Keywords
Pancreatobiliary (ERCP/PTCD) - ERC topics - Quality and logistical aspects - Quality
management - Hygiene
Introduction
During endoscopic retrograde cholangiopancreatography (ERCP) procedures, duodenoscopes
are heavily exposed to gastrointestinal bacteria. Consequently, these devices must
undergo comprehensive reprocessing to prevent patient-to-patient pathogen transmission
[1]
[2]. However, reprocessing may fall short, with microorganisms persisting in up to 15%
of cases [3]. Manual cleaning, crucial for removing organic debris before automated cleaning
and disinfection, involves brushing and flushing duodenoscope channels with water
and a detergent solution [4]
[5]. However, healthcare workers often face time pressure, complex protocols, and physical
discomfort during manual cleaning [6]
[7]. Surveillance studies by the U.S. Food and Drug Administration showed that more
than 60% of manual cleaning tasks are improperly executed [8].
Automated reprocessing could improve endoscope cleaning pre-disinfection by standardizing
practices, alleviating staff workload, and minimizing human errors [9]. The recently introduced AquaTYPHOON system (AT, Plasmabiotics; Pentax Medical),
which employs pulsating high-velocity water and compressed air instead of brushes
and detergent, shows promising preliminary validation results in clinical settings
[10]. Gastrointestinal endoscopes of all types were cleaned with the AT and validated
by demonstrating compliance with the defined target level of a residual bacterial
load of ≤ 6 colony-forming units (CFU) after reprocessing, as well as protein removal
in accordance with ISO standards 15883–4 and 15883–5 [10]. However, guidelines recommend that any CFUs of gastrointestinal microorganisms
warrant endoscope quarantine [11]
[12]. Because the types of microorganisms detected were not mentioned, true validation
of the AT has not been demonstrated. Moreover, the studies report that the AT has
been validated across multiple endoscope types from major endoscope manufacturers.
However, the number of duodenoscopes included in the validation studies is unclear.
Because most reported endoscope-associated outbreaks originate from contaminated duodenoscopes,
this must be confirmed prior to implementation [10]
[13]. This study aimed to show non-inferiority of the AT in patient-ready duodenoscopes
compared with conventional manual cleaning methods.
Methods
Setting
This retrospective-prospective before-and-after single-center intervention study was
conducted between January 2022 and June 2024 at the Erasmus University Medical Center
(Erasmus MC), a large Dutch tertiary care center that performs approximately 750 ERCP
procedures annually.
Data collection
Between January 2022 and December 2023, duodenoscope cultures from Pentax ED34-i10T2
duodenoscopes with disposable endcaps were collected as part of the PREVENT study
(unpublished). During this period, reprocessing was performed according to manufacturer
instructions, and the protocols have been described previously [14]
[15]. The cultures collected during this period were stored in a database. For the purpose
of this study, we excluded cultures from loaner duodenoscopes that were no longer
in active use. The remaining cultures from this database were used to represent the
first study period, during which conventional manual cleaning methods, including flushing
and brushing, were employed. These data were compared with cultures collected in the
subsequent prospective period, during which the AT was implemented, as described below.
Intervention
The AT includes the AquaTYPHOON device, a barcode scanner, a water pistol (AquaJET),
and a label printer ([Fig. 1]). The automated process includes a leak test and uses high-velocity air and water
to create a turbulent flow in the endoscope channels to remove organic material and
debris. During the cleaning process, the duodenoscope is not submerged in water and
no detergents are used. The AquaJET is used by reprocessing personnel to clean the
endoscope externally. The AquaTYPHOON device displays the current phase of the process
and its percentage of completion. The time needed for the AT to complete automated
cleaning is 5 minutes. If an error occurs, such as low air pressure, the cycle is
interrupted and the error is displayed. Data records are printed and stored on the
device. In this study, the printer was not used.
Fig. 1 Illustrations of the AquaTYPHOON system, showing the device's front and side views
(top left and center), the barcode scanner and AquaJET (top right), color-coded endoscope
connection tubes (bottom left), and the cleaning sink (bottom right).
After the AT received its CE mark in March 2023, we developed the protocol for this
study and the non-inferiority margin, endpoints, and analysis plan were specified
(detailed below). In January 2024, all duodenoscopes were inspected using a borescope
and those requiring maintenance were sent to the manufacturer for repairs. When the
duodenoscopes returned from the manufacturer, they were included in the study. Before
transitioning to the AT period, reprocessing personnel received training from the
manufacturer on use and maintenance of the system. In addition, all duodenoscopes
underwent four consecutive reprocessing cycles using the AT, followed by automated
cleaning and disinfection as a wash-out measure. These four cycles were performed
sequentially, without any intermittent use in a patient, and the duodenoscopes were
confirmed to be culture-negative before the start of the AT period. Furthermore, all
duodenoscopes that returned from the manufacturer were cultured prior to reintroduction
for clinical use. The process of bedside precleaning, automated cleaning, high-level
disinfection (HLD), and drying remained unchanged [15]. Duodenoscope cultures during the AT period were collected between January 2024
and June 2024.
Sampling
Sampling of the duodenoscope was performed shortly before its use for an ERCP procedure.
Initially, the distal tip of the duodenoscope was swabbed using a dry Copan Liquid
Amies Elution Swab (eSwab Copan). To neutralize any residual disinfectants, 1 mL of
a neutralizer (Dey-Engley broth) was introduced into the container. Subsequently,
the suction and biopsy channels were subjected to a combined flush-brush-flush procedure
that encompassed the entire length of the duodenoscope, from the umbilical connector
(processor end) to the distal tip. This involved flushing each channel with 20 mL
of sterile water, which was collected in a sterile container containing 40 mL of neutralizer.
A single-use endoscope cleaning brush (CS5522A, Pentax) was then passed through the
entire length of the channels and the distal tip of the brush was severed using sterile
scissors and added to the container. Flushing of both channels was then repeated to
complete the sampling process.
Microbiological protocols and interpretation
Microbiological methods used were as previously reported [4]. Contamination was defined as: 1) ≥ 1 CFU of microorganisms of gut or oral origin
(MGO), including Pseudomonas aeruginosa, Staphylococcus aureus, and yeasts; or 2) ≥ 20 CFU/20 mL of any microorganism of other origin (AM20) [16]. Culture results used in this study were collected separately from routine microbiological
surveillance conducted monthly at Erasmus MC. Consequently, duodenoscopes contaminated
with MGO were not quarantined. However, if cultures from routine surveillance tested
positive for MGO, the duodenoscopes were quarantined according to Dutch guidelines
[12]. These duodenoscopes were cleared for clinical use only after subsequent negative
culture results.
Outcomes
The primary endpoint was the proportion of duodenoscope cultures positive for MGO.
Secondary endpoints included the proportion of duodenoscope cultures positive for
gut, oral, and AM20 microorganisms.
Sample size determination
Sample size calculation was based on the database of duodenoscope cultures from the
PREVENT study, which at that time contained 270 culture results from the period using
conventional cleaning. The contamination rate for conventional cleaning was approximately
20%. Given implementation of the AT and considering outcomes from validation studies,
we anticipated a contamination rate of 10%, making a 10% reduction in contamination
a realistic expectation. We conducted a power analysis using simulation, with data
simulated through a random intercept logistic mixed model. This model was based on
assumptions about contamination rates from logistic mixed models fitted to the available
duodenoscope culture results from conventional cleaning. We assumed that the random
intercept standard deviation would remain consistent across different phases of the
study.
The risk-difference of contamination with MGO between conventional cleaning and AT
cleaning was assessed using a generalized estimating equation (GEE) to consider clustering
due to repeated measurements of the same duodenoscopes. MGO-positivity served as the
response variable, the study phase was the sole covariate, and the model used a Gaussian
distribution with identity link. Our simulations suggested that with an expected contamination
rate for the AT period of 10%, a sample of 100 duodenoscope cultures in the AT period
would achieve approximately 80% statistical power.
Because there was a possibility that the contamination rate might increase after implementation
of the AT, an interim analysis was performed after 50 duodenoscope cultures were collected
during the AT period. To ensure patient safety, if use of the AT had resulted in significantly
higher contamination rates compared with the conventional cleaning method, the study
would have been terminated prematurely. Specifics regarding the analysis and threshold
for early termination are described below. Because the interim analysis was conducted
solely for futility monitoring without formal hypothesis testing for non-inferiority,
no adjustments for multiplicity were deemed necessary.
Statistical analyses
Statistical analyses were performed in R version 4.1.3 [17]. Categorical variables are presented as counts or proportions (%), whereas continuous
variables are described using the median with the first and third quartiles (Q1, Q3)
or the mean and standard deviation (SD). The analysis was conducted on an intention-to-treat
basis, including all duodenoscope cultures collected during the study periods, except
those from loaner duodenoscopes no longer in active use. The primary analysis used
a GEE model to assess differences in contamination rates between study phases. This
model was the same as that used for sample size calculation. To determine non-inferiority
of the AT, the upper limit of the two-sided 90% confidence interval (CI) for the parameter
estimate of the study phase was compared with a margin of 5%. We chose a 90% CI, so
that, due to its one-sided use in the non-inferiority test, the corresponding significance
level is 0.05.
A futility interim analysis was conducted after collecting 50 duodenoscope cultures
during the AT period. The same GEE model described above was utilized, except for
a one-sided inferiority test that compared the lower bound of the 90% CI for the risk
difference with a specified threshold for early termination of 5% in case the AT performed
considerably worse than conventional manual cleaning.
Results
Culture characteristics
A total of 433 cultures were collected from eight Pentax ED34-i10T2 duodenoscopes.
During the period when conventional manual cleaning was employed (January 2022 to
December 2023), 333 duodenoscope cultures (76.9%) were collected, and 100 cultures
(23.1%) were collected during the AT period (January 2024 to May 2024). [Table 1] presents an overview of culture characteristics. During the period employing conventional
cleaning methods, 21.6% of cultures (72/333) were contaminated with MGO, of which
48 (14.4%) contained gut bacteria and 26 (7.8%) contained oral bacteria. Of 100 cultures
collected during the AT period, 16% (16/100) were contaminated with MGO, of which
nine (9%) contained gut flora and eight (8%) contained oral flora. Supplementary Table 1 in the supplementary appendix presents contamination rates of individual duodenoscopes
according to each contamination definition.
Table 1 Culture characteristics of periods employing conventional cleaning methods compared
with the AquaTYPHOON system.
|
Conventional cleaning
n = 333 (100%)
|
AquaTYPHOON system
n = 100 (100%)
|
AM20, 20 CFU/mL of any other microorganism; SD, standard deviation.
|
Microorganisms of gut or oral origin, n (%)
|
72 (21.6%)
|
16 (16.0%)
|
Gut, n (%)
|
48 (14.4%)
|
9 (9.0%)
|
Oral, n (%)
|
26 (7.8%)
|
8 (8.0%)
|
AM20, n (%)
|
303 (91.0%)
|
94 (94.0%)
|
Sampled Pentax ED34-i10T2 duodenoscopes, n (%)
|
A110077
|
35 (10.5%)
|
16 (16.0%)
|
A110095
|
45 (13.5%)
|
10 (10.0%)
|
A110096
|
54 (16.2%)
|
6 (6.0%)
|
A110098
|
33 (9.9%)
|
21 (21.0%)
|
A110100
|
48 (14.4%)
|
22 (22.0%)
|
A110280
|
36 (10.8%)
|
8 (8.0%)
|
A110377
|
39 (11.7%)
|
17 (17.0%)
|
A110409
|
43 (12.9%)
|
0 (0.0%)
|
Interim analysis
After 50 duodenoscope cultures were collected during the AT period, an interim analysis
was performed. Six of 50 duodenoscope cultures (12%) were positive for MGO. The risk
difference between the two periods was -9.3% (lower bound 90% CI -24.3%) in favor
of the AT. Because the lower bound of the 90% CI was -24.3%, and thus less than the
futility margin of 5%, the study was continued.
Cultured microorganisms
[Table 2] shows all cultured MGOs and their frequencies and all other cultured microorganisms
are shown in the supplementary appendix (Supplementary Table 2 and Supplementary Table 3). No contamination with P. aeruginosa, Klebsiella pneumoniae, or Enterobacter cloacae complex occurred during the AT period. However, contamination with Stenotrophomonas maltophilia occurred more frequently, seven times versus once in the conventional manual cleaning
group. In the primary analysis, the risk difference in MGO-positivity between the
AT and conventional manual cleaning methods was -5.6% (upper bound 90% CI 6.8%) ([Fig. 2]). For contamination with gut bacteria, the risk difference was -5.4% (upper bound
90% CI 3.9%), and for oral flora, it was 0.2% (upper bound 90% CI 5.7%). For contamination
with AM20, the risk difference was 3% (upper bound 90% CI 8.1%) in favor of conventional
manual cleaning. Non-inferiority could not be demonstrated for contamination with
MGO, oral flora, or AM20 because the upper bound of the 90% CI exceeded the 5% non-inferiority
margin. However, non-inferiority could be demonstrated for contamination with gut
bacteria.
Table 2 Cultured microorganisms of gut or oral origin.
|
Conventional cleaning
n = 333 (100%)
|
AquaTYPHOON system
n = 100 (100%)
|
Gut bacteria, n (%)
|
|
23 (6.9%)
|
0 (0.0%)
|
|
16 (4.8%)
|
0 (0.0%)
|
|
1 (0.3%)
|
7 (7.0%)
|
|
5 (1.5%)
|
0 (0.0%)
|
|
2 (0.6%)
|
1 (1.0%)
|
|
2 (0.6%)
|
0 (0.0%)
|
|
2 (0.6%)
|
0 (0.0%)
|
|
1 (0.3%)
|
0 (0.0%)
|
|
1 (0.3%)
|
0 (0.0%)
|
|
1 (0.3%)
|
0 (0.0%)
|
|
0 (0.0%)
|
1 (1.0%)
|
|
1 (0.3%)
|
0 (0.0%)
|
|
1 (0.3%)
|
0 (0.0%)
|
|
1 (0.3%)
|
0 (0.0%)
|
Oral bacteria, n (%)
|
|
16 (4.8%)
|
4 (4.0%)
|
|
6 (1.8%)
|
2 (2.0%)
|
|
2 (0.6%)
|
0 (0.0%)
|
|
1 (0.3%)
|
0 (0.0%)
|
|
1 (0.3%)
|
0 (0.0%)
|
|
1 (0.3%)
|
0 (0.0%)
|
|
1 (0.3%)
|
0 (0.0%)
|
|
0 (0.0%)
|
1 (1.0%)
|
|
1 (0.3%)
|
0 (0.0%)
|
|
0 (0.0%)
|
1 (1.0%)
|
|
0 (0.0%)
|
1 (1.0%)
|
Fig. 2 Forest plot with risk differences in contamination between the AquaTYPHOON system
and conventional manual cleaning methods according to the different definitions. AM20,
microbial growth with ≥ 20 colony-forming units/20 mL of water and/or skin type microorganism;
MGO, presence of microorganisms of gut or oral origin.
Environmental sampling
Because of the unexpected increase in contamination with S. maltophilia during the AT period, 13 environmental samples from the endoscope reprocessing department
were collected to check for a possible common source of contamination. The AquaTYPHOON
device connectors, touchscreen, and water pistol were swabbed, as well as the automated
endoscope reprocessors (AERs) and AER connectors, drying cabinet connectors, and a
hand alcohol dispenser. All samples were negative for S. maltophilia. The drain of the sink where the endoscopes were cleaned was positive for S. maltophilia. However, this was not considered a likely source of the contamination.
Discussion
After introduction of the AT to replace conventional manual cleaning, the MGO contamination
rate of patient-ready duodenoscopes declined by 5.6% (from 21.6% to 16%). This finding
illustrates that automated cleaning methods can improve the outcome of duodenoscope
reprocessing in a real-world clinical setting. This effect was predominantly caused
by a reduction in gut bacteria isolated from duodenoscope samples, which are known
to be notorious for causing duodenoscope-associated infections. Total absence of P. aeruginosa and K. pneumoniae during the AT period is particularly promising because these bacteria are frequently
involved in outbreaks caused by contaminated duodenoscopes [13].
Enhancing automation in endoscope reprocessing offers numerous benefits, including
improved efficiency, prevention of human error, standardization of procedures, and
full traceability. Introduction of AERs in cleaning and HLD has been shown to improve
guideline adherence, reduce physical discomfort associated with reprocessing, and
decrease need for manual labor [9]. The same benefits may apply to automating manual cleaning. In addition, automated
cleaning could significantly reduce the cognitive load imposed by manual reprocessing
protocols [6].
Manual cleaning and the AT system differ notably in their cleaning methodologies.
Unlike manual cleaning, the AT system relies solely on water, without use of detergents
or single-use brushes. In addition, the duodenoscope is not submerged during cleaning.
These differences may reduce the environmental impact of reprocessing by eliminating
detergent use and single-use components while potentially simplifying the cleaning
process. However, incorporating submersion in water with detergents could further
enhance AT effectiveness by breaking down organic residues on the outside of the endoscope.
Future research should explore this as a potential modification of the cleaning process.
Moreover, a comprehensive life cycle analysis and environmental impact assessment
are necessary to determine the duration of AT use required to achieve a meaningful
environmental benefit.
During the AT period, incidence of cultures contaminated with S. maltophilia increased, making it the most prevalent MGO contaminant. S. maltophilia is an opportunistic pathogen present in the gut, but also widely distributed in various
environments, including water and soil. Gut colonization with S. maltophilia can particularly occur after patients have used broad-spectrum antibiotics. Given
its resistance profile and ability to cause severe infections in vulnerable populations,
S. maltophilia is considered an important nosocomial pathogen and it has been involved in outbreaks
linked to contaminated bronchoscopes [18]
[19]
[20]. Bacteria that thrive in moist environments and readily form biofilms are prone
to contaminating the AT. Therefore, the AT should be regularly monitored for contamination.
Although the sudden increase in contamination prevalence with S. maltophilia suggested a common source of contamination other than a patient, such as contaminated
AquaTYPHOON device connectors or AER, the environmental cultures did not show an external
contamination source. However, S. maltophilia was cultured from the sink drain at the location where the AT was use. Because the
duodenoscope was not submerged in water during cleaning with the AquaJET, we cannot
completely exclude the possibility that splashes from the sink drain contaminated
the duodenoscopes during cleaning.
Implementation of the AT led to an increase in contamination with AM20 by 3% (upper
bound 90% CI 8.1%). In our previous research, we hypothesized that the high contamination
rate with AM20 might be partly explained by the design of the single-use brush with
a distal sweeper used in our center during manual cleaning [4]. However, even absent any materials introduced into the duodenoscope channels during
precleaning, the contamination rate with AM20 did not decrease. The biomatrix of non-MGO
bacteria might protect MGOs during HLD, preventing proper disinfection [21]. Thus, the source of such persistent contamination by AM20 remains unknown and requires
further investigation.
This study is subject to certain limitations that could have impacted the results.
This was a single-center study employing a single type of duodenoscope, which limits
generalizability of our findings. In addition, due to our limited sample size, the
CI of the main outcome was quite large, preventing us from showing non-inferiority
despite a clear difference in the contamination rate with MGO. Furthermore, the order
of the periods (conventional cleaning versus AT) was not randomized and no control
group was available; therefore, we cannot claim causality between introduction of
the AT and reduction in contamination with MGO. Finally, sampling and culturing of
the air/water channel was not performed, leaving the effectiveness of the AT in cleaning
this channel unestablished.
Conclusions
In conclusion, this study found that implementation of the AT led to a reduction in
contamination with MGO in Pentax ED34-i10T2 duodenoscopes, although non-inferiority
was not demonstrated. However, the AT was non-inferior to conventional manual cleaning
in reducing contamination with gut microorganisms. Therefore, the AT could offer an
alternative to conventional manual cleaning methods. Future larger studies are necessary
to confirm our findings, demonstrate generalizability, and investigate other potential
benefits regarding reprocessing efficiency, labor intensity, and environmental impact.
Bibliographical Record
Koen van der Ploeg, Juliëtte A. Severin, Margreet C. Vos, Nicole S Erler, Adriana
J.C. Bulkmans, Marco Bruno, Bibi C.G.C. Mason-Slingerland. Novel water-based automated
endoscope cleaning process vs conventional manual cleaning for reducing duodenoscope
contamination. Endosc Int Open 2025; 13: a25368061.
DOI: 10.1055/a-2536-8061