May 6, 2016 (1:00 pm) At least eight patients were infected with a deadly ‘superbug’ earlier this year — two of whom died — following an endoscopic procedure, my research has found.

Olympus (Center Valley, PA) filed a regulatory report with the Food and Drug Administration (FDA) on February 24, 2016, documenting at least six patients who were infected with deadly multidrug-resistant E. coli bacteria.

This deadly outbreak occurred earlier this year at University of Colorado Hospital, or “University Hospital” (Aurora, CO), according to an official familiar with the case.

This hospital’s outbreak has not been previously disclosed to the public.



UPDATE:  On May 10, 2016, The Denver Post and Aurora Sentinel confirmed this hospital’s deadly outbreak, which had not been previously disclosed. Both papers reported, however, that nine (not eight) patients who underwent ERCP earlier this year at University Hospital were infected with E. coli, three (not two) of whom died.

A spokesman for University Hospital told the Denver Post, “We thoroughly investigated this incident and determined that nine patients who underwent an ERCP using a particular endoscope developed infections; three of these patients later died.”

A spokesman for the Colorado State Department of Health — which has not previously discussed this outbreak publicly — reportedly will be releasing a statement soon in response to this E. coli outbreak and my findings, according to the Denver Post.

(Note: This article I wrote was originally published on March 24, 2016, although at that time the hospital was not known. Once its name was learned, I updated this article on May 6, 2016, and then, agafcoliin, on May 10, 2016, after the Denver Post and Aurora Sentinel published front-page articles discussing this outbreak and my research findings.)



The hospital’s infections appear to be this year’s most significant bacterial outbreak linked to ERCP and duodenoscopes.

Also according to its regulatory report, Olympus was informed five days later, on February 29, 2016, that two more patients had become infected with the outbreak’s resistant bacteria, totaling eight infected patients.

Denver PostThese patients were infected following ERCP, which the hospital performed using an Olympus TJF-Q180V duodenoscope — which the company recalled the previous month, on January 15, 2016, amid safety concerns.

When I asked a hospital official and a doctor at the Colorado Department of Public Health and Environment if this regulatory report filed by Olympus on February 24, 2016, describing 8 patient infections and two deaths occurred at University Hospital, neither issued a denial.

A deadly Pasadena outbreak

Just yesterday, the front page of The Los Angeles Times discussed a different, unrelated deadly outbreak at Huntington Hospital (Pasadena, CA) that officials linked last year to the older Olympus TJF-160V model.

Based on my original research too, that Times article disclosed publicly for the first time that Huntington Hospital’s three patients — each of whom was infected last summer with a multidrug-resistant strain of Pseudomonas following ERCP — had died. Previously, it was reasonably suspected that these infected patients may have survived.

Endoscopic retrograde cholangiopancreatography, or ERCP, is an endoscopic procedure commonly used to diagnose and treat certain disorders and diseases of the biliary and pancreatic ductal systems in the upper gastrointestinal tract.

LA Times ArticleFederal health officials have termed these multidrug-resistant bacteria ‘superbugs’ because of their resistance to most antibiotics, often including carbapenems — a “last resort” drug.  Some of the infections these germs cause are untreatable.

The multidrug-resistant E. coli bacteria responsible for University Hospital’s
outbreak reportedly is a ‘superbug’ called “ESBL-producing” E. coli.

Escherichia coli, or “E. coli,” is a member of the Enterobacteriaceae family and, if the strain is resistant to carbapenems, the bacteria are CRE, or “carbapenem-resistant Enterobacteriaceae.”

CRE have been linked to the majority of deadly patient infections following ERCP performed since 2012 using a duodenoscope. The mortality rate of patients infected with CRE can be as high as 50%.


More details about the Colorado outbreak

In a related article I wrote weeks ago, I discuss the profile of the hospital, whose name was unknown to me at the time, where this outbreak occurred.

In that earlier article, I suggested that that hospital where this outbreak occurred may not have told the infected patients or their families about this E. coli outbreak and its association with the Olympus TJF-Q180V model, which Olympus recalled in January.

Aurora

It remains unclear whether University Hospital’s infected patients were told about this device’s recall.

The Centers for Disease Control and Prevention (CDC) advises that “patients undergoing procedures using duodenoscopes should be informed during the consenting process that there is a risk of patient-to-patient bacterial transmission associated with the procedure, including uncommon transmission of a multidrug-resistant organism.”

Both The Los Angeles Times and the New York Post wrote articles discussing the significance of this E. coli outbreak (although the hospital’s name was not known at the time either article was written).

Both this Times and Post articles were based on my original research.

Hospitals investigating measures to prevent deadly superbug outbreaks linked to ERCP can read my peer-reviewed article — “Risk of transmission of carbapenem-resistant Enterobacteriaceae (CRE) and related ‘superbugs’ during gastrointestinal endoscopy” (World Journal of Gastrointestinal Endoscopy) — which provides a number of recommendations.



Outbreak Highlights

  • Nine patients, three of whom died, were infected more than three months ago with a deadly E. coli strain following ERCP.
  • The hospital where this outbreak occurred has not been previously disclosed. My research determined it to be the University of Colorado Hospital (Aurora, CO).
  • The hospital performed ERCP on the infected patients using a recalled duodenoscope — the Olympus TJF-Q180V model.
  • Neither the hospital, the CDC, the FDA, nor the Colorado Department of Health has issued a public statement acknowledging this deadly outbreak.
  • Medical device reports (MDRs) filed by hospitals do not include the hospital’s name, making it usually difficult for the public to learn where a deadly outbreak occurred and to take precautions.
  • Despite being recalled, this duodenoscope model remains in use throughout the U.S.
  • The hospital’s recalled duodenoscopes were cleaned and disinfected using an automated endoscope reprocessor (AER) that was never validated for reprocessing this model of endoscope.
  • Other outbreaks associated with this same recalled duodenoscope have been reported this year.
  • Several questions remain.


Implicated duodenoscope used 791 times on patients

University Hospital linked its deadly E. coli outbreak to a specific “suspect” duodenoscope, which Olympus stated in its regulatory report was found to be contaminated with bacteria.

This regulatory report also acknowledges that this one instrument was used 791 times on patients.

It is not yet clear whether University Hospital notified all of the other “at risk” patients who underwent ERCP using this same contaminated duodenoscope, and could have been exposed to the bacteria.

According to the Denver Post, medical procedures were performed using the implicated duodenoscope on only 19 patients, including the nine infected patients, during the outbreak’s seven week period.

Nor is it yet clear whether the hospital told the original eight (revised to nine) infected patients about this deadly outbreak, or that the duodenoscope used to perform their procedures has been recalled (and is without a legal clearance or regulatory approval).

For its part, however, the hospital told the Denver Post and Aurora Sentinel that it notified the infected patients, families and other patients who had undergone procedures using this “suspect” duodenoscope, as well as informing the manufacturer and the Colorado Department of Public Health and Environment about this outbreak.

In 2013, Advocate Lutheran General Hospital (Park Ridge, IL) linked a similar deadly superbug outbreak to ERCP and, violating no federal HIPAA laws, made a “public plea” then asking that any patient who underwent ERCP at the time of the outbreak — and therefore might have been exposed to the highly drug-resistant bacteria — return for screening. More than three dozen of this hospital’s patients were found to be “positive” for the outbreak’s bacteria.

Last year in February, UCLA’s Ronald Reagan Hospital similarly informed nearly 180 patients who underwent ERCP of their potential exposure to a duodenoscope contaminated with a deadly superbug.  UCLA had linked eight patients infected with CRE to contaminated duodenoscopes in early 2015. At least two of these infected patients died.

And Virginia Mason Medical Center (Seattle, WA), which encountered a deadly bacterial outbreak in 2012, notified dozens of potentially “at risk” patients. As many as 18 infected patients died.

A misbranded device

Prior to the recall of the Olympus TJF-Q180V duodenoscope last January, the FDA warned Olympus almost nine months ago about the safety of this model, concluding that this duodenoscope is “misbranded” (for violating a section of the Federal Food, Drug, and Cosmetic Act).

This specific model of endoscope has been linked to most of the more than 25 multidrug-resistant bacterial outbreaks in the U.S. and Europe between 2012 and 2015. As discussed in a January investigative report by Senator Patty Murray (D-WA), these outbreaks sickened at least 250 patients.

The Olympus TJF-Q180V duodenoscope is without a legal clearance or approval. However, Olympus received clearance from the FDA earlier this year to market a different, newly designed TJF-Q180V model. This modified duodenoscope has not yet been released in the U.S. en masse.

This article about this deadly E. coli outbreak is to be read along with its prequel: “Profile of a Hospital’s Deadly ‘Superbug’ Outbreak: Is Silence the New Norm?” which I wrote several weeks ago providing a profile of the hospital where these E. coli infections occurred. At the time I wrote that article, the hospital’s name was a mystery.

Two other cases reported in 2016

This E. coli outbreak that infected eight (revised to nine) patients at University Hospital earlier this year is not the only bacterial outbreak linked this year to Olympus’ recalled TJF-Q180V duodenoscope.

Earlier this year, Olympus filed other reports with the FDA documenting two additional instances of patients being infected with potentially deadly bacteria following ERCP, which was also performed using the Olympus TJF-Q180V duodenoscope.

One of these reports documents a CRE infection linked to ERCP performed using the Olympus TJF-Q180V model. According to this report, the medical facility used an AER model to clean and disinfect the duodenoscope that, like the Olympus TJF-Q180V model, was previously recalled by the FDA.

These reports filed by Olympus indicate that hospitals continue to use the recalled TJF-Q180V duodenoscope.  The incidence of such recalled medical devices being used to perform medical procedures in the U.S. is unclear.

Pentax and FujiFilm, the other two manufacturers of duodenoscopes, have also filed reports with the FDA earlier this year documenting the possible transmission of bacteria by a contaminated duodenoscope.

The FDA “warns” the three endoscope manufacturers

Almost two years ago, in March 2014, the FDA wrote Olympus a letter expressing concerns about the safety and regulatory status of its TJF-Q180V duodenoscope model, which the company had already begun marketing four years earlier, in 2010.

The FDA wrote in this March letter that this duodenoscope’s design may adversely impact patient safety by “preventing sterilization and high-level disinfection.” The FDA concluded in the letter that the Olympus TJF-Q180V duodenoscope lacks a legal clearance.

Almost a year later, in February 19, 2015, the FDA notified the public for the first time that the duodenoscope’s design can “impede” effective cleaning, resulting in the increased risk of the endoscope transmitting potentially deadly bacterial infections.

This warning may have been prompted by the disclosure the previous day of a deadly superbug outbreak at UCLA’s Ronald Reagan Medical Center that officials linked to Olympus’ duodenoscope.

The FDA did not warn the public that the Olympus TJF-Q180V lacked a legal clearance, however, until the next month, on March 4, 2015 — one year after writing Olympus to express its concerns about the safety of this model.

Noted earlier, the FDA wrote Olympus in August 2015 again warning the company about the safety and regulatory status of the TJF-Q180V model.

This same month, the FDA similarly warned the two other manufacturers of duodenoscopes sold in the U.S. — Pentax/Hoya (Montvale, NJ) and FujiFilm (Wayne, NJ) — about the quality of their devices.

Federal prosecutors are currently investigating Olympus, Pentax and FujiFilm to better understand the causes of these outbreaks.

Automated endoscope reprocessors (AERs)

Olympus’ regulatory report acknowledges that the hospital used an Olympus automated endoscope reprocessor, or “AER” — the Olympus OER-Pro model — to clean and disinfect the TJF-Q180V duodenoscope at the time of its E. coli outbreak.

In February the FDA listed a number of models of AERs that it claims have been “validated” for reprocessing duodenoscopes. Olympus’ OER-Pro model is not included in this list.

At the time of its outbreak, the University of Colorado Hospital used, too, a second AER manufactured by another company to reprocess the (recalled) TJF-Q180V duodenoscope. The brand and model of this other AER model were not disclosed in Olympus’ report.

According to a second regulatory report that Olympus filed with the FDA discussing this hospital’s same deadly E. coli outbreak, a “non-Olympus” AER was also used by this medical facility (in addition to the OER-Pro model) to reprocess the (recalled) TJF-Q180V duodenoscope. The brand and model of this other AER model are not yet known and were not named in Olympus’ report.

Despite these deadly outbreaks, the FDA two weeks ago reversed its order for a manufacturer to “immediately remove” its recalled AER model from U.S. hospitals. This AER model has been used to reprocess duodenoscopes and other types of flexible endoscopes.



Confidential Quality and Safety Healthcare Services, Legal Reviews for Hospitals, Manufacturers and the Public:  Click here to read about Dr. Muscarella’s quality and safety services committed to educating and helping hospitals (and manufacturers and patients) reduce the risk of healthcare-associated infections, including those linked to contaminated duodenoscopes.



Duodenoscope sampled and found contaminated

Olympus provided several additional details in the regulatory report it filed with the FDA on February 24, 2016, documenting this E. coli outbreak, including:

  • The “suspect duodenoscope” (implicated in University Hospital’s E. coli outbreak) was sampled and tested negative. (Note, however, that the microbiological sampling of endoscopes for contamination is inherently prone to “false-negative” results; therefore, caution is warranted when interpreting the results of such sampling.)
  • The implicated duodenoscope’s suction channel was determined by an independent testing laboratory to be contaminated (not with the outbreak’s E. coli, but) with another bacteria called Stenotrophomonas maltophilia. (This finding can be a sampling “quirk” and does not rule out the duodenoscope also being contaminated with the outbreak’s E. coli strain.)
  • Olympus performed a visual examination of the implicated duodenoscope and determined its “bending section adhesive” to be whitish in color and to have open gaps at each side of the bending section cover.
  • During this same visual examination, Olympus found that “the glue around the nozzle had signs of cracks and gaps. The insertion tube had multiple buckles throughout the entire length. The light guide lens was inspected under a microscope and brownish stains were noted internally.”
  • Olympus’ report adds that: “Brown stains and a scrape marks were found on the biopsy channel. The suction channel had similar brown stains at various locations. Both channels had interior signs of damage which appear to be due to scrapes.”

Medical device reports (MDRs)

Because two of the infected patients expired, the hospital would have been required to file a medical device report, as Olympus did, with the FDA. These reports are called MDRs.

However, I could not identify such a regulatory report in the FDA’s database filed by a hospital earlier this year that would correspond to University Hospital’s now revealed deadly E. coli outbreak. (Reports filed with the FDA discussing an outbreak or other type of adverse event are public, but the FDA redacts the hospital’s name form the report.)

F0r its part, the hospital told the Denver Post and Aurora Sentinel that it also notified the FDA about this outbreak. Neither the FDA nor the CDC has publicly discussed University Hospital’s E. coli outbreak.

Senator Murray’s investigative report published last found that hospitals do not typically notify the FDA or file these regulatory reports, which are required by federal regulations whenever a patient’s death is related to the use of a medical device use, including a duodenoscope.

According to Sen. Murray’s report, “Additionally, although at least 16 separate U.S. hospitals traced antibiotic-resistant infections directly to duodenoscopes, the hospitals generally did not raise alarms about these infections with federal regulators.”

Senator Murray’s report further wrote, “It appears that not a single hospital that experienced infection outbreaks tied to the duodenoscopes sent the required adverse event form to the device manufacturers.”

The FDA’s supplemental measures

Last year the FDA recommended that hospitals consider employing any of four supplemental measures — including using ethylene oxide (EtO) gas sterilization, as well as the culturing and quarantining of duodenoscopes, among two other measures — to prevent CRE outbreaks following ERCP.

Still to be learned is whether the hospital where these eight (revised to nine) E. coli infections occurred has adopted any of these measures to prevent additional infections.

Naryzhny and colleagues recently reported that sterilizing duodenoscopes using EtO gas, in addition to and after cleaning and high-level disinfecting them, terminated a deadly CRE outbreak in 2013 at Advocate Lutheran General Hospital (Park Ridge, IL).

Outstanding questions

In closing, a number of outstanding questions remain about University Hospital’s E. coli outbreak, including:

  • Whether the hospital informed the eight (revised to nine) infected patients or their families about this E. coli outbreak.
  • If yes, whether the hospital told these patients that their infections were linked to a recalled Olympus TJF-Q180V, and that the hospital reprocessed this recalled endoscope using Olympus’ OER-Pro (along with another unnamed AER model) — which the FDA has not validated for the safe and effective reprocessing of duodenoscopes. (Note: This recalled duodenoscope model could be considered an “investigational” device requiring the patient’s consent.)
  • Whether the hospital notified other “at risk” patients, possibly dozens or more, who might have been exposed to the deadly E. coli strain while undergoing ERCP using the same “suspect duodenoscope” that the hospital linked to the outbreak. This endoscope was used 791 times on patients.
  • Whether this outbreak’s strain of E. coli was resistant to carbapenem antibiotics and therefore is CRE, which is most likely but warrants confirmation.
  • Whether the death certificates of the hospital’s two infected patients who expired list this confirmed E. coli outbreak as a possible cause of, or contributor to, death.
  • The brand and model of the “non-Olympus” AER that was used by the hospital (in addition to the Olympus OER-Pro model) to reprocess Olympus’ recalled duodenoscopes at the time of this E. coli outbreak.
  • Whether the hospital filed a medical device report (MDR), as required by federal regulations.

One other question with implications to public health and the prevention of superbug infections following ERCP is the FDA’s stance regarding hospitals currently using an AER model that has not been validated for reprocessing duodenoscopes — such as the Olympus OER-Pro model.

Last month the FDA issued a bulletin that listed those AER models that it claims have been “validated” by their manufacturers for reprocessing duodenoscopes (one model of which, however — the Olympus TJF-Q180V duodenoscope — the FDA previously recalled).

But this bulletin does not advise hospitals whether the FDA has concluded that the “un-validated,” unlisted AER models can, or cannot, be used safely to reprocess duodenoscopes.


Article by: Lawrence F Muscarella, PhD. Originally posted March 24, 2016. Revised: May 6, 2016. Updated: May 11, 2016, Rev A. Copyright, 2016. LFM Healthcare Solutions, LLC is the owner and publisher of this article’s content. All rights reserved.

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E: Larry@LFM-HCS.com. Twitter: @MuskiePhD

One thought on “‘Superbug’ Infects 9 Patients, 3 Die From Previously Undisclosed Outbreak in Colorado”
  1. Thank YOU and Mr Terhune and Ms. Petersen for holding steady spotlights! Informed consent, yes, transparency, oversight, dna/resistance/sensitivity testing? YES! Nothing is so revealing as shining a light into the darkness.

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