January 28, 2022 (1:06 pm): This study aims to be the most comprehensive review to date of adverse events involving a flexible endoscope. It analyzes and counts the number of medical device reports submitted to FDA since 2014 describing the contamination of these devices with or without associated patient infections.

The safe and effective cleaning and disinfection of flexible endoscopes — also termed “reprocessing” — is crucial to public health as millions of flexible endoscopic procedures are performed in the U.S. each year.

This analysis was performed by Lawrence F Muscarella, PhD of LFM Healthcare Solutions, LLC, a healthcare quality company featuring several safety services that focus on the causes and prevention of disease transmissions and hospital infections.



STUDY HIGHLIGHTS

  • More than 10,000 adverse event reports, and as many as 15,000 reports or more, submitted to FDA since 2014 describing contamination of a flexible endoscope were reviewed. A single researcher performed this analysis.
  • The safe and effective cleaning and disinfection — also termed “reprocessing” — of flexible endoscopes is crucial to public health, as millions of procedures using an endoscope are performed annually in the U.S.
  • This analysis focused on six (6) types of flexible endoscopes from several different medical fields and sold by various manufacturers were included in this analysis:  bronchoscopes, colonoscopes, duodenoscopes, ear-nose-throat (“ENT”) endoscopes, gastroscopes and urological endoscopes.
  • This analysis’s objectives included evaluating whether current endoscope reprocessing practices are sufficient to prevent infections.
  • This analysis found that the number of adverse event reports submitted to FDA last year (2021) satisfying this study’s inclusion criteria, compared to seven years earlier in 2014, increased significantly for each of these six endoscope types — with gastroscopes displaying the most pronounced increase.
  • Similarly, the number of relevant adverse event reports submitted to FDA last year, compared to the previous year (2020), also increased for each of the six studied endoscope types — and most markedly for ENT endoscopes (during this timeframe).
  • The total number, or count, of relevant adverse event reports submitted to FDA during this study’s 8-year timeframe (from 2014 to 2021) was greatest for gastroscopes.
  • Reviewed cases link infections of multidrug-resistant bacteria — often called “superbugs” — to each of the six studied endoscope types. Cases were identified linking infections specifically of CRE (carbapenem-resistant Enterobacteriaceae) to each of the three studied GI endoscope types (as well as to bronchoscopes).
  • Antimicrobial resistance is a global public health threat. The mortality rates of patients infected with a superbug can be as high as 50%, or higher.
  • Reports submitted to FDA suggest that current endoscope reprocessing practices may not always be sufficient and sometimes may require additional, supplemental measures to prevent flexible endoscopes from infecting patients with multidrug-resistant microorganisms, including CRE.
  • Adverse event reports were identified describing each of the six studied endoscope types testing “positive” for microorganisms (e.g., during microbiological surveillance testing) after reprocessing, indicating that this specific risk — contamination of a “patient-ready” endoscope — is seemingly broad and not exclusive to only one or two endoscope types.
  • FDA recently advised healthcare providers about the risk of reprocessed bronchoscopes, duodenoscopes and urological endoscopes remaining contaminated with infectious organisms. This review did not identify similar types of alerts advising about the potential for reprocessed gastroscopes, colonoscopes and ENT endoscopes to remain contaminated.
  • This analysis’s findings are in general agreement with the FDA’s recent safety communication recommending that healthcare providers consider sterilization of bronchoscopes when feasible, and to consider using single-use (disposable) bronchoscopes in certain clinical situations as warranted.
  • Several adverse event reports discuss the deterioration of an adhesive, sealant or glue used at the distal end of some flexible endoscope types. Reports discuss this device irregularity causing a gap or crack to form in the adhesive, resulting in the potential for microbial contamination and an increased infection risk due to ineffective reprocessing. The cause of this deterioration is unclear, although this article discusses several possible contributing factors.
  • Although the presence of a gap (or similar type of deterioration, crack or discontinuity) in the adhesive at the distal end of a duodenoscope featuring a fixed-endcap design can pose an increased risk of contamination, an FDA analysis published in 2019 focusing on the infection risk of duodenoscopes apparently did not include and count such reports describing this type of irregularity unless the report specifically described contamination of the duodenoscope, patient exposure to a contaminated duodenoscope and/or patient infection.
  • Based on this study’s findings, it can be reasonably debated whether the risk of a reprocessed gastroscope remaining contaminated and transmitting infectious organisms is a sufficiently recognized concern, or may warrant updated attention and published guidance to improve safety.
  • Based on this analysis’s review, healthcare provides may consider sterilization of gastroscopes (when feasible), or the use of a single-use gastroscope (when available and as warranted) to improve patient safety. Performing a risk assessment to help guide this consideration is recommended.
  • FDA recommends that semi-critical devices — such as gastroscopes and each of the other five studied endoscope types — undergo sterilization (after cleaning) but high-level disinfection if the device’s design does not permit sterilization.
  • Since 2014, each of the six studied endoscope types has been associated with a recall due to a potential device contamination issue or concern.
  • While the risk of a reprocessed colonoscope infecting patients with a multidrug-resistant organism is reported to be significantly lower than a duodenoscope, this study’s findings suggest updated guidance and recommendations addressing the contamination of colonoscopes be considered to improve patient safety.
  • This analysis’s findings are in general agreement with the FDA’s recent safety communications recommending that healthcare providers — in addition to considering reprocessing duodenoscopes with supplemental measures such as sterilization — begin transitioning from duodenoscopes with a fixed endcap design to newer, more modern duodenoscope featuring innovative designs that include disposable components, such as a removable, single-use endcap intended to facilitate more effective cleaning.
  • Although FDA and others in recent years have diligently published recommendations to reduce the contamination and infection risk of reprocessed duodenoscopes (and other endoscope types), recent cases were identified (in 2021) linking use of a duodenoscope featuring a fixed-endcap design to infections of multidrug-resistant organisms including CRE, requiring continued vigilance and care to reduce the infection risk.
  • This analysis’s findings are in general agreement with the FDA’s recent letter recommending that healthcare providers carefully follow the manufacturer’s instructions for reprocessing urological endoscopes and their components, as well as for inspecting these devices routinely and servicing them per the manufacturer’s periodic maintenance schedule.
  • This analysis’s findings suggest healthcare providers also consider sterilization of urological endoscopes (when possible and practical), or the use of a single-use urological endoscope (if and/or when available and as warranted). Performing a risk assessment to help guide this decision — for example, the sterilization of ureteroscopes — is recommended.
  • Factors that this analysis found can increase the risk of a reprocessed flexible endoscope remaining contaminated include: the complex design of the endoscope; improper cleaning and/or inadequate storage and mishandling of the endoscope; endoscope damage; a faulty device component; and faulty repairs and/or improper device servicing and maintenance.
  • Several additional recommendations are provided to improve patient safety during an endoscopic procedure including the further development of low-temperature sterilization technologies and new endoscope designs that feature enhanced materials’ durability to ensure safe and effective reprocessing of flexible endoscopes – for example, endoscopes with removable disposable components, or that are fully disposable.
  • This study, as with others of this type, has limitations requiring that its results be interpreted critically and circumspectly.

The following is a detailed synopsis of Dr. Muscarella’s analysis of relevant FDA adverse events. The entire, more complete (unpublished) draft of this analysis is pending submission to a medical journal for peer review, acceptance and publication.


SYNOPSIS (ABSTRACT)

INTRODUCTION

Antimicrobial resistance to a global public health threat. The mortality rates of patients infected with a multidrug-resistant organism can be as high as 50%, or higher. Focusing on this international scourge, a recently published study attributes an estimated 1.27 million deaths globally in 2019 to drug-resistant bacteria.

Several investigations performed during that past decade, both in the U.S. and overseas, linked ineffectively “reprocessed” flexible endoscopes, most notably duodenoscopes, to outbreaks of multidrug-resistant bacteria with associated morbidity and mortality. These “superbugs” include carbapenem-resistant Enterobacteriaceae (“CRE”) and other carbapenemase-producing bacteria.

The safe use of flexible endoscopes is crucial to public health, as millions of procedures are performed annually in the U.S. using a reusable flexible endoscope.

The development of new device designs and advanced technologies that enhance the cleaning and disinfection or sterilization of flexible endoscopes, or that eliminate reprocessing altogether as offered by disposable device designs, are encouraged to prevent patient infections.

OBJECTIVES

This study aimed to be the most comprehensive review and analysis to date of adverse event reports submitted to FDA involving a flexible endoscope.

A primary objective was to review the FDA’s adverse events database, also known as the Manufacturer and User Facility Device Experience (or “MAUDE”) database, and count the number of reports submitted annually since 2014 describing the actual or potential contamination of a reprocessed flexible endoscope.

Another objective was to analyze the MAUDE database to identify general trends and determine whether submitted adverse events reports describing endoscope contamination have been decreasing from one year to the next, remaining relatively stable and constant through the years, or increasing.

This study also aimed to provide insight into (among other factors) the adequacy of current reprocessing measures designed to prevent a flexible endoscope from transmitting diseases, and to identify evidence-based practices that improve patient safety.

This analysis’s other objectives include evaluating the relative contamination risk of different endoscope types; determining whether different types of endoscopes may be prone to similar (or different) adverse events; and assessing whether any of the studied endoscope types might pose an under-recognized contamination risk.

METHODS

Data source: The FDA’s MAUDE database was the source of all of the adverse event reports that this study reviewed and analyzed.

Study design: More than 10,000 adverse event reports, and as many as 15,000 reports or more, submitted to the MAUDE database between January 1, 2014, and December 31, 2021, were retrospectively reviewed and manually vetted for relevancy by a single researcher.

The year of 2014 was selected as the start date for reviewing data because in that year U.S. health officials, for the first time, linked a duodenoscope at a single facility to multiple infections of CRE and associated patient deaths despite healthcare staffers reportedly having cleaned and disinfected the endoscope in compliance with manufacturer instructions.

This outbreak marked a watershed moment as virtually every previous case of infection linked to a contaminated flexible endoscope had been attributed to one or more specific endoscope reprocessing breaches (or a device design flaw).

Published peer-reviewed articles and other FDA databases were also reviewed to provide additional understanding and insight.

Inclusion criteria: Only those medical device reports filed in the MAUDE database (since 2014) describing actual or potential contamination of a flexible endoscope were included in this analysis.

Examples of relevant adverse events satisfying this requirement include reports describing:

  • contamination of the reprocessed endoscope with microorganisms, patient fluids and/or biofilms
  • a documented association between infection and patient exposure to a flexible endoscope
  • failure to clean or otherwise reprocess the endoscope correctly according to manufacturer instructions
  • use of a damaged, cracked or otherwise broken endoscope that could pose an infection risk

These examples of relevant adverse events are not inclusive of all of the device problems that this analysis deemed relevant, counted and used to achieve its objectives.

Endoscope types: This analysis reviewed adverse event reports involving the following six (6) types of flexible endoscopes used in gastrointestinal endoscopy, otolaryngology, pulmonology and urology:

  • colonoscopes, duodenoscopes and gastroscopes (which are each a type of GI endoscope)
  • bronchoscopes
  • ear-nose-throat (“ENT”) endoscopes, including tracheal intubation endoscopes
  • urological endoscopes, including cystoscopes

Models of bronchoscopes and gastroscopes that feature an ultrasonic transducer at the endoscope’s distal end for imaging internal structures, organs and tissues were included in this analysis.

FDA classifies flexible endoscopes as semi-critical devices because they routinely contact mucous membranes and do not ordinarily contact normally sterile tissues or only intact skin.



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RESULTS

This analysis identified several notable contamination trends.

An endoscope cleaning workstation

For example, this analysis found that the number of relevant adverse event reports submitted to the FDA’s MAUDE database in 2021, compared to the previous year (2020), increased for each of the six studied endoscope types, particularly for colonoscopes, ENT endoscopes and gastroscopes.

Urological endoscopes displayed the smallest increase during this timeframe, while ENT endoscopes displayed the most marked increase.

This analysis also found that the number of relevant adverse event reports submitted to FDA in 2021, compared to seven (7) years earlier in 2014, also increased, and significantly, for each endoscope type. This increase was most pronounced for gastroscopes.

Bronchoscopes: Although bronchoscopes were associated with the least marked relative increase in the number of relevant reports in 2021 compared to 2014, this number nonetheless increased by almost 400%, from 52 to 259 relevant reports, which is notable.

FDA in September 2015 issued the first of two safety alerts publicizing the risk of reprocessed bronchoscopes transmitting infections. The FDA issued a second alert six years later, in 2021, the focus and emphasis of which are consistent with this analysis’s findings.

This analysis of adverse events found, however, that almost half a decade after this first alert was issued (in 2015), the number of relevant reports involving a reprocessed bronchoscope submitted to FDA last year, compared to the number submitted during the previous 12 months (2020), increased from 193 to 259 relevant reports, or by approximately 34%.

This review identified several cases linking bronchoscopes to infections of CRE and related superbugs with associated patient morbidity and mortality.

Since 2014, the recalls of several bronchoscope models were created or initiated to reduce the potential for insufficient reprocessing, persistent contamination and disease transmissions.

Bronchoscopes are used to used to view, diagnose and treat diseases and disorders of the respiratory tract and lungs.

Duodenoscopes: The risk of duodenoscopes transmitting CRE and related superbugs has received more FDA scrutiny, including U.S. Senate oversight, than any other type of flexible endoscope.

This robust surveillance began in February 2015 when FDA issued the first of several safety communications advising the public that due to their complex physical designs, duodenoscopes may impede effective reprocessing posing a risk of transmitting diseases including CRE. According to this FDA alert, meticulously cleaning duodenoscopes may not entirely eliminate the risk of transmitting infections.

Nevertheless, apart from bronchoscopes (398%), this review found that, when comparing 2021 (n=651 reports) to 2014 (n=72 reports), the number of FDA reports satisfying this analysis’s inclusion criteria increased less markedly for duodenoscopes (804%), though still significantly by any reasonable measure, than for any of the other four studied endoscope types (when similarly comparing data from 2021 to 2014).

This review identified multiple cases linking reprocessed duodenoscopes to outbreaks of CRE and related multidrug-resistant organisms with associated patient morbidity and mortality. Several of these cases were discussed in a U.S. Senate report published in 2016.

These identified cases include two recent, unrelated U.S. reports submitted to FDA last year in September and in November (2021) linking clusters of patients testing “positive” for (e.g., colonized or infected with) CRE to the use of a duodenoscope featuring a fixed endcap design. (This type of endoscope design has been the standard used in the U.S. and is distinguished from some newer duodenoscope models featuring a disposable, removable endcap.)

These two reports, among others, appear to confirm that duodenoscopes with a fixed endcap, the safety of which FDA questioned publicly in a 2015 safety communication, remain in use today in U.S. facilities (and overseas), warranting additional vigilance and care to prevent superbug infections.

Moreover, this analysis found that the number of relevant adverse event reports involving duodenoscopes submitted to FDA last year, compared to the previous year (2020), increased from 431 to 651 reports, or by approximately 50%.

Duodenoscope models have been recalled since 2014 to provide updated specifications designed to reduce the risk of contamination and disease transmission.

Duodenoscopes are used during a procedure called “ERCP” (endoscopic retrograde cholangiopancreatography) to view, diagnose and treat diseases and disorders in the bile and pancreatic ducts.

[Note: Discussed in the more complete version of this article, which is currently pending submission to a medical journal for peer review and acceptance, a second supplemental analysis was performed for duodenoscopes that includes additional MAUDE reports describing a gap, crack, bubble, defect, discontinuity and/or other type of apparent failure in the seal or adhesive at the distal end of duodenoscopes featuring a fixed-endcap design but without the report associating this irregularity specifically with device contamination or patient infection.

This second set of data is presented separately, and is not included in this first analysis herein, primarily because an FDA analysis published in 2019 focusing on the risk of reprocessed duodenoscopes transmitting diseases apparently did not include and count these types of reports describing this type of device irregularity unless the report specifically described contamination of the duodenoscope; patient exposure to a contaminated duodenoscope; and/or patient infection.]

Urological endoscopes: The number of relevant adverse event reports submitted to FDA last year in 2021 involving a urological endoscope, compared to those submitted seven years earlier in 2014, increased noticeably from 11 to 244 relevant report, or by almost 2,120%.

Moreover, this analysis identified several bacterial outbreaks, including almost a dozen apparent outbreaks reported between 2015 and 2016, that were linked to a urological endoscope. These findings are consistent with the focus of the FDA’s letter issued to healthcare providers last year discussing the risk of infections associated with reprocessed urological endoscopes, including cystoscopes, ureteroscopes, and cystourethroscopes.

That FDA letter focused on some of the adverse event reports this review identified linking a urological endoscope to bacterial infections, including reports associating an accessory component sometimes used with a urological endoscope to Pseudomonas infections and patient morbidity. Additionally, this analysis identified adverse event reports associating urological endoscope with multidrug-resistant bacterial infections.

This analysis also found that the number of relevant adverse event reports submitted to FDA involving a urological endoscope in 2021, compared to the previous year, increased from 209 to 244 relevant reports, or by approximately 17%, which is the smallest percentage increase of any of the studied endoscope types (when similarly comparing the data from these same two years).

Like some bronchoscopes (and ENT endoscope models too), urological endoscopes have been associated with recalls created or initiated since 2014 because of a potential device contamination issue.

Urological endoscopes are used to view, diagnose and treat diseases and disorders affecting the urinary tract including the urethra, bladder and ureters.

Gastroscopes:  When comparing the number of adverse reports submitted to the FDA in 2021 to those submitted in 2014 satisfying this analysis’s inclusion criteria, gastroscopes displayed the most significant increase of any of the studied endoscope types, rising from 13 to 1,135 reports, or by approximately 8,630%, which is a salient finding and the reasons for which are not entirely clear.

This number of reports filed in 2021 (n=1,135) is greater than the number of relevant reports submitted to FDA in the same year (2021) for any of the other endoscope types studied.

Moreover, this number of FDA reports submitted in 2021 involving a gastroscope, compared to the previous year (2020) when 623 relevant reported were filed, increased by almost 80%.

Focusing on the total sum of all of the relevant adverse event reports submitted to FDA between 2014 and 2021 for each of the six studied endoscope types, the count for gastroscopes (n=3,797) was also greater than for any of the other studied endoscope types: bronchoscopes (n=1,350); colonoscopes (n=2,196); duodenoscopes (n=2,546); ENT endoscopes (n=137); and urological endoscopes (n=854).

This analysis of gastroscopes included models that use a curved, linear array ultrasound transducer at the device’s distal end for imaging. These models are sometimes called ultrasound gastroscopes or “EUS” (endoscope ultrasound) endoscopes. Similar to duodenoscopes, ultrasound gastroscopes are designed with an elevator mechanism at their distal tip.

This review identified adverse event reports linking a gastroscope to clusters of patients infected with CRE or a related superbug with associated morbidity.

Like the other studied endoscope types, gastroscope models have been recalled since 2014 because of a potential device contamination issue.

Gastroscopes are used during a procedure called “EGD” (esophagogastroduodenoscopy) to view, diagnose and treat diseases and disorders of the esophagus, stomach and duodenum.

ENT endoscopes: The number of relevant adverse event reports submitted to FDA in 2021 involving an ENT endoscope, compared to those submitted in 2014, increased dramatically by 5,400%, from 1 to 55 relevant reports, which on its face is a significant finding despite last year’s number (n=55) being the lowest number for all of the studied endoscope types (also during 2021).

Klebsiella pneumoniae (CDC)

This relatively low number of relevant reports filed in 2021 is understandable considering the expected low risk of infection associated with an ENT endoscope, compared to the other studied endoscope types and specifically to GI endoscopes, which are more complex in physical design and more demanding to reprocess.

Nevertheless, this review identified reports linking an ENT endoscope to patients infected with multidrug-resistant bacteria (albeit one of the reports was submitted to FDA in 2013). A 2017 report was identified linking this type of endoscope to infections of Klebsiella pneumoniae and patient mortality. Strains of Klebsiella spp. displaying resistance to carbapenem antibiotics are a type of CRE.

Further, the increase in the number of relevant adverse reports submitted to FDA in 2021 involving an ENT endoscope, compared to the previous year (2020) when 19 relevant reports were filed, was the most percentagewise (189%) than for any of the other five studied endoscope types.

For comparison, the number of relevant adverse reports submitted in 2021, compared to 2020, involving a urological endoscope increased by 17%, which was the smallest increase of any of the studied endoscopes (when similarly comparing the data from these same two years).

Like some bronchoscopes and urological endoscope models too, ENT endoscopes have been associated with recalls since 2014 because of a device irregularity that could pose a device contamination risk.

ENT endoscopes are used to view, diagnose and treat diseases and disorders, as its name indicates, of the ears, nose, sinuses, larynx, and throat.

Colonoscopes: This analysis found that the number of relevant adverse reports submitted to FDA in 2021 involving a colonoscope, compared to those submitted in 2014, increased significantly from 23 to 820, or by approximately 3,465%.

Further, this analysis found that this number of FDA reports filed in 2021, compared to the previous year (2020) when 459 reports were filed involving a colonoscope, demonstrated an increase of almost 80%.

These findings are significant and similar to this analysis’s findings for gastroscopes (82%) when also comparing the data from 2021 to 2020. Moreover, only the number of relevant reports submitted to FDA in 2021 involving a gastroscope (n=1,135) was greater than the corresponding number submitted during this same year involving a colonoscope (n=820).

These data notwithstanding, this review found MAUDE reports filed since 2014 linking a reprocessed colonoscope to possible patient infection to be relatively few. Many factors can contribute to this finding, including the underreporting of disease transmissions due to limited post-endoscopic surveillance designed specifically to detect and record true infections, and inadvertent oversight (i.e., failure to submit to FDA a case of confirmed infection linked to a colonoscope).

While the possibility that contaminated colonoscopes might inherently pose a relatively low risk of infection warrants consideration and discussion, several reviewed reports nevertheless describe a reprocessed colonoscope contaminated with bacteria including E. coli, Klebsiella spp., which the FDA defines as “high concern” organisms. Again, strains of these bacteria displaying non-susceptibility to carbapenem antibiotics can be CRE.

Moreover, an adverse event report filed in 2019 links a patient testing “positive” for CRE to a colonoscopy procedure raising the possibility that the endoscope was the mode of transmission. Another report filed in 2018, among other reported cases, links two patients infected with CRE to exposure to a colonoscope.

Even in the absence of confirmed infection, however, patient exposures to colonoscopes or to any endoscope type contaminated with infectious organisms is inconsistent with infection control and safety standards, and would necessarily pose an increased risk of infection.

And, as with each of the other endoscope types, colonoscopes have also been recalled since 2014 because of a potential device contamination issue (i.e., the risk of a therapeutic device becoming lodged in the instrument channel).

Colonoscopes are used to view, diagnose and treat diseases and disorders of the colon and rectum.

Shared, unique adverse events: This analysis found that different endoscope types can be associated with the same types of adverse events, while certain other endoscope types may be associated with a relatively unique adverse event.

For example, both colonoscopes and gastroscopes were found during this analysis to be similarly associated with therapeutic accessories (e.g., a hemostatic clip, stent or forceps) becoming stuck in the instrument channel, posing a risk of ineffective reprocessing and patient infection if not removed prior to the device’s cleaning.

This review found this specific adverse event, which has been associated with a device recall, to be reported much less often than for any of the other studied endoscope types unrelated to a GI endoscopic procedure, such as a bronchoscope, however.

Moreover, MAUDE reports were identified during this analysis describing each of the six of the studied endoscope types testing “positive” for microorganisms (e.g., during microbiological surveillance testing) after reprocessing, indicating that this specific adverse event — contamination of a “patient-ready” endoscope — is seemingly broad and not exclusive to only one or two endoscope types.

In contrast, only urological endoscopes were associated with reports linking ineffective reprocessing of an accessory component called a forceps/irrigation plug to patient infection.

Similarly, reports involving ENT endoscopes, much more often than for any of the other studied endoscope types, describe users not necessarily being aware that the entire device, as stated in its instructions for use, requires both cleaning and at least high-level disinfection after each use, not for example, merely wiping the ENT endoscope’s insertion tube with a disinfectant like 70% alcohol.

Microorganisms: In a similar manner, different endoscope types were found during this analysis to be contaminated with the same types of bacteria, while some endoscope types were reported to be contaminated with a somewhat unique type of organism. For example, some of the same organisms contaminating a GI endoscope were also reported to contaminate a bronchoscope, such as CRE, Klebsiella pneumoniae and E. coli.

In contrast, however, few of the studied endoscope types other than bronchoscopes were found to be contaminated with nontuberculous (or, atypical) mycobacteria, such as Mycobacterium abscessus. Moreover, bronchoscopes were generally the only studied endoscope type found to be associated with reports describing a pseudo-infection, pseudo-cluster or pseudo-outbreak (meaning contamination of patient cultures or specimens but without the patient displaying symptoms of infection).

Adhesive deterioration, discontinuity: Identified adverse event reports discuss deterioration or a similar type of defect, gap, crack, bubble or discontinuity in the adhesive, sealant or glue at the distal end of the endoscope, particularly duodenoscopes but also ultrasonic gastroscopes (and reports suggest bronchoscopes and cystoscopes too), which can pose a risk of device contamination and patient infection.

A few recent reports claim the possibility that “chemical stress” or chemical damage linked to reprocessing over time could be contributing to deterioration of the adhesive at the device’s distal end, adversely impacting the performance and safety of the endoscope. (For context, FDA states that the data submitted to the MAUDE database have not been independently reviewed and could potentially be inaccurate.)

It can be reasonably assumed that, in general, the methods and chemical agents used for reprocessing have been validated for compatibility with the endoscope’s materials, including its adhesives, to minimize if not eliminate the potential for endoscope damage.

However, reports acknowledge that factors contributing to an observed association between device damage and foreign debris entering and contaminating the inside of the duodenoscope (e.g., inside the light guide lens) can include a “chemical stress caused by the chemical agent used at the reprocessing.”

Other possible contributing factors discussed in some of the reviewed reports include damage to the adhesive at the distal end possibly due to mishandling of the endoscope, wear and tear, or to a physical stress such as dropping the endoscope on a hard surface.

Notably, some of the reports describe a gap or crack in the adhesive on the distal end of the endoscope that may have facilitated bioburden, a stain or visible dirt contaminating the inside of the device (i.e., inside the lens or behind the device’s light guide lens), posing a potential infection risk.

Addressing this concern, last year a duodenoscope was recalled because use of the device with “adhesive deterioration or other damages” can interfere with effective reprocessing and pose an infection risk.

One of this recall’s recommendations was to increase the frequency for returning the duodenoscope to the manufacturer for inspection and preventative maintenance from annually to every six months. Another recommendation was to perform a more detailed visual inspection of the endoscope (per a manufacturer-provided checklist), including to examine and evaluate the condition of the glue at the endoscope’s distal end.

While the causes of the deterioration may not be clear, FDA has acknowledged that cracks and gaps in the adhesive on the endoscope’s distal end — for example, where the duodenoscope’s distal cap is sealed to its distal tip — “can lead to microbial and fluid ingress” that can hinder reprocessing and “may increase the risk of infection transmission among patients.

This analysis found that this type of device irregularity, which can pose a risk of contamination and infection, is not limited to duodenoscopes, however.

Method and data validation

Other published studies and data appear to validate some of this analysis’s methods and findings.

For example, this analysis’s design, along with its data regarding duodenoscopes, is generally consistent and in agreement with the methods and results FDA presented in its November 2019 analysis discussing the risk of infections associated with reprocessed duodenoscopes.

This analysis’s methods and results are also generally consistent with those FDA adopted and published in a safety communication and a letter, each published in 2021, discussing the risk of reprocessed bronchoscopes and urological endoscopes, respectively, remaining contaminated and transmitting infections. FDA derived conclusions in those two communications, similar to this analysis’s conclusions, based on FDA’s review and analysis of submitted MAUDE reports.

Similar to this analysis’s design and findings, FDA has also used the MAUDE database to monitor the safety of medical devices and specifically of flexible endoscopes (e.g., bronchoscopes, duodenoscopes and urological endoscopes), to evaluate infection trends, and to develop important recommendations to reduce the risk of patient harms.



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SUMMARY, CONCLUSIONS, RECOMMENDATIONS

Aiming to be the most comprehensive investigation and analysis of adverse event reports, to date, involving a flexible endoscope, more than 10,000 (and possibly as many as 15,000 or more) medical device reports submitted to the FDA’s MAUDE database since 2014 describing actual or potential contamination of a flexible endoscope were reviewed.

Reports in the FDA’s MAUDE database suggest that current endoscope reprocessing practices may not always be sufficient and sometimes may require additional actions (e.g., visual inspections) or supplemental measures (e.g., sterilization) to prevent flexible endoscopes from exposing patients to potentially infectious organisms, including CRE and other multidrug-resistant organisms.

This analysis found that for all of the studied endoscope types, the number of reports satisfying the inclusion criteria has increased significantly since 2014. This increase was most pronounced for gastroscopes whose number of relevant reports submitted in 2021 compared to 2014 increased by approximately 8,631%.

In fact, this analysis identified more relevant adverse reports, as a total sum, submitted to FDA since 2014 involving a reprocessed gastroscope (n=3,797 relevant reports) than any of the other studied endoscope types.

However, this review did not identify a safety notice similar to the communications FDA recently issued for reprocessed bronchoscopes, duodenoscopes and urological endoscopes but focusing on the risk of reprocessed gastroscopes remaining contaminated, as detailed in reports in the MAUDE database and in the medical literature, and potentially exposing patients to multidrug-resistant organisms.

Based in part on this study’s findings, it can be reasonably debated whether the risk of a reprocessed gastroscope exposing patients to infectious organisms including CRE is a sufficiently recognized concern, or may warrant updated attention and guidance. Consideration of additional measures including the issuance of updated recommendations addressing this risk is suggested to improve the safety of reprocessed gastroscopes.

This review’s findings further suggest that healthcare providers may consider sterilization of gastroscopes (when feasible), or the use of a single-use (disposable) gastroscope (when available and as warranted). Performing a risk assessment to help guide this consideration is also recommended.

FDA has clarified that semi-critical devices, such as gastroscopes and each of the other five studied endoscope types, should undergo sterilization (after cleaning) although adding that if the device’s design “does not permit sterilization, (e.g., device materials cannot withstand sterilization), then high level disinfection should be used.”

For all six of the studied endoscope types, the number of relevant reports submitted to FDA in 2021, compared to the previous year (2020), increased. Urological endoscopes displayed the smallest increase (17%) during this timeframe, and ENT endoscopes demonstrated the greatest increase (189%).

Any marked increase in the number of relevant reports submitted since early 2020, when COVID-19’s pandemic was first identified, for any endoscope type is notable because during this time the number of elective or non-urgent endoscopic procedures performed using a flexible endoscope reportedly decreased in the U.S. and globally pursuant to adopted measures designed to optimize resources and ensure the proper care and equipment for patients infected with the disease. (Ordinarily, a decrease in the number of procedures performed using a flexible endoscope would be expected, in general, to trend toward a decrease in the number of filed adverse reports.)

Although FDA and others in recent years have diligently worked to reduce the contamination and infection risk of reprocessed duodenoscopes (and other endoscope types), the findings of this analysis suggest that use of a duodenoscope remains a risk factor for patient exposure to multidrug-resistant organisms including CRE, warranting continued vigilance and care to ensure safety. That said, this analysis found that the number of reports submitted to FDA linking a duodenoscope to patient deaths was significantly less in 2021 than just a few years ago.

This analysis’s finding that the number of relevant reports submitted to FDA in 2021, compared to 2020, increased most significantly for ENT endoscopes (189%) (and less so for each of the other five studied endoscope types including GI endoscopes) raises for discussion whether a notification focusing on today’s risk of reprocessed ENT endoscopes remaining contaminated, as detailed in reports in the MAUDE database, may be justified to improve patient safety.

For perspective, however, the number of relevant reports submitted in 2021 involving an ENT endoscope was still the lowest of all the studied endoscopes (n=55). The number submitted in 2021 involving a gastroscope, for reference and comparison, was approximately 21 times higher (n=1,135). ENT endoscopes, which include tracheal intubation endoscopes, are relatively simple in physical design featuring only one channel. GI endoscopes, in contrast, generally feature several internal channels, one or two of which cannot usually be cleaned with a brush.

As is the case for gastroscopes (and ENT endoscopes) too, this review did not identify a safety notice or letter similar to the recent guidance published for bronchoscopes, duodenoscopes and urological endoscopes but focusing on the potential for reprocessed colonoscopes to remain contaminated, as detailed in reports in the MAUDE database and in the medical literature.

While the reported risk of a colonoscope infecting patients is relatively low compared to a duodenoscope, a 2018 report (among other reports) links two patients infected with CRE to exposure to a colonoscope. These findings suggest updated guidance and recommendations addressing the contamination of reprocessed colonoscopes be considered to improve patient safety.

Reviewed adverse event reports discuss the deterioration of an adhesive or sealant used at the distal end of some of the studied endoscope types. These findings suggest that focused research be performed to understand with greater clarity the factors that contribute to this type of damage, and that appropriate corrective actions be considered and adopted to maintain the integrity of the endoscope’s materials and prevent gaps and cracks from forming in the adhesives and glues used at the distal end of at least some flexible endoscopes including but not limited to duodenoscopes, as these gaps can increase the risk of device contamination.

Consistent with this analysis’s findings, a manufacturer recommends that the objective lens and light guide lens at the distal end of the duodenoscope’s insertion tube be inspected “for scratches, cracks, stains, or other irregularities,” and similarly that the air/water nozzle at the distal end be inspected “for abnormal swelling, bulges, dents, or other irregularities.” Certainly, irregularities also include visible contamination.

Adverse event reports submitted to FDA since 2014 link reported infections of CRE or multidrug-resistant bacteria to gastroscopes and each of the other studied endoscope types, including colonoscopes and ENT endoscopes. The mortality rates of patients infected with CRE or a related superbug can be as high as 50%, or higher.

Contact of the disinfectant or sterilant with all of the endoscope’s potentially contaminated surfaces is a necessary requirement for reprocessing to be effective and prevent disease transmissions. Some of the factors that can hinder effective reprocessing, however, and increase the risk of a flexible endoscope remaining contaminated and exposing patients to potentially infectious organisms include:

  • complex endoscope designs that can interfere with proper cleaning of every surface
  • improper cleaning and/or inadequate storage and mishandling of the endoscope
  • endoscope damage (which includes gaps and cracks forming in the adhesives used at the endoscope’s distal end)
  • a faulty device component (e.g., a loosened biopsy port)
  • inadequate repairs and/or improper servicing and maintenance of the endoscope, among other factors.

Ideally, the endoscope’s design specifications (which would include the device’s labeling and instructions) would address and mitigate, if not eliminate entirely, the contamination risk associated with each of these listed factors.

OTHER RECOMMENDATIONS, GUIDANCE

This analysis’s findings underscore the importance, consistent with FDA guidance, of meticulously cleaning and performing at least high-level disinfection flexible endoscopes in accordance with current infection control guidelines and the manufacturer’s reprocessing, handling and storage instructions, as well as assuring quality and safety measures are in place to prevent the use of damaged flexible endoscopes on patients, which can pose an infection risk.

This analysis’s findings are in general agreement with the FDA’s recent recommendation that healthcare providers consider sterilization of bronchoscopes when feasible, and to consider using single-use (disposable) bronchoscopes in certain clinical situations as warranted – for example, when the risk of transmitting multidrug-resistant microorganisms is increased, or if the bronchoscope cannot be promptly reprocessed.

The analysis’s findings are also in general agreement with FDA federal guidance advising healthcare facilities not only to consider adopting one or more “supplemental measures” to the reprocessing of duodenoscopes such as sterilization, but also to begin transitioning from duodenoscopes with a fixed-endcap design to newer, more modern duodenoscope models featuring innovative designs that include disposable components such as a removable, single-use (as opposed to a fixed) endcap that facilitates reprocessing, or to fully disposable duodenoscope models (that eliminate reprocessing).

FDA has advised that sterilization provides a greater margin of safety. In 2015 FDA provided a list of additional steps, or “supplemental duodenoscope reprocessing measures,” to consider to increase the safety of duodenoscopes. In addition to sterilization, these measures include microbiological culturing, use of a liquid chemical sterilant processing system and repeat high-level disinfection.

This analysis’ results suggest that healthcare facilities consider (when deemed appropriate, feasible and warranted per a risk assessment, and if consistent with the endoscope manufacturer’s reprocessing instructions) adopting and applying these same supplemental measures to bronchoscopes and each of the other studied endoscopes, too, to mitigate the risk exposing patients to multidrug-resistant bacteria during an endoscopic exam.

This analysis’s findings are in general agreement with FDA’s recently published letter discussing the risk of reprocessed urological endoscopes transmitting infections, and the FDA’s recommendation that healthcare providers follow the manufacturer’s reprocessing instructions for urological endoscopes and their accessory components, as well as maintain and repair these devices according to the manufacturer’s servicing schedule.

This analysis’s findings suggest healthcare providers also consider sterilization of urological endoscopes (when possible and practical), or the use of a single-use urological endoscope (if and/or when available and as warranted) to improve patient safety. Performing a risk assessment to help guide this decision — for example, the sterilization of ureteroscopes — is recommended. Several factors may impact this a facility’s assessment of the infection risk, including the patient population.

Based on published data and his development of a unique three-tiered classification scheme, this article’s author wrote in 2019 that not every type of flexible endoscope is necessarily associated with the same risk of contamination and transmission of multidrug-resistant organisms. This analysis’s review of the FDA’s adverse events database is consistent with this 2019 assessment.

Further development of low-temperature sterilization technologies and new endoscope designs that feature enhanced materials’ durability to ensure safe and effective reprocessing of flexible endoscopes (e.g., endoscopes with removable disposable components) or that are fully disposable would provide healthcare facilities, whether large or small in size, high or low in-patient volume, private or non-profit, or urban or rural, with important options in today’s global effort to improve public health and prevent disease transmissions.

Improved monitoring and tracking of the safety of medical devices is needed to reveal potential risks timelier. Analyses such as this study’s review are important to detect trends and improve patient safety. At least in the context of one of the studied endoscope types at the time (six years ago), the 2016 U.S. Senate investigation reported that the current regulatory system for monitoring the safety of devices “failed to quickly identify and resolve the spread of duodenoscope-linked, antibiotic-resistant infections.”

Additional recommendations designed to improve the effectiveness of reprocessing a flexible endoscope, whether performed manually or using an automated reprocessing device, include:

  • visual inspection of the endoscope for cleanliness after reprocessing
  • confirming the endoscope is not damaged and that none of its components feature an irregularity, are performing improperly or are potentially defective (e.g., a loosened biopsy port or suction arm, or deterioration of an adhesive)
  • continuing to maintain a dedicated commitment to education, staff training and risk management.

STUDY LIMITATIONS

As with many analyses of this type, this study has limitations, and its results require critical and circumspect interpretation. For example, this study’s methodology cannot prevent the potential for the introduction of inadvertent bias (e.g., publication bias) into the results. An adverse event report that this study concluded was relevant and therefore included in this analysis another investigator, however, might deem irrelevant and exclude. Supplementing this analysis’s findings with additional data when possible and available is encouraged.

While housing this key data set, the MAUDE database has notable limitations. For example, FDA states that the submitted reports and data have not been independently reviewed and could potentially be “inaccurate, untimely, unverified, or biased,” and that adverse-event reports “are not, by themselves, definitive evidence of a faulty or defective medical device, and cannot be used to establish or compare rates of event occurrence.” That said, FDA has used the MAUDE database to monitor the safety of medical devices and specifically of flexible endoscopes (e.g., bronchoscopes, duodenoscopes and urological endoscopes), and to develop important recommendations to reduce the risk of patient harms.

While this study’s investigator was not blinded from any of the details of any of the reviewed MAUDE reports including the manufacturer of the implicated endoscope, diligent efforts were made to be thorough, fair, objective and to include in this analysis only those reports satisfying the study’s inclusion criteria. The manufacturer of the implicated device was not a factor that was considered, or a criterion to satisfy, when evaluating a report’s relevancy for inclusion in this study.

An increase in the number of relevant adverse events describing contamination of an endoscope during a certain timeframe is not necessarily associated with a corresponding increase in the infection risk. An increasing contamination trend can be misinterpreted and be due instead to some type of unrelated anomaly or artifact, for instance.

Nevertheless, the two are necessarily related: endoscope contamination is a prerequisite for the device to become a fomite and transmit infection. It is therefore necessary always to adopt effective measures to reduce further the contamination rate, no mater the endoscope type.

Ideally, the number of reported adverse events infections involving a specific endoscope type (the numerator) during a specified time period would have been normalized by dividing it by the number of procedures (the denominator) performed during that same time period using that endoscope type. This would permit a better understanding of whether the number of relevant adverse events per procedure has increased from one year to the next for each of the studied endoscope types, as opposed to this analysis’s findings being based only the numerator.

However, identifying the number of procedures performed using a certain endoscope type are elusive data. No matter, any increase in the number of reported adverse events (numerator) associated with an endoscope type from one year to the next is a potential concern in its own right.

Notably, this analysis’s use of only the number of reported infections (the numerator) to evaluate infection trends without dividing these data by the respective number of procedures performed was the same method FDA used in 2019 to study the risk of infection associated with duodenoscopes, to conclude that a certain decrease in the number of reported infections involving these devices yields meaningful data and to suggest specifically that efforts to reduce the risk of infection from these devices have yielded improvements.

Finally, a medical device report linking or associating a flexible endoscope with an infection (or outbreak) does not confirm the endoscope caused the infection, as one or more other factors could be, in part or solely, responsible. Additional data would be required to conclude more definitively that the endoscope caused the infection.



Disclosure: This study was supported by AMBU. While AMBU was provided a draft of this analysis prior to its release and provided suggestions and some of the photos to improve the draft and its readability including editorial commentary, inclusion of these recommendations in this article were solely at the discretion of Dr. Muscarella, who via LFM Healthcare Solutions, LLC had complete and unfettered control over this study’s preparation, design, methods, results, recommendations, discussed limitations and other content. Dr. Muscarella intends to submit this study, along with graphs and a more detailed discussion of its findings, to a medical journal for peer review and publication consideration.



Article by: Lawrence F Muscarella, PhD. Copyright (2022). 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-2.48]



 

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