross-transmission.”[3]

References

[1]. Srinivasan A, et al. An Outbreak of Pseudomonas aeruginosa infections associated with flexible bronchoscopes. N Engl J Med 2003;348:221-7.

[2] Ameran C,  et al. Multidrug-resistant Klebsiella pneumoniae outbreak after endoscopic retrograde cholangiopancreatography. Endoscopy 2010 Nov;42(11):895-9.

[3] Centers for Disease Control and Prevention (CDC). Interim Duodenoscope Surveillance Protocol.Interim Protocol for Healthcare Facilities Regarding Surveillance for Bacterial Contamination of Duodenoscopes after Reprocessing. 2015.


Article by: Lawrence F Muscarella, PhD; posted: 7-16-2015; updated: 7-21-2015, Rev A.

Note: Dr. Muscarella is the president of LFM Healthcare Solutions, LLC, an independent quality improvement company. Click here for a discussion of his quality improvement healthcare services.

Leave a Reply

Your email address will not be published. Required fields are marked *

Verify *