Risk of transmission of carbapenem-resistant Enterobacteriaceae and related “superbugs” during gastrointestinal endoscopy

Table 1 Several questions that this article answers

(1) What is a “superbug”?

(2) What are carbapenem-resistant Enterobacteriaceae, or “CRE,” and their related superbugs?

(3) What are carbapenem-producing Enterobacteriaceae, or “CPE”?

(4) What important mechanism can cause CRE to become resistant to carbapenem antibiotics?

(5) What is a “carbapenemase” enzyme?

(6) What is a “β-lactam antibiotic” and a “β-lactam ring”?

(7) What are ESBL-producing Enterobacteriaceae and how do they differ from CRE?

(8) What types of infections do CRE cause?

(9) By what three mechanisms may Enterobacteriaceae acquire the genetic coding necessary to produce carbapenemases and become carbapenem-resistant?

(10) Prior to the emergence of CRE, what types of infectious agents have been historically transmitted during GI endoscopy?

(11) Is GI endoscopy a risk factor for CRE transmissions?

(12) What are some of the details and possible causes of the well-publicized CRE outbreak following ERCP performed by “Hospital X” in the mid-west (United States) that has recently raised public concerns about the risk of transmission of CRE during GI endoscopy?

(13) What are some of the details of other CRE outbreaks that similarly have been linked to GI endoscopy since this superbug’s emergence and have been published either in the medical literature or the FDA’s MAUDE database?

(14) Is high-level disinfection (whether automated or performed manually) of GI endoscopes sufficiently robust to prevent CRE transmissions? Or, is EtO sterilization of GI endoscopes required to prevent CRE transmissions?

(15) What do professional organizations including the CDC, FDA, SGNA, and ASGE currently recommend for reprocessing GI endoscopes potentially contaminated with CRE?

(16) What are some important recommendations that healthcare professionals may follow to minimize the risk of CRE transmission during GI endoscopy?

CRE: Carbapenem-resistant Enterobacteriaceae; GI: Gastrointestinal; EtO: Ethylene oxide gas; ASGE: American Society of Gastrointestinal Endoscopy.

Table 2 Reasons why the recent emergence of carbapenem-resistant Enterobacteriaceae and their related superbugs is a serious public-health concern

(1) While HAIs caused by CRE are relatively uncommon, their incidence both in the United States and globally is increasing, posing a growing public health threat[16,19,25,32]

(2) Strains of Enterobacteriaceae that are responsible for HAIs are becoming CRE at an alarming rate

(3) Infections of the bacterial strains that have emerged as CRE were once treatable with carbapenems, but are no longer, even though these antibiotics have been reserved by clinicians as a “last resort” or “last line” of defense for treating patients infected with multidrug-resistant bacteria

(4) CRE’s resistance to carbapenems significantly limits the number of available treatment options

(5) Those very few antibiotics that remain effective for treating CRE infections are generally undesirable because, among some other limitations, they can be nephrotoxic

(6) Some strains of CRE are pan-resistant (meaning they cannot be treated using any type of antibiotic)

(7) The mortality rate of infections caused by CRE and related superbugs is relatively high (compared to carbapenem-susceptible Enterobacteriaceae), causing the death of as many as 50% of patients with a bloodstream infection of CRE

(8) Not only are the number of patient deaths attributed to CRE infection (from all causes, not just bacteremia) significant, both in the United States and globally, but also the rate of death among patients with CRE infections (primarily of the bloodstream) has been reported to be as much as 2 times higher than that of patients infected with carbapenem-susceptible Enterobacteriaceae[35]

(9) The genetic code that confers the antibiotic resistance of CRE and their related superbugs can be shared or exchanged with other bacteria of the same, or of even of a different, species (i.e., “gene swapping”)

(10) CRE and related superbugs are highly transmissible in the healthcare setting (and have the potential to spread in the community too)

CRE: Carbapenem-resistant Enterobacteriaceae; HAIs: Healthcare-associated infections.

Table 3 Recommended practices for the effective reprocessing of gastrointestinal endoscopes

1 Reprocess the GI endoscope promptly after the endoscopic procedure in accordance with its manufacturer’s step-by-step set of instructions

(1) As required, supplement these instructions with the recommendations of published infection-control guidelines

(2) Always reprocess the GI endoscope’s air/water channels (Also, always reprocess the GI endoscope’s suction and air/water valves and other accessories)

(3) Before its reprocessing, visually examine the GI endoscope, especially its distal sheath, for excessive wear and tear, having it servicing when required

(4) Practice Standard Precautions when reprocessing GI endoscopes (As required, also employ Contact Precautions to prevent CRE transmission)

(5) Confirm that the high-level disinfectant is contacting all of the GI endoscope's potentially contaminated surfaces

(6) The use of ethylene oxide (EtO) gas to sterilize ERCP endoscopes, in lieu of high-level disinfection, may be considered. (No matter, thorough cleaning of the endoscope is required)

2 Place emphasis on cleaning and brushing (prior to high-level disinfection) the area near, around and behind the ERCP endoscope’s forceps elevator (Figure 1B)

(1) Ensure that, if it is exposed, the ERCP endoscope’s elevator wire channel, which houses the cable that controls and angulates this forceps elevator, is thoroughly flushed with a detergent solution. The complete manual reprocessing (i.e., cleaning, high-level disinfection, and drying) of this (exposed) channel may be necessary for some ERCP endoscope models, to prevent disease transmission

(2) Routinely train and evaluate the knowledge of reprocessing staffers

(3) Periodically audit reprocessing staffers’ practices to verify the proper cleaning and brushing of all models of GI endoscopes, especially the ERCP endoscopes[61]

(4) Use cleaning brushes and detergents that have been validated, recommended, and/or “approved” for use by the GI endoscope’s manufacturer[31,62,63]

(5) Manually “leak test” the GI endoscope prior to its cleaning in accordance with its manufacturer’s instructions (unless otherwise instructed by the automated endoscope reprocessor’s [or, AER’s] manufacturer, if the AER is equipped with an automated leak tester)

3 Routinely monitor (i.e., at least once a day, if not more often) the concentration of the high-level disinfectant to ensure its effectiveness. Record the results in a log book or use an electronic format that permits archiving and documentation retreival

(1) In addition to its concentration, verify and record for each processed GI endoscope that the high-level disinfectant’s immersion time and temperature are appropriate

4 Use bacteria-free (or sterile) water to rinse the GI endoscope following its high-level disinfection

(1) Compliance with this instruction may require: (A) proper maintenance and replacement of a water filtration system, if one is used; and (B) routine monitoring of the rinse water to confirm its lack of bacteria[64]

5 Consider using sterile water in the water bottle for lens cleaning and irrigation during GI endoscopy, especially during ERCP[15,65]

6 Terminally dry all of the GI endoscope’s internal channels (including the ERCP elevator wire channel, if it is exposed) using 70% alcohol and forced air[5,66]

7 Store the GI endoscope with its insertion tube hanging freely and vertically in a clean, dry, and well-ventilated area or cabinet[66,67]

(1) Consider reprocessing the GI endoscope again before its reuse if it has been stored for more than 5 d[68]. Reprocessing ERCP endoscopes before each use may be advisable

8 If using an AER, ensure that it is performing properly; has been validated for the effective reprocessing of each GI endoscope in inventory; has been serviced and maintained as required; and that its internal surfaces and components are being routinely self-disinfected as instructed by its manufacturer

9 Manufacturers may consider enhanced design controls and validation measures to ensure the adequate reprocessing of ERCP endoscopes and other complex reusable instrumentation, to further minimize the risk of disease transmission during GI endoscopy

CRE: Carbapenem-resistant Enterobacteriaceae; GI: Gastrointestinal.

Table 4 Several reports of outbreaks of carbapenem-resistant Enterobacteriaceae (or a related superbug) following gastrointestinal endoscopy that were filed in the Food and Drug Administration’s MAUDE database between 2012 and 2014 by manufacturers of gastrointestinal endoscopes and related medical equipment

Reports filed in 2014:

(1) Food and Drug Administration. Report date: May 2, 2014. Report number: 2951238-2014-00225. (Infections or colonizations of patients following ERCP with an extended β-lactamase [ESBL] strain of E. coli strain. Also refer to Report number: 2951238-2014-00004)

(2) Food and Drug Administration. Report date: March 7, 2014. Report number: 2518897-2014-00001[36]. (Infections or colonizations of patients following ERCP with CRE)

(3) Food and Drug Administration. Report date: January, 28, 2014. Report number: 2951238-2014-00027[38]. (Infections or colonizations of patients following ERCP with CRE)

(4) Food and Drug Administration. Report date: January 16, 2014. Report number: MW5033987[39]. (Infections or colonizations of patients following ERCP with CRE)

(5) Food and Drug Administration. Report date: May 27, 2014. Report number: MW5036408. (One patient infected or colonized with CRE following ERCP)

Reports filed in 2013:

(1) Food and Drug Administration. Report date: March 4, 2013. Report number: MW5029305[37]. (Infections or colonizations of patients following ERCP with CRE)

(2) Food and Drug Administration. Report date: September 30, 2013, and October 28, 2013. Report number: 2518897-2013-00005. (Also refer to Report number: 2523209-2013-00013). Note: This report was presumably filed by Hospital X documenting its CRE outbreak identified between January and September, 2013

Reports filed in 2012:

(1) Food and Drug Administration. Report date: September 25, 2012. Report number: 8010047-2012-00404. (Infections or colonizations of patients following ERCP with a multidrug-resistant E. coli)

(2) Food and Drug Administration. Report date: November 21, 2012. Report number: 8010047-2012-00454. (Possible infections or colonizations of patients following ERCP with E. coli; the bacterial strain is not necessarily resistant to antibiotics; and this incident may be a pseudo-outbreak, not true infections or colonizations)

These reports, which do not identify the medical facility by name, associate a contaminated ERCP endoscope with a confirmed patient infection or colonization, or with an outbreak of CRE or a related superbug. (Some of these reports are included in this article’s reference section. This table's listed reports for each year may not be inclusive of every report filed in that year). CRE: Carbapenem-resistant Enterobacteriaceae; GI: Gastrointestinal.