key: cord-0715825-n2br1mh2
authors: Chua, Tiffany; Halim, Nasir; Reicher, Sofiya
title: Recent advances in endoscope disinfection: where do we stand in the COVID era?
date: 2020-10-19
journal: Tech Innov Gastrointest Endosc
DOI: 10.1016/j.tige.2020.10.001
sha: f07bc5da4e49e4ec42bb22bc6426c2fb47ff8665
doc_id: 715825
cord_uid: n2br1mh2

Over sixteen million cases worldwide, severe acute respiratory syndrome coronavirus 2 has profoundly affected healthcare as we know it. Given reports of GI involvement and viral shedding in the stool, it is unsurprising there are concerns that endoscopic equipment may be a potential vector of viral transmission. Here, we provide an overview of existing practices for endoscope reprocessing, recent developments in the field, and challenges in the COVID-19 environment. Current multi-society guidelines do not advise any change to endoscope disinfection protocols but emphasize strict adherence to recommended practices. However, endoscopy reprocessing staff may benefit from supplemental personal protective equipment measures, especially in high risk situations. Because thorough endoscope reprocessing is highly operator dependent, adequate training of personnel is critical for proper manual cleaning and disinfection of endoscopes that have potential to harbor virus. Bacterial contamination of duodenoscopes has caused outbreaks of infection from multidrug resistant organisms, highlighting vulnerable areas. The emphasis of current studies is on optimization of disinfection and drying, minimization of simethicone use, and on quality control of endoscope reprocessing with sampling and microbiological culturing. Recent advances include novel approaches to endoscope sterilization, infection barrier methods, and design of partially or fully disposable duodenoscopes. Overall, the available data indicate that, when correctly executed, current reprocessing practices are sufficient in preventing SARS-COV-2 transmission.

severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in the healthcare setting has been described: a 1% rate of suspected and 0.12% of confirmed COVID-19 infection after endoscopic procedures was reported in a recent survey. (3) (4) Human coronaviruses can remain infectious on plastic surfaces for up to nine days at room temperature. SARS-COV-2 was detected on polyvinyl chloride (PVC), silicone, rubber, and Teflon surfaces for up to five days at room temperature, with a similar initial inoculum titer across varying media types. (5) Available data on surface stability of SARS-COV-2 are consistent with prior studies on human coronaviruses. (6) While specific data regarding the transmissibility of coronavirus from inanimate objects to hands via touch are lacking at this time, prior modeling of influenza A and parainfluenza noted transmissibility rates of 31.6% and 1.5% of viral load, respectively, underscoring the potential of fomite transmission. (7) (8) Furthermore, real-world environment and surface testing demonstrated virus-positive samples from various areas within a COVID-19 patient room, highlighting the potential for exposure that staff may encounter. (9) Gastrointestinal (GI) complains are frequent among COVID-19 patients, with 7.4% rate of diarrhea and 4.6% of nausea and vomiting. (10) Several studies demonstrated that viral RNA could be detected in small and large intestinal biopsies of human coronavirus patients and in stool of COVID-19 patients with or without GI symptoms. (10) (11) (12) (13) (14) . Clinical implications of these findings on viral transmissibility through the GI tract are not fully understood; despite presence of viral RNA in the stool, viable virus was not isolated in a recent detailed virological assessment of hospitalized COVID-19 patients. (15) Given the evidence of GI tract involvement and the resiliency of the SARS-COV-2 virus on inanimate surfaces, it is unsurprising that concerns have been raised about endoscopic equipment being a potential vector of viral transmission. Here, we discuss best practice guidelines on endoscope reprocessing, recent developments in the field, and current challenges in the COVID-19 pandemic environment.

Current multi-society best practice guidelines (endorsed jointly by AGA, ASGE, ACG, SGNA, ASCRS, and SAGES) advise no changes to established endoscope reprocessing procedures during the COVID-19 pandemic.(16) Based on available evidence, the standard protocol including bedside pre-cleaning followed by leak testing, manual cleaning and high-level disinfection (HLD) is sufficient in eradicating SARS-COV-2. Historically, the risk of viral transmission related to endoscopy has been rare to nonexistent. (21) (22) Previous reports of hepatitis C (HCV) transmission were due to nonadherence to aseptic techniques in drug administration, lapses in reprocessing protocols, and failure to adequately disinfect reusable biopsy forceps. (21) (22) Multicenter prospective studies of endoscopic procedures on HCV carriers or hepatitis B seropositive patients did not demonstrate post-procedural transmission following appropriate disinfections protocols. (23) (24) To date, there have been no reported cases of endoscope-associated SARS-COV-2 transmission.

Based on the Spaulding classification schema for disinfection of medical equipment, flexible endoscopes are 'semi-critical' devices and should at minimum undergo HLD.(21) HLD is achieved by complete immersion of the endoscope and associated removable parts in an approved chemical disinfectant at a specified temperature and duration. HLD is defined as a six-log reduction of Mycobacteria and ensures that devices are essentially free of all microorganisms, apart from low-level bacterial spores that do not increase transmission risk. (25) Certain devices in endoscopic procedures that are in contact with sterile tissues or anatomical spaces, such as sphincterotomes and biopsy forceps, are classified as critical devices and must be sterile. (22) Endoscope reprocessing is a multistep sequential process, with HLD as its cornerstone. The standard protocol for endoscope reprocessing is detailed in Figure 1 . It is impossible to overemphasize manual cleaning as the most critical step in disruption of biofilm and removal of microbial burden. Manual cleaning is performed using a detergent solution and meticulous cleaning with appropriate brushes of endoscope interior, exterior, and working channel. FDA and manufacturer-specified instructions should be followed for disinfection of elevator mechanisms and double channel endoscopes. (22, 25) Because thorough endoscope reprocessing is highly operator dependent, extensive training of Social distancing should be practiced within the reprocessing areas as well as frequent cleaning of all surfaces using chemical agents known to inactivate SARS-COV-2. As more data become available regarding seroconversion and viral immunity, deploying seroconverted staff in highrisk scenarios may be preferable, including in endoscope reprocessing areas. (30) 

In August 2015, in response to multiple multi-drug resistant organism (MDRO) infections linked to duodenoscope use, the Food and Drug Administration (FDA) strongly recommended that all endoscopy units adopt a series of supplemental measures to reduce infection transmission. (31) FDA recommendations included adoption of one or more of the following measures: culture surveillance of endoscopes, Ethylene oxide (EtO) sterilization, use of a liquid chemical sterilant processing system, and/or repeat HLD. FDA recommendations led to rapid changes in endoscope reprocessing practices in the US. Based on a recent survey of 249 endoscopy units (32) , most centers had implemented at least one of the supplemental measures; the most common was repeat HLD (63%) followed by culture surveillance (53%).

Repeat HLD was proposed by the FDA as a logical next step in the effort to mitigate infection transmission risk. In practice, it is unclear if this recommendation achieves the desired goal. The Attention has also turned to endoscope channel wear and tear as a potential nidus of infection.

Borescope inspection, a process used for endoscope repair, was proposed to evaluate endoscope channels for occult damage that can harbor bacteria. A borescope is a cylindrical tool with a light source that can be advanced forward and retrograde in the working channel for detailed inspection. Several studies have attempted to better characterize the correlation between borescope findings and endoscope post-processing bacterial growth. These studies presented quantitative data obtained from cultures and ATP bioluminescence, an assay that measures ATP, a surrogate marker for organic matter and a potential substrate for microbial growth. 

Another approach to reducing infection risk is optimization of drying protocols. Biofilm formation is a key factor in persistent bacterial contamination of endoscopes, and residual moisture facilitates their growth. Routine wear and tear has also been implicated: damaged surfaces in the endoscope could provide a potential space for biofilm development. While endoscope reprocessing guidelines emphasize the importance of thoroughly drying the endoscope, there is limited data on the optimal dryness threshold and best methods to achieve it. (45, 46) A recent study (45) compared the efficacy of standard drying cabinets commonly used in the US for endoscope storage versus automated drying cabinets. Automated drying yielded dry inner channels after 1 hour versus 24 hours of storage in a standard cabinet. After 48 hours of drying in automated cabinet, the Pseudomonas aeruginosa inoculated endoscopes had 7 log and 9 log fewer recovered organisms from colonoscopes and duodenoscopes respectively; in contrast, standard drying cabinets allowed bacterial growth. (45) To identify the optimum time for endoscope drying, Barakat et al. (46) compared a manual airdrying protocol versus 5-minute and 10-minute automated drying. Extending the automated drying time to 10 minutes yielded the best results: zero droplets were identified on borescope examination at 48 and 72 hours post-drying. Automated drying was also associated with lesser ATP bioluminescence values in the endoscope working channel. Of significant concern were the study findings of "pools of liquid" on borescope examination after standard reprocessing with an alcohol flush and a 1-minute air purge. Interestingly, vertical versus coiled endoscope storage did not affect residual channel fluid content in the automated drying group. In the manual drying group, vertical storage yielded fewer water droplets.(46)

Simethicone is a commonly used additive in endoscopy to remove bubbles from the mucosal surface. It is often mixed in water irrigation bottle or administered via a syringe during the procedure and significantly improves visualization.(47) However, all three major endoscope manufacturers recommend against the use of simethicone in endoscopy as it can provide a potential source for bacterial growth. Simethicone is water and alcohol insoluble, making its removal challenging. If necessary, administration with a syringe at the lowest concentration possible is recommended. Several studies described residual simethicone in endoscopes after following manufacturer recommended reprocessing protocols. (48) (49) (50) The impact of simethicone use on water droplet retention and residual biomatter was investigated in recent study (49) using borescope inspection of the working channel and ATP bioluminescence measurement. The mean volume of simethicone solution used per procedure was higher when added to the irrigation water bottle versus injection via a syringe. Use of medium/high concentrations of simethicone resulted in retention of more fluid droplets and greater ATP bioluminescence values in the working channel. In this study the endoscopes that underwent a second reprocessing cycle retained no fluid droplets and had ATP bioluminescence values comparable to water use alone. This finding supports the manufacturer (Olympus America, Inc.) recommendations of two HLD cycles for endoscopes exposed to simethicone. (49) 

The FDA required post-market surveillance studies from all three major endoscope manufacturers to assess the "real-world" failure rate of endoscope reprocessing and to determine if reprocessing personnel can adhere to manufacturers' reprocessing instructions.

The 2019 findings demonstrated unacceptably high post-processing contamination rates ranging from 4 to 6% and the failure to perform critical steps of manual cleaning in almost one third of participants. (51) The inherent limitations of current endoscope reprocessing practices, highlighted by post-marketing studies, led to significant advances in both disinfection protocols and infection barrier methods, and triggered the development of novel partially and fully disposable endoscopes.

Low temperature plasma-activated gas (PAG) may represent a promising new method for sterilization. PAG was shown to have antimicrobial effects on a wide range of organisms including spores, fungi, and drug-resistant bacteria due to the production of ultraviolet light and free radicals. High frequency voltage applied at atmospheric pressure to gases such as hydrogen, nitrogen or inert gases generates reactive oxygen and nitrogen species; these interact with the surface of interest without impacting its bulk properties. While this method has not been used in endoscopy to date, it has been commercially available since the 1990s and utilized for sterilization of total joint replacement components. (52) A recent proof-of-concept bench study (53) showed that application of argon PAG for 9 minutes resulted in dispersal of 48-hour biofilms without regrowth. Importantly, when the current was turned off, ozone concentration fell to less than detectable levels in 30 seconds. Finally, no evidence of structural damage was seen on electron microscopy after PAG exposure. (53) Argon plasma is readily available and has already been FDA-approved in GI procedures for coagulation purposes. The plasma generating apparatus is housed in a compact (10x15x8 inch) box and reasonably cost-effective (<$2000). Another potential benefit is shortening of processing time by obviating the need for rinsing and drying after HLD. While argon PAG is a promising new method for endoscope disinfection, a commercial device tailored to GI use will need to be developed and studies performed with commonly used endoscopes to establish comparability to current HLD and sterilization techniques.(52-53)

An "endoscopic contamination prevention sheath" presents an alternative barrier approach to decreasing endoscope contamination, focusing particularly on the elevator mechanism. Scopeseal's utility was recently demonstrated in a bench study (55) ; the integrity of its barrier function was tested with bacterial inoculum to outside of the duodenoscope and to the elevator mechanism, evaluating both outside-in and inside-out contamination protection. The ERCP accessories were also evaluated in a fluorescent dye-immersion test for any inadvertent exposure. No bacterial or inadvertent dye exposure were detected confirming compete seal with two-way protection from microbial contamination. (55) Thus far, there have been no reports of the use of Scopeseal in real-life clinical scenarios. It may be a viable option in the category of disposable duodenoscope accessories, but studies will need to evaluate its comparable or improved cost-effectiveness vis-à-vis disposable tip duodenoscopes.

In 2019, the FDA issued several safety communications recommending that endoscopy units transition from fixed-end duodenoscopes to those with partially or completely disposable components. (35, 56) As of August 2020, the FDA has cleared six such duodenoscope models. All three of the major endoscope manufacturers have produced models with variations on a disposable distal tip.

The ED34-i10T model (Pentax Medical USA) was the first disposable endcap duodenoscope cleared for use by the FDA.(57) Since then, it has been largely replaced by the ED34-i10T2 which consists of a disposable endcap with an elevator. (58) This current model is the subject of ICECAP, an ongoing Canadian randomized controlled trial investigating the persistent bacterial contamination rate and therapeutic efficacy of ED34-i10T2. Eligible patients will be allocated to ERCP with the ED34-i10T2 model or its previous iteration, ED 34-i10T . Results of the study are pending at this time. (59) The ED-580XT model (Fujifilm Healthcare USA) with a disposable distal endcap (60) was recently studied (61) and basket sweeping. Endpoints of interest included the following: the ability to complete all four tasks, time for completion of each task, ratings on navigation/pushability by 6 experienced endoscopists, tip control, and image quality.(64) All tasks were completed in both the reusable and disposable endoscope groups. There were no significant differences in the time-tocompletion of the tasks. However, the performing endoscopists did rate the EXALT Model D lower on navigation/pushability. Overall, the disposable model had comparable functionality, although maneuverability may have been impacted (64) . As the first fully disposable duodenoscope, its projected costs are also an important factor in potential replacement of currently used instruments. Data on clinical applications are not yet available but a recent costbenefit analysis suggested that replacing one reusable duodenoscope in a center performing approximately 200 ERCPs/year would incur a 10x increase in cost. (65) The most recent addition to the field is AScopeDuodeno (Ambu Inc.), which was approved by the FDA for marketing in July 2020.(66) Similar to the EXALT Model D, this is a combination of a disposable duodenoscope and reusable processor. Currently, there are no available reports regarding its performance in clinical practice, and post-marketing studies are underway.

The coronavirus pandemic has brought new and rapidly evolving challenges throughout the medical field. Evidence of nosocomial transmission in health care settings has enhanced attention to both occupational safety and appropriate disinfectant practices, including in the endoscopic unit. In the COVID-19 pandemic, it is even more important for endoscope reprocessing personnel to have adequate protective equipment. Historical data concerning pathogen transmission in endoscopic procedures emphasize the importance of strict adherence to regimented protocols in maintaining the integrity of endoscope reprocessing. Furthermore, recent public health experiences have highlighted the challenges and shortcomings of existing practices and spurred innovative approaches to obviate them. A number of unanswered questions remain, first and foremost about "real world" effectiveness of novel methods of endoscope reprocessing and of endoscopes with disposable components. Where the balance lies between the risks, albeit quite low, of endoscope associated post-procedural infection and the cost (and environmental impact) of the disposable devices, remains to be determined.

Overall, prior experience and available data suggest that, when correctly executed, current reprocessing practices are sufficient in preventing SARS-COV-2 transmission. 

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Special thanks to Jimmy Leal, central services technician, for his demonstration of appropriate donning of PPE.