September 2, 2015 — Lawyers representing the family of an 82-year-old woman who died from a ‘superbug’ infection linked to a contaminated medical endoscope have filed a wrongful death lawsuit against both the hospital and the device’s manufacturer.

The patient became infected with “CRE” after undergoing ERCP at Advocate Lutheran General Hospital, in Park Ridge (IL). In late 2013, the patient died from her infection, according to her family’s lawyers.

ERCP — more formally known as endoscopic retrograde cholangiopancreatography — is used to examine, diagnose and treat certain diseases of the duodenum, the first part of the small bowel. It’s performed more than 650,000 times per year in the U.S.

At the time the patient underwent ERCP, unbeknownst to her, the hospital was battling an outbreak of CRE, or carbapenem-resistant Enterobacteriaceae, in 2013.

This superbug is resistant to most available antibiotics, including carbapenems — the “big gun” and “last resort” antibiotic. Some strains of CRE are untreatable and can be associated with a mortality rate of as high as 50%.

Officials linked Advocate Lutheran’s CRE outbreak — which began in January 2013 and took almost a year to control, ending in December 2013 — to contaminated duodenoscopes sold by Pentax Medical.

This wrongful death lawsuit was filed last week, on August 31st, in Cook County (IL).

Quality and Safety Services for Hospitals, Manufacturers, Patients: Click here to read about Dr. Muscarella’s quality and safety services committed to reducing the risk of healthcare-associated infections, including CRE outbreaks linked to contaminated endoscopes and other reusable medical equipment.

FDA warning letters to endoscope manufacturers

This wrongful death lawsuit follows hard on the heels of a recent FDA action against the Pentax Medical, FujiFilm and Olympus — the three Japan-based companies that manufacture all of the duodenoscopes sold in the U.S.

While acknowledging that the designs of duodenoscopes may hinder cleaning, causing them to transmit superbugs even if hospitals clean these devices as instructed by the manufacturers’ labeling, the FDA asserts that the clinical benefits of these devices, at least for some patients, continues to outweigh their recently acknowledged infection risk.

Two weeks ago, on August 12, 2015, the FDA sent warning letters to these three duodenoscope companies concluding that their devices are “adulterated” or “misbranded.” According to USA TODAY, these warning letters are a first step toward formal legal action.

The FDA’s conclusion that these companies’ duodenoscopes, used to perform ERCP on a daily basis in the U.S., are adulterated or misbranded is as much a regulatory bombshell as it is a clinical concern for hospitals scrambling to comply with federal regulations and mitigate the risk of superbug infections following ERCP.

The safety and effectiveness of adulterated or misbranded devices cannot be assured, as these devices have neither been approved nor cleared by the FDA, respectively.

Instead, devices that are without an approval or clearance, yet used in the clinical setting, would be classified as “investigational,” subject to stringent federal rules and regulations, including the hospital’s receipt of an investigational device exemption (IDE) and its establishment of an institutional review board (IRB). Most hospitals already have on file a policy governing the use of investigational devices.

Centers for Medicare and Medicaid Services

CMS (or, the Centers for Medicare and Medicaid Services) require hospitals participating in the federal Medicare and Medicaid programs to comply with certain safety standards, including to provide a “sanitary environment” for the prevention of disease transmissions.

To date, CMS and national accreditation firms have not publicly discussed whether a hospital’s use of one of the three companies’ duodenoscopes — which the FDA’s warning letters of August 12, 2015, state are adulterated or misbranded — would result in a citation. CMS which is the single largest payer for healthcare services in the U.S.

Additional details about these three FDA warning letters may be read in my related articles:

A CDC outbreak investigation of Advocate Lutheran’s CRE outbreak in 2013

Advocate Lutheran General Hospital’s deadly CRE outbreak in 2013 was investigated by the Centers for Disease Control and Prevention (CDC), which published its findings in the Journal of the American Medical Association (JAMA) in 2014.

In this JAMA article, the CDC wrote: “exposure to duodenoscopes with bacterial contamination was associated with apparent transmission of (CRE) among patients at (Advocate Lutheran General Hospital). Bacterial contamination of duodenoscopes appeared to persist despite the absence of recognized reprocessing lapses.”

The CDC also wrote in JAMA that two of the outbreak’s infected patients died, one of whom presumably is the woman whose family just filed the aforementioned wrongful death lawsuit.

But, without providing a clear rationale, the CDC concludes that neither patient’s death was likely due to the outbreak, writing in JAMA that two of the eight infected patients died during hospitalization, “but their deaths did not appear related to the CRE infection.”

The CDC’s conclusion may prove to be controversial, not only as it applies to the wrongful death lawsuit, but also because, according to a federal hospital inspection report, dated January 16, 2014, one of these two patients had a urine culture of “greater than 100,000 CFU/ml (or, colony forming units per milliliter)” of CRE — an indicator of a CRE infection.

In fact, the death certificate declares the cause of death to be “sepsis with multi organ failure, enterococcal urinary tract infection, and cholysystitis,” according to this inspection report.

Understanding, then, that the CRE-infected patient died of sepsis — according to the Mayo Clinic, sepsis “occurs when chemicals released into the bloodstream to fight (an) infection trigger inflammatory responses throughout the body” — it is not clear why the CDC would write in JAMA that the patient’s death did not appear to be related to the hospital’s outbreak of CRE.

The CDC’s assessment in JAMA raises a number of other questions, too, including why the death certificate does not directly state that CRE — the superbug with which the patient was infected at the time of death and that is associated with a mortality rate of as high as 50% — could have at least contributed to this patient’s death.

Other CRE outbreaks

Almost a year later, another outbreak of CRE — which, like Advocate Lutheran’s in 2013, was also linked to patient deaths following ERCP, but involved contaminated duodenoscopes sold by Olympus, not Pentax — was confirmed in early 2015, at UCLA’s Ronald Reagan Medical Center (Los Angeles, CA).

Other superbug outbreaks similarly linked to duodenoscopes sold by Olympus, Pentax or FujiFilm have been confirmed in Seattle (WA), Connecticut, Pittsburgh (PA), Worcester (MA), Florida and Wisconsin, among other cities and states, since 2008, but primarily since 2012.

Other similar lawsuits involving contaminated duodenoscopes

This is not the first lawsuit filed against Advocate Lutheran General Hospital as a result of its 2013 outbreak of CRE linked to Pentax’s duodenoscopes. Court records indicates that three other medical malpractice lawsuits were also filed against the hospital and Pentax.

Last October (2014), a suit was filed by a woman who claims that she and 43 other patients were also infected with CRE while undergoing ERCP at Advocate Lutheran General Hospital during its outbreak, in 2013.

That suit claims that the duodenoscopes used to perform these endoscopic procedures were not properly cleaned and was “colonized” with CRE, resulting in more than three dozen potentially deadly infections.

Other considerations: endoscopic accessories

USA TODAY reports that each of the U.S. hospitals that have linked an outbreak of CRE (or a related deadly superbug) to ERCP, since 2012, including Advocate Lutheran General Hospital, used an automated endoscope reprocessor, or AER, to remove bacteria from the contaminated duodenoscopes prior to ERCP.

The significance of the AER’s use by each of these hospitals that confirmed an outbreak of CRE following ERCP is not clear.

But this fact raises a reasonable question: Whether the FDA might soon write warning letters to each of the manufacturers of AERs in the U.S., citing them, too, for any identified regulatory lapses.

I discuss the potential for such a lapse, for the first time, in my related article: namely, failure of the AER to have been validated for reprocessing the newer duodenoscope models with “sealed” elevator wire channels, such as the Olympus TJF-Q180V (older models featured an “open” channel that required reprocessing).

Another possible lapse might be for the manufacturer having labeled the AER to reprocess duodenoscopes that are without a legal approval. As discussed above, the FDA’s warning letters, dated August 12, 2015, sent to the three duodenoscope companies conclude that their devices are adulterated or misbranded.

According to federal rules, legal devices in the U.S., such as an AER, may only be labeled for use with (i.e., to reprocess) other legally cleared (or approved) devices (e.g., medical endoscopes).

Medical device reports, or MDRs

In its warning letter to Pentax, dated August 12, 2015, the FDA cites the company for failing to file medical device reports, better known as “MDRs,” in a timely manner, as federal regulations require.

More specifically, the FDA’s warning letter states that Pentax failed to inform the FDA within 30 calendar days after “it received or otherwise became aware of information, from any source, that reasonably suggests that (its duodenoscope) may have caused or contributed to a death or serious injury.”

As an example, the FDA’s letter cites Pentax for failing to submit a MDR within 30-calendar days for each patient who developed a CRE infection after an endoscopic procedure involving Pentax’s duodenoscopes. As demonstration of the company’s incomplete filing of MDRs, the FDA references the details provided in a MDR, whose reference number is 2518897-2013-00005 and which Pentax filed in 2013.

Similarly, the FDA’s warning letter to Olympus, dated August 12, 2015, cited the company for this same regulatory breach. The focus that the FDA is now placing on MDRs could be a direct result of several recent media reports investigating this topic, including USA TODAY’s “Reports to Feds on deadly bacteria outbreaks arrived late” (April 15, 2015)

The FDA requires that manufacturers file a MDR for each patient who might have been infected, colonized or otherwise potentially harmed by a contaminated duodenoscope. If 10 patients are infected by a hospital’s use of a contaminated duodenoscope, the FDA requires that the device’s manufacturer file, not just one MDR documenting the outbreak, but 10 different MDRs, one for each potentially harmed patient.

My research suggests that the infections that the FDA is referring to in Pentax’s warning letter is Advocate Lutheran General Hospital’s deadly CRE outbreak, in 2013.

The MDR that Pentax filed in 2013 — the FDA references this MDR in its warning letter (again, Report No. 2518897-2013-00005) — refers to the company having a “conference call with ‘advocate’ on (a redacted date),” presumably referring to Advocate Lutheran General Hospital.

Two years later, on July 24, 2015, the FDA received a MDR filed by Pentax discussing the association of this company’s duodenoscope with a CRE infection following ERCP performed on a patient in 2013. This MDR also states that Pentax was served a compliant (summons) earlier in 2015 regarding this patient’s superbug infection.

Referencing a CRE outbreak in 2013 of which this infected patient appears to have been a part, Pentax states in this MDR, filed in 2015, that previous MDRs were filed in 2013, but that “the patient identified in the lawsuit complaint … cannot be matched to patients that were previously the subject of” the MDR filed in 2013. As a result, it appears that Pentax filed this additional MDR in 2015, to comply with the federal regulations overseeing MDRs.

Whether the “compliant (summons)” that Pentax was served in 2015, as noted in this filed MDR, is directly related to this wrongful death lawsuit, which, as mentioned previously, was filed against this same company in early September 2015, is unclear, but possible.

Article by: Lawrence F Muscarella, PhD; posted: September 8, 2015, Rev B.

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