Highlights:

  • An adverse event report filed in November — publicized now for the first time — links gastroscopes to three patients testing positive for a “rare strain” of resistant E. coli. 
  • Another FDA report filed in 2021, also publicized now for the first time, links a gastroscope to six patients with the same strain of resistant Pseudomonas aeruginosa. Three of the patients reportedly died.
  • In addition, a recent analysis by Muscarella (2022) found that the total number of adverse event reports submitted to FDA between 2014 and 2021 describing endoscope contamination was greater for gastroscopes than for any of the other studied endoscope types, which included bronchoscopes and duodenoscopes. 
  • Despite these data and other cases, federal safety alerts notifying healthcare providers about the risk of reprocessed gastroscopes remaining contaminated and infecting patients with multidrug-resistant organisms (MDRO) have not been published.
  • This review raises questions about whether the risk of gastroscope-related “superbug” infections is sufficiently recognized in the U.S., and whether additional updated measures may be necessary to enhance gastroscope safety.
  • The mortality rates of patients infected with a MDRO can be as high as 50%, or higher.

January 6, 2023 (updated: Jan. 20, 2023): Just weeks ago, FDA received a report — publicized now for the first time — linking gastroscopes to infections caused by a rare resistant organism.

According to the report, “three patients who underwent unspecified procedures using one of two different gastroscopes tested positive for a rare strain of antibiotic resistant E. coli.” FDA received this report from the gastroscope’s manufacturer on November 22.

The FDA report clarifies, however, that the medical facility is “unsure” if the gastroscopes cross-infected the patients with the bacteria. The facility is not identified by name, although the report states that the facility is located in the U.S.

The facility sampled the two gastroscopes and the cultures were negative, the manufacturer elaborates in the report, meaning that the cluster’s E. coli was not detected in the samples.

Resistant strains of E. coli can be carbapenem-resistant Enterobacteriaceae, also called CRE, whose association the past decade with deadly endoscope-related outbreaks is well documented.

Endoscope reprocessing is a multi-step process that includes cleaning, high-level disinfection or sterilization, and proper storage. When the process is ineffective, the flexible endoscope can remain contaminated and pose a cross-infection risk.

Three reports, in total, were submitted to the FDA in November, one report for each of the three patients.

None of these three FDA reports discusses the clinical outcomes of these three patients. The mortality rates of patients infected with CRE or a related multidrug-resistant organism can be as high as 50%, or higher.

Not the first time

This November FDA report is not the first to describe a U.S. facility linking a reprocessed gastroscope to infections of resistant bacteria.

In another recent case, an FDA report describes a U.S. facility that, with the help from the state’s health department, had identified six gastroenterology patients “with the same strain of carbapenemase-producing Pseudomonas aeruginosa (CPPA) during a six-month period.” FDA received this report from the gastroscope’s manufacturer in July 2021.

According to this 2021 report, all six patients underwent procedures using the same gastrointestinal videoscope. This implicated gastroscope was cultured, and all cultures were negative for the P. aeruginosa, the report stated.

This resistant Pseudomonas bacteria is not CRE per se, but a related MDRO. (Carbapenemase-producing Pseudomonas bacteria are not in the Enterobacteriaceae family and therefore cannot technically be CRE.)

This 2021 FDA report describing these six cases of carbapenemase-producing P. aeruginosa added that no breaches in the facility’s “standard high-level disinfection processes” had been identified, and that the “definitive cause of the user’s experience” (e.g., the cause of the infections) “cannot be determined at this time.”

Six reports, in total, were submitted to the FDA in July 2021, one report for each of the six patients.

At least five of these patients underwent esophagogastroduodenoscopy (EGD) using the gastroscope, which did not malfunction during the procedures, according to the six FDA reports.

EGD is an upper GI procedure that routinely uses a gastroscope to diagnose and treat diseases and disorders of the upper GI tract’s esophagus, stomach and duodenum. Some gastroscope models may feature a ultrasound transducer for imaging deeper tissues.

According to three of the FDA reports (unpublished spreadsheet data available upon request), three of the P. aeruginosa cluster’s patients are reportedly “deceased,” although the reports stated that the respective patient’s cause of death “is not known to be associated with the device at this time.” The reports do not identify the U.S. facility by name.

Like the November 22 report involving resistant E. coli cases, this is the first time that this 2021 case linking a reprocessed gastroscope to infections of carbapenemase-producing P. aeruginosa is being publicized.

A third case

A third case published five years earlier, in 2016, described a cluster of carbapenem-resistant Klebsiella pneumoniae cases among surgical intensive care unit patients at a medical center in western Pennsylvania. A preliminary review found that all six cases of the CRE had been exposed to the same gastroscope.

No deficiencies in the gastroscope’s reprocessing were identified, according to the 2016 abstract that first disclosed this Pennsylvania facility’s cluster. CRE are MDROs — or “superbugs” — that are not susceptible to carbapenem antibiotics, which can cause the treatment of CRE infections often to be challenging and to require “last resort” antibiotics.

Like E. coli and P. aeruginosa, K. pneumoniae may be found in the human GI tract and can contaminate an endoscope during routine use, posing a risk of cross-infection if the endoscope is not reprocessed properly after each use.

This 2016 abstract emphasized that not only duodenoscopes — which have been under scrutiny from the FDA since 2015 due to their documented associations with superbug outbreaks — but also less physically complex endoscopes, like gastroscopes, “may fail high level disinfection and cause infections.”

Duodenoscopes are a type of upper GI endoscope used to perform endoscopic retrograde cholangiopancreatography, or ERCP — a medical procedure used to examine and treat disorders of the bile and pancreatic ducts.

Further, cultures of the implicated gastroscope were negative for the CRE, this 2016 abstract noted. Nevertheless, the abstract clarifies that failure to recover an infection’s organism from an implicated endoscope “should not preclude” the device “from suspicion.” Others have similarly, and critically, published that “an endoscope with a culture-negative result is not necessarily free of bacteria.”

A search of the FDA’s “MAUDE” database found a 2016 report that appears to describe this CRE cluster in western Pennsylvania. The clinical outcome of the six CRE cases was not discussed in this FDA report or the 2016 abstract.

This 2016 FDA report stated that “improper maintenance of the device cannot be ruled out as a contributory factor to the reported events.”* According to the 2016 abstract, visual examination of the gastroscope’s internal channel using a borescope “revealed several deep scratches and luminal debris.

Patients testing positive for an organism are infected or colonized with the strain. Colonization indicates only the presence of the organism, whereas infection additionally requires the patient display symptoms of sickness.

Disposable flexible endoscopes, which offer an alternative to reusable flexible endoscopes, are not reprocessed but are discarded after a single use.

The FDA’s MAUDE database houses medical device reports submitted to FDA primarily by manufacturers and healthcare facilities but also by healthcare professionals and even patients and consumers.* These FDA reports are submitted voluntarily (e.g., by patients) or as mandated by law (e.g., by manufacturers).


Still more gastroscope-related infection cases (updated: January 20, 2023)

A review of the FDA’s adverse events database two weeks after this article’s original publication (on January 6, 2023) identified three more recent FDA reports linking a gastroscope to patient infections.*

One of these reports, publicized now for the first time, associates the use of a flexible endoscope — specifically, a gastroscope — to a patient with Candida auris.** This report may be the first case, ever, in the FDA’s medical device database (as well as the medical literature) to link a flexible endoscope to a case involving this drug-resistant fungus.

According to this report, “six days after an upper GI endoscopy with peg-tube placement (for nutritional support)” using a gastrointestinal videoscope, “Candida auris was identified in the patient’s blood culture.”

FDA received this report on December 9, 2022. The report does not identify the U.S. facility where this incident occurred.

Candida auris is an emerging multidrug-resistant fungus that presents a global health threat. The mortality rate of patients infected with C. auris can exceed 30%.

These cases, along with other findings and data I have reviewed, raise important questions for me about whether the risk of a reprocessed gastroscope exposing patients to multidrug-resistant organisms has received the attention it warrants. — Lawrence F. Muscarella Ph.D.

Risk factors for C. auris infection include longer stays in healthcare facilities and use of tracheostomies and percutaneous endoscopic gastrostomy tubes. Patient exposure to an endoscope has not been identified as a risk factor for C. auris infection.

In addition to this C. auris case, two other FDA reports, also filed in December 2022, describe an association between gastroscopes and two unrelated outbreaks (seemingly occurring overseas in Germany and Japan).

The first case links a gastroscope to an outbreak of four multidrug-resistant Klebsiella pneumoniae infections. According to the report, the bacteria was detected in the gastroscope’s water channel.

Similar to other cases, the report states that the “exact cause of the reported event cannot be conclusively determined” and that the investigation is still ongoing.

The second case links an outbreak of extended spectrum β-lactamase-resistant bacteria to patients exposed to a gastrointestinal videoscope (i.e., a gastroscope). It is not known at this time if this outbreak (which apparently occurred in Japan) is related to the gastroscope, the report states.

Extended spectrum β-lactamases, or ESBLs, are enzymes, produced by certain types of bacteria, that can break down, or hydrolyze the physical structure of, many common antibiotics, rendering them ineffective.

These cases, among others, linking gastroscope exposure to multidrug-resistant infections raise reasonable questions about whether the risk of a reprocessed gastroscope remaining contaminated and exposing patients to a MDRO is sufficiently recognized today, and whether additional updated measures may be necessary to improve awareness and enhance gastroscope safety.


Gastroscope contamination cases

In addition to these cases, and others, linking reprocessed gastroscopes to infections (or colonizations), many more FDA adverse event reports describe facilities detecting bacterial contamination of a gastroscope during routine surveillance culturing.

Such reports of endoscope contamination in FDA’s MAUDE database during periodic microbiological testing, without detected infection, nonetheless can indicate a safety risk, warranting prompt attention and often necessary corrective action to prevent cross-infections.

A FDA report filed in 2021, for instance, describes a gastroscope used in a U.S. facility that twice cultured positive for CRE after reprocessing. No patients were infected, according to the report.

I manually reviewed more than 10,000 adverse event reports, even as many as 15,000, involving potential contamination, and I found that the total number of reports, submitted to FDA between 2014 and 2021, satisfying my study’s requirements was greatest, not for duodenoscopes, but for gastroscopes. — Lawrence F Muscarella, PhD

Another FDA report submitted two years earlier, in 2019, describes a gastroscope testing positive for multidrug-resistant bacteria. No serious injury was reported, although visual inspection of the gastroscope’s instrument channel at a servicing center identified “major tear marks near the distal end side.

Medical facilities may periodically (e.g., quarterly) sample a reprocessed endoscope microbiologically prior to patient use, as dictated by their relevant quality control policies and procedures. In addition to verifying the effectiveness of the facility’s reprocessing protocol, the results of these surveillance sampling and culturing tests can reveal a cleaning or disinfection breach or contamination due to a damaged endoscope, which can pose an increased infection risk.

Alternatively, facilities may sample the reprocessed endoscope in response to the FDA’s safety alert, released in 2015, recommending healthcare facilities consider adopting one or more “supplemental measures” to increase the safety of duodenoscopes.

In addition to sterilization of the endoscope after thorough cleaning, these additional steps include microbiological culturing “to identify duodenoscopes with persistent contamination despite reprocessing,” the FDA’s 2015 alert stated.

The safe use of gastroscopes is crucial to public health and to preventing patient infections. As many as 6 million procedures are performed annually in the U.S. using a gastroscope.

Related publications by this article’s author addressing the risk of gastroscopes exposing patients to MDROs include:



Adverse Event Device Reviews; Expert Guidance in the Causes, Prevention of Hospital Infections; and Case Reviews: LFM-Healthcare SolutionsLLC provides medical expertise for healthcare facilities, device manufacturers and the public, specializing in healthcare-associated infections linked to contaminated reusable medical equipment. Value-oriented advice with years of experience and trust.



A “most pronounced” increase

A recent analysis by Muscarella (2022) focused on medical device reports submitted to FDA since 2014 describing the actual or potential contamination of several types of flexible endoscopes after reprocessing.

Among other results, this analysis found that the number of FDA reports in 2021 satisfying the study’s inclusion criteria, compared to seven years earlier in 2014, increased significantly for each of the six studied endoscope types — with gastroscopes displaying the most pronounced increase.

This analysis’s manual review of more than 10,000 adverse event reports also found that the total number of relevant adverse event reports submitted to FDA between 2014 and 2021 was greatest for gastroscopes.

The other types of flexible endoscopes included in Muscarella’s (2022) analysis were bronchoscopes, colonoscopes, duodenoscopes, ear-nose-throat (ENT) endoscopes, and urological endoscopes. Each endoscope included in this analysis was reusable.

Despite Muscarella’s (2022) findings along with other published data and cases involving contamination of reprocessed gastroscopes — with some of the reports linking a reprocessed gastroscope to infections (or colonizations) of CRE or a related MDRO, and in at least one recent case to associated patient death** — federal alerts specifically addressing this risk have not been recently issued.

These findings, in addition to other published data, again raise reasonable questions about whether the risk of a reprocessed gastroscope remaining contaminated and exposing patients to a MDRO is sufficiently recognized today, and whether additional updated measures may be necessary to improve awareness and enhance gastroscope safety.

Related peer-reviewed publications by this article’s author addressing the risk of bronchoscopes and duodenoscopes infecting patients with MDROs include:

Endoscope contamination risk factors

The November FDA report linking the use of two gastroscopes to infections of a rare strain of antibiotic-resistant E. coli is brief and provides few details about what infection-control lapses might have contributed to the infections.

In general, however, several factors can increase the risk of a reprocessed endoscope exposing patients to bacteria including CRE and related MDROs. These factors include:

  • faulty manual cleaning (and brushing) of the endoscope
  • inadequate high-level disinfection of the endoscope
  • the endoscope design’s physical complexity, which can hinder access and cleaning
  • incomplete or invalid endoscope reprocessing instructions
  • endoscope damage, which can facilitate persistent contamination and biofilm growth
  • a defective endoscope component (e.g., a loosened component, a gap in an adhesive)
  • improper endoscope maintenance or servicing (e.g., repairing the endoscope using unqualified or non-certified parts)
  • inadvertent use of contaminated water to rinse the endoscope following disinfection or chemical immersion
  • mishandling the endoscope during reprocessing
  • not properly storing the reprocessed endoscope consistent with the manufacturer’s instructions

The extent to which any of these factors might have contributed to this these three infections of the rare resistant E. coli strain remains unclear.** According to the November (2022) report, the “definitive cause” of this incident “cannot be determined at this time. The investigation is ongoing.”

To enhance endoscope safety, FDA recommends sterilization (after thorough cleaning) of the endoscope when practical and feasible, because sterilization has a greater safety margin (compared to high-level disinfection), according to FDA.



Infection Prevention Expertise; Scientific Affairs; and Webinar and White Paper Authorship: LFM-Healthcare SolutionsLLC provides medical expertise for healthcare facilitiesmanufacturers and the public, specializing in healthcare-associated infections linked to contaminated reusable medical equipment.



Recommendations

Several recommendations are provided to improve the safety of gastroscopes. These include reviewing the device manufacturer’s reprocessing instructions; confirming that the endoscopy unit’s policies and procedures are consistent with these instructions; and monitoring reprocessing practices to ensure compliance with these policies and procedures.

Additional reprocessing steps may be required if the gastroscope features an ultrasound transducer and elevator mechanism (similar in design to the duodenoscope’s forceps lever). Refer to the gastroscope model’s reprocessing manual for detailed instructions.

Enhanced measures, similar to the “supplemental measures” FDA published in 2015 for healthcare facilities to consider to improve the safety of duodenoscopes, may be considered for gastroscopes when feasible and deemed warranted (e.g., in response to the individual facility’s assessment of the risk of MDRO infections).

I recommend that federal agencies consider issuing a notice or letter featuring updated guidance to raise awareness, enhance safety, and further reduce the risk of a reprocessed gastroscope remaining contaminated and exposing patients to MDROs, such as CRE and possibly even C. auris. — Lawrence F Muscarella, PhD

In addition, publication of federal safety notices featuring updated guidance to raise awareness among healthcare providers and further reduce the risk of gastroscope-related infections – similar in advice, emphasis, rationale and actions as FDA’s previously issued notifications publicizing the risk of infections associated with reprocessed bronchoscopes, duodenoscopes and urological endoscopes — is recommended for consideration.

Other recommendations FDA has previously published for some of these other types of flexible endoscopes (based in part on feasibility and the individual facility’s assessment of the infection risk), but which can be reasonably applied also to gastroscopes to further improve safety include:

Additional updated guidance to improve endoscope safety is provided in a related article entitled, “Contamination of Flexible Endoscopes and Associated Infections: A Comprehensive Review and Analysis of FDA Adverse Event Reports.

Summary, Conclusions

The safe use of gastroscopes is crucial to public health. As many as 6 million endoscopic procedures using a gastroscope are performed annually in the U.S.

A FDA report filed in November — publicized now for the first time — links a gastroscope to 3 patients testing positive for a rare strain of antibiotic-resistant E. coli bacteria.*

Other reports have similarly linked gastroscopes to infections (or colonizations) of CRE or a related MDRO. At least one report links use of a gastroscope to patient death.** The mortality rates of patients infected with a MDRO can be as high as 50%, or higher.

In addition, Muscarella (2022) found that the total number of relevant adverse event reports submitted to FDA, between 2014 and 2021, involving endoscope contamination was greatest for gastroscopes.

Despite these data and other cases, federal safety notices advising healthcare providers about the risk of reprocessed gastroscopes remaining contaminated and exposing patients to MDROs including CRE have not been recently issued.

Summarizing the conclusion, the findings presented herein raise reasonable questions about whether the risk of a reprocessed gastroscope remaining contaminated and exposing patients to a MDRO is sufficiently recognized today, and whether additional updated measures may be necessary to improve awareness and enhance gastroscope safety.

Several factors can increase the risk of a reprocessed gastroscope remaining contaminated with MDROs, including use of a damaged device. FDA recommends sterilization (after thorough cleaning) of flexible endoscopes when practical and feasible, because sterilization has a greater safety margin (compared to high-level disinfection).

Endoscopes less physically complex than duodenoscopes can fail high-level disinfection, some studies have reported. Moreover, data suggest that failure to recover an outbreak’s organism from a suspected endoscope does not confirm the device is not contaminated. Under certain circumstances, the sampling of a contaminated endoscope can yield culture-negative results.

Publication of federal safety notices featuring updated guidance to raise awareness among healthcare providers and reduce the risk of reprocessed gastroscopes remaining contaminated and exposing patients to MDROs – similar in advice, emphasis, rationale and actions as FDA’s previously issued notifications publicizing the risk of reprocessed bronchoscopes, duodenoscopes and urological endoscopes infecting patients — is recommended for consideration.



* Regarding the accuracy of reports housed in the MAUDE database, FDA states that: “Although (medical device reports) are a valuable source of information, this passive surveillance system has limitations, including the potential submission of incomplete, inaccurate, untimely, unverified, or biased data.

** “Linking” or “associating” an endoscope with an infection or outbreak (with or without associated patient death) does not confirm the endoscope contributed to caused the infection (or colonization), as one or more other factors could be, in part or solely, responsible. More data would be required to conclude more definitively that a contaminated reusable device caused an infection.



Funding: This article’s research and writing were funded, in part, by AMBU. This article was written by Dr. Muscarella, who (via LFM Healthcare Solutions, LLC) had complete and unfettered control over its preparation, design, content and recommendations. The company did not edit, revise or otherwise change this article’s content prior to publication.



Article by: Lawrence F Muscarella, PhD. Copyright (2023). LFM Healthcare Solutions, LLC. All rights reserved. Dr. Muscarella is the president and founder of LFM Healthcare Solutions, LLC, an independent quality improvement company. Click here for a list of his quality improvement healthcare services E: Larry@LFM-HCS.com. Twitter: @MuskiePhD    [LFM-ver-3.2]

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