The ERCP Patient: Risk Factors for Infection

“Every infection prevented is one that needs no treatment.”
(World Health Organization)

Background

In September of 2013 the Center for Disease Control and Prevention alerted the Food and Drug Administration (FDA) about a duodenoscope-associated NDM-E.coli outbreak (1). Since that time numerous outbreaks involving multidrug-resistant organisms (MDRO) have been reported worldwide, some resulting in patient deaths (2-4). The FDA has been diligent in its efforts to understand their etiology including a requirement for post-market surveillance studies aimed at assessing the burden of endoscope contamination following reprocessing by high-level disinfection (HLD). From this effort, and that of other investigators, three important learnings have emerged.

1. Despite using best practices in reprocessing duodenoscopes with high level disinfection (HLD), there remains >5% risk that duodenoscopes continue to harbor pathogenic organisms thus increasing the risk of patient infection due to cross-contamination (5).
2. A key factor in the resilience of microorganisms, including MDROs, to withstand reprocessing is their ability to form biofilm. Biofilm, once established, is extremely difficult to remove compromising the effectiveness of manual cleaning that is essential to successful disinfection or sterilization (6, 7). While the complexity of the elevator mechanism in the distal tip of a duodenoscope makes it particularly vulnerable to inadequate cleaning practices, the entire scope, including accessories and the irrigation system, are also at risk (8).
1. The use of “enhanced” reprocessing methods recommended by the FDA (e.g. double HLD or sterilization with ethylene oxide) has been shown to be unreliable in producing an endoscope that is free from contamination (9-12).

As a result, the FDA recommends that “Hospitals and endoscopy facilities should transition to innovative duodenoscope designs that include disposable components such as disposable endcaps, or to fully disposable duodenoscopes when they become available.” (5).

Purpose

Although the risk for infection following an ERCP procedure is rare (13) it is important to acknowledge that some patients are more vulnerable to infection than others (14). The goal of this white paper is to describe those factors that affect an ERCP patients’ risk for infection.

Identifying risk factors for infection: The ERCP patient.

Understanding the risk factors that facilitate the transmission of infectious agents is important for preventing their spread and can also be used to identify those patients most vulnerable to infection. This white paper provides a list of risk factors that may cause a patient who is undergoing ERCP to be more susceptible to infection or colonization or may put a reusable duodenoscope inventory at risk. This list is based on general principles of infection prevention, outbreak investigation literature, and professional association guidelines. This list is not a risk index or risk calculator. Actual post-ERCP infection and colonization rates in clinical practice are unknown (15) therefore not all risk factors are identified and thus this list is not comprehensive.

Infection risk depends on the complex interplay of patient status, the infectious agent, and the environment of care (Table 1). Some factors can be controlled, whereas others require the implementation of interventions to mitigate their effect. Because of this complexity, assessment of infection risk is best performed on a case by case basis (14).

Table 1: General Factors Contributing to Risk of Infection (14)

Patient factors that contribute to infection risk: Increased Susceptibility to Infection

Patient factors that contribute to infection risk: Risk of Post-procedure Infection

Patient factors that contribute to infection risk: Risk of Post-procedure Infection(Continued)

High-risk cardiac patients include those with a prosthetic valve, prior history of infectiousendocarditis (IE), cardiac transplant recipients who develop valvulopathy, and patients withcongenital heart disease (13). The prevalence of hospital-acquired IE may be increasing alongwith changes in the microbiology of the disease prompting a discussion on changing thestrategies to prevent this disease (26). 

Protection of Endoscope Inventory

Protection of Endoscope Inventory: Active Patient Infection and Colonization

Re-usable duodenoscopes (with or without removable endcaps) exposed to patients withactive infections are at risk of becoming persistently contaminated with pathogenic organismsand thus increasing the risk of patient infection and colonization (4). The emphasis on protectionof a duodenoscope inventory has evolved as the GI community has become aware of pathogentransmissions and outbreaks associated with ERCP procedures (17). Currently the focus is on theemerging MDROs involved in these outbreaks but there should also be concern for infectionscaused by pan-sensitive pathogens with a less remarkable profile as they also result insignificant patient morbidity and mortality (27). Active infections such as cholangitis, cholecystitis,localized infection, and septicemia all present risk for contamination of a duodenoscopeinventory (2-4, 28). Patients colonized with pathogenic organisms are of concern because theymay be asymptomatic or present with sub-clinical symptoms making them undetectableunless active screening is performed (14, 27, 29). Colonization also poses a risk to the patient asconversion to active infection may happen over a period of weeks to years (27). Travel historyand immigration status may be an important factor as well as there are many regions of theworld where MDROs are endemic (14).

Protection of Endoscope Inventory: Persistent Contamination of Endoscopes

Persistent contamination of a duodenoscope results from a complex interplay of events involvingexposure to infected/colonized patients, ineffective reprocessing protocols, and complexduodenoscope design (2, 4, 17, 30). Despite best efforts to follow current reprocessing guidelinesan endoscope that is known to be contaminated can remain contaminated despite multiplerounds of reprocessing (2, 4, 5, 16). Persistent contamination indicates that reprocessing is ineffective.The primary culprit that impedes effective reprocessing is the presence of biofilm which can beextremely difficult to remove even with adherence to best practice reprocessing protocols (6,7). Theprimary factors that contribute to persistent biofilm formation and microbial contamination are:

• Normal use of an endoscope results in damage that may include luminal shredding, scratches,gouges, staining, persistent debris, all of which provide a “safe harbor” for biofilm (1, 32, 33)
• Inadequate manual cleaning impedes high-level disinfection/sterilization (1)
  
• Incomplete drying resulting in storage of wet endoscopes (1,6, 34)
•  Complex endoscope design impedes proper reprocessing (1).

Protection of Endoscope Inventory (Continued)

Based on interim data from FDA post-market surveillance studies, up to 1 in 20 patient-readyduodenoscopes may be contaminated with pathogenic organisms (5, 31). Due to this ongoingchallenge, contaminated duodenoscopes are now recognized as a risk factor for transmissionof infection to ERCP patients (13). 

Conclusion

A patient’s risk of developing an infection involves complex interactions involving patientfactors, procedural factors, pathogen characteristics, and environmental factors (e.g. a contaminated duodenoscope) and therefore should be assessed on a case-by-case basis. Eventhough the infection rate associated with ERCP is considered low, the infections due toduodenoscope-associated transmissions and outbreaks are severe and life-threateningmaking infection prevention efforts critical to providing high quality patient care.

References

1. United States Food and Drug Administration. Infections Associated with ReprocessedDuodenoscopes [Available from: https://www.fda.gov/medical-devices/reprocessing-reusablemedical-devices/infections-associated-reprocessed-duodenoscopes.
2. Wendorf K, Kay M, Baliga C, Weissman S, Gluck M, Verma P, et al. Endoscopic RetrogradeCholangiopancreatography - Associated AmpC Escherichia coli Outbreak. Infection Control andHospital Epidemiology. 2015;36(6):634-42.
3. Epstein L, Hunter J, Arwady A, Tsai V, Stein L, Gribogiannis M, et al. New Dehli Metallo-B-LactamaseProducing Carbapenem-Resistant Escherichia coli Associated with Exposure to Duodenoscopes.New England Journal of Medicine. 2014;312(14):1447-55.
4. Kim S, Russell D, Mohamadnejad M, Makker J, Sedarat A, Watson RR, et al. Risk factors associatedwith the transmission of carbapenem-resistant Enterobacteriaceae via contaminatedduodenoscopes. Gastrointestinal Endoscopy. 2016;83:1121-9.
5. United States Food and Drug Administration. The FDA is recommending transition toduodenoscopes with innovative design to enhance safety: FDA Safety Communication. 2019.
6. Alfa MJ. Medical instrument reprocessing: current issues with cleaning and cleaning monitoring.American Journal of Infection Control. 2019;47:A10-A6.
7. Alfa MJ, Singh H, Nugent Z, Duerksen D, Schultz G, Reidy C, et al. Simulated-use polytetrafluoroethylenebiofilm model: repeated rounds of complete reprocessing lead to accumulation of organic debrisand viable bacteria. Infection Control and Hospital Epidemiology. 2017;38(11):1284-90.
8. Kovaleva J, Peters FT, van der Mei HC, Degener JE. Transmission of infection by flexible gastrointestinalendoscopy and bronchoscopy. Clinical Microbiology Reviews. 2013;26(2):231-54.
9. Snyder GM, Wright SB, Smithey A, Mizrahi M, Sheppard M, Hirsch EB, et al. Randomized Comparisonof 3 High-Level Disinfection and Sterilization Procedures for Duodenoscopes. Gastroenterology.2017;153:1018-25.
10. Bartles RL, Leggett JE, Hove S, Kashork CD, Wang L, Oethinger M, et al. A randomized trial of singleversus double high-level disinfection of duodenoscopes and linear echoendoscopes using standardautomated reprocessing. Gastrointestinal Endoscopy. 2018;88:306-13.
11. Rex DK, Sieber M, Lehman GA, Webb D, Schmitt B, Kressel AB, et al. A double-reprocessing highlevel disinfection protocol does not eliminate positive cultures from the elevators of duodenoscopes.Endoscopy. 2018;50:588-96.
12. Ofstead CL, Heymann OL, Quick MR, Johnson EA, Eiland JE, Wetzler HP. The effectiveness ofsterilization for flexible ureteroscopes: A real-world study. American Journal of Infection Control.2017;45(8):888-95.
13. ASGE. Adverse Events Associated with ERCP. Gastrointestinal Endoscopy. 2017;85(1):32-47.
14. Fiutem C. Risk Factors Facilitating Transmission of Infectious Agents 2014. Available from: https://text.apic.org/toc/microbiology-and-risk-factors-for-transmission/risk-factors-facilitating-transmission-of-infectious-agents.
15. Ofstead CL, Langlay AMD, Mueller NJ, Tosh PK, Wetzler HP. Re-evaluating endoscopy-associatedinfection risk estimates and their implications. American Journal of Infection Control. 2013(41):734-6.
16. Humphries RM, Yang S, Kim S, Muthusamy VR, Russell D, Trout AM, et al. Duodenoscope-RelatedOutbreak of a Carbapenem-Resistant Klebsiella pneumoniae Identified Using Advanced MolecularDiagnostics. Clinical Infectious Diseases. 2017;65:1159-66.
17. Rubin ZA, Kim S, Thaker AM, Muthusamy VR. Safely reprocessing duodenoscopes: current evidenceand future directions. Lancet Gastroenterology and Hepatology. 2018;13(3):499-508.
18. Flood A. The Immunocompromised Host 2019. Available from: https://text.apic.org/toc/microbiologyand-risk-factors-for-transmission/the-immunocompromised-host.
19. ASGE. Anitbiotic prophylaxis for GI endoscopy. Gastrointestinal Endoscopy. 2015;81(1):81-9.
20. Alferink LJM, Oey RC, Hansen BE, Polak WG, Buuren HRv, Man RAd, et al. The impact of infections ondelisting patients from the liver transplantation waiting list. Transplant International. 2017;30:807-16.
21. Fagiuoli S, Colli A, Bruno R, Craxì A, Gaeta GB, Grossi P, et al. Management of infections pre- andpost-liver transplantation: Report of an AISF consensus conference. Journal of Hepatology.2014;60:1075-89.
22. Reddy KR, O’Leary JG, Kamath PS, Fallon MB, Biggins SW, Wong F, et al. High Risk of Delisting orDeath in Liver Transplant Candidates Following Infections: Results From the North AmericanConsortium for the Study of End-Stage Liver Disease. Liver Transplantation. 2015;21:881-8.
23. Thosani N, Zubarick R, S., Kochar R, Kothari S, Sardana N, Nguyen T, et al. Prospecitive evaluationof bacteremia rates and infectious complications amoung patients undergoing single-operatorcholedochoscopy during ERCP. Endoscopy. 2016;48:424-31.
24. Wang P, Xu T, Ngamruengphong S, Makary MA, Kalloo A, Hutfless S. Rates of infection aftercolonoscopy and osophagogastroduodenoscopy in ambulatory surgery centres in the USA. Gut.2018;67:1626-36.
25. ASGE. Antibiotic prophylaxis for GI endoscopy. Gastrointestinal Endoscopy. 2015;81(1):81-9.
26. Moreyra AE, East S-a, Zinonos S, Trivedi M, Kostis JB, DPhill, et al. Trends in Hospitalization forInfective Endocarditis as a Reason for Admission or a Secondary Diagnosis. American Journal ofCardiology. 2019;124:430-4.
27. Thornhill G, David M. Endoscope-associated infections: A microbiologist’s 27. Thornhill G, David M. Endoscope-associated infections: A microbiologist’s perspective on currenttechnologies. Techniques in Gastrointestinal Endoscopy. 2019.
28. Baggs J, Jernigan J, Laufer-Halpin A, Epstein L, Hatfield K, McDonald LC. Risk of Subsequent Sepsiswithin 90 days after a Hospital Stay by Type of Antibiotic Exposure. Clinical Infectious Diseases.2018;66:1004-12.
29. Lutgring JD, Limbago BM. The Problem of Carbapenemase-Producing-Carbapenem-ResistantEnterobacteriaceae Detection. Journal of Clinical Microbiology. 2016;54(3):529-34.
30. Ofstead CL, Wetzler HP, Heymann OL, Johnson EA, Eiland JE, Shaw MJ. Longitudinal assessment ofreprocessing effectiveness for colonoscopes and gastroscopes: Results of visual inspections,biochemical markers, and microbial cultures. American Journal of Infection Control. 2017;45:e26-e33.
31. United States Food and Drug Administration. The FDA Continues to Remind Facilities of theImportance of Following Duodenoscope Reprocessing Instructions: FDA Safety Communication 2019[Available from: https://www.fda.gov/medical-devices/safety-communications/fda-continuesremind-facilities-importance-following-duodenoscope-reprocessing-instructions-fda.
32. Ofstead CL, Hopkins KM, Eiland JE, Wetzler HP. Widespread clinical use of simethicone, insolublelubricants, and tissue glue for endoscopy: A call to action for infection preventionists. AmericanJournal of Infection Control. 2019
33. Thaker AM, Kim S, Sedarat A, Watson RR, Muthusamy VR. Inspection of endoscope instrumentchannels after reprocessing using a prototype borescope. Gastrointestinal Endoscopy. 2018;88:612-9.
34. Ofstead CL, Heymann OL, Quick MR, Eiland JE, Wetzler HP. Residual moisture andwaterborne pathogens inside flexible endoscopes: Evidence from a multisite study of endoscopedrying effectiveness. American Journal of Infection Control. 2018;46(6):689-96.
35. Rauwers AW, Voor in’t holt AF, Bujis JG, de Groot W, Hensen BE, Bruno MJ, et al. High prevalence rateof digestive tract bacteria in duodenoscopes: a nationwide study. Gut. 2018;67(9):1637-45.

Quick Reference Guide: ERCP Patient – Risk Factors for Infection

Understanding the risk factors that facilitate the transmission of infectious agents duringERCP procedures is important for preventing their spread and can also be used to identifythose patients most vulnerable to infection. Risk factors may be grouped into two generalcategories: patient factors and those factors that increase the risk of contamination of theendoscope inventory. 

Patient factors that contribute to infection risk: Susceptibility to Infection

Patient factors that contribute to infection risk: Risk of Post-procedure Infection 

Protection of Endoscope Inventory 

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CAUTION: U.S. Federal Law restricts this device to sale by or on the order of a physician. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device.All photographs taken by Boston Scientific.