Adriënne S. van der Schoor MOVEing Microorganisms The effect of the built environment of the hospital and screening strategies on microbial safety
MOVEing Microorganisms The Effect of the Built Environment of the Hospital and Screening Strategies on Microbial Safety Adriënne S. van der Schoor
2023 © A.S. van der Schoor Cover design: Cynthia P. Haanappel Layout and printing: Ridderprint | www.ridderprint.nl. ISBN: 978-94-6483-367-6 All rights reserved. No part of this publication may be reproduced, distributed, stored in a retrieval system, or transmitted in any form or by any means, without prior written permission of the author or, when appropriate, from the publishers of the corresponding journals. The work presented in this thesis was part of the PE-ONE consortium, supported by the board of directors of the Erasmus MC. Printing of this thesis was financially supported by PE-ONE.
MOVEing Microorganisms: The Effect of the Built Environment of the Hospital and Screening Strategies on Microbial Safety MOVEing micro-organismen: het effect van de ziekenhuisomgeving en screening strategieën op microbiologische veiligheid Proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof.dr. A.L. Bredenoord en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op dinsdag 24 oktober 2023 om 15:30 uur door Adriënne Stephanie van der Schoor geboren te Noordwijk, Zuid Holland
Promotiecommissie Promotor: Prof.dr. M.C. Vos Overige leden: Prof.dr.ir. A. Burdorf Prof.dr. A. Timen Prof.dr. J.H. Richardus Copromotoren: Dr. A.F. Voor in ’t holt Dr. J.A. Severin
Contents Chapter 1 General Introduction and outline of thesis 7 Chapter 2 Patients 23 Chapter 2.1 The effect of 100% single-occupancy rooms on acquisition of extended-spectrum beta-lactamase-producing Enterobacterales and intra-hospital patient transfers: a prospective before-andafter study 25 Chapter 2.2 Pre-COVID-19 international travel and admission to hospital when back home: travel behavior, carriage of highly resistant microorganisms, and risk perception of patients admitted to a large tertiary care hospital 51 Chapter 2.3 Universal screening or a universal risk assessment combined with risk-based screening for multidrug-resistant microorganisms upon admission: comparing strategies 77 Chapter 2.4 Dynamics of Staphylococcus aureus in patients and the hospital environment in a tertiary care hospital in the Netherlands 97 Chapter 3 Environmental sampling and contamination 127 Chapter 3.1 Environmental sampling practices of innate hospital surfaces: a survey of current practices and the need for guidelines 129 Chapter 3.2 Environmental contamination with highly resistant microorganisms after relocating to a new hospital building with 100% single-occupancy rooms: a prospective observational before-and-after study with a three-year follow-up 147 Chapter 4 Summarizing discussion and future perspectives 183 Chapter 5 Nederlandse samenvatting 207 Chapter 6 Appendices 219 Chapter 6.1 Dankwoord 221 Chapter 6.2 Curriculum vitae 229 Chapter 6.3 List of publications 231 Chapter 6.4 PhD portfolio 233
Chapter 1
Chapter 1 General introduction and outline of thesis GENERAL INTRODUCTION AND OUTLINE OF THESIS
Multidrug-resistant microorganisms A microorganism is defined as a multidrug-resistant microorganism (MDRO) when it is resistant to one or more classes of antimicrobial agents (1). MDRO are considered as an important threat to public health (2, 3). Examples of MDRO are extended-spectrum betalactamase-producing Enterobacterales (ESBL-E), carbapenemase-producing Enterobacterales (CPE), methicillin-resistant Staphylococcus aureus (MRSA), vancomycinresistant Enterococcus faecium (VRE) and carbapenemase-producing Pseudomonas aeruginosa (CP-PA). Among Enterobacterales, Escherichia coli, Klebsiella pneumoniae, and Citrobacter freundii are most frequently encountered. The worldwide increase in MDRO is causing increasing healthcare costs, morbidity, and mortality in patients (3, 4). The prevalence of MDRO differs per country and per type of MDRO, ranging from less than one percent to more than 50% of isolates. Within the Netherlands, the prevalence of MDRO is generally low, although it differs per type of microorganism. The prevalence of MRSA nasal carriage upon admission to the hospital ranged between 0.03-0.17% between 2010 and 2017 (5), while the prevalence of ESBL-E intestinal carriage in the Netherlands between 2011 and 2016 ranged between 4.5% and 8.6% (6-8). MDRO are a common cause of healthcare-associated infections (HAI), which are infections caused by pathogens acquired by patients during their stay in a healthcare institution (9). HAI can be caused by microorganisms from an endogenous or exogenous source. Endogenous sources are body sites, including skin; exogenous sources are external sources, such as the hospital environment, its surfaces, or health care workers. This thesis is focused on endogenous sources by screening patients to identify microorganisms present upon admission to the hospital, and on exogenous sources, specifically the hospital innate environment and the transmission from the environment to the patient and vice versa. Relocation of the Erasmus MC The Erasmus MC University Medical Center (Erasmus MC) in Rotterdam, the Netherlands, is the largest academic hospital of the Netherlands. It includes the adult clinic (“Dijkzigt”), the Sophia Children’s hospital, the Erasmus MC Cancer Institute and the Faculty of Medicine and Health sciences of the Erasmus University Rotterdam. From 1961 until May 18, 2018, the hospital was located in the Dijkzigt hospital building, while the Erasmus MC Cancer Institute was on a location named “Daniel den Hoed”. In 2009, the Erasmus MC started the construction of a new hospital building, directly next to the old hospital building (Figure 2) as replacement of the Dijkzigt hospital and the Erasmus MC Cancer Institute. At the beginning of the design process, it became clear that the relocation would be accompanied by a reduction in the number of beds due to expected changes in the organization of health care, resulting in less admission days. To optimize microbial safety and to make the most use out of the available number of beds, the decision 1 9 General introduction
was made to implement 100% single-occupancy rooms with private bathrooms. Additionally, the implementation of 100% single-occupancy rooms was part of providing a safe and healing environment. The aim of a healing environment is to provide an environment for patients, staff, and visitors, that is calm, non-institutional, and can positively impact the recovery time of patients (10, 11). The decision for 100% single occupancy room was largely based on expert opinion, as evidence for its effects on infections and on other patient related outcomes was limited back then. Figure 1a. The old hospital building of the Erasmus MC (the Dijkzigt hospital) Figure 1b. The Daniel den Hoed Cancer Institute Figure 2. The new hospital building of the Erasmus MC 10 Chapter 1
The old hospital building The old hospital building of the Erasmus MC (the Dijkzigt hospital building) had 1,125 beds, mainly divided over two- and four-person occupancy rooms (Figure 3), and 42 Intensive Care Unit (ICU) single-occupancy beds. Bathrooms were shared and located on the ward, with an average of four patients sharing a toilet, and seven patients sharing a shower. When a patient on the ward was placed in contact isolation, i.e., standard precautions, and use of gloves and gowns, the other bed(s) in the room were blocked for admissions. For patients in isolation, a designated bathroom was appointed to that patient, or washing and toileting occurred on bed and by bedpan. Exceptions to the multiple-occupancy rooms were the ICU, the isolation department, and the hematology departments. The ICU consisted of 100% single-occupancy rooms, of which some were designated isolation rooms with an anteroom and negative air pressure. The isolation department consisted of 100% single-occupancy rooms, all with anteroom, negative air pressure and private bathrooms. The hematology departments, which were located at both location Dijkzigt and location Daniel den Hoed, consisted of a number of two- and three-patient occupancy rooms, with attached bathrooms, but the majority of the rooms were single-occupancy rooms, all with anteroom, HEPA filtered air and private bathroom. Figure 3. One side of a four-person occupancy room in the old hospital building of the Erasmus MC. The new hospital building The new hospital building was officially opened on May 18, 2018, when all patients were transferred in one day from the old hospital building to the new hospital building. All patients from the Daniel den Hoed were also relocated to the new hospital building on this date in a custom-made moving truck. The new hospital building has 525 beds, all singleoccupancy rooms with private bathrooms and rooming-in facilities (Figure 4), and 56 ICU beds. Where in the old building there was an isolation department, the isolation rooms in the new hospital building are located at multiple wards. 1 11 General introduction
Figure 4. A single-occupancy room in the new hospital building of the Erasmus MC. Impact of single-occupancy rooms The transition to 100% single-occupancy rooms was expected to have positive effects, among others on infection prevention and control (IPC). For example, research has shown that transitioning from two-person to single-occupancy rooms on an ICU decreased the number of patient transfers with 90%, and the number of medication errors with 67% (12). Other studies have found comparable effects on medication errors (13). Additionally, singleoccupancy rooms are expected to improve patient sleep and social support, and potentially decrease the length of stay (11-13). The relocation to the new building of the Erasmus MC provided the unique opportunity to determine the effect of transitioning to single-occupancy rooms on different aspects. For this purpose, the board of directors of the Erasmus MC funded the consortium Program Evaluating – Our New Erasmus (PE-ONE), which aimed to determine the transition to 100% single-occupancy rooms from a multidisciplinary point of view. PE-ONE consisted of three pillars: CHANGE, which looked at the transition from the old to the new building from a management point of view, WELCOME, which looked at experiences from patients and staff and evaluating work situations and efficiency, and MOVE, which looked at the effect of single-occupancy rooms on the microbial safety. The latter was subject of this thesis. MOVE study; microorganisms in the environment of single- and multipleoccupancy rooms The aim of the MOVE study was determining the effect of transitioning from an old hospital building with multiple-occupancy rooms and shared bathrooms to a newly constructed hospital building with single-occupancy rooms and private bathrooms on the microbial safety. We hypothesized that single-occupancy rooms would provide a microbial safer environment for patients compared to multiple-occupancy rooms (14). We define the environment of the new hospital microbial safer when the environmental contamination in 12 Chapter 1
general and/or with MDRO is lower, and/or when acquisition and/or transmission of MDRO is lower compared to the old hospital. This overarching hypothesis could be divided into several sub-hypotheses; first, 100% single-occupancy rooms will decrease the risk on the acquisition of MDRO during hospitalization as direct patient to patient transmission between roommates cannot occur in single-occupancy rooms. Research has indicated that there is a significant relation between being exposed to roommates and acquisition of microorganisms, especially for the same microorganism the roommate was colonized with (15, 16). Although a number of studies have been performed on the effect of single-occupancy rooms on acquisition of MDRO, and consequently the impact on HAI, literature is conflicted on the added benefit of single-occupancy rooms on IPC (14). While several studies showed a significant reduction in healthcare-associated colonization with MDRO after transitioning to mainly or only singleoccupancy rooms (17-22), some studies showed no effect (23-25). The majority of the studies were performed on pediatric or adult ICUs or on a neonatology department (17-19, 21, 22, 24). Furthermore, only four studies studied the transition to 100% single-occupancy rooms (18-21). A recent study of McDonald et al., looked at the effect of relocating to a newly constructed building with only single-occupancy rooms on colonization and infection rates (26). They identified a decrease in colonization and infection rates with VRE and MRSA colonization, but not for MRSA and Clostridioides difficile infections. Overall, the effect of single-occupancy rooms on general wards on acquisition is lacking, specifically for ESBL-E and CPE. Besides the elimination of transmission from roommates and the shared environment, introducing single-occupancy rooms eliminates specific reasons for intra-hospital patient transfers (i.e., transferring patients from one patient room to another patient room in the same hospital). For example, intra-hospital patient transfers for small procedures, social circumstances, or for contact isolation will no longer be essential (27). The number of intrahospital patient transfers on an ICU after transitioning to single-occupancy rooms was reduced by 90% (12). The hypothesis is that the number of intra-hospital patient transfers will decrease by the transition to 100% single-occupancy rooms. Limiting the number of intra-hospital patient transfers leads to less exposure of the patient to different hospital environments or in short; the patient is exposed to less square meters of the hospital environment. This potential reduction of exposure to different hospital environments, could also lead to a reduced risk of MDRO acquisition and transmission (28). In this thesis (chapter 2.1), we aim to determine the effect of transitioning to 100% singleoccupancy rooms on the odds on acquiring an ESBL-E during hospitalization. Additionally, we aim to determine the effect on the number of intra-hospital patient transfer. A second hypothesis is that implementation of 100% single-occupancy rooms could lead to lower environmental contamination rates. This is based on the assumption that, since there 1 13 General introduction
will only be one patient admitted to a room, only one patient can contaminate the environment. After the patient is discharged, the room can be cleaned and any contamination can be removed. However, there is no literature yet to support this assumption. In this thesis (chapter 3.2), we aim to determine the differences in environmental contamination, for the total bioburden and the presence of MDRO, between multipleoccupancy rooms and single-occupancy rooms. Moreover, we will determine the change over time and potential build-up of environmental contamination in the new hospital building over a three-year follow up-period. Universal risk assessment and risk-based screening To prevent spread of MDRO throughout hospitals, transmission-based precautions are installed for known carriers of MDRO, in addition to standard precautions. These additional precautions differ per type of microorganism, e.g., ESBL-E carriers are cared for in contact isolation (i.e., single-occupancy room, gloves and gowns), while patients known to carry MRSA are cared for in strict isolation (i.e., isolation room with ante room, gloves, gowns, surgical masks, and hair caps) (29). In the Netherlands, patients are not routinely screened for MDRO colonization upon admission. Yet, the risk on being colonized with a MDRO upon admission is determined for all patients through the MDRO universal risk assessment and, when patients are deemed at risk, a risk-based screening (30). This nationally implemented risk assessment consists of six questions: i) Is the patient a known carrier of a MDRO, ii) has the patient recently been treated in or admitted to a healthcare institution abroad, iii) did the patient stay in a healthcare facility known with a MDRO outbreak in the past two months, and if yes, was the patient approached for screening, iv) has the patient lived in an institution for asylum seekers in the past two months, v) does the patient live or work where pigs, veal calves or broilers are kept commercially, and vi) is the patient a partner, housemate or caregiver of someone who is MRSA positive? Additionally, at the Erasmus MC, the question “are you a professional seafarer” is added due to the finding that the prevalence of MRSA is higher among seafarers who are frequently visiting our hospital as they come from the nearby located port of Rotterdam (31). When the universal risk assessment indicates that a patient is deemed high risk to be a carrier (e.g., patient is a professional seafarer, or the housemate, caregiver or partner of a MRSA carrier), screening cultures (i.e., nasal, throat, and perineal/rectal cultures) are obtained and the patient is cared for in strict isolation until the results of the screening cultures are known. When a patient is deemed low risk (i.e., patient was admitted in a hospital abroad over two months ago, but did undergo surgery or had a wound), screening cultures are obtained, but the patient is not preemptively placed in isolation. When the patient is categorized as having no risk for MDRO carriage, no cultures are taken and the patient is not preemptively placed in isolation. The MDRO universal risk 14 Chapter 1
assessment and risk-based screening were first developed to identify risk factors for MRSA carriage, later questions to determine carriage of other MDRO were added. Recently, the efficacy of the MDRO universal risk assessment and risk-based screening is questioned (32). As timely identification and isolation of MDRO carriers is essential in preventing transmission throughout the hospital, improvement of the universal risk assessment should be considered. For instance, while in the universal risk assessment patients are asked if they have been hospitalized abroad, there is no question regarding recent travel history. Recently, literature has focused on the risk of HRMO acquisition during travelling, specifically to south-east Asia (33-35). However, the studies were performed with healthy travelers, and consequently cannot directly be extrapolated to patients admitted to our hospital. Besides improving the universal risk assessment and risk-based screening, other screening strategies should also be considered, such as a universal screening strategy. In order to generate further evidence for improving universal or risk-based risk assessment on colonization of HRMO, we performed two studies. In this thesis (chapter 2.2), we assess if colonization with MDRO following international travel among patients is high enough to include this as a risk factor in the risk assessment. In chapter 2.3 of this thesis, we aim to compare the yield of a universal screening strategy with the currently installed universal risk assessment and risk-based screening. Environmental contamination Surfaces in hospitals can act as reservoirs for pathogenic microorganisms, and hence for MDRO. The time period microorganisms are able to survive on surfaces differs per type of microorganism and can range from a few hours up to several months (36). Consequently, when a surface is not correctly cleaned and/or disinfected, the surface can be a lasting source for transmission. Studies determining the environmental contamination with MDRO in non-outbreak settings have showed contamination rates of up to 55%, even after terminal disinfection of the surface (37-40). Environmental sampling practices Environmental sampling can be performed for a number of reasons, but is mainly performed in outbreak situations to determine the source of the outbreak. Other reasons for environmental sampling could be evaluating cleaning/disinfection practices, routine sampling, or for research purposes. Environmental sampling methods can be divided into direct or indirect sampling methods. Direct sampling methods are methods that require no further processing, while extra processing is necessary for indirect methods (41). Examples of direct sampling methods are contact plates, dip slides and petriflm, examples of indirect sampling methods are sponges, wipes, and different types of swabs (e.g., cotton swabs, flocked swabs, rayon swabs). Swabs are most often used when performing sampling of the 1 15 General introduction
environment, which can be explained by the fact that they are easily available in a healthcare setting, easy in use, and associated costs are low (41). Results of environmental sampling can be reported as presence/absence, as the abundance in which a target microorganism is present, or the total bacterial load of a surface can be presented as the number of colony forming units (CFU). Currently, there are no guidelines on how to perform environmental sampling (41, 42). In this thesis (chapter 3.1), we aim to determine what the current environmental sampling practices within Europe are, and if there is a consensus on how and when to sample the hospital environment. Transmission from the hospital environment to patients Transmission from the hospital environment to patients can take place through either direct contact with the contaminated surfaces, or indirect contact, e.g., via the hands of healthcare workers (HCW). The crucial role of the hospital environment in outbreaks was highlighted by a study of Gastmeier et al., in which they identified the source of 1,561 published outbreaks (43). No source was identified for 37.1% of outbreaks. For the outbreaks where a source was identified, the source was an index patient (40.3%), equipment and devices (21.1%), personnel (15.8%), and the environment (19.8%) (43). The role of the environment in transmission is also highlighted by the study of Wu et al. (16). They determined that, when the previous roommate was colonized or infected with a MDRO, the current room occupant has a higher chance on becoming colonized or infected with that MDRO (16). Since there is no direct contact with a previous roommate, this transmission is most likely through the environment, either via direct or indirect contact. Staphylococcus aureus is a well-known commensal, and an important cause of both community- and hospital-acquired bacteremia and other severe infections (44, 45). While the majority of nosocomial S. aureus infections (~80%) are endogenous, patients with exogenous infections, although not well understood, tend to have longer hospitalizations after bacteremia and a higher risk of mortality (46, 47). Furthermore, exogenous infections are, due to their origin, theoretically preventable. Consequently, it is important to strive for 100% prevention of spread of S. aureus. For this we have to understand the mode and factors of transmission to be able to install adequate IPC measures. Since S. aureus can survive on surfaces from hours up to several months, the hospital environment can be an important source of transmission (36, 48). Transmission of S. aureus from the hospital environment or hands of HCW to patients have been shown (49, 50). However, the dynamics of S. aureus in patients, in the hospital environment and between the hospital environment and patients are relatively unknown, specifically in non-outbreak settings. In this thesis (chapter 2.4), we aim to determine colonization and acquisition rates of patients with S. aureus and environmental contamination with S. aureus, and subsequently 16 Chapter 1
to determine if transmission of S. aureus occurred between patients and the hospital environment and vice versa. To prevent transmission from the environment to the patient, correct cleaning and disinfection of hospital surfaces is needed. This is confirmed by the study of Chen et al., in which they report on frequent transmission between the hospital environment and patients, early in their admission (37). They suggest that room disinfection after discharge of patients might be inadequate in preventing transmission of MDRO. In the study of Chen et al., all rooms where disinfected after patient discharge. However, in the Netherlands, disinfection is only indicated after discharge of a patient that was a known carrier of a MDRO or other specific pathogens (e.g., Clostridioides difficile). In all other situations, rooms are dry cleaned and with damp microfiber cloths and not disinfected. This could result in a high environmental contamination rate, since not all MDRO carriers are identified, and thus their rooms are not disinfected upon discharge. However, the current environmental contamination rates are not known. In this thesis (chapter 3.2) we aim to determine the environmental contamination with MDRO in patient rooms of the old and new hospital building. Aim and outline of this thesis The main aim of this thesis is to determine the effect of an intervention, the transition of the Erasmus MC to a new hospital building with 100% single-occupancy rooms and single occupancy rooms, on two elements of microbial safety; the odds on the acquisition of MDRO, and the extent of and effect on environmental contamination. A secondary aim of this thesis is to determine screening methods to identify patients colonized with MDRO upon admission. This thesis is divided in two main chapters: patient related and hospital environment related research. In chapter 2 we will focus on patients and acquisition of, colonization with, and screening for MDRO. In chapter 2.1, the effect of the intervention (the transition to 100% single-occupancy rooms) on the odds of acquisition of ESBL-E is determined in a prospective before-and-after study. The effect of the intervention on intra-hospital patient transfers is also investigated. In chapter 2.2, the travel behavior of patients is studied via a questionnaire upon admission, and the association between travel and MDRO colonization upon admission is determined. In chapter 2.3, we compare a universal screening strategy for MDRO upon admission to the currently installed universal risk assessment and riskbased screening upon admission for MDRO in a observational prospective cohort study. In chapter 2.4, we determine the carriage and acquisition rates of methicillin-susceptible S. aureus (MSSA) and MRSA in patients, and we determine transmissions between patients and the environment, and vice versa. 1 17 General introduction
Chapter 3 will focus on the contamination of the hospital environment In chapter 3.1, we present the results of a web-based survey to determine surface sampling practices throughout Europe, and to determine if consensus regarding sampling practices exists. In chapter 3.2, we determine the effect of the intervention on environmental contamination, in a prospective before-and-after study, where we sampled the hospital environment over a three-year period. Finally, in chapter 4 the data and findings presented in this thesis will be discussed in a summarizing discussion and future perspectives are provided. 18 Chapter 1
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35. Voor In 't Holt AF, Mourik K, Beishuizen B, van der Schoor AS, Verbon A, Vos MC, et al. Acquisition of multidrug-resistant Enterobacterales during international travel: a systematic review of clinical and microbiological characteristics and meta-analyses of risk factors. Antimicrob Resist Infect Control. 2020;9(1):71. 36. Kramer A, Schwebke I, Kampf G. How long do nosocomial pathogens persist on inanimate surfaces? A systematic review. BMC Infect Dis. 2006;6:130. 37. Chen LF, Knelson LP, Gergen MF, Better OM, Nicholson BP, Woods CW, et al. A prospective study of transmission of Multidrug-Resistant Organisms (MDROs) between environmental sites and hospitalized patients-the TransFER study. Infect Control Hosp Epidemiol. 2019;40(1):47-52. 38. Mody L, Washer LL, Kaye KS, Gibson K, Saint S, Reyes K, et al. Multidrug-resistant Organisms in Hospitals: What Is on Patient Hands and in Their Rooms? Clin Infect Dis. 2019. 39. Shams AM, Rose LJ, Edwards JR, Cali S, Harris AD, Jacob JT, et al. Assessment of the Overall and Multidrug-Resistant Organism Bioburden on Environmental Surfaces in Healthcare Facilities. Infect Control Hosp Epidemiol. 2016;37(12):1426-32. 40. Tanner WD, Leecaster MK, Zhang Y, Stratford KM, Mayer J, Visnovsky LD, et al. Environmental Contamination of Contact Precaution and Non-Contact Precaution Patient Rooms in Six Acute Care Facilities. Clin Infect Dis. 2021;72(Suppl 1):S8-S16. 41. Rawlinson S, Ciric L, Cloutman-Green E. How to carry out microbiological sampling of healthcare environment surfaces? A review of current evidence. J Hosp Infect. 2019;103(4):363-74. 42. Galvin S, Dolan A, Cahill O, Daniels S, Humphreys H. Microbial monitoring of the hospital environment: why and how? J Hosp Infect. 2012;82(3):143-51. 43. Gastmeier P, Stamm-Balderjahn S, Hansen S, Zuschneid I, Sohr D, Behnke M, et al. Where should one search when confronted with outbreaks of nosocomial infection? Am J Infect Control. 2006;34(9):603-5. 44. Asgeirsson H, Thalme A, Weiland O. Staphylococcus aureus bacteraemia and endocarditis - epidemiology and outcome: a review. Infect Dis (Lond). 2018;50(3):175-92. 45. Uslan DZ, Crane SJ, Steckelberg JM, Cockerill FR, 3rd, St Sauver JL, Wilson WR, et al. Age- and sex-associated trends in bloodstream infection: a population-based study in Olmsted County, Minnesota. Arch Intern Med. 2007;167(8):834-9. 46. Wertheim HF, Vos MC, Ott A, van Belkum A, Voss A, Kluytmans JA, et al. Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers. Lancet. 2004;364(9435):703-5. 47. von Eiff C, Becker K, Machka K, Stammer H, Peters G. Nasal carriage as a source of Staphylococcus aureus bacteremia. Study Group. N Engl J Med. 2001;344(1):11-6. 48. Baede VO, Tavakol M, Vos MC, Knight GM, van Wamel WJB, group Ms. Dehydration Tolerance in Epidemic versus Nonepidemic MRSA Demonstrated by Isothermal Microcalorimetry. Microbiol Spectr. 2022;10(5):e0061522. 49. Price JR, Cole K, Bexley A, Kostiou V, Eyre DW, Golubchik T, et al. Transmission of Staphylococcus aureus between health-care workers, the environment, and patients in an intensive care unit: a longitudinal cohort study based on whole-genome sequencing. The Lancet Infectious Diseases. 2017;17(2):207-14. 50. Dancer SJ, Adams CE, Smith J, Pichon B, Kearns A, Morrison D. Tracking Staphylococcus aureus in the intensive care unit using whole-genome sequencing. Journal of Hospital Infection. 2019;103(1):13-20. 1 21 General introduction
Chapter 2 Patients Chapter 2 PATIENTS
Chapter 2.1
Chapter 2.1 The effect of 100% single-occupancy rooms on acquisition of extended-spectrum beta-lactamase-producing Enterobacterales and intra-hospital patient transfers: a prospective before-and-after study Adriënne S. van der Schoor1, Juliëtte A. Severin1, Anna S. van der Weg1, Nikolaos Strepis1, Corné H.W. Klaassen1, Johannes P.C. van den Akker2, Marco J. Bruno3, Johanna M. Hendriks4, Margreet C. Vos1#, Anne F. Voor in ’t holt1# # Authors contributed equally Antimicrob Resist Infect Control. 2022 Jun 2;11(1):76. Affiliations 1Department of Medical Microbiology and Infectious Diseases 2Department of Intensive Care Adults 3Department of Gastroenterology and Hepatology 4Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands THE EFFECT OF 100% SINGLEOCCUPANCY ROOMS ON ACQUISITION OF EXTENDEDSPECTRUM BETA-LACTAMASEPRODUCING ENTEROBACTERALES AND INTRA-HOSPITAL PATIENT TRANSFERS: A PROSPECTIVE BEFORE-AND-AFTER STUDY Adriënne S. van der Schoor, Juliëtte A. Severin, Anna S. van der Weg, Nikolaos Strepis, Corné H.W. Klaassen, Johannes P.C. van den Akker, Marco J. Bruno, Johanna M. Hendriks, Margreet C. Vos, Anne F. Voor in ’t holt Antimicrob Resist Infect Control. 2022 Jun 2;11(1):76.
Abstract Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) are a well-known cause of healthcare-associated infections. The implementation of single-occupancy rooms is believed to decrease the spread of ESBL-E. Additionally, implementation of singleoccupancy rooms is expected to reduce the need for intra-hospital patient transfers. We studied the impact of a new hospital with 100% single-occupancy rooms on the acquisition of ESBL-E and on intra-hospital patient transfers. In 2018, the Erasmus MC University Medical Center moved from an old, 1200-bed hospital with mainly multiple-occupancy rooms, to a newly constructed 522-bed hospital with 100% single-occupancy rooms. Adult patients admitted between January 2018 and September 2019 with an expected hospitalization of ≥48 hours were asked to participate in this study. Perianal samples were taken at admission and discharge. Patient characteristics and clinical information, including number of intra-hospital patient transfers, were collected from the patients’ electronic health records. Five hundred and ninety-seven patients were included, 225 in the old and 372 in the new hospital building. Fifty-one (8.5%) ESBL-E carriers were identified. Thirtyfour (66.7%) patients were already positive at admission, of which 23 without recent hospitalization. Twenty patients acquired an ESBL-E, seven (3.1%) in the old and 13 (3.5%) in the new hospital building (P=0.801). Forty-one (80.4%) carriers were only detected by the active screening performed during this study. Only 10 (19.6%) patients, six before and four during hospitalization, showed ESBL-E in a clinical sample taken on medical indication. Fiftysix (24.9%) patients were transferred to other rooms in the old hospital, compared to 53 (14.2%) in the new hospital building (P=0.001). Intra-hospital patient transfers were associated with ESBL-E acquisition (OR 3.18, 95%CI 1.27-7.98), with increasing odds when transferred twice or more. Transitioning to 100% single-occupancy rooms did not decrease ESBL-E acquisition, but did significantly decrease the number of intra-hospital patient transfers. The latter was associated with lower odds on ESBL-E acquisition. ESBL-E carriers remained largely unidentified through clinical samples. 26 Chapter 2.1
Introduction Highly resistant microorganisms (HRMO) are a common cause of healthcare-associated infections (HAI), and are a worldwide threat to public health and modern healthcare (1). Among HRMO, extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) are most frequently identified. Worldwide, the prevalence of ESBL-E in the community differs from 2% to 46% (2). In hospitals, this prevalence is higher and outbreaks with ESBLE occur. Hospital design is thought to play an essential role in the spread of HRMO including ESBL-E (3-5). To decrease the spread of HRMO within hospitals, the Facility Guideline Institute recommends transitioning to 100% single-occupancy rooms for medical/surgical units (6). Moreover, their 2018 report advises 100% single patient rooms in adult critical care units (7). An added benefit of single-occupancy rooms is that they remove the necessity for intra-hospital patient transfers for small procedures, social circumstances (e.g. end-oflife care), or for an indication of contact isolation (8). By reducing the number of intrahospital patient transfers, which leads to less exposure of the patient to different hospital environments, and by reducing the exposure to unidentified infected or colonized roommates, the implementation of 100% single-occupancy rooms is expected to reduce the risk of HRMO acquisition and transmission (9). However, current literature shows conflicting results for the effect of single-occupancy rooms on the acquisition of HRMO (4, 10, 11). Furthermore, literature on the effect of single-occupancy rooms on ESBL-E acquisition is limited to the comparison of ESBL-E acquisition between an intensive care unit (ICU) with an open plan and an ICU with single-occupancy rooms, which showed no significant difference (11). In May 2018, the Erasmus MC University Medical Center (Erasmus MC) relocated from an old hospital building, with mainly multiple-occupancy rooms, to a newly constructed hospital building with 100% single-occupancy rooms. We used this unique opportunity to determine the effect of relocating to a new hospital with 100% single-occupancy rooms on the acquisition of ESBL-E by determining ESBL-E carriage in patients at admission and discharge in both buildings. Whole genome sequencing (WGS) was used to determine if strains at discharge were identical to those present at admission or the result of acquisition during hospitalization. Additionally, we aimed to determine the effect of intra-hospital patient transfers on ESBL-E acquisition, and to identify the percentage of ESBL-E carriers that remained undetected by clinical samples. Methods Study design and setting This study was performed at the Erasmus MC, a university medical center located in Rotterdam, the Netherlands. On May 18, 2018, the adult clinic of the Erasmus MC relocated from an old, 1200-bed hospital building with mainly multiple-occupancy rooms and shared bathrooms, to a newly constructed 522-bed hospital building with 100% single-occupancy rooms and private bathrooms. To determine the prevalence of colonization with ESBL-E and the incidence of acquisition of ESBL-E in the old and new hospital building, a prospective before-and-after study was performed. Participating departments were cardiology, 2 27 Effect of single-occupancy rooms on ESBL-E acquisition
gastroenterology and hepatology, general surgery, hematology, adult ICU, internal medicine, nephrology, neurology, neurosurgery, orthopedics, and plastic surgery, which do not always correspond to the admission specialization of the patients. Room types In the old building, almost all departments consisted of two- and four-patient rooms, and bathrooms were shared, with an average of four patients per toilet (range four to seven) and seven patients per shower (range five to nine). Exceptions were the isolation department, the adult ICU, and three hematology departments. The isolation department consisted of solely single-occupancy rooms with anterooms and private bathrooms, and the ICU consisted of solely single-occupancy rooms, some with anterooms but all without bathrooms. The three hematological departments consisted of 83.3, 80.0 and 69.2% singleoccupancy rooms and private bathrooms. All multiple-occupancy rooms, two- or threepatient rooms, had attached shared bathrooms. Two of the hematology wards were located at another location in Rotterdam; the Erasmus MC Cancer Institute, location Daniel den Hoed. The Cancer Institute also relocated to the new hospital building on the same day. In the new hospital building, all departments consisted of only single-occupancy rooms with private bathrooms, with anterooms for hematology and isolation rooms. Patient inclusion From January 1, 2018 until September 1, 2019, all adult patients with an expected hospital stay of ≥48 h admitted to participating departments were asked to participate. Additionally, patients needed to understand and read Dutch. Patients who were admitted in the weekend or on holidays, via the emergency room, or who were cared for in airborne isolation were not approached for participation, as well as patients who were legally incapable in making decisions regarding participating, or patients who were in end-of-life stage. Patients with multiple hospitalizations during the study period were allowed to participate more than once. No additional information on HRMO risk factors were obtained before including patients (i.e. non-targeted screening). After obtaining written informed consent, perianal samples were collected within 24 h of admission, and on the day of discharge from the hospital. Patients who were admitted to the ICU during their hospital stay were considered as new admissions, even when they were already included in the study. Admission samples were taken on the day of admission to the ICU and discharge samples on the day patients were discharged from the ICU. Samples were either taken by trained members of the research team or patients could self-sample with clear verbal instructions of the members of the research team. Patients missed at discharge (e.g. unforeseen earlier discharge) received a letter asking them to take the sample at home, as well as a swab, swab-instructions with clear pictures and directions, and return-envelope. Patients admitted during the relocation of the hospital were asked for an additional swab, one day before relocation of the hospital. That sample was both the discharge sample for the old hospital building, and the admission sample for the new hospital building. ESBL-E colonization was defined as having a positive sample at admission. ESBL-E acquisition was defined as having a negative sample at admission and a positive sample for ESBL-E at discharge. It was also considered acquisition when patients were positive for a different ESBL-E at discharge. A different ESBL-E was defined as either being positive for a different 28 Chapter 2.1
microorganism, or when WGS showed that the discharge isolate was not identical to the admission isolate. Results of the perianal sample were not communicated to medical staff or patients, were not registered in the electronic health records (EHR), and hence, no infection prevention measures were taken based on the results, as stated in the protocol approved by the medical ethical research committee of the Erasmus MC (MEC-2017-1011). Microbiological methods Perianal samples were taken with flocked swabs and transported in the accompanying 1mL Amies medium (e-Swabs (Copan Italia, Brescia, Italy)). Perianal samples collected from January 1, 2018, until January 19, 2019, were stored in a -80°C freezer before being processed. To prevent freezing/defrosting damage, 0.2 mL 99% glycerol was added to the samples before freezing (12). Samples taken after January 19, 2019 were processed directly. All samples, regardless of being frozen, were processed following the same protocol. Samples were vortexed for 10 s before 250µL of the sample was inoculated in a tryptic soy broth with vancomycin (50mg/L) and incubated overnight at 35°C. A BrillianceTM ESBL Agar (Oxoid, Basingstoke, UK) was inoculated from the broth with a 10 µl loop and incubated twice overnight at 35°C. Colonies were identified to species level using Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight mass spectrometry (MALDI-TOF [Bruker Daltonics, Bremen, Germany]) and antibiotic susceptibility was tested with the VITEK®2 (bioMérieux, Marcy l’Etoile, France). Antibiotic susceptibility results were interpreted according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines (13). All ESBL-E isolates were stored in a -80°C freezer. Whole genome sequencing WGS was performed for all identified ESBL-E isolates. Total genomic DNA was extracted using the MagNA Pure 96 platform (Roche Applied Science, Mannheim, Germany). Genomic DNA was fragmented by shearing to a size of ~350 bp. Libraries were prepared using the NEBNext® DNA Library Prep kit (New England Biolabs, Ipswich, MA, USA) and subjected to 150 bp paired-end sequencing creating >100x coverage using Illumina technology (Novogene, HongKong, China). De novo genomic assemblies were generated using CLC Genomics Workbench v21 (Qiagen, Hilden Germany) using default parameters. Antimicrobial resistance (AMR) genes were detected and identified using the web-based Comprehensive Antibiotic Resistance Database (CARD) interface (https://card.mcmaster.ca/) restricted to perfect and strict hits (14). Conventional multi locus sequence types (MLST) and core-genome MLST cluster types were determined using each species’ corresponding scheme (https://cgmlst.org/ncs) in SeqSphere+ v5 software (Ridom, Munster, Germany). The identity of all strains was verified by analyzing the genomic assemblies using the online TYGS platform (https://tygs.dsmz.de/) (15). Data collection Patient characteristics were collected from the EHR, including the demographic variables age at admission and sex. For the hospitalization period, data on admission specialization, all antibiotic usage, surgical procedures, ICU admission, length of hospital stay, and number of intra-hospital patient transfers were collected. Intra-hospital transfers were defined as being transferred to another patient room for ≥4 h, and did not include transfers to e.g. the 2 29 Effect of single-occupancy rooms on ESBL-E acquisition
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