A Bronchoscope is Linked Again in the U.S. to an Outbreak of the Feared ‘CRE’ Superbug Safety Notice: Is enough being done to improve the safety of bronchoscopes? And, several bronchoscope models are recalled.

Oct. 1, 2018 (updated: Oct. 5, 2018) — A bronchoscope has been linked again to a ‘superbug’ outbreak involving multiple patients, according to a regulatory report filed last spring.

Providing few additional details, the report does not disclose the specific number of patients infected, whether the patients are aware of the outbreak, or if any infected patients expired.

Nor does the report identify the type of bacteria responsible for the infections, other than revealing it as an “unspecified” strain of the feared carbapenem-resistant Enterobacteriaceae, or CRE.[*]  

The bronchoscope’s manufacturer reported these infections t.o the FDA on May 31st. 

This article is likely the first time this incident is being publicly discussed. CRE can spread in healthcare settings and cause infections with mortality rates of as high as 50%, according to the U.S. Centers for Disease Control and Prevention (CDC).

Duodenoscopes, another type of flexible endoscope, have received most of the public’s attention and federal scrutiny. Warnings about the risk of reprocessed bronchoscopes remaining persistently contaminated and infecting patients with CRE and related multidrug-resistant organisms, or MDROs, are scant.

Since 2012, more than two dozen outbreaks of CRE and related bacteria have been linked to duodenoscopes, according to a U.S. congressional report published in January 2016. Klebsiella species and E. coli are two types of CRE often responsible for duodenoscope-related infections, and may also contaminate bronchoscopes.

CRE are resistant to several antibiotics including carbapenems, which are a “last defense” against serious healthcare-associated infections. Colistin is often the only remaining antibiotic effective against CRE infections.

Bronchoscopes are used about 500,000 times a year in the U.S by lung specialists to diagnose and treat a variety of lung- and airway-related diseases in patients. Gastrointestinal physicians use duodenoscopes to examine and treat diseases of the pancreatic and bile ducts.

The thorough cleaning and disinfection (or sterilization) of both of these types of flexible endoscopes, known as reprocessing, is necessary to prevent life-threatening infections.

Duodenoscopes and bronchoscopes are not the only types of flexible endoscopes that can transmit multidrug-resistant bacteria, however. Gastroscopes and urologic endoscopes have also been linked to infections of CRE and related strains of carbapenem-resistant bacteria.

Last week, a manufacturer recalled several bronchoscope models distributed in the U.S. and Canada due to an identified quality issue.



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More about this May 31st regulatory report 

The regulatory report filed on May 31, 2018 discussing this CRE outbreak. (Source: FDA’s medical device database.)

According to this May 31st regulatory report, a manufacturer representative visited the medical facility in response to these multiple infections of CRE and identified only “one minor” reprocessing lapse.

At least as of May 31st, the hospital was unsure if the bronchoscope caused the outbreak, the report added.[*]

A portion of this May 31st regulatory report is provided to the right. The name of this U.S. medical facility is redacted from the report.

Suggesting this may be both an emerging and underrecognized risk, this May regulatory report was not the first submitted to the FDA revealing a possible association between bronchoscopes and infections of CRE (and other potentially concerning bacteria).

Nevertheless, in addition to scant warnings about the risk of reprocessed bronchoscopes infecting patients with CRE, federal safety alerts have not advised the public whether enhanced cleaning measures may be necessary to improve the safety of bronchoscopes, or that a manufacturer voluntarily recalled several bronchoscope models last week.

A bronchoscope is linked to a CRE cluster in 2014

Four years ago on Dec. 24, 2014, a manufacturer notified the FDA that 14 patients had reportedly tested “positive” for CRE following exposure to a bronchoscope.[*]  This incident may document the first time the FDA was notified of the potential for a bronchoscope to infect patients with CRE.

Fourteen regulatory reports appearing to describe this same one incident were filed, likely one for each of the 14 patients. A portion of one of these Dec. 24th regulatory reports is provided immediately below and to the right.

According to these reports, the bronchoscope was apparently cultured after reprocessing and repeatedly tested positive for the bacteria (which also included pan-susceptible Pseudomonas aeruginosa)The name of the U.S. medical facility where this incident occurred is redacted from the report.

Portion of one of 14 similar regulatory reports filed on Dec. 24, 2014 discussing another CRE outbreak. (Source: FDA’s medical device database.)

This regulatory report states that the bronchoscope had been repaired by “a third-party vendor,” and that “use of a third party components on this scope may compromise the device and could result in harboring bacteria if the inside of the device becomes damaged.”

The manufacturer’s reprocessing procedures “are only validated for devices that meet (the manufacturer’s) specifications. The device is not validated when it serviced/repaired by a third party vendor,” the report further states.

Reprocessing is a detailed, multistep process used by medical facilities to clean and disinfect or sterilize reusable devices, including bronchoscopes and duodenoscopes. Safe reprocessing is necessary to prevent the device from harboring and transmitting CRE and MDROs.

This and other more recent reports, including the May 31st report filed earlier this year, suggest that reprocessed bronchoscopes can pose a safety risk and, like duodenoscopes, may transmit infections of CRE even when the device is cleaned and disinfected correctly (i.e., according to the manufacturer’s instructions).

Other regulatory reports linking bronchoscopes to infections of suspect bacteria

Other regulatory reports submitted to the FDA similarly link bronchoscopes to other recent infections of suspect bacteria including of Klebsiella and Pseudomonas species.

On Oct. 11, 2016, a healthcare professional notified the FDA of a medical facility’s “recent trend of increased diagnosis of Pseudomonas aeruginosa” in patients following bronchoscopy.

Few other details are provided in the report, except its stating that the bronchoscope was “found to have a defective port that was moving (is supposed to be stationary) and the o-ring was displaced allowing bio-matter to accumulate.”[*]

The manufacturer voluntarily recalled this bronchoscope model in September because of a quality concern regarding the device’s instrument channel port.

On Nov. 3, 2016, a manufacturer submitted 13 similar (and seemingly related) reports to the FDA linking a bronchoscope to 13 patients who tested positive for P. aeruginosa.  According to the reports,  approximately “2 out of the 13 patients were identified as having comorbidity medical conditions and have since expired.”[*]

The bronchoscope identified in this report is the same model identified in the Oct. 11th report filed the previous month.

According to the Nov. 3rd reports, the bronchoscope tested positive for P. aeruginosa after reprocessing. Also linking this bronchoscope model’s o-ring to bacterial contamination, these reports stated that “biomatter (was) found underneath the o-ring of the scope.

These regulatory reports do not disclose whether the cluster’s Pseudomonas bacteria were tested and determined to be  multidrug-resistant. The reports states, however, that the cause of the reported positive culture could not be determined but improper maintenance of the device cannot be ruled out as a contributory factor.

A concern about contamination of the o-ring of the bronchoscope model cited in these Oct. 11th and Nov. 3th reports had been reported to the FDA two years earlier, in 2014.

On Aug. 28, 2014, a manufacturer notified the FDA that 22 patients had reportedly tested positive for E. coli, P. aeruginosa and/or Candida after undergoing bronchoscopy performed using the same bronchoscope on each patient.[*]

The bronchoscope’s o-ring was tested and cultured twice, according to the report, and found the cultures to be positive for microorganisms.  The facility removed the device from use in 2014.

This regulatory report, one of 22 filed with the FDA in 2014, does not disclose whether the E. coli and P. aeruginosa bacteria were tested and found to be carbapenem-resistant. Many of the 22 patients received intravenous antibiotics, however, and all of the patients recovered, according to the report.

Bronchoscopes are not the only type of flexible endoscope whose design includes an o-ring that has been linked to infections of P. aeruginosa.

Three year ago, Verfaillie et al. (2015) investigated an 2012 outbreak of carbapenem-resistant P. aeruginosa linked to a duodenoscope model. These investigators suggested that the device’s o-ring “did not function properly and that adequate sealing of the elevator wire channel could not be guaranteed.”

Another adverse event filed earlier this year

Another incident linking bacterial contamination to the same bronchoscope model cited in these Oct. 11th and Nov. 3th reports was reported to the FDA seven weeks ago on Aug. 14th.

According to this report filed by a healthcare facility, a contaminated bronchoscope was found to have a loose cap on the biopsy port, and this “area was cultured revealing 2+ growth” of bacteria, including Enterobacter cloacae, Serratia marcescens and P. aeruginosa.[*]

This Aug. report does not disclose whether any of these bacteria were multidrug-resistant, although strains of these bacteria found in healthcare settings can be carbapenem-resistant.

“Based on what is known, no (patient) developed an infection related to this issue” and “[n]o issues were identified related to high-level disinfection,” this report states.

Several bronchoscope models recalled last week

The bronchoscope model cited in this Aug. 14th report, along with several other models, was voluntarily recalled by the manufacturer the next month affecting many devices distributed in the U.S. and Canada.

The reason for the recalls of these devices on Sept. 29th (2018), according to several of the recall notices (that were randomly reviewed), the attachment of third-party accessories to the bronchoscope’s instrument channel port “may have resulted in more applied force than expected and lead to loosening” of this port.

The recalled models do not necessarily pose a safety concern, according to the manufacturer’s recall notices.

These recall notices instruct the customer to visually inspect and test the bronchoscope. If the instrument channel port can be manually rotated or turned, or if this port is not loose but “the rubber part” around it “is lifted from the molding parts,” the manufacturer recommends the device be removed from use and returned for repair, according to at least some of the reviewed recall notices.

If the instrument channel port does not rotate or turn and the rubber part is “in a normal condition,” however, the bronchoscope “can be used in a patient procedure,” according to the manufacturer’s recall notice.

Whether the FDA agrees with the manufacturer’s assessment about safety is unclear. To date, the FDA has not issued an official communication notifying the public of last week’s recalls of these bronchoscope models.

For completeness and accuracy, click here to read the recall’s instructions, in their entirety, associated with at least one of the recalled models.



Quality, Safety and Case Reviews:  Click here to read about Dr. Muscarella’s quality and safety services designed to help clients reduce the risk of healthcare-associated infections, including superbug outbreaks linked to contaminated duodenoscopes and other types of reusable medical equipment.



Earlier reports discussing a bronchoscope’s loose biopsy-port cap

More than a decade ago, investigators reported the contamination of bronchoscopes with both S. marcescens and P. aeruginosa due, at least in part, to a loose biopsy-port cap.

According to a study published in 2003 in the New England Journal of Medicine (NEJM), inspection of two bronchoscopes “revealed that the caps of the biopsy ports were not securely fastened and were easily removable, contrary to manufacturing specifications. The port caps were loose enough to be unscrewed with two fingers but not so loose that the problem was apparent to the bronchoscopy staff.

This study further reported that “[w]hen the threads of the biopsy ports and the inside of the caps of (the two bronchoscopes) were swabbed, a dark green film was noted, and 9 of 12 swab specimens were positive for P. aeruginosa and S. marcescens. The other three swab specimens were positive for P. aeruginosa alone, including one specimen obtained after three cycles of (automated) cleaning and disinfection.”

A second study published in the same issue of NEJM reported a large outbreak of P. aeruginosa infections “apparently caused by a loose biopsy-port cap in the bronchoscopes.”

The study’s authors reported that “the contamination appeared to be related to a loose biopsy-port cap on the bronchoscopes, which may have sheltered organisms and thus rendered disinfection procedures ineffective. Several findings support this hypothesis …

The study concluded that instrument safety and surveillance methods for bronchoscopy “must be improved, and better recall procedures are needed for medical devices.”

(The quality issues discussed in these two studies from 2003 may be entirely unrelated to those discussed in the several bronchoscope recall notices issued last week.)

An accompanying letter published four months later in NEJM further questioned the efficiency of the bronchoscope’s recall, writing that it “seems that a recall of bronchoscopes related to specimen contamination and possible nosocomial infections would be classified as involving a high-risk problem, yet this was a voluntary recall by the manufacturer with no official notice from the FDA.

This letter’s authors concluded that “the experience with the bronchoscope recall merits a reexamination of procedures for the recall of medical devices. We encourage the FDA, the medical community, and industry to work together to optimize the management of medical-device recalls.”

FDA issues a safety alert about duodenoscopes on Feb. 19, 2015 

Since early 2015, the FDA has issued several safety communications informing the public that duodenoscopes (but not bronchoscopes) could remain persistently contaminated and transmit CRE and related multidrug-resistant bacteria even when cleaned and disinfected correctly.

The FDA issued the first of these alerts on Feb. 19, 2015, writing that it “is closely monitoring the association between reprocessed duodenoscopes and the transmission of infectious agents, including multidrug-resistant bacterial infections caused by Carbapenem-Resistant Enterobacteriaceae (CRE) such as Klebsiella species and Escherichia coli.”

These alerts marked a watershed moment for endoscope reprocessing, because virtually all cases of cross-infection linked the previous 20 years to a contaminated endoscope were due to a cleaning or disinfection lapse (or, for example, to a design or manufacturing flaw) — not to a properly reprocessed endoscope.

Published guidelines report that the likelihood of a properly reprocessed flexible endoscope, including duodenoscopes (and bronchoscopes), transmitting any type of disease is very small.

An image of a duodenoscope is provided on the right.

A duodenoscope model.
(Source: FDA)

The FDA also stressed in this Feb. 19th alert that “the complex design of ERCP endoscopes (also called duodenoscopes) may impede effective reprocessing,” inauspiciously adding in the alert that “[m]eticulously cleaning duodenoscopes prior to high-level disinfection should reduce the risk of transmitting infection, but may not entirely eliminate it.”

FDA issues a safety alert in Sept. 2015 about bronchoscopes

Seven months later — and two months after this blog posted its July 2015 article discussing, for the first time, that bronchoscopes too can pose a risk of CRE transmissions, — the FDA issued a notice entitled, “Infections Associated with Reprocessed Flexible Bronchoscopes: FDA Safety Communication.

This Sept. 2015 federal alert, however, did not specifically advise the public that reprocessed bronchoscopes also may be prone to infecting patients with CRE (and related MDROs). A portion of this FDA Sept 2015 safety communication is provided immediately below.

A portion of the FDA’s Sept. 17, 2015 alert.

This safety alert did advise the public, however, that a few submitted regulatory reports “indicate persistent device contamination (of bronchoscopes) despite following the manufacturer’s reprocessing instructions,” as the FDA had similarly reported with duodenoscopes.

Three years ago, the Los Angeles Times reported that, at that time, the FDA was investigating reports that bronchoscopes are causing infections in patients even after being cleaned and disinfected. “The (FDA) said no deaths from tainted bronchoscopes have been reported thus far, and it’s still evaluating what factors contributed to the infections,” the Times wrote in this article published on Sept. 17, 2015.

Alipour et al. (2017) reported last year that standard cleaning and high-level disinfection of bronchoscopes may not be effective “against biofilm embedded forms,” and that bronchoscopes can also transmit colistin-resistant bacteria.

4 supplemental reprocessing measures to improve safety

Nor did this FDA’s Sept. 2015 alert advise U.S. hospitals to consider adopting and applying to bronchoscopes at least one of the four supplemental measures the agency had published the previous month, on Aug. 4th, to improve the safety of duodenoscopes.

These supplemental measures are: (1) microbiologic sampling of the duodenoscope prior to reuse; (2) disinfecting the duodenoscope twice; (3) use of a liquid chemical sterilant processing system; and (4) use of ethylene oxide gas to sterilize the duodenoscope.

A portion of the Aug. 4th safety communication is provided to the right.

A portion of the FDA’s Aug. 4, 2015 notice.

This reasons for the FDA’s recommending these four supplemental measures to improve the safety of  duodenoscopes — but not similarly promoting the application of these measures to enhance the safety of bronchoscopes (and other types of flexible endoscopes), too — are unclear. Perhaps the FDA has concluded that current data only support consideration of these four additional steps for the reprocessing of duodenoscopes.

According to the FDA, factors that can contribute to a device remaining persistently contaminated and transmitting bacteria include “[c]ontinued use of devices despite integrity, maintenance and mechanical issues.”

Colistin-resistant bacteria

The risk of bronchoscopes and other flexible endoscopes infecting patients with nightmarish bacteria is not limited only to CRE and related carbapenem-resistant bacteria.

Last December, this blog posted an article publicizing for the first time a regulatory report linking a duodenoscope to “probable transmission” of a colistin-resistant K. pneumoniae harboring the mcr-1 gene.[*]

Just three weeks ago, Shenoy et al. (2018) confirmed this risk, reporting in the Sept. 11 issue of Clinical Infectious Diseases a case of healthcare-associated transmission of mcr-1 in the U.S. linked to shared exposure to a duodenoscope.

Cases linking a bronchoscope in the U.S. to infections of colistin-resistant Enterobacteriaceae bacteria (harboring the mcr-1 gene), however, have not been reported.

Colistin is a “last resort” antibiotic that may be used to treat infections of CRE. Some infections caused by colistin-resistant bacteria may be virtually untreatable.

Recommendations to improve bronchoscope safety

The following recommendations are provided to help U.S. hospitals improve the safety of bronchoscopes:

  • U.S. hospitals might also consider adopting a fifth supplemental measure, when available, appropriate and warranted, to improve endoscope safety: use of sterile instrumentation, or a FDA-cleared sterile sheath to cover the endoscope and reduce the risk of transmitting CRE or a related MDRO.
  • Consider other preventive measures too, including use of a borescope to examine the bronchoscope’s working channel for cleanliness as well as for abnormalities that could pose an infection risk — for example, tears, scratches, perforations and other damage, and the presence of residual soils and blood.

These bulleted recommendations are not all-inclusive and are intended to supplement, not replace, the advice the FDA published in its Sept. 17 (2015) safety alert focusing on bronchoscope reprocessing, the bronchoscope manufacturer’s instructions.

Klebsiella pneumoniae growing in a Petri dish. (Source: CDC)

Consideration of application of this first bulleted recommendation to other types of flexible endoscopes that have also been linked to CRE outbreaks — such as gastroscopesurologic endoscopes and gastrointestinal linear echoendoscopes — is suggested, when clinically warranted and deemed feasible to implement.

In June, the FDA was informed that a gastrointestinal linear echoendoscope had tested positive for CRE (carbapenem-resistant Enterobacter) during routine endoscope culturing. The report acknowledges that this device had been “used 11 times,” and was then repaired.

Conclusion

Published data now suggest that bronchoscopes pose an emerging risk of remaining persistently contaminated and transmitting infections of CRE and related MDROs even when reprocessed according to the manufacturer’s instructions.

Enhanced safety measures and reprocessing practices may be necessary, depending on the clinical circumstances (e.g., in an outbreak setting), to improve safety and mitigate this risk.

The importance of federal notices informing the public about new emerging infection risks associated with reusable medical instrumentation, especially recalled devices, cannot be overstated.


[*Footnote: (i) “Linking” (or “associating”) an endoscope or another type of reusable device to (or with) an infection or an outbreak does not confirm the device necessarily transmitted and caused the infection. More data would be required to conclude more definitively a causal relationship between the device and the infection. (ii) Regulatory reports submitted to the FDA routinely describe important clinical cases and experiences, but the findings and conclusions of these reports generally have not been peer-reviewed and may be incomplete, or, at least in part, inaccurate.

Article by: Lawrence F Muscarella, PhD. Posted Oct. 1, 2018; updated Oct. 5, 2018. Copyright (2018). LFM Healthcare Solutions, LLC. All rights reserved. Dr. Muscarella is the president of LFM Healthcare Solutions, LLC, an independent quality improvement company. Click here for a discussion of his quality improvement healthcare services

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