Introduction

The Centre for International Blood and Marrow Transplant Research (CIBMTR) coordinated the Guidelines for Preventing Infectious Complications among Hematopoietic Stem Cell Transplantation (HSCT) recipients [1]. International guidelines on protective environment for health-care facilities in which HSCT recipients are treated as announced in 2009 by CIBMTR, National Marrow Donor Program (NMDP), European Society for Blood and Marrow Transplantation (EBMT), American Society for Blood and Marrow Transplantation (ASBMT), Canadian Blood and Marrow Transplant Group (CBMTG), Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), Association of Medical Microbiology and Infectious Disease (AMMI), and Centres for Disease Control (CDC), hereby referred as Global Recommendations on Protective Environment (GRPE).

A set of 10 recommendations, based on CDC criteria, were presented with respect to guidelines on hospital room design and ventilation for HSCT setting (Supplementary Tables 1 and 2) [1,2,3]. Specifically, HSCT recipients should ideally be accommodated in a protective environment that incorporates several features, including central or point-of-use HEPA (high-efficiency particulate air) filters with 99.97% efficiency for removing particles ≤0.3 µm in diameter, and ≥12 air exchanges per hour. As there were no well-executed randomised or controlled trials, very little evidence to hand from cohort case-controlled or multiple time-series studies and limited data from uncontrolled experiments, reliance had to be placed on descriptive studies, reports of expert committees or on the opinions of respected authorities. Hence, these recommendations could only be based on level III evidence.

Since the issue is clearly of practical importance to the global transplant community, the Infectious Diseases Working Party (IDWP) of the EBMT created a survey in order to determine the current status on protective environment for HSCT recipients with the aim of reporting current practices in hospital transplant room design and ventilation and their agreement with GRPE recommendations.

Methods

The questionnaire

A total number of 543 registered EBMT centres were invited to complete the questionnaire and return it to the EBMT Data Centre to establish what is actually done in Europe to fulfil the norms proposed. The questionnaire was designed to capture sufficient information to assess how many centres were able to meet the criteria proposed in the guidelines and also to gain an accurate impression of what was done to provide a protective environment. The questionnaire consisted of 37 questions in all (Supplementary Table 3) and was divided into 5 sections, which included the contact information and details of the protective isolation facility, including air filtration, air changes, maintenance, combination of isolation, protective environment room/unit and floor. Centres were asked to complete the form on a single computer and responses could be updated while the survey was open online from April to December 2012. The information obtained was handled to guarantee the anonymity of each centre. Only those questions that corresponded directly to the GRPE recommendations were used to assess whether centres were able to comply (Supplementary Table 1).

Definitions

HEPA filter was defined as a high-efficiency particulate air filter with a 99.97% efficiency for removing particles ≥0.3 μm in diameter.

A laminar air-flow room was one that contains HEPA-filtered air that moves in a parallel, unidirectional flow, i.e., the air enters the room from one wall and exits the room from the other wall.

Combined room was a room designed to accommodate patients for isolation to protect against air-borne infection and provide protective environment by means of laminar air flow and positive air pressure.

Statistical analysis

Descriptive statistics were computed for each variable with absolute and percentage frequencies being reported. Percentage of known and missing information were also reported. A statistical comparison was performed in order to detect differences in the proportion of information known according to the function of person completing the survey. Comparisons were performed using Χ2 test or Fisher’s exact test, as appropriate. A p value < 0.05 was considered statistically significant. All the analyses were performed using SAS v. 9.4 (SAS Institute Inc., Cary, NC, USA).

Results

Contact information

Overall, 238 (38.3%) of 543 centres from 37 countries responded and returned the questionnaire. However, reliable information was provided by 177 (32.6%) centres from 36 countries once duplicate responses had been eliminated, with an average response rate of 33% per country. Physicians completed 62%, nurses 19% and support staff 19% of the survey questionnaire. A total number of 71% of answers were provided to all questions. The total number of answered questions was higher among physicians than among other staff: 84% (range, 6–100%) vs. 63% (range, 3–97%), p < 0.001.

Responses were given from European countries (n = 25), Africa (n = 3), Asia (n = 3), South America (n = 2), Canada (n = 1), Australia (n = 1) and New Zealand (n = 1). The responding centres cared for adults (n = 93; 52.5%), children (n = 32; 18.1%), adults and children (n = 41; 23.2%), while 11 (6.2%) centres did not specify the age of patients.

The rate of results fulfilling GRPE recommendations are shown in Table 1 with further details shown in Supplementary Tables 4A, B, C and D.

Table 1 Overall positive results of the survey with respect to Global Recommendations GRPE
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Air filtration and air changes

Among the participating centres, 99.4% of patient rooms were equipped with HEPA filters, with central or point-in-use room system being used in 45.8% and 48%, respectively (Supplementary Table 4A). The use of HEPA filters with 99.97% efficiency for removing particles ≤ 0.3 µm in diameter, and room ventilation with the rate of at least 12 air changes per hour were confirmed by 70.1% and 71.2% of centres, respectively. Only 48.6% of centre staff were aware of, and could confirm, regular replacement of filters based on manufacturers’ recommendations, while 53.7% centres had a written procedure (Supplementary Table 4B) for regular filter maintenance and removal and to monitor filtration efficiency in order to best determine appropriate time for replacement, especially in case of ongoing construction. In 48% of centres, the transplant staff had access to air changes measurements, and in 18.1% a sensor monitor was available in the patient’s room.

Maintenance

Half of the centres (50.3%) were using pre-filters (Supplementary Table 4B). In 59.3% centres, the airflow was directed so that air intake occurred at one side of the room while the air exhaust was placed at the opposite end, and 42.9% centres were equipped with a particle counter. A consistent positive air pressure differential between the patient’s room and the hallway ≥ 2.5 Pa (i.e., 0.01 inches by water gauge) was reported by 38.4% centres that had a permanently installed device/mechanism to constantly monitor the differential air pressure between the room and the corridor. A policy for cleaning air duct grills was available for the transplant staff in 58.2% centres.

Combined air-borne infectious isolation and protective environment room

Combined rooms and anterooms were available in 52% and 45.8% of centres, respectively (Supplementary Table 4C), although most of the centres (85.9%) reported that they needed combination rooms. The pressure in the anteroom was reported to be positive in 19.2% centres, and negative in 19.8% centres, while an air pressure monitoring device/mechanism in the anteroom in addition to the patient room was present in 17.5% of centres. The ability to reverse the air flow in the patient’s rooms was reported by 16.9% centres.

Well-sealed rooms were used in order to prevent infiltration of air from outside the room that could allow entry of spores and hinder maintenance of proper pressure differential, with respect to: windows (70.6%), monolithic ceilings (35%), and plumbing in the room (51.4%) of centres. Periodic air samples were cultured for fungi in 54.2% of centres.

Unit and floor

The heating ventilated air conditioning system and emergency power was present in 62.7% and 58.2% of centres, respectively (Supplementary Table 4D). In order to guarantee the continuous positive pressure, a monitoring system that would set off an alarm when the pressure differential falls to <2.5 Pa between the room and the adjacent hallway or anteroom to alert staff to possible engineering failures was installed in 33.9% of centres. Self-closing doors to maintain constant pressure differentials were present in 37.3% of centres. The sensor monitors in the patient room that is used to determine when the HEPA filters required changing was installed in 18.1% of centres. The nursing staff was able to observe the HSCT recipient through a window installed in the door or wall of the HSCT recipient’s room or by a monitoring system was present in 61.6% of centres. In 38.4% of centres, protective isolation rooms were also available in Intensive Care Units (ICU) with signage being present in 70.6% cases to identify them clearly.

Overall ability of centres to fulfil the recommendations

Knowledge about the presence and maintenance of protective environment among the staff of HSCT units was limited, reflecting a lack of communication between health personnel working in the ward and hospital maintenance services. The rate of centres fulfilling respective survey questions corresponding to specific recommendations ranged between 17.5 and 99.4% (Table 1), while the rate of centres fulfilling complete requirements of respective recommendations ranged between 5 and 71% (Fig. 1). Only 1 centre was able to meet all 10 Global Recommendations GRPE [1] and few centres were able to meet all the relevant technical requirements (Fig. 2). Only 16 out of 53 (30.2%) JACIE accredited centres scored 3 out of 3 level “A” recommendations.

Fig. 1
figure 1

Number of centres fulfilling respective Global Recommendations GRPE. Recommendations 1–3 are graded AIII, 4–8 graded BIII and 9–10 graded CIII

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Fig. 2
figure 2

Number of centres which fulfilled a specific number of GRPE recommendations

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Discussion

This survey among EBMT centres was designed to determine the current status of technical aspects of protective environment and isolation facilities for recipients of HSCT and current practices in hospital transplant room design and ventilation and to assess their compliance with the 2009 GRPE recommendations [1]. Certain sections of the survey were dedicated to details of air filtration, air changes, maintenance, combined of air-borne infection isolation and protective environment room, ventilation systems for unit and floor in transplant centres. Direct anti-infective management of transplant patients was not the subject of this study.

The response rate to this IDWP survey was 32.6%, which is relatively high compared to other EBMT surveys. Some questions only required knowledge of the accommodation such as monolithic ceilings, ability to observe the patient, whereas others required access to engineer’s reports on filter maintenance and monitoring systems. Establishing certain details such as the number of air exchanges or the efficiency and regular changes of the filters (GRPE 5 and GRPE 9) were found to be most difficult for personnel of HSCT units, whilst almost everyone reported that patient rooms were equipped with HEPA filters (GRPE 1 and GRPE 2). Similarly, only a few could confirm whether the pressure in the anteroom was monitored or not and provide affirmative answers to questions about ceilings and monitoring.

An earlier survey of the EBMT conducted in 2008 reported that most recipients of an allogeneic HSCT were housed in HEPA-filtered rooms, however, it concluded that recommendations for accommodating patients who were colonised or infected with an opportunistic pathogen were either poorly understood or not properly implemented [4].

Most centres were unable to show that their centre had implemented the recommendations endorsed by the EBMT, even the most important ones. This may be due to two factors. Firstly, the lack of specific technical facilities in the transplant ward. Secondly, physicians and other health care personnel of transplant ward do not have ready access to the necessary information on technical matters in their own centre. This also makes it difficult for inspectors to determine whether the protective isolation provided in a given centre meets the required standards.

Protective isolation in various forms has been promoted for patients with neutropenia for nearly 50 years [5]. However, there has been no economic analysis to show that it is cost-effective. Indeed, the data showing that protective isolation prevents infection is sparse and arose from the experience of a few early pioneers [6]. Others have questioned the practice altogether as they could not find any benefits in terms of reducing infection and suggested that accurate hygiene measures would prove just as effective, while improving the quality of care and patient satisfaction as well as being less expensive [7]. There are also adverse effects of protective isolation to consider, not least that patients can suffer from being isolated in every sense of the word [8,9,10].

This survey shows that knowledge about the maintenance of protective environments in the HSCT setting is inadequate, reflecting poor communication between health care personnel working in the ward, hospital infection control and hospital maintenance services. Only one centre was able to meet all 10 GPRE recommendations listed by Tomblyn et al. [1] and only few centres were able to meet all the relevant technical requirements. This may simply be a consequence of the fact that, in most cases, transplant wards were constructed many years ago and major reconstruction is either not possible or is prohibitively expensive. Hence, maintaining the current technical structure and facilities in the transplant ward is crucial to ensure protective environment for transplant patients.

The results of the survey show that, in general, health care personnel are interested in implementation of procedures shown to be protective (i.e., HEPA filters) but not in maintenance, which falls to other services to deal with. Although detailed knowledge about protective environments in the HSCT setting is not necessary for all health care staff, communication between them and hospital engineering services is mandatory for effective prevention of infectious complications.

We suggest that dedicated health care personnel should be selected to cooperate with the appropriate hospital maintenance services with regard to:

  • Review of type and incidence of selected infections either once yearly or after introduction of new equipment, and their association with protective environment systems and what has been changed;

  • Provide general information on protective environments to health care staff, patients and their relatives on notice boards of the ward/department;

  • Ensure detailed information on protective environments is easy to find;

  • Offer training in the field annually in order to inform and highlight the importance of the protective environment;

  • Undertake economic analysis to estimate cost effectiveness.

A protective environment plays a key role in ensuring the safety of patient after transplant so we propose a range of responsibilities for the transplant team in order to ensure they possess sufficient knowledge about what this entails (Table 2). It should be noted that daily check-up performed by physicians, nurses and cleaning staff is based on routine activity and does not require additional work, except when reporting failures in the system. A meeting of transplant ward personnel and hospital technical personnel responsible for environmental services is recommended once a year. In parallel, hospital infection control group should implement and run program of epidemiology, prophylaxis and management of infections in transplant unit.

Table 2 Proposed recommendations for responsibilities of health-care and hospital personnel regarding supervision of protective environment facilities in transplant ward
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In conclusion, GRPE recommendations on the technical aspects of protective isolation were based on expert opinion and very limited data and the results of this IDWP survey provide an overview of whether or not they are being fulfilled. It was clear that knowledge on the details and maintenance of protective environments in the HSCT setting was inadequate reflecting a lack of communication between the health personnel involved, hospital infection control and the hospital maintenance services.