Background

Clean healthcare facilities look appealing, offer a sense of security and increase patient satisfaction [1]. Although visually clean facilities have become the standard of healthcare settings in high-income countries, cleanliness not only plays a role in quality of care, but in its safety. The microbiological aspect of cleanliness, healthcare environmental hygiene (HEH), has remained a neglected field, with little investment beyond what is considered the norm. Few high-quality studies link interventions in HEH to a reduction in either patient colonization with epidemiologically relevant pathogens or healthcare-associated infections (HAI). Though there are many reasons for this, one is the lack of literature critically evaluating the role of HEH in patient safety.

HAI are acquired during hospital stay [2] and cause more deaths worldwide than malaria, tuberculosis, and AIDS combined, and the burden of the six main types of HAI is higher than the total burden of the 32 major communicable diseases [3, 4]. These infections also increase morbidity, prolong hospital stay, and are a major financial burden to healthcare systems [5, 6]. The total annual global cost for five of the most common types of HAI is estimated at $8.3–$11.5 billion [7]. Despite their ubiquity, still much is unknown about how to prevent HAI, and no single hospital or healthcare facility in the world can claim to be unaffected.

While HAIs are usually the result of an infection with the patient’s own flora, this flora can change due to colonization with hospital pathogens through HCWs’ hands or from the hospital environment. Definitively knowing whether an HAI came from the patient’s environment or from another source is difficult. Though it is known that some bacteria are more often transmitted through the patient environment than others, it is comparatively rare that extensive investigations are performed at the time of diagnosis. Usually such investigations are reserved for unusual infections or outbreak situations, in hospitals with sufficient resources to undertake them.

Over the past 25 years, best practice interventions such as hand hygiene in patient care have reduced the number of HAIs [8, 9]. Poor hand hygiene has been recognized as being one of the main drivers of HAIs among patients [9]. Even if such practices can reduce HAIs by up to 50%, there is still a remaining proportion that needs to be addressed and where HEH may play a role [10]. A prerequisite for addressing some of these challenges is to review the literature to evaluate whether HEH interventions have a direct effect on HAI and thus, on patient safety.

HEH is essential for all types of healthcare facilities, from hospitals and long-term care facilities to home care environments. Environmental hygiene builds on both technical and human components, and it includes all aspects of the healthcare environment that are not the patient or the HCWs themselves. The technical component includes cleaning and disinfection of surfaces, water management, air control, waste management, laundry, and sterilization and device reprocessing. The human component includes best practice implementation, staff management, and environmental services departments’ structural organization [11]. This component includes the evaluation of the cost and value of HEH interventions and programs, the training and monitoring of staff, their career development and workflow organization. Both of these components carry major implications for the well-being of patients, HCWs, the community and the larger natural environment.

Beyond the biological plausibility that the healthcare environment has a direct effect on patient safety, a number of reports over the last decades increasingly highlighted the potential impact of environmental hygiene on health [12, 13]. Most common healthcare-associated pathogens are known to survive on surfaces for hours or days, some for weeks and a few for over a year [14, 15]. It has been shown that hygiene failures correlate strongly with HAI in an ICU setting [16]. There is an increase of 150–500% in the chance of acquiring a pathogen if the prior room occupant was colonized with it [17].

This paper reviews the evidence-base for the ability of interventions in the hospital environment to reduce patient colonization with multidrug-resistant microorganisms (MDROs) and other epidemiologically relevant pathogens, and to prevent HAI. This exercise is difficult for a number of reasons. First, high-quality randomized controlled trials in HEH are sparse. Secondly, the bulk of studies are retrospective or prospective before-and-after studies with limited methodological quality. Third, there is heterogeneity of the field about “clean environment” and how environmental hygiene is defined. Finally, HEH interventions are often combined with other infection prevention and control (IPC) interventions such as hand hygiene or a reorganization of patient care. These confounding factors can cause difficulty when determining whether outcomes are a direct effect of an HEH intervention.

Methods

We performed the systematic review protocol according to the PRISMA checklist [18], in both the PubMed and Web of Science databases. The full search strategies are available in the Additional file 1. The primary outcome is a comparison of the measure of patient colonization or HAI compared to baseline/control. HAI was defined according to the WHO definition [2].

The secondary outcome was environmental bioburden as defined as either cultured environmental samples or adenosine tri-phosphate (ATP) sampling. Although ATP sampling is technically a proxy measure of bioburden, it correlates closely with microbiological sampling in the literature [19]. Other proxy measures for bioburden such as the use of florescent dye were not included. Though the use of fluorescent techniques can show a measurable improvement in cleaning procedures, they do not necessarily demonstrated an impact on bioburden, depending on what is being used to remove the fluorescent dye. Therefore, studies that used improved cleaning practices or fluorescent marking as a proxy measure of bioburden were marked as “NA”.

All original studies were eligible if they were published before December 31, 2019, and if they measured the effect of an HEH intervention on HAI or patient colonization. Studies with an English abstract were eligible when published in English, French, German, or Spanish and only included if they were original research.

Studies were not eligible if they were conducted in vitro, did not include patient colonization or HAI as an outcome, were bundled with hand hygiene interventions, or were implemented during an outbreak. Outbreaks were excluded because outbreak management broadens the intervention, and it would not be possible to adjust for that effect. Complete structural rebuilds were excluded, because interventions such as renovating a building or replacing a plumbing system are not feasible HEH interventions in most contexts. There is also evidence that such interventions result in reduction of the studied pathogen for a limited time, after which the environment can become recolonized [20].

Interventions of interest were either mechanical, chemical, or they applied a human factors design. The standardized extraction forms included type of intervention, study title, authors, year of publication, study design, type of intervention(s), intervention(s), sample size or sample size proxy, control, microorganisms studied, outcome, whether the method is recommended for application by the authors, quality score and grade, reduction in bioburden, and comments.

Interventions were stratified into chemical, mechanical, human factors, and bundles of combining two or more of the aforementioned categories. Titles, abstracts and the full text of all potentially eligible studies were screened independently by at least two reviewers. Inclusions and exclusions were recorded following the PRISMA guidelines, and reasons for exclusion were detailed. Data were extracted by two authors. Any disagreement was resolved through discussion with a third author. Any missing data was requested from original study authors by email. Ethical approval was not required for this review.

As a wide variety of procedures and methodologies were identified, a descriptive analysis with a narrative synthesis was performed. Due to this heterogeneity, additional sub-group analyses by type of intervention, type of microorganism, and study quality were performed.

The study designs were divided into the following categories: randomized controlled trials (RCTs), quasi-experimental studies (prospective and retrospective), and before-and-after studies (prospective and retrospective). Sample sizes were categorized by ranges from less than 10 to more than 100′000 patients/patient-days/room cleanings. Presence of a study control was adjusted to include proxies for a control. The main confounding factors that were analyzed included hand hygiene compliance, antibiotic use, and the seasonality of certain HAI.

Available tools for analyzing study quality were assessed, and selected using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for conducting observational studies which had been previously used for such a review [21, 22]. The STROBE checklist was, however, difficult to apply to some HEH interventions, in particular when a study had no control, its primary outcome was laboratory-based or based on bioburden measurements. We therefore also constructed a specifically-designed quality scoring system which included what the reviewers deemed the most important elements in the studies. Obviously, this scoring system is only meant to compare this specific list of studies and is not applicable in other contexts. After discussion in a working group, the following five elements were included in the quality assessment: study design, sample size, control, confounders, and issues with reporting. Among issues with reporting, conflict of interest (COI) was defined as minor if less than half of the authors disclosed a COI, such as having worked for industry as a consultant in the same field, and major if more than half of authors were funded by industry for the study.

Table 1 summarizes the quality scoring scale used in the review. Studies were graded from 0 to 20 points. “High quality” studies referred to studies that received an A or B grade according to the quality scale (Table 1). Some studies that ranked lower on the quality scale were well-performed, but simply not designed or powered to determine significant changes in patient colonization or HAI.

Table 1 Healthcare environmental hygiene intervention studies; quality scoring scale; systematic review
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Findings

Of the 952 retrieved and deduplicated studies, 44 were included for full-text review. A total of 26 studies were included in the final analysis (Fig. 1 and Table 2). Studies reported mechanical (n = 8) [23,24,25,26,27,28,29,30], chemical (n = 7) [31,32,33,34,35,36,37], human factors (n = 3) [38,39,40], and bundled interventions (n = 8) [41,42,43,44,45,46,47,48]. All of the studies that examined HAI only examined HAI in patients, not HCWs. Two studies were published before the year 1990 [25, 28], while the others (24/26) were published between 2013 and 2020. Of all of the 26 interventions, only five (19%) were not recommended for application by the study authors [23, 25, 30, 39, 42]. Among them, three were mechanical interventions [23, 25, 30], one was a human factors intervention [39], and one was a bundled intervention [42]. All of the chemical interventions were recommended for application by the study authors [31,32,33,34,35,36,37].

Fig. 1
figure 1

Effects of healthcare environmental hygiene interventions on healthcare-associated infections and patient colonization; Systematic review-PRISMA flow chart

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Table 2 Results of the environmental hygiene studies organized by type of intervention; systematic review; N = 26
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Five studies were RCTs [32, 37, 39, 47, 48]. The remaining studies had prospective quasi-experimental designs (n = 3) [25, 33, 44], retrospective quasi-experimental design (n = 1) [38], prospective before-and-after designs (n = 11) [23, 24, 27, 28, 30, 31, 34, 41,42,43, 45], and retrospective before-and-after designs (n = 6) [26, 29, 35, 36, 40, 46]. In total, only 31% (8/26) studies had a true control [25, 32, 37, 39, 42, 44, 47, 48].

Over half (15/26, 58%) of the studies demonstrated a significant decrease in patient colonization or HAI following the chosen intervention for all microorganisms tested [24, 26, 29, 31, 33, 35,36,37,38, 40, 41, 43,44,45,46]. In one study, the reduction was not significant for all patient groups [26]. If additional interventions that demonstrated a reduction in all microorganisms tested were included, whether significant or not, this increased to 69% [23, 28, 32]. If the additional interventions that demonstrated a reduction in at least one of the microorganisms tested (significant or not) were included, this increased to 88% [25, 27, 34, 47, 48].

Analysis by type of intervention (Table 2)

Of the eight studies that implemented mechanical interventions [23,24,25,26,27,28,29,30], 63% (5/8) reported statistically significant reductions in HAI or colonization for at least one tested microorganism [24,25,26,27, 29]. When all mechanical interventions showing any reduction in at least one of the microorganisms tested were included, including those not statistically significant, this increased to 88% (7/8) [23, 48]. Two of the three studies that implemented human factors interventions [38,39,40], showed a statistically significant reduction in HAI or colonization for all microorganisms tested [38, 40]. The remaining study demonstrated no reduction [39]. Of the seven studies that implemented chemical interventions [31,32,33,34,35,36,37], 6 (86%) demonstrated statistically significant reductions for at least one of the microorganisms tested [31, 33,34,35,36,37]. If all the interventions that demonstrated a reduction (not significant) in all microorganisms tested were considered, this increased to 100%. Eight studies implemented bundled interventions, and 88% (7/8) demonstrated statistically significant reductions in HAI or colonization for at least one of the microorganisms tested [41, 43,44,45,46,47,48], although the study by Anderson et al. [48] only demonstrated significant reduction in one of the two test wards. The remaining study demonstrated no reduction [42].

Sub-group analyses were conducted for the most frequently implemented interventions (Table 3): ultraviolet-C light (UVC), hydrogen peroxide (both liquid and gaseous), and human factors. UVC interventions were implemented in six studies [23, 24, 27, 29, 30, 48]. Of these, one study was bundled [48]. The interventions were recommended for application by the authors in four (67%) of the studies [24, 27, 29, 48]. Reductions in colonization/HAI were significant in those same four studies, though not for all microorganisms tested [27, 48].

Table 3 Healthcare environmental hygiene interventions according to the individual type of intervention; systematic review
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Five studies assessed the implementation of gaseous hydrogen peroxide [31, 35, 36, 45, 46]; two were bundled interventions [45, 46]. The interventions were recommended for application by authors in all studies, and all reductions were statistically significant. Three studies assessed liquid hydrogen peroxide [32, 33, 46]. The interventions were recommended in all studies, and the reductions in colonization/HAI were statistically significant in two studies [33, 46].

Human factors studies encompassed all interventions that included training and education, monitoring and feedback, and promotion of institutional safety climate. Nine studies assessed the implementation of human factors [38,39,40,41,42, 44,45,46,47]; six were bundled interventions [41, 42, 44,45,46,47]. The interventions were recommended by the authors in 78% (7/9) of the studies [38, 40, 41, 44,45,46,47], though one only recommended it for VRE [47]. Reductions in colonization/HAI were significant in those same studies.

One study performed a cost analysis. The installation of high efficiency particulate air (HEPA) filters was found to decrease the cost per patient; it is to note that these findings were significant in both $ and €, but did not reach the threshold for significance in Turkish Lira [26]. Another article suggested that gaseous hydrogen peroxide decontamination was cost-effective for C. difficile, based on the estimated minimum cost of nosocomial C. difficile infection per year [36].

Analysis by microorganism (Table 2)

Half of the studies (13/26) observed the impact of an intervention on methicillin-resistant Staphylococcus aureus (MRSA) and/or S. aureus [25, 27, 29, 30, 32,33,34, 37, 41, 42, 46,47,48]. Of these, 62% (8/13) were recommended for application by the study authors [29, 32,33,34, 37, 41, 46, 48]. One study that recommended the intervention compared a disinfectant to a detergent [46], and one which did not recommend the intervention was not powered to demonstrate a reduction in HAI [30]. 46% of the interventions (6/13) demonstrated a significant decrease in HAI/colonization [29, 33, 34, 37, 41, 46]. In one study that did not, the rate of MRSA infection increased significantly, which is unsurprising, as the intervention was only implemented in C. difficile rooms in the arm of the study with the increase [27].

Sixty-five percent of studies (17/26) observed the impact of an intervention on C. difficile [23, 27, 29,30,31,32,33,34,35,36, 38,39,40, 42, 44, 47, 48]. Among these, 59% of the interventions (10/17) were recommended for application by the study authors [27, 29, 31,32,33, 35, 36, 38, 40, 44]. Of the seven studies that were not recommended, one was not powered to be able to show a reduction in HAI and not all hospitals disinfected appropriately for C. difficile in another [30, 47]. Fifty-three percent of the interventions (9/17) demonstrated a significant decrease in HAI/colonization [27, 29, 31, 33, 35, 36, 38, 40, 44].

Forty-six percent of studies (12/26) observed the impact of a HEH intervention on VRE [23, 27, 29, 32,33,34, 37, 41, 42, 45, 47, 48]. Of these, 75% (9/12) recommended the intervention [27, 29, 32, 33, 37, 41, 45, 47, 48]. 58% of studies (7/12) demonstrated a significant decrease in HAI/colonization [29, 33, 37, 41, 45, 47, 48]. One study demonstrated that the intervention reduced the rate of colonization but not of HAI [41]. One study demonstrated that VRE colonization was reduced even when compliance to the intervention was lower than necessary for significantly reducing other pathogens [33].

Seven studies assessed the effect of interventions on Gram negative bacteria [25, 29, 30, 34, 41, 43, 48]. Three studies observed the impact of an intervention on A. baumannii (including carbapenem-resistant and multidrug-resistant strains) [34, 41, 48], and three on Pseudomonas (two on P. aeruginosa and one on Pseudonomas spp.) [25, 30, 43]. Klebsiella, extended spectrum beta-lactamase Enterobacteriaceae, S. maltophilia, Proteus sp. and coliform bacilli were each analyzed by only one study [25, 30, 43]. Fifty-seven percent of interventions (4/7) were recommended for application by the authors, each of which demonstrated a significant decrease in HAI/colonization [29, 41, 43, 48]. One older study [28] evaluated the role of negative air pressure rooms to prevent Varicella zoster and Herpes zoster infection. Although statistical significance was not calculated, there were no new cases after the intervention and the method was recommended by the authors [28]. Another study demonstrated the effect of air control to prevent invasive fungal infections during construction and showed an effect among oncology-haematology patients [26].

Analysis by quality (Table 4)

Table 4 Quality scoring of included studies; systematic review; N = 26
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The quality scoring system (Table 1) considered study design, sample size, whether there was a control, how the study adjusted for confounding factors, and issues in reporting. Table 4 shows the detailed quality scoring system results for the 26 studies. Forty-two percent of the studies (11/26) were considered to be of high-quality (grade A or B, Table 4). All studies that were of quality “A” and 1 study of quality “B” were RCTs [32, 39, 47, 48]. 27% of high-quality study interventions (3/11) were not recommended for application by the authors [23, 25, 39]. The interventions in 64% (7/11) of these studies significantly reduced colonization/HAI [33,34,35, 38, 44, 47, 48]. In 43% (3/7) of these studies, the reduction was only significant for specific bacteria [34, 44, 47]. Fifty-eight percent of the studies (15/26) were of lower quality (grade of C or D, Table 4). Eighty-six percent of these (13/15) significantly reduced colonization/HAI [24, 26,27,28,29, 31, 36, 37, 40, 41, 43, 45, 46]. In one of these studies, the reduction was only significant for specific bacteria [27].

A further analysis was conducted which included only the higher quality studies that used a true control, and the most commonly studied microorganisms (S. aureus, C. difficile, and VRE), in order to assess whether there was a significant reduction per pairing of each microorganism and intervention (Table 5). This resulted in 15 of pairings from five studies [32, 39, 44, 47, 48]. The distribution included five interventions for each S. aureus, C. difficile, and VRE. Eighty-seven percent of the pairings (13/15) demonstrated a reduction in colonization or HAI [32, 44, 47, 48], but only 27% of them (4/15) demonstrated a significant reduction in patient colonization or HAI [44, 47, 48]. Studies were too heterogenous to perform any kind of metanalysis, and in those high quality studies, no two interventions on the same microorganism were comparable. Future studies in the field should aim to calculate sample sizes and be adequately powered to be able to demonstrate such reductions.

Table 5 Effects of healthcare environmental hygiene interventions on healthcare-associated infections and patient colonization
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Bioburden (Table 6)

Table 6 Relation between the reduction in environmental bioburden and patient colonization or healthcare- associated infection following an environmental hygiene intervention; systematic review
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Fifty percent (13/26) of studies observed the impact of HEH interventions on environmental bioburden [24, 25, 30,31,32, 34, 37, 39, 41, 42, 44, 46, 48]. 100% of them demonstrated that the interventions decreased environmental bioburden. Over half (7/13) of the studies demonstrated bioburden reductions paralleled directly with a significant reduction in colonization/HAI for at least one of the microorganisms of interest [31, 34, 37, 41, 44, 46, 48].

Interpretation

This systematic review demonstrated that interventions in environmental hygiene were often associated with a reduction in HAI in a seemingly causal way. Over half of studies demonstrated a significant decrease in colonization or HAI for all of the microorganisms tested. These results are indicative of the importance of environmental hygiene in patient safety.

There were major issues with both the heterogeneity of the interventions and the settings, as well with the quality in a number of the studies, hence the sub analyses. There are relatively few high quality studies in HEH compared to other fields, and even the use of RCTs in the field is exceedingly rare [11]. One high-quality study [49] in particular would have been useful for the review, but was excluded due to a hand hygiene intervention. Often, the primary study outcome evaluated environmental bioburden. Though HAI or patient colonization was a secondary outcome obtained from hospital data, these studies were not necessarily designed and powered to analyze this outcome. The measurable impact of HEH is likely to be more apparent if future studies are sufficiently powered.

Most of the studies that did not show a statistically significant reduction in HAI or patient colonization nonetheless recommended their interventions for application because they did greatly reduce environmental bioburden [28, 32, 38]. Though eight studies had controls [25, 32, 37, 39, 42, 44, 47, 48], many had before-and-after study designs [23, 24, 26,27,28,29,30,31, 34,35,36, 40, 41, 43, 45, 46], and thus did not implement appropriate controls. Two used similar institutions as “proxy” controls [33, 38]. Often, studies used the baseline rate of colonization or HAI before the intervention was implemented, and attempted to account for some confounding factors such as hand hygiene, antimicrobial use, and seasonality of the diseases of interest. In retrospect, it may have been more useful to only analyze more recent studies, because the two that were published before 2000 [25, 28] (in 1971 and 1985, respectively) were exploring different research questions and microorganisms.

The success of the interventions also depended on which microorganisms were studied, and how successfully or not specific pathogens spread through the healthcare environment. For example, VRE, known to spread through the environment, was sometimes more successfully reduced than pathogens known to frequently spread through hands from patient to patient. One study [26] testing air filters gave further support to the fact that not all microorganisms are able to be transmitted by air, unlike what some manufacturers claim.

Considering the subset analysis targeted on specific pathogens, it is important to note that not all studies were designed to demonstrate the efficacy of a particular intervention on colonization/HAI, as this was not always the primary outcome. Some interventions were recommended by the authors for application because they demonstrated a significant reduction in some pathogens but not in others. Though these outcomes were often coupled with a significant decrease in environmental bioburden, some studies were not sufficiently powered to demonstrate that the reduction was statistically significant.

Overall, the selected studies were very heterogenous; both in terms of the types of interventions and their quality. The review attempts to address some of these limitations by performing subset analyses. However, the results reflect the reality of this field; there is a significant amount of work left to be done. Though COVID-19 has generated an increased global interest in HEH, the bulk of newer studies were performed during a pandemic, and were not included in this review, as interventions conducted during outbreak situations were excluded.

Conclusion

Although more high quality studies are needed, this review demonstrates a strong relation between interventions to improve HEH and a reduction in both environmental bioburden and in patient colonization or HAI. Optimal HEH practices are an integral part of patient safety and a key component to improving infection prevention and control. Healthcare institutions may be able to lower their HAI rates by improving HEH practices. The domain of HEH deserves further and better-designed field research.