February 9, 2015 — The FDA’s “MAUDE” database (or, “Manufacturer and User Facility Device Experience” database) lists medical device reports, or MDRs, which document the association of one or more marketed medical devices, including gastrointestinal (GI) endoscopes, with an adverse event in the healthcare setting.
Federal regulations mandate that these reports be filed by hospitals and manufacturers within 10 or 30 days, respectively, of their learning that a medical device might have caused or contributed to death or injury.
The FDA’s rules regarding filing a MAUDE report may be read here.
MAUDE reports linking GI endoscopes to adverse events
The MAUDE database documents several reports linking contaminated GI endoscopes to outbreaks of the “superbug” or “nightmare bacteria” called carbapenem-resistant Enterobacteriaceae, or “CRE,” with associated patient morbidity and mortality.
These filed reports, most of which describe outbreaks of CRE in the U.S. since 2012, demonstrate that superbug outbreaks in the GI endoscopic setting require prompt attention and corrective actions to ensure patient safety and prevent the outbreak’s recurrence.
Moreover, for the most part, these MAUDE reports link these recent superbug outbreaks to the specific type of GI endoscope that is exclusively used to perform endoscopic retrograde cholangiopancreatography, or “ERCP.” (Other types of endoscopes — namely, endoscopic ultrasound [or “EUS”] endoscopes, bronchoscopes, and cystoscopes — have also been linked to outbreaks of CRE).
These MAUDE reports (which, due to under-reporting, certainly do not include every CRE outbreak in the U.S. since 2012) include the following:
- Food and Drug Administration. Incident report. March 7, 2014. Report number: 2518897-2014-00001 — click here.
- Food and Drug Administration. Incident report. March 4, 2014. Report number: MW5029305 — click here.
- Food and Drug Administration. Incident report. January, 28, 2014. Report number: 2951238-2014-00027 — click here.
- Food and Drug Administration. Incident report. November 13, 2013. Report number: MW5033987 — click here.
- Food and Drug Administration. Incident report. January 1, 2013. Report number: 2951238-2014-00349 — click here.
A forthcoming FDA safety alert
This latter article by Dr. Muscarella, like another related article entitled, “Superbugs, Contaminated Gastrointestinal Endoscopes, and a Growing Number of Hospital Infections: Is an FDA Action Imminent?” — click here, discuss the possibility that the FDA may soon publish a safety advisory alerting the public to the risk of transmissions of CRE and their related superbugs during GI endoscopy.
This advisory would presumably also provide guidance for healthcare practitioners, including the specific actions they should take to prevent CRE outbreaks during GI endoscopy.
CRE outbreaks: increasing in incidence
A more complete list of reports of CRE outbreaks encountered since 2008 in hospitals residing in the U.S. and in Europe, including these five listed reports filed in the FDA’s MAUDE database, are provided in Dr. Muscarella’s related article: “Investigation and Prevention of Bacterial Outbreaks following Endoscopic Retrograde Cholangiopancreatography, or ERCP” — click here.
As these several outbreaks of CRE demonstrate, instances of superbug transmissions linked to contaminated GI endoscopes in the U.S. and globally, with associated patient morbidity and mortality, are not isolated events and appear to be increasing in incidence.
In fact, based on published data, it can be reasonably argued that, since its emergence in the U.S. almost a decade ago, outbreaks of CRE are approaching “epidemic” levels. The reader is directed to Dr. Muscarella’s related article entitled, “Overlooked Outbreaks of ‘CRE’ Following GI Endoscopy: A “Superbug” Epidemic in Our Midst?” — click here.
Sidebar #1: In the context of this article (and most of Dr. Muscarella’s other articles about CRE), “related superbugs” are defined as bacteria that are related to, but are not, CRE, per se. Specifically, they are gram-negative bacteria that are either:
- resistant to carbapenem antibiotics, although not of the Enterobacteriaceae family (and therefore not CRE); or
- are a multidrug-resistant member of the Enterobacteriaceae family, although at this time remain susceptible to carbapenem antibiotics.
The CDC’s investigation of Hospital X
A recently published hospital inspection report from the files of the Centers for Medicare and Medicaid Services, or CMS, cites some infection-control deficiencies observed at the hospital (“Hospital X”) outside of Chicago (IL; USA) that experienced the well-publicized outbreak of CRE in 2013 following ERCP. (Refer to: CMS Report No.: 3413, dated January 16, 2014.)
Hospital X’s outbreak was one of the largest outbreaks of CRE in U.S. history, and some of its details were published by the Centers for Disease Control and Prevention (CDC) in the January 3, 2014, issue of Morbidity and Mortality Weekly Report (MMWR) — click here to read: “Notes from the Field: New Delhi Metallo-β-Lactamase–Producing Escherichia coli Associated with Endoscopic Retrograde Cholangiopancreatography — Illinois, 2013.”
Legal Reviews for Consumers, Hospitals, Manufacturers: Click here to read about Dr. Muscarella’s expertise and legal assessments of the causes of healthcare-associated infections, including “superbug” outbreaks linked to contaminated GI endoscopes and other reusable medical equipment.
More recently, in October, 2014, a second article by the CDC discussing this same outbreak of CRE at Hospital X following GI endoscopy was published in the Journal of the American Medical Association (or, JAMA) — click here.
Also in October, 2014, Dr. Muscarella published his conclusions about Hospital X’s outbreak of CRE in the peer-reviewed article entitled, “Risk of transmission of carbapenem-resistant Enterobacteriaceae and related ‘superbugs’ during gastrointestinal endoscopy,” which was published in the World Journal of Gastrointestinal Endoscopy — click here.
A CMS inspection report
The CMS’s recently published inspection report, dated January 16, 2014, detailing some of Hospital X’s deficiencies was in response to the confirmation by this hospital that 38 of its patients, most of whom had recently undergone ERCP between January, 2013, and September, 2013, were either infected or colonized with a single strain of CRE.
For clarity, 10 of these 38 patients were infected with the outbreak’s strain of CRE, some critically, whereas the remaining 28 were colonized with this same superbug strain. (“Colonized” patients harbor the bacterium but, unlike those who are infected, do not display symptoms of infection.)
More specifically, the majority of these 38 patients: (i) underwent ERCP at Hospital X using one of three implicated side-viewing duodenoscopes, also known as ERCP endoscopes, of the same model type; and (ii) were infected with NDM-1-producing Escherichia (or, “E”) coli, the outbreak’s strain of CRE.
In its published report in MMWR, the CDC concluded that inadequately reprocessed ERCP endoscopes were a source of Hospital X’s CRE outbreak strain, adding that the ERCP endoscope’s physical design was likely a primary contributor to disease transmission.
Two patient deaths linked to contaminated GI endoscopes: Illinois
Twenty to 30 years ago, GI endoscopy had been linked to instances, albeit rarely, not just of patient morbidity (i.e., infection), but also of patient mortality.
In general, these reports of disease transmission were attributed to GI endoscopes, usually ERCP endoscopes, that were often contaminated with Pseudomonas aeruginosa (which is not of the Enterobacteriaceae family of bacteria and, therefore, even if resistant to antibiotics, necessarily is not CRE).
Healthcare facilities: Click here to download a brochure that discusses Dr. Muscarella’s auditing program specifically designed to prevent infection-control breaches and disease transmission during ERCP and other GI endoscopic procedures.
Examples of these published reports from more than 20 years ago documenting transmission of P. aeruginosa by contaminated ERCP endoscopes include:
- Allen JI, Allen MO, Olson MM et al. Pseudomonas infection of the biliary system resulting from use of a contaminated endoscope. Gastroenterology 1987 Mar; 92(3): 759-63.
- Alvarado CJ, Stolz SM, Maki DG. Nosocomial infections from contaminated endoscopes: a flawed automated endoscope washer. An investigation using molecular epidemiology. Am J Med 1991 Sep 16; 91(3B): 272S-280S.
- Cryan EMJ, Falkiner FR, Mulvihill TE, et al. Pseudomonas aeruginosa cross-infection following ERCP. J Hosp Infect 1984; 5: 371-6.
- Struelens MJ, Rost F, Deplano A, et al. Pseudomonas aeruginosa and Enterobacteriaceae bacteremia after biliary endoscopy: an outbreak investigation using DNA macrorestriction analysis. Am J Med 1993 Nov; 95(5): 489-98.
Since these reports published in the 1980s and 1990s, GI endoscopy in the U.S. has been linked at times to patient infections, but rarely to reported instances of patient mortality.
Now, years later, in 2014, the CMS’s aforementioned hospital inspection report (dated January 16, 2014) citing infection-control deficiencies at Hospital X confirms the death of two of its 10 patients who were infected with the outbreak’s strain of CRE.
The findings of CMS’s hospital inspection report notwithstanding, some contemporaneously published news articles — for example, one published in the Chicago-Sun Times two weeks earlier (January 3, 2014; click here; also read the relevant quotes from another publication, dated January 12, 2014: click here) — reported that Hospital X’s outbreak of CRE linked to contaminated ERCP endoscopes was not associated with any patient deaths.
The claim that Hospital X’s outbreak of CRE was not associated with any patient deaths appears consistent with at least one manufacturer’s filed MAUDE report (click here), and, too, with the CDC’s aforementioned article published in JAMA, whose authors wrote in that article that:
“Two of the 8 case patients (C1, C2) with clinical cultures died during their hospitalization but their deaths did not appear related to the CRE infection.“
Yet, this claim is anything but as clear as these reports may suggest. In fact, the published facts do not rule out the possibility that Hospital X’s CRE outbreak played a significant role in the death of at least one of these two infected patients.
The reasons for the discrepancy between, on the one hand, reports stating that no patients deaths were associated with Hospital X’s CRE outbreak in 2013, while, on the other hand, the CMS’s inspection report revealing that two of the patients infected with the outbreak’s strain of CRE died are unclear and warrant further investigation.
A fallacy known as the “argument of silence,” the absence of data demonstrating that a bacterial outbreak was a primary contributor to a patient’s death does not, by itself, exculpate the outbreak of any blame.
Rather, a factor often overlooked, clinical evidence definitively ruling out an outbreak as a contributor to an infected patient’s death is necessarily required to exonerate it of any responsibility.
Hospital X’s outbreak documents one of the first reported instances in the past 30 years of patient death linked to a contaminated GI endoscope — Lawrence F. Muscarella, Ph.D.
A more detailed discussion of this fallacy — which is also known (in Latin) as the argumentum e silentio — is provided in more detail both in Box A, below. It is also discussed in Dr. Muscarella’s article entitled, “Tap Water Used for Irrigation during GI Endoscopy: A Recommendation and Assessment of the Infection Risk” — click here.
Four patient deaths linked to contaminated GI endoscopes: Washington
The last of the five MAUDE reports listed above (namely, report number: 2951238-2014-00349, dated January 1, 2013 — click here) describes a notable outbreak of CRE at a hospital in Washington state that was linked in 2013 to more than three dozen patient infections and colonizations, along with the deaths of 4 infected patients.
This outbreak, which shares many features in common with Hospital X’s CRE outbreak, is the focus of Dr. Muscarella’s accompanying article entitled, “Four More Deaths Linked to Contaminated Gastrointestinal Endoscopes in the Past Two Years: Washington, 2014” — click here.
Prompt implementation of corrective and preventive actions, as required, to reduce the risk of transmission of CRE during GI endoscopy is necessary to ensure patient safety. And, this article herein is provided as an alert to enhance awareness of this concerning risk.
Among other troubling traits, CRE are resistant to carbapenems, which are “last resort” antibiotics indicated for the treatment of some types of infections caused by antibiotic-resistant bacteria. In fact, some strains of CRE have become resistant to all antibiotics, and when they infected the bloodstream, CRE can be associated with a mortality rate of as high as 50%.
Once published, the public’s review and implementation of the recommendations and corrective actions provided by the FDA in its forthcoming safety advisory (which is reputed to be published in early 2015) discussing the risk of outbreaks of CRE (and their related superbugs) following GI endoscopy is urged.
Attention: Manufacturers: Click here to download a brochure that discusses a program Dr. Muscarella developed to improve the quality, safety, designs and reprocessing instructions of reusable medical instruments including GI endoscopes.
A number of Dr. Muscarella’s recommendations for the prevention of CRE transmission during GI endoscopy are provided in his related article: “Investigation and Prevention of Bacterial Outbreaks following Endoscopic Retrograde Cholangiopancreatography, or ERCP” — click here.
Dr. Muscarella has written the most comprehensive set of articles, to date, discussing the risk of CRE transmissions during GI endoscopy. Each of the following is discussed in this article, above:
- “Risk of transmission of carbapenem-resistant Enterobacteriaceae and related ‘superbugs’ during gastrointestinal endoscopy” — click here.
- “Four More Deaths Linked to Contaminated Gastrointestinal Endoscopes in the Past Two Years: Washington, 2014” — click here.
- “Superbugs, Contaminated Gastrointestinal Endoscopes, and a Growing Number of Hospital Infections: Is an FDA Action Imminent?” — click here.
- “Overlooked Outbreaks of ‘CRE’ Following GI Endoscopy: A “Superbug” Epidemic in Our Midst?” — click here.
- “Investigation and Prevention of Bacterial Outbreaks following Endoscopic Retrograde Cholangiopancreatography, or ERCP” — click here.
These and other articles by Dr. Muscarella that focus on the risk of transmission of CRE (and related superbugs) during GI endoscopy are listed in the dedicated webpage: “Superbugs & Endoscopy” — click here.
Box A: Argumentum e silentio
The “argument of silence” is important to consider and understand, because it may, at times, be used in health care. Awareness of this fallacy is a step toward avoiding its use during assessments of the clinical impact of bacterial outbreaks and whether an infection (or another factor) was responsible for a patient’s death.
Also known as an ‘argumentum e silentio’ (or, to argue based on silence), this common fallacy may be used unwittingly to assert that a conclusion is valid, not based on data confirming the conclusion’s truth, but based on the absence of data demonstrating it to be false.
This fallacy may be employed more often than is realized vis-a-vis assessments about whether a bacterial outbreak or infection may have been a primary cause of an infected patient’s death.
Namely, a number of reviewed reports of recent bacterial outbreaks indicates that a hospital may, at times, conclude (and possibly write in the patient’s medical file or on the death certificate) that a patient’s death was due to nondescript “sepsis” without noting, too, that “a hospital infection” could have also contributed.
This conclusion can be illogical because the hospital’s conclusion may be based almost entirely on the lack (or “silence”) of data demonstrating this assessment to be false, rather than being based on clinical data or evidence confirming this assessment to be true.
Chicago (IL): By way of an example, the CDC concluded in the aforementioned article in JAMA (see: main article) that the strain of CRE that infected 10 patients in 2013 at Hospital X (near Chicago, Illinois) “did not appear to be” responsible for the deaths of either of two infected patients, despite:
- first, certain CRE infections are documented to be associated with a mortality rate of as high as 50%; and,
- second, the necessary data for the CDC to advance this conclusion (that the outbreak likely did not contribute to the deaths of either of the two infected patients) lacking.
Due to this absence of data, the possibility remains that at least one of these two infected patients’ death was due, at least in part, to the hospital’s CRE outbreak.
Pittsburgh (PA): A second outbreak of CRE was similarly linked to contaminated GI endoscopes, this time in Pittsburgh (PA) in 2012.
According to a hospital official, no patients died as a direct result of the CRE infection.
This conclusion would be a fallacy, however, if it was based on the lack (or “silence”) of data demonstrating that the outbreak of CRE was a primary cause of the patient’s death, rather than being based on clinical data or evidence definitively ruling out the outbreak as a contributor.
Interestingly, a newspaper article that reported on this outbreak noted this same hospital official as saying that “it’s impossible to say whether that infection was a contributor” — click here.
Translation: there certainly remains the possibility that this hospital’s outbreak of CRE could have contributed to the death of one or more of the infected patients —- a conclusion that is reasonably inconsistent with the hospital’s implied finding that the CRE outbreak linked to contaminated GI endoscopes was not associated with any patient deaths.
(Note: This outbreak could not be identified by this article’s author in the FDA’s MAUDE database, despite the hospital acknowledging that it had linked at least three medical devices to its CRE outbreak.)
Oakland (PA): According to a newspaper report, in 2010 and 2011 officials identified an outbreak of Legionnaires’ disease at the Department of Veterans Affairs (VA) hospital in Oakland (PA) — click here to read more.
Some of these patients infected by this disease while receiving medical treatment and care at this VA hospital were told by hospital officials that their infection was “community-acquired” (translation: that the hospital was not responsible for the infection), despite an investigation of this outbreak by the CDC in 2012 concluding that the patients’ infections were probably acquired at the hospital (i.e., healthcare-associated infections).
In each of these cases, clinical data confirming that the infection did not play a direct or indirect role in the deaths of any infected patients were lacking. Yet, conclusions that the outbreak was not responsible for any patient deaths were advanced.
This is a potential fallacy because for each of these three examples, the possibility cannot be ruled out that a hospital-associated infection could have been at least in part responsible for the morbidity or mortality of one or more infected patients.
In general, clearer, more accurate assessments of the causes of a patient’s infection or death are crucial to accountability, transparency, and the improvement of health care.
Article by: Lawrence F. Muscarella, Ph.D., President; LFM Healthcare Solutions, LLC (A Quality Improvement Company). Posted: 6/26/2014; Rev A; updated: 12/30/2014, Rev C