- Email: [email protected]
Infection Using ERCP Endoscopes
Gastroenterology 2016;-:1–5
Infection Using ERCP Endoscopes Q5
Bret T. Petersen,1 Johannes Koch,2 and Gregory G. Ginsberg3 1 Mayo Clinic, Rochester, Minnesota; 2Virginia Mason Medical Center, Seattle, Washington; and 3University of Pennsylvania, Philadelphia, Pennsylvania
T
he issue of patient-to-patient transmission of infection during endoscopic retrograde cholangiopancreatography (ERCP) continues to evolve. The occurrence of carbapenem-resistant Enterobacteriaceae infections after ERCP reached the awareness of the medical community in 2014 when the Centers for Disease Control and Prevention (CDC) published the findings of their investigation of a suburban Chicago case cluster.1,2 In early 2015, reports of similar outbreaks at several major medical centers across the United States prompted the US Food and Drug Administration (FDA) to issue safety alerts3–5 and convene an FDA expert panel6; there was intense media attention and both the CDC7 and industry8 provided guidance regarding steps for ensuring safe clinical care in the absence of definitive solutions. In 2016, the release of a US Senate committee investigative report9 culminated in a closely coordinated FDA and industry recall of duodenoscopes for refurbishment and replacement of suspect parts,10,11 among other related actions. Despite progress in our awareness and understanding of the problem, the currently proposed solutions remain cumbersome and unproven. Endoscope cleaning and reprocessing technologies and practices progressed greatly in the latter part of the 20th century, culminating in enduring standards for high-level disinfection (HLD).12,13 In the Spaulding classification for reprocessing of durable medical devices, endoscopes are designated as “semicritical” devices that make contact with mucous membranes and thus are suitable for HLD. Transmission of infection by flexible endoscopes has historically been ascribed to inconsistent practice of manual cleaning and HLD. Outbreaks of Pseudomonas aeruginosa after ERCP using side-viewing duodenoscopes dating to the 1980s14 were noted to occur particularly in the first patient of the day after overnight storage and shortly after reprocessing. This problem was largely eliminated with adoption of complete channel drying by alcohol flushing and forced air perfusion after HLD.12 Clinical infections occasionally follow the use of ERCP in patients with preexisting chronic colonization of bacteria (owing to obstructing pathology, abnormal anatomy, indwelling prostheses, or prior interventions). The recent occurrences of interpatient transmission via the duodenoscope only became evident when infections with newly recognized, highly resistant species prompted point source investigations using sophisticated bacterial typing to determine their origin. A recent single-center study using universal culturing of reprocessed endoscopes demonstrated that 2% of patient-ready instruments harbored
persistent enteric pathogens.15 Thus, we now realize that contaminated endoscopes can transmit some antibioticsensitive, as well as highly resistant cases, of post-ERCP cholangitis. Furthermore, the unusual resistant cases can result in chronic colonization of the gastrointestinal tract, with delayed infectious complications weeks to months later in unrelated organ systems.16 Infectious cross-contamination also occurs from other hospital or institutional sources, as demonstrated in outbreaks of carbapenem-resistant Enterobacteriaceae in intensive care units and chronic nursing facilities. The frequency of transmission through the environment, however, is generally far lower than for iatrogenic exposure and investigations strongly suggest that the endoscope is the transmission source in most outbreaks of post-ERCP multidrug-resistant infections. The recent report of the Senate’s Health, Education, Labor, and Pensions Committee thoroughly outlines the breadth of the problem and potential regulatory and industry factors contributing to the delay in response to the risk of duodenoscope transmission of infection (Table 1).9
Why Are Duodenoscopes Prone to Persistent Contamination? Despite the time-tested efficacy of current HLD practices, reprocessing of flexible endoscopes yields a narrow safety margin for eradication of contaminating organisms. Sterile devices are generally held to a standard of harboring less than 1 organism in 106 reprocessed instruments (Sterility Assurance Level of 10-6). A similar standard holds for HLD, with the exception of some tolerant spores. Endoscopes, however, harbor 109–1012 organisms at procedure completion. This bioburden is reduced by 103 (1000-fold) during bedside precleaning and further by 106 during manual washing, leaving the final 106–109 reduction to be achieved by exposure to liquid chemical germicides during HLD.17 This can be a tall order, given the need to achieve optimal reprocessing on every instrument every day, despite the circumstances (eg, space, pace, staffing, and resources) of many busy endoscopy units. Lapses in reprocessing can result in chronic colonization by adherent biofilm that cannot be eradicated by repeated and thorough cleaning and HLD. The aggregation of biofilm permits otherwise
© 2016 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2016.05.040
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Table 1.Current Understandings Regarding CRE Increasingly prevalent in the United States. Transmitted despite apparent optimal HLD. Not inherently more resistant to HLD agents and process. Patients with multiple comorbidities or immunosuppression at greatest risk of infection and death. Many patients develop silent carriage, with risk of future infection or transmission. Clinical infections often removed in time (months) and organ location from exposure. Mortality of clinical infection is significant (50%). Regarding CRE and ERCP outbreaks 4 US sites published in medical literature. >5 more sites publicly disclosed. Overall, 25 outbreaks of MDRO after duodenoscope use.9 1 cluster before 2010, most exposures 2012-2014. 250 clinical infections and 20þ deaths worldwide.9 >1000 patients notified for screening; estimated >100 silent carriage. Some transmissions confirmed by endoscope culture, others negative. Occurrence with all 3 endoscope manufacturers and multiple designs. Occurrence with multiple automated endoscope reprocessors, but one with greater prevalence.9 Attributed to persistent contamination at elevator region and/or cable channels.
CRE, carbapenem-resistant Enterobacteriaceae; ERCP, endoscopic retrograde cholangiopancreatography; HLD, high-level disinfection; MDRO, multidrug-resistant organism. Adapted from references 9 and 16.
susceptible microorganisms to defy HLD.18 These challenges are greater for complex instruments with tight crevices and mechanical joints that are exposed repeatedly to highly infectious bioburden, as are duodenoscopes and some ultrasound endoscopes. Last, recent durability data suggest that inert surfaces exposed to significant wear become more susceptible to contamination and less amenable to easy clearance of bioburden.19
How Can the Risk of Persistent Contamination Be Reduced
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It should be emphasized that adherence to existing and enhanced endoscope HLD practice is largely effective. Evidence supports that there are several important aspects to endoscope reprocessing that combine to reduce the risk of biofilm accumulation and colonization and are worthy of reinforcement here. Routine postprocedure manual cleaning of the endoscope—wiping the exterior, flushing the channels, and brushing the elevator lever immediately after use and before the surfaces have become dried—is most effective. Ensuring that the disinfecting agent is being used at proper concentration, temperature, and duration and proper functioning of automated endoscope reprocessing equipment seems obvious enough, but bears emphasis. Biofilm can only develop in a moist environment, so routine
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flushing of the channels with alcohol as a desiccant followed by forced air drying and dry storage are equally important steps. The recent outbreaks have prompted a plethora of recommendations for further reducing the risk of duodenoscope transmission while also maintaining an adequate supply of instruments for patient care. The FDA has advised (a) enhanced oversight, training, and competency assurance for front line reprocessing staff, (b) assiduous attention to precleaning and cleaning steps before usual automated HLD, (c) adherence to manufacturer’s instructions for use, including use of singular proprietary cleaning brushes used by the manufacturers in their validation studies for reprocessing, and (d) new emphasis on record keeping regarding all of these varied measures. Specific short term recommendations from the American Gastroenterological Association include surveillance of all patients who have had a procedure using an elevator channel endoscope, tracking of each elevator channel endoscope by patient and device serial number, and periodic collection of cultures from all elevator equipped endoscopes currently in use within a practice.20 Most centers should have intensified their efforts in these regards. Most technical tasks in health care involve annual competency testing, but more frequent confirmation of performance has been encouraged by some groups such as the American Gastroenterological Association, which suggests requiring demonstration of competency semiannually. Certification of endoscope reprocessing staff has been proposed but, so far, not adopted beyond that required in the operating room setting where tasks and expectations extend far beyond one type of instrument. A collaborative, focused approach to certification for flexible endoscope reprocessing alone may prove useful, particularly for smaller settings where training and supervisory personnel may be unable to ensure expertise in all tasks. Adherence to manufacturer’s instructions for use is required to ensure their extension of warranty claims and shared liability. In May 2015, a majority of the FDA’s independent advisory panel felt that current reprocessing standards for existing duodenoscope designs were insufficient for ensuring patient safety. The FDA subsequently encouraged facilities to consider adoption of optional supplemental measures to enhance duodenoscope reprocessing, including (a) use of surveillance endoscope cultures, (b) double reprocessing cycles between patients, (c) ethylene oxide (ETO) sterilization, and/or (d) use of a liquid chemical sterilant processing system (Table 2).6 Surveillance culturing of endoscopes is expensive, challenging to perform well, and difficult to interpret, largely owing to the presence of nonsignificant organisms in many samples. The CDC has proposed surveillance culture techniques analogous to their existing methods for outbreak investigations.7 They use sampling via sterile flushes of the biopsy channel, and both swabbing and swirling immersion of the elevator region at the tip of the endoscope. Because the CDC culture regimen is not validated for confirmation of sterility, or even post-HLD clearance of pathogens, the American Microbiology Association and some clinical
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laboratories have declined to process what they interpret as ‘environmental’ cultures.21 The CDC advises that units quarantine cultured endoscopes away from use until negative results return after 2-3 days. One group used this approach on a per-procedure basis to break their cycle of contamination on some instruments.15 However, adoption of this approach may substantially curtail instrument availability or require a considerable increase in duodenoscope inventory. Because contaminated endoscopes may harbor culture-negative but biologically viable residue, culturing is imperfect. Others use cultures intermittently to identify gross breaches in their endoscope reprocessing process, as suggested by the CDC. The expense of additional endoscopes can be reduced when a subset of instruments is cultured at the end of every work week. The FDA proposal for double reprocessing cycles or routine sequential duplication of the manual cleaning and HLD steps (washing / HLD / washing / HLD), without quarantine, extends from the “culture-quarantine” experience cited, wherein repeat reprocessing for those duodenoscopes with positive cultures reduced the culture positive rate of pathogenic bacteria by one additional log (w2% to 0.2%).15 This is perhaps the most simple and readily
Table 2.Opportunities for Reducing Risks of Transmission of Infection Through ERCP Improved QA of reprocessing Optimal training, oversight, and competency evaluation of existing processes. Surveillance testing of bioburden (ATP) for QA of washing processes before HLD. Selective culture and quarantine after HLD after use in MDRO (þ) patient. Per procedure culture and quarantine after HLD. Surveillance culture for QA of HLD process. Alternative approaches to reprocessing Double cycles of washing and HLD after each procedure. Selective ETO sterilization, intermittently (for biofilm) or after use in MDRO (þ) patient. Per procedure ETO sterilization after HLD. Peracetic acid liquid sterilization Identification of high-risk endoscopes Routine anal swab in selected or all ERCP patients for detection of CRE (via PCR) or CRE and other MDROs (via culture and sensitivity) to elect alternative or enhanced reprocessing. Scheduled endoscope maintenance, upgrade, parts replacements. Scheduled endoscope retirement. New technologies Alternative duodenoscope designs with: Enhanced access for cleaning (removable tips); Tolerance to high temperature autoclaving; and Single-use disposable components. Alternative low temperature sterilization technologies. Adjunctive tools for enhanced precleaning, washing, and storage.
ATP, adenosine triphosphate; CRE, carbapenem-resistant Enterobacteriaceae; ERCP, endoscopic retrograde cholangiopancreatography; ETO, ethylene oxide; HLD, high-level disinfection; MDRO, multidrug-resistant organism; PCR, polymerase chain reaction; QA, quality assurance. Adapted from reference 16.
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adopted additional measure to consider, however it has not been validated and staffing, space, and equipment considerations may be challenging impediments in some environments. ETO achieves chemical sterilization of endoscopes. Endoscope manufacturers provide guidance on the use of ETO for endoscope reprocessing. Some have provided validated time and temperature conditions for their instruments; however, ETO has not been subjected to FDA review for this purpose and some manufacturers do not approve of this treatment. Informal experience suggests routine ETO treatment may stiffen or otherwise alter some functional aspects of flexible instruments. Moreover, although once used commonly in hospitals, ETO has fallen out of favor in part owing to extensive controls required to avoid its carcinogenic and teratogenic risks.22 As such, few enterprises are equipped to perform ETO sterilization and it is simply not readily available for most endoscopy facilities. When available, the instrument turnaround time may be long (17–48 hours) and costs of sterilization, instrument transport, and increased endoscope inventory to compensate for downtime are significant. Considerations like these make the prospect of the wide adoption of ETO unlikely. The FDA also encouraged consideration of endoscope sterilization using automated reprocessing with liquid chemical sterilants, such as peracetic acid, which has been touted as a sterilant appropriate for devices that do not require terminal point of use sterility, as in gastrointestinal endoscopy. This approach, however, has yet to be validated and approved as a chemical sterilant for duodenoscopes. Given the recent transmissions after appropriate treatment with other liquid chemical germicides, it is not intuitively clear that an alternative liquid-based process will overcome the challenge of inaccessible crevices in these complex instruments. Several other alternatives to limiting endoscope transmitted infections, particularly those of resistant organisms, have not been subjected to rigorous study. Prophylactic antibiotics have only been demonstrated useful and are deemed appropriate in those procedures with an expectation of persisting obstruction, such as intervention for primary sclerosing cholangitis, hilar tumors, duct leaks, or fluid collections.23 Screening of patients for multidrug-resistant organisms or carbapenem-resistant Enterobacteriaceae, before their procedure, would enable subsequent intensified reprocessing of instruments that are potentially at risk for transmission of these more serious infections. Testing of anal swabs by polymerase chain reaction is a potentially efficient mechanism for avoiding the delayed turnaround of culture techniques. This approach, however, does not address the risk of transmission of common antibioticsensitive organisms. Last, real-time testing of the outcome of endoscope reprocessing remains elusive. A variety of tests for biologic contaminants seem to be useful for evaluating the adequacy of intermediate steps in reprocessing, but none correlate well with terminal culture negativity. Testing for adenosine triphosphate after manual washing is the best studied and most easily used (via a 5-minute assessment of test swabs or solutions). It may prove most
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useful for training and intermittent surveillance washing performance. Industry has a responsibility to manufacture endoscopes that will achieve routine, reliable, and effective HLD. Recent submissions by all 3 manufacturers (Olympus, Pentax, and Fujinon) have validated current reprocessing outcomes in test environments and the FDA has ruled that post market studies of reprocessing in clinical settings are expected,24,25 but these results will not be forthcoming for several years. Ultimately, instrument redesign should emphasize performance enhancements for both the endoscopist and instrument processing staff. Endoscope redesign should emphasize features that reduce the impact of inevitable human error. Industry will need to partner with their customers in regular education, training, certification, and monitoring of instrument reprocessing practices. AER manufacturers similarly should promote systems that monitor and record the integrity of their functionality. The recent events have also highlighted the opportunity for preventive maintenance to include scheduled instrument inspection for material degradation and biofilm accumulation. Patients and physicians want and expect no transmission of infections by any medical instrument. It is the collective responsibility of endoscope manufacturers, health systems, and providers to ensure endoscope reprocessing is mistake proof, establishing systems to identify and eliminate the risk of infection for patients undergoing flexible endoscopy. With >650,000 ERCPs performed in the United States annually, even the lowest reported defect rate of 0.7%, will expose 4500 patients to a preventable risk. Although the ultimate solution may require redesign of duodenoscopes, the near term imperative of endoscopy units and providers is strict adherence to FDA/CDC recommendations, maintenance of measurable unit-based quality control, and surveillance for infectious complications associated with endoscopic procedures. Parallel physician responsibilities include use of judicious indications and thorough informed consent discussions for all endoscopic procedures. These goals for the endoscopists will uphold the trust that we must achieve and maintain with our patients.
References
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1. CDC. Notes from the field: New Delhi metallo-blactamase–producing Escherichia coli associated with endoscopic retrograde cholangiopancreatographyIllinois, 2013. MMWR 2014;62. 1051–1051. 2. Epstein L, Hunter JC, Arwady MA, et al. New Delhi metallo-betalactamase–producing carbapenem-resistant Escherichia coli associated with exposure to duodenoscopes. JAMA 2014;312:1447–1455. 3. US Food and Drug Administration (FDA). Design of endoscopic retrograde cholangiopancreatography (ERCP) duodenoscopes may impede effective cleaning: FDA safety communication. Available: www.fda.gov/MedicalDevices/ Safety/AlertsandNotices/ucm434871.htm. Accessed February 16, 2016.
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4. US Food and Drug Administration (FDA). endoscopic retrograde cholangiopancreatography (ERCP) duodenoscopes: FDA safety communication - design may impede effective cleaning. Available: www.fda.gov/Safety/MedWatch/ SafetyInformation/SafetyAlertsforHumanMedicalProducts/ ucm434922.htm. 5. US Food and Drug Administration (FDA). Supplemental measures to enhance reprocessing: FDA safety communication. Available: www.fda.gov/MedicalDevices/ Safety/AlertsandNotices/ucm454766.htm. Accessed February 16, 2016. 6. US Food and Drug Administration (FDA). Brief Summary of the Gastroenterology and Urology Devices Panel Meeting, May 14-15, 2015. Available: www.fda.gov/downloads/ AdvisoryCommittees/CommitteesMeetingMaterials/Medical Devices/MedicalDevicesAdvisoryCommittee/Gastroenter ology-UrologyDevicesPanel/UCM447407.pdf. Accessed February 16, 2016. 7. Centers for Disease Control and Prevention (CDC). Interim duodenoscope surveillance protocol. Available: www.cdc.gov/hai/organisms/cre/cre-duodenoscope-sur veillance-protocol.html. Accessed February 16, 2016. 8. http://medical.olympusamerica.com/sites/default/files/ pdf/150326_TJF-Q180V_Customer_letter.pdf. Accessed Q3 February 16, 2016. 9. United States Senate. Preventable tragedies: superbugs and how ineffective monitoring of medical device safety fails patients. Available: www.help.senate.gov/imo/ media/doc/Duodenoscope%20Investigation%20FINAL %20Report.pdf. Accessed February 16, 2016. 10. Food and Drug Administration (FDA). FDA clears Olympus TJF-Q180V duodenoscope with design modifications intended to reduce infection risk. Available: www. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ ucm481956.htm. Accessed February 16, 2016. 11. Available: http://medical.olympusamerica.com/sites/us/ files/pdf/160118-Olympus-TJF-Q180V-Customer-Letter. Q4 pdf. Accessed February 26, 2016. 12. Nelson DB, Jarvis WR, Rutala WA, et al. Multisociety guideline for reprocessing flexible gastrointestinal endoscopes. Gastrointest Endosc 2003;58:1–8. 13. Petersen BT, Chennat J, Cohen J, et al. Multisociety guideline on reprocessing flexible gastrointestinal endoscopes: 2011. Gastrointest Endosc 2011; 73:1075–1084. 14. Allen JI, O’Connor Allen M, Olson MM, et al. Pseudomonas infection of the biliary system resulting from use of a contaminated endoscope. Gastroenterology 1987; 92(3):759–763. 15. Ross AS, Baliga C, Verma P, et al. A quarantine process for the resolution of duodenoscope-associated transmission of multidrug resistant E. coli. Gastrointest Endosc 2015;82:477–483. 16. Petersen BT. Duodenoscope reprocessing: risk and options coming into view. Gastrointestinal Endoscopy 2015;82:484–487. 17. Rutala WA, Weber DJ. CDC Guideline for Disinfection and Sterilization in Healthcare Facilities, 2008. Available: www.cdc.gov/hicpac/pdf/guidelines/Disinfection_Nov_ 2008.pdf. Accessed April 20, 2016.
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18. Pajkos A, Vickery K, Cossart Y. Is biofilm accumulation on endoscope tubing a contributor to the failure of cleaning and decontamination? J Hosp Infect 2004; 58(3):224–229. 19. Lee DH, Kim DB, Kim HY, et al. Increasing potential risks of contamination from repetitive use of endoscope. Am J Infect Control 2015;43:e13–e17. 20. American Gastroenterological Association. AGA press release: recommendations from “getting to zero”: first meeting of regulators, endoscope manufacturers and gastroenterologists. Available: www.gastro.org/ press_releases/2015/3/23/how-to-stop-duodenoscopeinfections. Accessed March 9, 2015. 21. ASM Public and Scientific Affairs Board Committee on Laboratory Practices, Susan E. Sharp, PhD, DABMM, FAAM, Chair. April 2015. 22. Centers for Disease Control and Prevention (CDC), National Institute for Occupation Safety and Health (NIOSH). Ethylene oxide (EtO): evidence of
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carcinogenicity. Available: www.cdc.gov/niosh/docs/81130/. Accessed April 20, 2016. 23. ASGE Standards of Practice Committee, Khashab MA, Chithadi KV, Acosta RD, et al. ASGE guideline: antibiotic prophylaxis for GI endoscopy. Gastrointest Endosc 2015;81:81–89. 24. US Food and Drug Administration (FDA). FDA News Release. FDA orders duodenoscope manufacturers to conduct post-market surveillance studies in health care facilities Available: www.fda.gov/NewsEvents/Newsroom/ PressAnnouncements/ucm465639.htm. Accessed October 14, 2015. 25. Rutala WA, Weber DJ. ERCP scopes: what can we do to prevent infections? Infect Control Hosp Epidemiol 2015; 36:643–648. Conflicts of interest The authors have made the following disclosures: Johannes Koch has been a consultant to Sedasys, Inc. Gregory Ginsberg is a paid consultant to Olympus Q1 Inc.
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Infection Using ERCP Endoscopes Q5
Bret T. Petersen,1 Johannes Koch,2 and Gregory G. Ginsberg3 1 Mayo Clinic, Rochester, Minnesota; 2Virginia Mason Medical Center, Seattle, Washington; and 3University of Pennsylvania, Philadelphia, Pennsylvania
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he issue of patient-to-patient transmission of infection during endoscopic retrograde cholangiopancreatography (ERCP) continues to evolve. The occurrence of carbapenem-resistant Enterobacteriaceae infections after ERCP reached the awareness of the medical community in 2014 when the Centers for Disease Control and Prevention (CDC) published the findings of their investigation of a suburban Chicago case cluster.1,2 In early 2015, reports of similar outbreaks at several major medical centers across the United States prompted the US Food and Drug Administration (FDA) to issue safety alerts3–5 and convene an FDA expert panel6; there was intense media attention and both the CDC7 and industry8 provided guidance regarding steps for ensuring safe clinical care in the absence of definitive solutions. In 2016, the release of a US Senate committee investigative report9 culminated in a closely coordinated FDA and industry recall of duodenoscopes for refurbishment and replacement of suspect parts,10,11 among other related actions. Despite progress in our awareness and understanding of the problem, the currently proposed solutions remain cumbersome and unproven. Endoscope cleaning and reprocessing technologies and practices progressed greatly in the latter part of the 20th century, culminating in enduring standards for high-level disinfection (HLD).12,13 In the Spaulding classification for reprocessing of durable medical devices, endoscopes are designated as “semicritical” devices that make contact with mucous membranes and thus are suitable for HLD. Transmission of infection by flexible endoscopes has historically been ascribed to inconsistent practice of manual cleaning and HLD. Outbreaks of Pseudomonas aeruginosa after ERCP using side-viewing duodenoscopes dating to the 1980s14 were noted to occur particularly in the first patient of the day after overnight storage and shortly after reprocessing. This problem was largely eliminated with adoption of complete channel drying by alcohol flushing and forced air perfusion after HLD.12 Clinical infections occasionally follow the use of ERCP in patients with preexisting chronic colonization of bacteria (owing to obstructing pathology, abnormal anatomy, indwelling prostheses, or prior interventions). The recent occurrences of interpatient transmission via the duodenoscope only became evident when infections with newly recognized, highly resistant species prompted point source investigations using sophisticated bacterial typing to determine their origin. A recent single-center study using universal culturing of reprocessed endoscopes demonstrated that 2% of patient-ready instruments harbored
persistent enteric pathogens.15 Thus, we now realize that contaminated endoscopes can transmit some antibioticsensitive, as well as highly resistant cases, of post-ERCP cholangitis. Furthermore, the unusual resistant cases can result in chronic colonization of the gastrointestinal tract, with delayed infectious complications weeks to months later in unrelated organ systems.16 Infectious cross-contamination also occurs from other hospital or institutional sources, as demonstrated in outbreaks of carbapenem-resistant Enterobacteriaceae in intensive care units and chronic nursing facilities. The frequency of transmission through the environment, however, is generally far lower than for iatrogenic exposure and investigations strongly suggest that the endoscope is the transmission source in most outbreaks of post-ERCP multidrug-resistant infections. The recent report of the Senate’s Health, Education, Labor, and Pensions Committee thoroughly outlines the breadth of the problem and potential regulatory and industry factors contributing to the delay in response to the risk of duodenoscope transmission of infection (Table 1).9
Why Are Duodenoscopes Prone to Persistent Contamination? Despite the time-tested efficacy of current HLD practices, reprocessing of flexible endoscopes yields a narrow safety margin for eradication of contaminating organisms. Sterile devices are generally held to a standard of harboring less than 1 organism in 106 reprocessed instruments (Sterility Assurance Level of 10-6). A similar standard holds for HLD, with the exception of some tolerant spores. Endoscopes, however, harbor 109–1012 organisms at procedure completion. This bioburden is reduced by 103 (1000-fold) during bedside precleaning and further by 106 during manual washing, leaving the final 106–109 reduction to be achieved by exposure to liquid chemical germicides during HLD.17 This can be a tall order, given the need to achieve optimal reprocessing on every instrument every day, despite the circumstances (eg, space, pace, staffing, and resources) of many busy endoscopy units. Lapses in reprocessing can result in chronic colonization by adherent biofilm that cannot be eradicated by repeated and thorough cleaning and HLD. The aggregation of biofilm permits otherwise
© 2016 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2016.05.040
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Table 1.Current Understandings Regarding CRE Increasingly prevalent in the United States. Transmitted despite apparent optimal HLD. Not inherently more resistant to HLD agents and process. Patients with multiple comorbidities or immunosuppression at greatest risk of infection and death. Many patients develop silent carriage, with risk of future infection or transmission. Clinical infections often removed in time (months) and organ location from exposure. Mortality of clinical infection is significant (50%). Regarding CRE and ERCP outbreaks 4 US sites published in medical literature. >5 more sites publicly disclosed. Overall, 25 outbreaks of MDRO after duodenoscope use.9 1 cluster before 2010, most exposures 2012-2014. 250 clinical infections and 20þ deaths worldwide.9 >1000 patients notified for screening; estimated >100 silent carriage. Some transmissions confirmed by endoscope culture, others negative. Occurrence with all 3 endoscope manufacturers and multiple designs. Occurrence with multiple automated endoscope reprocessors, but one with greater prevalence.9 Attributed to persistent contamination at elevator region and/or cable channels.
CRE, carbapenem-resistant Enterobacteriaceae; ERCP, endoscopic retrograde cholangiopancreatography; HLD, high-level disinfection; MDRO, multidrug-resistant organism. Adapted from references 9 and 16.
susceptible microorganisms to defy HLD.18 These challenges are greater for complex instruments with tight crevices and mechanical joints that are exposed repeatedly to highly infectious bioburden, as are duodenoscopes and some ultrasound endoscopes. Last, recent durability data suggest that inert surfaces exposed to significant wear become more susceptible to contamination and less amenable to easy clearance of bioburden.19
How Can the Risk of Persistent Contamination Be Reduced
AGA SECTION
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Petersen et al
It should be emphasized that adherence to existing and enhanced endoscope HLD practice is largely effective. Evidence supports that there are several important aspects to endoscope reprocessing that combine to reduce the risk of biofilm accumulation and colonization and are worthy of reinforcement here. Routine postprocedure manual cleaning of the endoscope—wiping the exterior, flushing the channels, and brushing the elevator lever immediately after use and before the surfaces have become dried—is most effective. Ensuring that the disinfecting agent is being used at proper concentration, temperature, and duration and proper functioning of automated endoscope reprocessing equipment seems obvious enough, but bears emphasis. Biofilm can only develop in a moist environment, so routine
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flushing of the channels with alcohol as a desiccant followed by forced air drying and dry storage are equally important steps. The recent outbreaks have prompted a plethora of recommendations for further reducing the risk of duodenoscope transmission while also maintaining an adequate supply of instruments for patient care. The FDA has advised (a) enhanced oversight, training, and competency assurance for front line reprocessing staff, (b) assiduous attention to precleaning and cleaning steps before usual automated HLD, (c) adherence to manufacturer’s instructions for use, including use of singular proprietary cleaning brushes used by the manufacturers in their validation studies for reprocessing, and (d) new emphasis on record keeping regarding all of these varied measures. Specific short term recommendations from the American Gastroenterological Association include surveillance of all patients who have had a procedure using an elevator channel endoscope, tracking of each elevator channel endoscope by patient and device serial number, and periodic collection of cultures from all elevator equipped endoscopes currently in use within a practice.20 Most centers should have intensified their efforts in these regards. Most technical tasks in health care involve annual competency testing, but more frequent confirmation of performance has been encouraged by some groups such as the American Gastroenterological Association, which suggests requiring demonstration of competency semiannually. Certification of endoscope reprocessing staff has been proposed but, so far, not adopted beyond that required in the operating room setting where tasks and expectations extend far beyond one type of instrument. A collaborative, focused approach to certification for flexible endoscope reprocessing alone may prove useful, particularly for smaller settings where training and supervisory personnel may be unable to ensure expertise in all tasks. Adherence to manufacturer’s instructions for use is required to ensure their extension of warranty claims and shared liability. In May 2015, a majority of the FDA’s independent advisory panel felt that current reprocessing standards for existing duodenoscope designs were insufficient for ensuring patient safety. The FDA subsequently encouraged facilities to consider adoption of optional supplemental measures to enhance duodenoscope reprocessing, including (a) use of surveillance endoscope cultures, (b) double reprocessing cycles between patients, (c) ethylene oxide (ETO) sterilization, and/or (d) use of a liquid chemical sterilant processing system (Table 2).6 Surveillance culturing of endoscopes is expensive, challenging to perform well, and difficult to interpret, largely owing to the presence of nonsignificant organisms in many samples. The CDC has proposed surveillance culture techniques analogous to their existing methods for outbreak investigations.7 They use sampling via sterile flushes of the biopsy channel, and both swabbing and swirling immersion of the elevator region at the tip of the endoscope. Because the CDC culture regimen is not validated for confirmation of sterility, or even post-HLD clearance of pathogens, the American Microbiology Association and some clinical
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laboratories have declined to process what they interpret as ‘environmental’ cultures.21 The CDC advises that units quarantine cultured endoscopes away from use until negative results return after 2-3 days. One group used this approach on a per-procedure basis to break their cycle of contamination on some instruments.15 However, adoption of this approach may substantially curtail instrument availability or require a considerable increase in duodenoscope inventory. Because contaminated endoscopes may harbor culture-negative but biologically viable residue, culturing is imperfect. Others use cultures intermittently to identify gross breaches in their endoscope reprocessing process, as suggested by the CDC. The expense of additional endoscopes can be reduced when a subset of instruments is cultured at the end of every work week. The FDA proposal for double reprocessing cycles or routine sequential duplication of the manual cleaning and HLD steps (washing / HLD / washing / HLD), without quarantine, extends from the “culture-quarantine” experience cited, wherein repeat reprocessing for those duodenoscopes with positive cultures reduced the culture positive rate of pathogenic bacteria by one additional log (w2% to 0.2%).15 This is perhaps the most simple and readily
Table 2.Opportunities for Reducing Risks of Transmission of Infection Through ERCP Improved QA of reprocessing Optimal training, oversight, and competency evaluation of existing processes. Surveillance testing of bioburden (ATP) for QA of washing processes before HLD. Selective culture and quarantine after HLD after use in MDRO (þ) patient. Per procedure culture and quarantine after HLD. Surveillance culture for QA of HLD process. Alternative approaches to reprocessing Double cycles of washing and HLD after each procedure. Selective ETO sterilization, intermittently (for biofilm) or after use in MDRO (þ) patient. Per procedure ETO sterilization after HLD. Peracetic acid liquid sterilization Identification of high-risk endoscopes Routine anal swab in selected or all ERCP patients for detection of CRE (via PCR) or CRE and other MDROs (via culture and sensitivity) to elect alternative or enhanced reprocessing. Scheduled endoscope maintenance, upgrade, parts replacements. Scheduled endoscope retirement. New technologies Alternative duodenoscope designs with: Enhanced access for cleaning (removable tips); Tolerance to high temperature autoclaving; and Single-use disposable components. Alternative low temperature sterilization technologies. Adjunctive tools for enhanced precleaning, washing, and storage.
ATP, adenosine triphosphate; CRE, carbapenem-resistant Enterobacteriaceae; ERCP, endoscopic retrograde cholangiopancreatography; ETO, ethylene oxide; HLD, high-level disinfection; MDRO, multidrug-resistant organism; PCR, polymerase chain reaction; QA, quality assurance. Adapted from reference 16.
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adopted additional measure to consider, however it has not been validated and staffing, space, and equipment considerations may be challenging impediments in some environments. ETO achieves chemical sterilization of endoscopes. Endoscope manufacturers provide guidance on the use of ETO for endoscope reprocessing. Some have provided validated time and temperature conditions for their instruments; however, ETO has not been subjected to FDA review for this purpose and some manufacturers do not approve of this treatment. Informal experience suggests routine ETO treatment may stiffen or otherwise alter some functional aspects of flexible instruments. Moreover, although once used commonly in hospitals, ETO has fallen out of favor in part owing to extensive controls required to avoid its carcinogenic and teratogenic risks.22 As such, few enterprises are equipped to perform ETO sterilization and it is simply not readily available for most endoscopy facilities. When available, the instrument turnaround time may be long (17–48 hours) and costs of sterilization, instrument transport, and increased endoscope inventory to compensate for downtime are significant. Considerations like these make the prospect of the wide adoption of ETO unlikely. The FDA also encouraged consideration of endoscope sterilization using automated reprocessing with liquid chemical sterilants, such as peracetic acid, which has been touted as a sterilant appropriate for devices that do not require terminal point of use sterility, as in gastrointestinal endoscopy. This approach, however, has yet to be validated and approved as a chemical sterilant for duodenoscopes. Given the recent transmissions after appropriate treatment with other liquid chemical germicides, it is not intuitively clear that an alternative liquid-based process will overcome the challenge of inaccessible crevices in these complex instruments. Several other alternatives to limiting endoscope transmitted infections, particularly those of resistant organisms, have not been subjected to rigorous study. Prophylactic antibiotics have only been demonstrated useful and are deemed appropriate in those procedures with an expectation of persisting obstruction, such as intervention for primary sclerosing cholangitis, hilar tumors, duct leaks, or fluid collections.23 Screening of patients for multidrug-resistant organisms or carbapenem-resistant Enterobacteriaceae, before their procedure, would enable subsequent intensified reprocessing of instruments that are potentially at risk for transmission of these more serious infections. Testing of anal swabs by polymerase chain reaction is a potentially efficient mechanism for avoiding the delayed turnaround of culture techniques. This approach, however, does not address the risk of transmission of common antibioticsensitive organisms. Last, real-time testing of the outcome of endoscope reprocessing remains elusive. A variety of tests for biologic contaminants seem to be useful for evaluating the adequacy of intermediate steps in reprocessing, but none correlate well with terminal culture negativity. Testing for adenosine triphosphate after manual washing is the best studied and most easily used (via a 5-minute assessment of test swabs or solutions). It may prove most
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useful for training and intermittent surveillance washing performance. Industry has a responsibility to manufacture endoscopes that will achieve routine, reliable, and effective HLD. Recent submissions by all 3 manufacturers (Olympus, Pentax, and Fujinon) have validated current reprocessing outcomes in test environments and the FDA has ruled that post market studies of reprocessing in clinical settings are expected,24,25 but these results will not be forthcoming for several years. Ultimately, instrument redesign should emphasize performance enhancements for both the endoscopist and instrument processing staff. Endoscope redesign should emphasize features that reduce the impact of inevitable human error. Industry will need to partner with their customers in regular education, training, certification, and monitoring of instrument reprocessing practices. AER manufacturers similarly should promote systems that monitor and record the integrity of their functionality. The recent events have also highlighted the opportunity for preventive maintenance to include scheduled instrument inspection for material degradation and biofilm accumulation. Patients and physicians want and expect no transmission of infections by any medical instrument. It is the collective responsibility of endoscope manufacturers, health systems, and providers to ensure endoscope reprocessing is mistake proof, establishing systems to identify and eliminate the risk of infection for patients undergoing flexible endoscopy. With >650,000 ERCPs performed in the United States annually, even the lowest reported defect rate of 0.7%, will expose 4500 patients to a preventable risk. Although the ultimate solution may require redesign of duodenoscopes, the near term imperative of endoscopy units and providers is strict adherence to FDA/CDC recommendations, maintenance of measurable unit-based quality control, and surveillance for infectious complications associated with endoscopic procedures. Parallel physician responsibilities include use of judicious indications and thorough informed consent discussions for all endoscopic procedures. These goals for the endoscopists will uphold the trust that we must achieve and maintain with our patients.
References
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1. CDC. Notes from the field: New Delhi metallo-blactamase–producing Escherichia coli associated with endoscopic retrograde cholangiopancreatographyIllinois, 2013. MMWR 2014;62. 1051–1051. 2. Epstein L, Hunter JC, Arwady MA, et al. New Delhi metallo-betalactamase–producing carbapenem-resistant Escherichia coli associated with exposure to duodenoscopes. JAMA 2014;312:1447–1455. 3. US Food and Drug Administration (FDA). Design of endoscopic retrograde cholangiopancreatography (ERCP) duodenoscopes may impede effective cleaning: FDA safety communication. Available: www.fda.gov/MedicalDevices/ Safety/AlertsandNotices/ucm434871.htm. Accessed February 16, 2016.
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4. US Food and Drug Administration (FDA). endoscopic retrograde cholangiopancreatography (ERCP) duodenoscopes: FDA safety communication - design may impede effective cleaning. Available: www.fda.gov/Safety/MedWatch/ SafetyInformation/SafetyAlertsforHumanMedicalProducts/ ucm434922.htm. 5. US Food and Drug Administration (FDA). Supplemental measures to enhance reprocessing: FDA safety communication. Available: www.fda.gov/MedicalDevices/ Safety/AlertsandNotices/ucm454766.htm. Accessed February 16, 2016. 6. US Food and Drug Administration (FDA). Brief Summary of the Gastroenterology and Urology Devices Panel Meeting, May 14-15, 2015. Available: www.fda.gov/downloads/ AdvisoryCommittees/CommitteesMeetingMaterials/Medical Devices/MedicalDevicesAdvisoryCommittee/Gastroenter ology-UrologyDevicesPanel/UCM447407.pdf. Accessed February 16, 2016. 7. Centers for Disease Control and Prevention (CDC). Interim duodenoscope surveillance protocol. Available: www.cdc.gov/hai/organisms/cre/cre-duodenoscope-sur veillance-protocol.html. Accessed February 16, 2016. 8. http://medical.olympusamerica.com/sites/default/files/ pdf/150326_TJF-Q180V_Customer_letter.pdf. Accessed Q3 February 16, 2016. 9. United States Senate. Preventable tragedies: superbugs and how ineffective monitoring of medical device safety fails patients. Available: www.help.senate.gov/imo/ media/doc/Duodenoscope%20Investigation%20FINAL %20Report.pdf. Accessed February 16, 2016. 10. Food and Drug Administration (FDA). FDA clears Olympus TJF-Q180V duodenoscope with design modifications intended to reduce infection risk. Available: www. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ ucm481956.htm. Accessed February 16, 2016. 11. Available: http://medical.olympusamerica.com/sites/us/ files/pdf/160118-Olympus-TJF-Q180V-Customer-Letter. Q4 pdf. Accessed February 26, 2016. 12. Nelson DB, Jarvis WR, Rutala WA, et al. Multisociety guideline for reprocessing flexible gastrointestinal endoscopes. Gastrointest Endosc 2003;58:1–8. 13. Petersen BT, Chennat J, Cohen J, et al. Multisociety guideline on reprocessing flexible gastrointestinal endoscopes: 2011. Gastrointest Endosc 2011; 73:1075–1084. 14. Allen JI, O’Connor Allen M, Olson MM, et al. Pseudomonas infection of the biliary system resulting from use of a contaminated endoscope. Gastroenterology 1987; 92(3):759–763. 15. Ross AS, Baliga C, Verma P, et al. A quarantine process for the resolution of duodenoscope-associated transmission of multidrug resistant E. coli. Gastrointest Endosc 2015;82:477–483. 16. Petersen BT. Duodenoscope reprocessing: risk and options coming into view. Gastrointestinal Endoscopy 2015;82:484–487. 17. Rutala WA, Weber DJ. CDC Guideline for Disinfection and Sterilization in Healthcare Facilities, 2008. Available: www.cdc.gov/hicpac/pdf/guidelines/Disinfection_Nov_ 2008.pdf. Accessed April 20, 2016.
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18. Pajkos A, Vickery K, Cossart Y. Is biofilm accumulation on endoscope tubing a contributor to the failure of cleaning and decontamination? J Hosp Infect 2004; 58(3):224–229. 19. Lee DH, Kim DB, Kim HY, et al. Increasing potential risks of contamination from repetitive use of endoscope. Am J Infect Control 2015;43:e13–e17. 20. American Gastroenterological Association. AGA press release: recommendations from “getting to zero”: first meeting of regulators, endoscope manufacturers and gastroenterologists. Available: www.gastro.org/ press_releases/2015/3/23/how-to-stop-duodenoscopeinfections. Accessed March 9, 2015. 21. ASM Public and Scientific Affairs Board Committee on Laboratory Practices, Susan E. Sharp, PhD, DABMM, FAAM, Chair. April 2015. 22. Centers for Disease Control and Prevention (CDC), National Institute for Occupation Safety and Health (NIOSH). Ethylene oxide (EtO): evidence of
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carcinogenicity. Available: www.cdc.gov/niosh/docs/81130/. Accessed April 20, 2016. 23. ASGE Standards of Practice Committee, Khashab MA, Chithadi KV, Acosta RD, et al. ASGE guideline: antibiotic prophylaxis for GI endoscopy. Gastrointest Endosc 2015;81:81–89. 24. US Food and Drug Administration (FDA). FDA News Release. FDA orders duodenoscope manufacturers to conduct post-market surveillance studies in health care facilities Available: www.fda.gov/NewsEvents/Newsroom/ PressAnnouncements/ucm465639.htm. Accessed October 14, 2015. 25. Rutala WA, Weber DJ. ERCP scopes: what can we do to prevent infections? Infect Control Hosp Epidemiol 2015; 36:643–648. Conflicts of interest The authors have made the following disclosures: Johannes Koch has been a consultant to Sedasys, Inc. Gregory Ginsberg is a paid consultant to Olympus Q1 Inc.
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