Impact of wet storage and other factors on biofilm formation and contamination of patient-ready endoscopes: a narrative review

The 2019 U.S. Food and Drug Administration report indicates that the clinical studies undertaken by the 3 main GI endoscope manufacturers demonstrate 5.4% of patient-ready duodenoscopes remain culture positive for high-concern organisms. The root causes of this persistent contamination are poorly understood. The objectives of this review include summarizing (1) the impact of inadequate manual cleaning and inadequate drying during storage on the formation of build-up biofilm in endoscope channels, (2) the impact of defoaming agents used during patient procedures on drying efficacy, (3) the data showing the importance of build-up biofilm on persistent microbial survival, and (4) the potential impact of implementation of a quality systems approach in GI endoscopy reprocessing.

Introduction

Endoscopic procedures have become some of the most commonly performed medical procedures. They are used to diagnose and treat a range of problems in the human GI tract. GI procedures using endoscopes are becoming increasingly more complex and invasive¹ and are being performed in sicker patients, many of whom are unable to withstand further deterioration. Concomitantly, there is an increasing recognition of residual microbial contamination of reprocessed patient-ready endoscopes. Reprocessing of flexible GI endoscopes has come under intense scrutiny because of multi-drug–resistant organisms (MDROs) transmitted by contaminated endoscopes that have caused infectious outbreaks.2, 3, 4, 5, 6, 7, 8 The 9 clinical infections reported by Epstein et al⁵ were culture positive for the New Delhi metallo-beta-lactamase (NDM) Escherichia coli outbreak strain in 13 clinical samples, including urine (3), abscess (2), blood (2), catheter tip (2), sputum (2), and wound (13). The identical NDM E coli strain was found to have contaminated the duodenoscopes used on these patients. The carbapenem-resistant Enterobacteriaceae (CRE) Klebsiella pneumoniae outbreak described by Humphries et al⁸ did not indicate the types of infections for the 9 patients involved in the outbreak, but they did indicate that the source patient had a positive urine culture with the outbreak strain. Furthermore, they reported that of the 6 patients infected with the CRE K pneumonia strain who died within 1 year of the outbreak, 2 deaths were attributable to the outbreak strain. Humphries et al⁸ cautioned that “Reports of outbreaks due to CRE probably predominate largely because these organisms are flagged for additional investigation by hospital laboratories. However, clusters due to susceptible bacteria may be missed.” They also recommended that improved surveillance after ERCP procedures is needed and that review of positive blood cultures after ERCP or active surveillance may improve detection of infections transmitted from contaminated duodenoscopes.⁸

McCafferty et al⁹ recently reviewed PubMed, ScienceDirect, and CINAHL for publications describing infections and outbreaks from 2008 to 2018 that were related to contaminated GI endoscopes. The contributing factors and the outcomes of the outbreaks were assessed. They identified 16 publications that described duodenoscope-associated infections, and 2 that described colonoscope and gastroscope infections. There were outbreaks in the Netherlands, United States, United Kingdom, France, China, and Germany. The causative organisms included Pseudomonas aeruginosa, E coli, K pneumoniae, and Salmonella enteritidis. Contributing factors included lapses in reprocessing, biofilm formation, endoscope design issues, and endoscope damage. The authors indicated that improving endoscope reprocessing, detection of endoscope damage, and screening for contamination may prevent colonization and infection with MDROs and/or transmission of sensitive organisms by contaminated endoscopes. The retrospective study by Wang et al¹⁰ provided the first insight into the risk of any type of infection after endoscopy. They reviewed all-payer claims data from 6 states in the United States and reported infection rates that occurred 7 days after endoscopy procedures for colonoscopy, osophagogastroduodenoscopy, and bronchoscopy in ambulatory surgery centers in the United States (they did not include data related to ERCP procedures). They found significantly higher 7-day postprocedure infection rates for screening colonoscopy (1.1 cases per 1000 procedures), nonscreening colonoscopy (1.6 cases per 1000 procedures), osophagogastroduodenoscopy (3.0 cases per 1000 procedures), and bronchoscopy (16.6 cases per 1000 procedures) compared with screening mammography (0.6 cases per 1000 procedures). The most-common types of infection involved the respiratory tract (eg, pneumonia), septicemia, and the GI system. The most-common organisms causing infection included E coli, K pneumoniae, Clostridium difficile, Staphylococcus spp, and unidentified Gram-negative bacteria. They concluded that postendoscopy infection rates were higher than previously thought. The Wang¹⁰ study was limited, because it did not differentiate endogenous infections (ie, infections arising from the patient’s own microorganisms) from exogenous infections with organisms originating from contaminated endoscopes.

The published clinical data clearly indicate that endoscopy procedures are not without risk and that transmission of infectious organisms (both MDROs and sensitive organisms) from contaminated endoscopes is a problem that needs to be addressed.

Transmission to patients from a contaminated endoscope can cause infection and/or colonization. The rectal screening data reported by Epstein et al⁵ demonstrated that of 89 asymptomatic patients exposed to contaminated duodenoscopes, 27 (30%) became carriers. There were 8 infections directly linked to contaminated endoscope exposure and 27 carriers detected indicating a 3.4 times higher rate of transmission resulting in carriage versus infection. Data from some of the outbreaks have shown that once exposed to MDROs via a contaminated endoscope, the GI tract of patients can remain colonized for many months.⁵ Zimmerman et al¹¹ reported that duration of carriage varied depending on whether the organism was initially detected in a diagnostic clinical specimen from a symptomatic patient (mean duration of carriage of 641 days) or the organism was detected from a rectal swab taken as part of surveillance culture from asymptomatic patients (mean duration of carriage 337 days). In addition, a recent review indicated that the 30-day mortality rates for blood stream infections with CRE, one of the MDROs, was 65.4% compared with 6.4% for non-CRE strains.¹² Even nonsystemic infections with CRE strains showed higher re-admission rates and higher 90-day mortality rates.¹³ The combination of long-term persistence of the carrier state and markedly adverse outcomes if there is a clinical infection has important implications. Even if the GI tract is only colonized with an MDRO from a contaminated endoscope, this still poses a long-term risk because subsequent patient exposure to antibiotics that kill the normal GI microbiome would allow the MDRO to replicate and potentially cause invasive infection, which can have much worse outcomes than with non-MDRO strains.

Contamination of patient-ready GI endoscopes linked to infectious outbreaks of MDROs led to a directive from the U.S. Food and Drug Administration (FDA) in 2015¹⁴ to the 3 main GI endoscope manufacturers (ie, Olympus, Pentax, Fujinon) to conduct postmarket surveillance studies. The objective as stated by Shuren in the FDA statement (April 12, 2019)¹⁵ was “Specifically, as part of their approved study plans, all 3 manufacturers are required to conduct a study to sample and culture reprocessed duodenoscopes that are in clinical use to learn more about issues that contribute to contamination, as well as a human factors study to assess whether trained hospital staff are following reprocessing instructions.” The April 12, 2019 FDA interim report on the clinical studies undertaken by the 3 main GI endoscope manufacturers has demonstrated that 5.4% of patient-ready duodenoscopes remain culture positive for high-concern organisms.

A key driver of persistent endoscope contamination is biofilm or build-up biofilm (BBF) formation during storage after full reprocessing, which includes cleaning and rinsing, high-level disinfection (HLD), alcohol flushing, and forced air drying.16, 17, 18, 19, 20, 21, 22, 23 Biofilm should not form inside dry, disinfected endoscope channels. However, if channels are wet during storage, then biofilm could form. The importance of drying endoscope channels is clearly stated in the manufacturer’s instructions for use (MIFU) for all types of GI endoscopes. The following statement from the Olympus duodenoscope user manual²⁴ is an example of MIFUs regarding endoscope drying: “All equipment must be thoroughly dried prior to storage. Microorganisms proliferate in wet/moist environments.” Furthermore, endoscope reprocessing guidelines from many countries reiterate the significance of drying reprocessed endoscopes for storage.25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 In some of these guidance documents, an alcohol flush of each channel is recommended to facilitate the drying process. Endoscope channel drying recommendations have been in place for many years. Despite these powerful cautionary statements, endoscope reprocessing personnel are unable to define “How dry is dry enough?” and moisture has been reported to persist in stored endoscope channels, facilitating microbial replication.^22,36,37

The objective of this review is to provide the current data on the extent of moisture persistence in endoscope channels, the impact of simethicone (a defoaming agent) on drying efficacy, the impact of moisture and the potential impact of simethicone on biofilm and BBF formation, and most importantly, the urgent need for quality system (QS) audits in endoscopy clinics.