ANNOTATED BIB WRTG 391

Review

Environmental contamination and hospital-acquired infection:

factors that are easily overlooked

Abstract There is an ongoing debate about the reasons for and factors contributing to healthcare-associated infection (HAI). Different solutions have been proposed over time to control the spread of HAI, with more focus on hand hygiene than on other aspects such as preventing the aerial dissemination of bacteria. Yet, it emerges that there is a need for a more pluralistic approach to infection control; one that reflects the complexity of the systems associated with HAI and involves multidisciplinary teams including hospital doctors, infection control nurses, microbiologists, architects, and engineers with expertise in building design and facilities management. This study reviews the knowledge base on the role that environmental contamination plays in the transmission of HAI, with the aim of raising awareness regarding infection control issues that are frequently overlooked. From the discussion presented in the study, it is clear that many unknowns persist regarding aerial dissemination of bacteria, and its control via cleaning and disinfection of the clinical environment. There is a paucity of good-quality epidemiological data, making it difficult for healthcare authorities to develop evidence-based policies. Consequently, there is a strong need for carefully designed studies to determine the impact of environmental contamination on the spread of HAI.

C. Beggs1, L. D. Knibbs2, G. R. Johnson3, L. Morawska3

1Centre for Infection Control and Biophysics, University of Bradford, Bradford, UK, 2School of Population Health, The University of Queensland, Herston, Qld, Australia, 3International Laboratory for Air Quality and Health, Queensland University of Technology, Brisbane, Qld, Australia

Key words: Healthcare-associated infection; Aerial dissemination; Environmental contamination; Hospital microbiome; Duct cleaning.

C. Beggs Centre for Infection Control and Biophysics School of Engineering Design & Technology University of Bradford Bradford West Yorkshire BD7 1DP UK Tel.: +44(0)1274-233679 Fax: +44(0)1274-234124 e-mail: [email protected]

Received for review 30 May 2014. Accepted for publication 16 October 2014.

Practical Implications The article highlights specific issues associated with environmental contamination in hospitals that have been largely overlooked and shows how these may contribute to the spread of infection. As such, the article reveals new insights that should be helpful to infection control practitioners, hospital designers, and all those involved in formulating policy regarding the design of healthcare facilities.

Introduction

In recent years, there has been awareness that micro- bial contamination of the clinical environment may contribute to the spread of healthcare-associated infec- tion (HAI) (Boyce et al., 1997; Dancer, 2004, 2008; Dancer et al., 2009). Consequently, there has been increased emphasis on surface disinfection and ward cleaning, with some authorities placing a statutory obligation on hospitals to ensure that the clinical environment is clean and well maintained (N.P.S.A,

2007). While this has made the cleaning and disinfec- tion of hospital wards a higher priority, the role that environmental contamination plays in the transmission of HAI is poorly understood. Indeed, there is little firm epidemiological evidence to support the widely held and intuitive belief that cleaner hospitals result in fewer infections (Dancer, 2008; Dancer et al., 2009; Rhame, 1998). There is, however, a considerable evidence that the touching of contaminated surfaces by healthcare workers (HCWs) frequently results in the transient col- onization of hands or gloves (Bhalla et al., 2004; Boyce

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doi:10.1111/ina.12170

et al., 1997; Duckro et al., 2005; Hayden et al., 2008; Ray et al., 2002), suggesting that there is a link between surface contamination and transient coloniza- tion of the hands of HCWs. In fact, numerous studies have implicated contamination of the clinical environ- ment in outbreaks of Gram-positive (Cotterill and Al, 1996; Fawley and Wilcox, 2001; Hardy et al., 2006; Hota, 2004; Kumari et al., 1998; Malamou-Ladas et al., 1983) and Gram-negative (Allen and Green, 1987; Beggs et al., 2006a; Breathnach et al., 2012; Das et al., 2002; Engelhart et al., 2002; McDonald et al., 1998; Sherertz and Sullivan, 1985; Weernink et al., 1995) bacterial infection. However, while much effort has been expended investigating environmental con- tamination and HAI, most of this has been detective work undertaken in response to specific hospital out- breaks. By comparison, very few controlled trials have been undertaken, with the result that the contribution made by environmental contamination to the overall body of HAI is difficult to quantitate and characterize. It is therefore difficult to address with confidence, even basic questions regarding the cleanliness of hospitals. For example, it is not known which ward surfaces should be cleaned or disinfected, and how often such cleaning is required in order to minimize HAI rates. Indeed, it is not known if heavily contaminated sur- faces such as hospital ventilation ducts, (which can accumulate particulate debris to a depth of several mil- limeters) pose any threat to the safety of patients. Con- sequently, healthcare authorities have great difficulty specifying meaningful performance criteria for general hospital cleanliness.

To explore the role of environmental contamination in the transmission of infection within healthcare facili- ties, this study aims to highlight infection control issues relating to building design and facilities management that have been overlooked, but might be worthy of fur- ther investigation. We limit our scope to sources of bacterial and fungal infection, as these have been more extensively described in the literature than viral patho- gens.

Gulf between disciplines

Traditionally, infection control has been the sole pre- serve of hospital doctors, infection control practitio- ners and microbiologists. However, in recent years, other professionals such as engineers have become involved in infection control, primarily because of their expertise in building design, facilities management, and modeling airflows within and between room spaces. In addition, many commercial organizations have devel- oped hygiene related products for use in the healthcare sector. This increased activity has led to new insights into the transmission of some HAIs. However, while engineers and physical scientists have been able to make significant contributions to the infection control

knowledge base, a gulf in thinking still exists between these professionals and hospital clinicians. This gulf reflects the various approaches inherent in these differ- ent occupations and is exemplified by a general belief among clinicians that the battle against HAI can be won only through greater hand hygiene compliance. Conversely, engineers and manufacturers tend to believe that gadgets and technical fixes might offer the optimum solution. This has polarized the debate, with clinicians tending to be very skeptical of infection con- trol strategies not primarily focused on hand hygiene compliance, despite the fact that several studies have shown that the efficacy of hand hygiene measures can be severely limited by other factors (Beggs et al., 2006b, 2008b, 2009; DiDiodato, 2013; Silvestri et al., 2005; Talon et al., 2009). A middle ground between the two viewpoints that takes a ‘whole of system’ approach to HAI control would be able to capitalize on the expertise of all involved. Unfortunately, this has been conspicuous in its absence to date.

Complexity of the systems associated with HAI

HAIs arise from complex systems influenced by many factors, not the least of which are the biological charac- teristics of the infectious agents involved. In particular, the logistics associated with the management of patients and staff appear to be critical (Beggs et al., 2006b). This complexity has largely been ignored by many in the infection control community, with the result that there has been a tendency to rely on single- measure strategies rather than taking a more holistic approach. However, the evidence suggests that single- measure strategies are not sufficient and that a more multifaceted approach is required. Take, for example, the contrasting experiences of the health services in the Netherlands and United Kingdom. The Netherlands was quick to introduce a search-and-destroy (S&D) policy to counteract the emergence of drug resistant bacteria such as methicillin-resistant S. aureus (MRSA). The S&D policy was introduced as soon as cases of methicillin resistance were reported, although no official protocol existed until 1989 (Dekker and Van Den Broek, 2010). As the name implies, the Dutch authorities employed a comprehensive strategy that sought to isolate, contain and destroy MSRA when- ever an infection was suspected or diagnosed. As such, the main focus of the strategy was on the screening, and isolation of patients considered to be at increased risk for the carriage of MRSA (Van Rijen and Kluyt- mans, 2009). All suspected patients were isolated and only released if cultures proved negative. When cul- tures were positive, the bacteria were first eradicated before the patient was released. In addition, hospital employees that had unprotected contact with MRSA- positive patients were screened and prohibited from returning to work until they were culture negative

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(Dekker and Van Den Broek, 2010). This S&D strat- egy proved to be highly effective, maintaining the level of bacteraemia caused by MRSA at very low levels (≤1%) compared with other European countries that in some cases reached levels of up to 50% (Tiemersma et al., 2005). Similar screening and isolation strategies were adopted by healthcare trusts in the United King- dom, but these were relaxed or abandoned in 1995 because of a lack of suitable isolation rooms, and also because ward closures and the cohorting of staff and patients caused considerable clinical disruption (Farrington et al., 1998). Instead, the United Kingdom focused on hand hygiene measures alone to fight MRSA—a policy encapsulated in the Cleanyourhands campaign (Stone et al., 2012). Unlike the Dutch expe- rience, this policy resulted in a steady year-on-year increase in deaths associated with MRSA in England and Wales from 1993 to 2006, peaking at >1600 in 2006 (Pearson, 2009). Likewise, deaths associated with Clostridium difficile rose steadily from <1000 in 1999 to >8000 in 2007 (Pearson, 2009). While there is some evi- dence that the Cleanyourhands campaign, initiated in 2004, was responsible for stopping the steady rise of HAIs (Stone et al., 2012), it was not until a raft of additional infection control measures were introduced around 2007 that HAI rates began to fall. With the introduction of care bundles (i.e., simple infection con- trol guidelines for placing catheters, invasive lines, and ventilator tubes); widespread deep cleaning of wards, cohorting of staff and patients, and improved screening of patients, MRSA and C. difficile infection rates fell by >50% (H.P.A., 2012a,b). Collectively, these mea- sures highlight the need for a more pluralistic approach to infection control, one that reflects the complexity of the systems associated with HAI.

Aerial dissemination

One interesting difference between the Dutch and Brit- ish approaches to the control of MRSA is that the for- mer assumed that MRSA can be disseminated by the airborne route, whereas the latter did not, as this route of transmission is generally not considered to be of great importance. Consequently, in the Netherlands, MRSA isolation rooms are required to have an ante- chamber and to be negatively pressurized (Van Rijen and Kluytmans, 2009), whereas in the United Kindom, patients colonized with MRSA tend to be barrier nursed through placement in ward side rooms and the implementation of additional precautions to prevent the spread of infection. The differences between the approaches taken in the United Kingdom and the Netherlands, highlights the tension that exists regard- ing the airborne transmission of infection in hospitals (Beggs, 2003)— something that clinicians in many countries believe is of negligible importance compared to the spread of infection via the handborne route

(Ayliffe et al., 1999; Rhame, 1998). Yet, there is a large body of evidence, which suggests that both Gram-neg- ative and Gram-positive pathogens are frequently dis- seminated by the aerial route in the clinical environment. Contaminated clothing and bedding of colonized patients release S. aureus into the air when disturbed (Noble and Davies, 1965; Shiomori et al., 2002; Solberg, 1965). Bed making in particular liber- ates large numbers of particles (Roberts et al., 2006), many of which carry staphylococci into the air, and these are then deposited on surfaces within the environ- ment (Noble, 1962; Shiomori et al., 2001, 2002). For example, Rutala et al. (Rutala et al., 1983) investigated a MRSA outbreak in a burn unit and found that MRSA accounted for 16% of all bacterial isolates sam- pled from the air, and 31% of the isolates cultured from elevated surfaces. In another study, Shiomori et al. (2002), sampling the environment around MRSA-colonized and MRSA-infected patients under normal conditions, found an average of 4.7 cfu/m

3

MRSA-carrying particles in the air near infected patients; however, during bed making, this figure increased to 116 cfu/m

3 , confirming that this activity

results in considerable aerosolization of particles con- taining staphylococci. Similarly, it has been demon- strated that Acinetobacter spp. (Allen and Green, 1987; Beggs et al., 2006a; Das et al., 2002; Gerner-Smidt, 1987; Houang et al., 2001; Obbard and Fang, 2003; Thornton et al., 2004) and C. difficile (Roberts et al., 2008) can be readily disseminated into the clinical envi- ronment by the aerial route. The different levels of rec- ognition and acknowledgement of such evidence supporting airborne dissemination in the Netherlands and the United Kingdom may have been a key factor in determining their relative success.

Surface contamination due to aerial dissemination

The extent to which aerial dissemination of bacteria contributes to surface contamination in hospitals has received little attention. Of the few studies undertaken, most have been carried out under controlled conditions in aerosol chambers (Hathway et al., 2007; King et al., 2013; Wong et al., 2010), with only a handful of studies linking particle dissemination with clinical activities (Ayliffe et al., 1999; Greene et al., 1960; Hathway et al., 2011; Roberts et al., 2006). Consequently, while it is known that aerial dissemination can result in sur- face contamination, there is a little quantitative data on deposition rates and their variation, with which to make clinical judgments. It is, however, possible to make a rough estimate of particle deposition rates based on published data and using reasonable assump- tions. For example, consider a 10 9 8 9 2.7 m ward room containing four patients (ignoring the presence of visitors, doctors, nurses, etc.), which experiences a ventilation rate of six air changes per hour. On the

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basis of the earlier work by Roberts and Marks (1980), Milstone (2004) estimated that humans shed between 2 9 10

8 and 10 9 10

8 skin squamae per day, which

equates to a combined average liberation rate of between 9259 and 46 296 squamae per second for the four patients on the ward. If the air in the room space is well mixed and the squamae evenly distributed, then the calculated steady-state mean concentration of skin squamae in the air would be in the range of 25 719–128 600 squamae/m3. If it is then conservatively estimated that each squamae carries 10 bacteria [Lund- holm estimated that squamae frequently carry >100 bacteria (Lundholm, 1982)], we arrive at a theoretical steady-state figure of 257 190–1 286 000 bacteria/m3

of air, which is a similar order of magnitude to that found by Toivola et al. (2004). If only 10% of the bac- teria carrying particles deposit at an average rate of 2 mm/s (the settling velocity of an 8 lm particle), then a conservative estimate of the deposition rate would be of the order of 51–257 bacteria/m2 per second. Of course, in reality, the particles would not be evenly dis- tributed throughout the room space, or shed at a con- stant rate; rather, they would be liberated into the air periodically in great numbers during bed making and other activities. This calculation should therefore be treated with caution. Notwithstanding, this crude cal- culation does serve to illustrate an important and much over-looked point, namely that aerial dissemination must be responsible for widespread surface contamina- tion within the clinical environment. Evidence supporting this supposition comes from a 22-month surveillance study in which air vents and high horizon- tal surfaces were found to be contaminated with C. dif- ficile, suggesting the aerial dissemination of isolates (Fawley and Wilcox, 2001; Fawley et al., 2003). Fur- thermore, outbreak strains of MRSA are frequently recovered from elevated surfaces (Rutala et al., 1983) that are unlikely to have been touched by healthcare personnel, indicating that staphylococci must be trans- ported through the air. Indeed, Boyce et al. (1997) found that patients colonized/infected with MRSA fre- quently contaminated room surfaces, with environ- mental contamination occurring in the rooms of 73% of MRSA-infected patients.

Gram-negative bioaerosols

Immunocompromised patients in intensive care, high dependency, burns, and hematology/oncology settings are particularly vulnerable to infection, many of which are associated with Gram-negative bacteria. These bac- teria are strongly hydrophilic and are frequently cul- tured from sinks and hand wash basins in hospital wards (De Abreu et al., 2014; Kotsanas et al., 2013; Trautmann et al., 2001). There is increasing evidence that these microorganisms can become readily aerosol- ized. For example, Doring et al. (1991) found sinks

and basins on a hospital ward to act as reservoirs for Pseudomonas aeruginosa, with the result that the open- ing of water taps (faucets) generated bioaerosols con- taining P. aeruginosa, which contaminated the hands of HCWs during hand washing. An outbreak in a nurs- ery was traced to a new air-conditioning system, from which Acinetobacter isolates were cultured (McDonald et al., 1998). It was surmised that the outbreak was caused by the dissemination of a bioaerosol generated by the contaminated air-conditioning unit. Contami- nated air-conditioning units have also been implicated in outbreaks of P. aeruginosa infection (Pinna et al., 2009). Interestingly Ryan et al. (2011) showed that by installing germicidal ultraviolet irradiation in the air- conditioning system on a neonatal intensive care unit (NICU), it was possible to greatly reduce the incidence of ventilator-associated pneumonia (VAP).

The problem of Gram-negative bioaerosols becomes acute when the aerosols generated are specifically asso- ciated with medical equipment. With respect to this, the humidifiers and nebulizers associated with patient ventilator systems are particularly vulnerable (Jadhav et al., 2013). When contaminated, they can ‘inject’ bio- aerosols directly into the respiratory system, causing VAP. Contaminated ventilator humidifiers and nebu- lizers have been implicated in outbreaks of Pseudomo- nas (Phillips, 1967; Redding and McWalter, 1980) and Acinetobacter (Cefai et al., 1990; Ebenezer et al., 2011). Portable medication nebulizers have also been implicated in infections of Legionella pneumophila (Mastro et al., 1991), Burkholderia Cepacia (Hutchin- son et al., 1996), and Stenotrophomonas maltophilia (Denton et al., 2003). These items of equipment require frequent washing/cleaning, and in the case of humidifiers, filling with sterile water, and are therefore vulnerable to contamination. Sinks and hand wash basins can act as reservoirs for Gram-negative patho- gens, and a number of studies have implicated contam- inated water supplies with increased risk of ventilator/ nebulizer-related infection (Jarvis et al., 2014; Lucero et al., 2011; Mastro et al., 1991).

Ward cleanliness

Given that aerial dissemination of bacteria must be widespread in hospitals, why then is more attention not paid to this phenomenon? The simple answer to this question is that the clinical relevance of aerial dis- semination is not well understood, and therefore, it is not considered a major problem. Outside of a few countries, notably, the Netherlands and some Scandi- navian countries, aerial dissemination of bacteria appears to have been largely ignored. One reason for this indifference is that the whole subject of ward clean- liness has generally been viewed as being of secondary importance compared with hand hygiene compliance. While the general public might associate visibly dirty

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wards with the transmission of MRSA infection, rather surprisingly, there is relatively little epidemiological evidence that the environment is important in endemic HAI (Collins, 1988; Dancer, 2008; Dancer et al., 2009; Maki et al., 1982; McGowan, 1981; Rhame, 1998). Indeed, in a 2007 study (Boyce et al., 1997), the emi- nent microbiologist JM Boyce felt compelled to start his study with the words: ‘For several decades, there has been considerable controversy over whether or not con- taminated environmental surfaces contribute to transmis- sion of healthcare-associated pathogens’. Given that contaminated surfaces can readily contaminate the hands of HCWs (Bhalla et al., 2004; Boyce et al., 1997; Duckro et al., 2005; Hayden et al., 2008; Ray et al., 2002), one might wonder why there is any con- troversy. However, while it is relatively easy to show that colonized and infected patients can readily con- taminate the clinical environment, it is much more dif- ficult to demonstrate causality in the reverse direction. Consequently, epidemiological evidence supporting the link between ward cleanliness and HAI has been hard to obtain, with the result that healthcare authorities, hard-pressed by financial constraints, have tended to reduce the numbers of cleaners employed and the hours worked (Dancer, 2008). Furthermore, because the evidence base is sparse, cleaners’ specifications often focus on the cleaning of the most visible and widely accepted locations like floors and toilets, rather than cleaning near-patient hand-touch sites, such as bed rails, bedside lockers, and infusion pumps, which are more likely to be of clinical importance (Dancer, 2008). As a result, cleaning of these near-patient surfaces may all too easily be overlooked.

In 2007, partly due to political pressure, but also due recognition that existing infection control policies had failed, the Department of Health in the United King- dom rolled out a comprehensive hospital deep cleaning program (D.O.H., 2008). At approximately the same time, they also introduced a new national specification for hospital cleanliness (N.P.S.A, 2007) and imposed a statutory obligation on healthcare trusts to provide and maintain a clean clinical environment (N.P.S.A, 2007)—a noticeable departure from previous policy. Interestingly, the introduction of this policy coincided with a marked reduction in reported MRSA bactera- emia cases, which in England and Wales fell from 4451 in 2007–08 to 1114 in 2011–12 (H.P.A., 2012b)— something that was matched by a similarly large reduc- tion in C. difficile-associated infections (H.P.A., 2012a). This raises an obvious question about the extent to which the change in policy contributed to the reduction in HAI rates. However, this question is not easy to answer, because along with improved cleanli- ness, the Department of Health also introduced a raft of other measures, including improved strategies for placing and monitoring catheters and invasive lines, together with a continued push to improve hand

hygiene compliance (Cleanyourhands campaign). Indeed, Stone et al. (2012) attributed the reductions in MRSA and C. difficile infection rates almost entirely to the Cleanyourhands campaign, which was com- menced in 2004—despite the fact that C. difficile infec- tion rates did not start to fall until 2007. Noticeably, no mention was made, or analysis undertaken, of the contribution of improved ward cleanliness to the reduction in infection rates. Consequently, while intui- tively one might feel that environmental contamination must influence HAI rates, concrete epidemiological evi- dence to this effect remains elusive due to the difficulty in disentangling the role of other factors. Notwith- standing this, there is evidence that hardy pathogens, such as S. aureus can be widely disseminated through- out the clinical environment via the hands of HCWs. Oelberg et al. (2000) using a viral DNA marker to inoculate a single telephone in a neonatal intensive care unit (NICU), observed that inanimate surfaces throughout the NICU rapidly became contaminated, with the number of positive sites peaking after only 8 h. Similarly, Duckro et al. (2005) found vancomycin- resistant enterococci (VRE) to be rapidly disseminated around the clinical environment via HCW-surface interactions. Furthermore, Wilson et al. (2004) observed a strong correlation between the presence of MRSA-colonized or MRSA-infected patients and air samples yielding MRSA in an ICU, suggesting wide- spread aerial dissemination. Given that contact with contaminated surfaces can readily lead to transient col- onization of the hands of HCWs (Boyce et al., 1997), there is a good reason to believe that hospital cleanli- ness is likely to have an impact on HAI rates.

Hospital ventilation and duct contamination

Most modern hospital buildings that utilize mechanical ventilation air-conditioning systems to maintain a comfortable environment for patients and staff. These systems contain large stretches of ductwork in which particulate matter can deposit and accumulate. Conse- quently, ducts in hospitals can become highly contami- nated (see Figure 1). In recent years, concern has been expressed about the risks posed by contaminated mechanical ventilation ductwork in hospital buildings. Yet, relatively little research has been carried out into the health risks associated with contaminated ventila- tion ductwork, particularly in healthcare facilities, with the result that little epidemiological evidence exists.

While both supply and extract ducts may become heavily contaminated, in hospital buildings, it is important to distinguish between the two, because the nature of the contamination is likely to be very differ- ent in the two types of ductwork. In supply ducts, because the air comes from a mixture of outdoor and filtered return air, fungal species are likely to predomi- nate, whereas in the return air ducts, which extract

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from the ward spaces, contamination is likely to be predominately bacterial in nature. Of course, if the air is recirculated, as is the case in some healthcare facili- ties, then the bacterial pathogens from the ward space, such as MRSA, are likely to contaminate the supply duct, and this might pose a greater hazard. Dust from occupied sections of buildings is largely comprised of skin squamae and can accumulate in return ducts, especially when the air velocity is low (Batterman and Burge, 1995). It is therefore important when consider- ing the subject of ductwork contamination to also con- sider the type of ventilation system in use, as this may have a bearing on the risk. Clearly, if the recirculation of room air is permitted, then there is a greater likeli- hood of bacterial pathogens, being widely distributed around a healthcare facility via the mechanical ventila- tion system. Indeed, a number of studies relating to the transmission of tuberculosis have shown this to be the case (Beggs, 2003; Houk, 1980; Nardell et al., 1991).

Guidelines regarding the recirculation of air in healthcare settings vary greatly (Beggs et al., 2008a). For example, the American Institute of Architects (AIA) guidelines permit recirculation of ward air (A.I.A., 2001), whereas those for the United Kingdom in HTM 03 strongly discourage the use of recirculation systems (D.O.H., 2007). Because recirculation of air is permitted, in the United States, the air supplied to the patients in general wards must be first pre-filtered [min- imum efficiency reporting value (MERV) 7, 30% dust spot efficiency] and then filtered to a MERV 14 or 15 standard (90–95% dust spot efficiency) before delivery to the ward space (A.S.H.R.A.E., 2003). This standard of filtration ensures 85–95% collection efficiency for 0.3–1.0 lm particles and >90% efficiency for >1.0 lm particles. Given that skin squamae are generally 4–25 lm in size, this level of filtration should ensure

that the air supplied to the ward space is relatively clean, despite the fact that a large proportion of this air may be recirculated. By comparison in the United Kingdom, where ward mechanical ventilation systems tend to be full fresh air, HTM 03 simply specifies the use of EU4 filters (>90% synthetic dust weight arrest- ance) in the supply air ducts to general ward spaces. Such filters are capable of removing the larger, heavier particles found in outdoor air. For critical care set- tings, EU7 filters (80–90% dust spot efficiency) are specified, reflecting the higher perceived risk to patient safety in these areas (D.O.H., 2007).

Ductwork contamination

Given that heavily contaminated ductwork such as that shown in Figure 1 can be found in hospital build- ings, one might naturally assume that it poses a signifi- cant health hazard. However, the reality is that there are very little data directly relating environmental con- tamination of this type to adverse health effects (Ku- ehn, 2003). One reason for this might be that mechanical ventilation systems effectively act as a sink removing microbial particles from ward air—in effect, they act like a giant filter. If microbial particles are deposited within a ductwork system, then by definition, they are removed from the air stream that enters the ward space. So in effect, the ductwork traps larger air- borne particles preventing them from being distributed around the clinical environment. While the retention of particles might be considered beneficial, there is also a potential downside. If microbial particles from the ductwork become resuspended in the air for any rea- son, then they will be readily dispersed into the ward spaces. While relatively little is known about the resus- pension of bacterial matter, the same cannot be said for fungal spores that are uniquely adapted for aerial dissemination. Unlike bacterial matter, which generally requires the intervention of some mechanical force to create an aerosol, fungal spores are naturally dissemi- nated by the airborne route and so can easily re-enter the air stream within ventilation ducts. Given that hos- pital air-conditioning and ductwork systems can become heavily contaminated with nosocomial fungal pathogens, such as Aspergillus species (Curtis et al., 2005; Lentino et al., 1982; Lutz et al., 2003), there is a reason to believe that ductwork colonized with fungal species might pose an infection risk, especially to immunocompromised patients (Buttner et al., 1999).

There is an evidence implicating contaminated venti- lation systems with fungal infections in immunocom- promised patients. Walsh and Dixon (1989) cited contaminated ventilation systems as a common source of invasive aspergillosis, while Lentino et al. (1982) implicated contaminated window mounted air- conditioning units in an outbreak of pulmonary aspergillosis. In another study, Lutz et al. (2003)

Fig. 1 Typical example of a highly contaminated mechanical ventilation duct. Image courtesy of Total Ventilation Hygiene Pty Ltd and licensed for use in the HB2012 presentations and associated media

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identified mold contamination in an operating theater air-handling system as the source of Aspergillus infec- tions among post-surgical patients. They found that insulation material in variable air volume (VAV) units had become wet and had subsequently become colo- nized with several Aspergillus species. Insulation and filter media appear particularly vulnerable to fungal degradation when wet or under conditions of high humidity. Simmons and Crow (1995) found substantial growth of Aspergillus species on cellulosic filters at rel- ative humidities >70%, and Maus et al. (2001) observed significant growth of Aspergillus niger on used filters at relative humidities >85%.

With regard to the aerial dissemination of Aspergil- lus conidia, the case study described by Lutz et al. (2003) highlights the importance of using terminal fil- tration in locations where immunocompromised patients might be vulnerable to infection. In this case, Lutz et al., identified the fact that VAV units were mounted downstream of final filters as an issue of con- cern. When the insulation material in the ductwork became damp and degraded, there was no barrier to fil- ter the spores, and they were readily disseminated into the operating theater. Given that Aspergillus conidia have diameters in the region 2–4 lm (Lutz et al., 2003), somewhat smaller than skin squamae, it may be necessary to install high-performance terminal filtra- tion if the dissemination of spores is to be prevented— something highlighted in a study by Oren et al. (2001) who reported on an outbreak of pulmonary aspergillo- sis associated with construction activity. They found that airborne concentrations of Aspergillus species rose to a mean value of 15 cfu/m

3 in wards near a construc-

tion site. However, the installation of high-efficiency particulate air (HEPA) filters in hematological ward reduced the mean count to 0.18 cfu/m

3 and eliminated

invasive pulmonary aspergillosis completely.

Ductwork cleaning

Concerns regarding potential infection risks posed by contaminated ducting have led to a rise in the number of contractors offering specialist ductwork-cleaning services to healthcare authorities. However, the evi- dence base of the efficacy of these measures in hospitals is limited. A somewhat larger body of evidence exists in relation to duct cleaning in residential and non- industrial commercial buildings, and this was recently reviewed with an aim of answering the question: is ven- tilation duct cleaning useful? (Zuraimi, 2010). The review, which employed strict inclusion criteria to assure that only peer-reviewed, well designed, and rele- vant studies were considered, came to several impor- tant conclusions. It firstly confirmed the existence of evidence that ventilation ducts are often contaminated with dust and provide conditions for microbiological growth and that this happens under normal operating

conditions. However, no field studies have conclusively correlated concentration of indoor pollution with duct contamination, despite controlled experiments showing that there is a plausible basis for this happening. The review also examined the available duct-cleaning meth- odologies and showed that some of them are very effi- cient. However, again, it was unable to find consistent evidence that there is an improvement in indoor air quality after cleaning of the ducts. In fact, some of studies concluded that the opposite is the case and that post-cleaning indoor concentrations are higher than pre-cleaning.

There is a disparity between the lack of evidence that duct cleaning can improve occupants’ health or symp- toms, and some suggestive evidence from epidemiologi- cal studies highlighting the association of dirty ducts with higher risk of symptoms. In general, the review demonstrated that that there is a need for balance between duct cleanliness and negative effects related to the process of cleaning. Nevertheless, the study demon- strated that the body of the evidence on many of the aspects discussed is still small and identified specific areas requiring further research. While there are large differences between residential and commercial build- ings in their purpose, design, and operation, it is expected that the general conclusion on duct cleaning in such buildings is also generally applicable to hospital buildings and that the knowledge gaps on the impact of duct cleaning in hospital building are even greater. Consequently, because the evidence base is sparse, healthcare authorities find it difficult to develop objec- tive standards.

Most parts of ventilation systems can support micro- bial growth (Batterman and Burge, 1995), but fre- quently damp sections of ventilation air-handling equipment and ducting most effectively promote mold growth, particularly Aspergillus fumigatus and Asper- gillus flavus. This is especially true in areas where the primary role of the air handler is cooling, leading to substantial water condensation (Horner, 2006). These species are also present in accumulated dust inside ducts. There is an evidence to suggest that mechanical brushing is more efficient at removing such dust from metal ducts and compressed air cleaning is more effi- cient for plastic ducts and that reductions of 75–94% in surface dust levels can be achieved under field condi- tions (Holopainen et al., 2003). Of course, it is critical that the potential for resuspension of colonized dust and its liberation into supply air be minimized. Most mechanical brushing systems also incorporate a vac- uum collection device, but there is potential for fugitive dust to reach indoor areas (Zuraimi, 2010). Chemical disinfection treatments (biocides, ozone, etc.) may be required to deal with substantial fungal and bacterial growth. However, these can pose a potential health risk in their own right (Zuraimi, 2010). The health risk-benefit balance for duct cleaning is not clear, at

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least in non-healthcare indoor environments (Zuraimi, 2010). Given the specific nature of healthcare settings, the large number of potential infection sources within them, and the susceptible nature of their occupants, it is plausible that carefully performed and appropriate duct cleaning could reduce HAI risk. However, the evi- dence base on this topic is very limited, and there is a strong need for well-performed studies linking duct cleaning with health outcomes. In the meantime, it is prudent to prevent or limit microbial contamination in the first instance, through the use of ultraviolet germi- cidal irradiation (UVGI) in air handlers and ducting, for example (Horner, 2006).

Discussion and conclusions

The discussion above highlights the considerable hole in the knowledge base regarding the role that environ- mental contamination plays in the transmission of HAI. Not only is there no agreement on the risks posed by specific issues such as ductwork contamination, there is a little quantifiable evidence regarding the ben- efits, or otherwise, of cleaning and disinfecting hospital wards, despite a general consensus that it is probably a good thing to do. Because it is difficult to quantitate, the impact of hospital cleanliness is easily ignored. For example, the substantial fall in HAIs in the United Kingdom since 2007 has been attributed by some (Stone et al., 2012), almost entirely to the Cleanyour- hands campaign, despite the introduction of care bun- dles and hospital deep cleaning at approximately that time. Although hand hygiene is a key infection control measure of great importance, there is a growing evi- dence that a multifaceted approach is necessary. Evi- dence from several mathematical simulation studies (Beggs et al., 2006b, 2008b, 2009) suggests that poor hand hygiene compliance is only one factor in the spread of HAI and that other factors must be at work. In particular, the benefits of hand hygiene compliance appear to be threshold limited (Beggs et al., 2008b, 2009). Indeed, a recent large Canadian study involving 166 acute care hospitals (DiDiodato, 2013) found that despite significant improvements in reported rates of hand hygiene compliance among healthcare personnel, no consistent reduction in either C. difficile infections or MRSA bacteremia was achieved. This prompted the study’s author to state: ‘This study supports the emerg- ing evidence that once a threshold level of hand hygiene compliance is achieved, there is a very little if any benefit to attempting to achieve higher rates of hand hygiene compliance among healthcare providers’. The UK expe- rience since 2007 would tend to support this opinion. The introduction of a multifaceted approach involving the introduction of: patient screening; cohorting of patients and nurses; careful use of antibiotics; improved placement and management of intravenous lines and catheters; improved management of

ventilated patients; ward deep cleaning; and greater emphasis on hospital cleanliness; as well as improved hand hygiene, has led to a dramatic fall in MRSA and C. difficile infection rates. However, while great improvements have been made it is difficult to say which particular measures have been the most effective. So the contribution of improved ward cleanliness to the overall reduction in HAIs is difficult to quantitate. Consequently, more research is needed to understand and quantitate the role that ward cleaning plays in preventing HAIs.

One advance in recent years has been the trend toward a more multidisciplinary approach to infection control. In particular, the involvement of engineers in infection control has led to advances in the application of technologies such as UVGI (Beggs, 2002; Beggs and Sleigh, 2002; Beggs et al., 2000, 2006c; Cairns et al., 2001; Noakes et al., 2004a,b), negative air ionization (Fletcher et al., 2007, 2008; Kerr et al., 2006), and hydrogen peroxide terminal disinfection (Otter and French, 2009; Otter et al., 2006, 2007, 2008). While these technologies have merit, engineers can make the mistake of thinking that HAIs can be eliminated using a quick-fix technological solution. Indeed, many devices have not delivered reductions in HAI, primarily because their inventors failed to understand the com- plexity of the epidemiological systems associated with HAI. Having said this, if used appropriately as part of a multifaceted approach to infection control, some of these environmental technologies may prove to be an important part of the solution. It is critical for engi- neers and others involved in technological solutions to bear in mind that the ultimate success or failure of an intervention is likely to depend more on the human element than the capability of the technology.

The simple calculation presented in section Surface contamination due to aerial dissemination above sug- gests that aerial dissemination of bacteria may be a much greater problem than has been hitherto recog- nized. If staphylococci are being deposited onto sur- faces from air at a rate >50 bacteria/m2 per second, as the calculation indicates, it would suggest that aerial dissemination may be the principal mechanism by which contamination of the clinical environment occurs. Although the clinical relevance of aerial dis- semination is not known, there is a good reason for believing that it may be important. Ayliffe et al. (1999) reported that sterile gauze and forceps laid on a hori- zontal surface, became readily contaminated by bacte- ria through aerial dissemination after bed making and curtain shaking. Das et al. (2002) implicated heavily contaminated bed curtains in an outbreak of Acineto- bacter baumanii, which when moved promoted the air- borne spread of Acinetobacter species. Similarly, Weernink et al. (1995) implicated feather pillows in the aerial dispersal of Acinetobacter species. Boyce et al. (1997) found that 42% of personnel who had no direct

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contact with MRSA patients, but had touched contam- inated surfaces within the ward space, contaminated their gloves with MRSA. Furthermore, Noble et al. (Noble, 1981) found that the size distribution of parti- cles containing S. aureus was approximately 4–25 lm, which is roughly the size of skin squamae and well in excess of the size of single S. aureus cells (i.e., about 1 lm diameter). Noble et al., therefore surmised that most of the airborne S. aureus organisms were carried on skin squamae. Given that humans liberate >2 9 108

skin squamae into the air every day (Milstone, 2004), Noble et al., concluded that in many people a closed loop exists in which contaminated skin squamae are released into the air; they become impacted on the nasal turbinates; S. aureus grows on the nasal mucosa; hands then touch the nose and S. aureus bacteria are transferred to the skin; they colonize the skin and are ultimately disseminated back into the air on skin squa- mae.

The role of environmental contamination in the spread of Gram-negative bacterial infection is one that is becoming increasingly recognized. The ease with which contaminated sanitary fittings can lead to both the contamination of HCWs, and the generation of aerosols containing Gram-negative bacteria is aptly illustrated by Doring et al. (Doring et al., 1991). They found 81% of sinks in a children’s hospital to be con- taminated with P. aeruginosa, something that contrib- uted to the colonization of the hands of 42.5% of the HCWs on duty. Doring et al.’s study highlights the threat that sanitary fittings can pose to patient safety if they become contaminated. In critical care settings where patients are immunocompromised, the presence of contaminated sanitary fittings can easily lead to outbreaks of Gram-negative bacterial infection. Inves- tigating a cluster of Burkholderia cepacia complex col- onization in ventilated pediatric patients, Lucero et al. (2011) identified tap water from hospital sinks as the likely mode of transmission. While they could not explain the exact mechanisms involved, the emer- gence of new cases stopped only after staff ended the practice of using tap water for oral and tracheostomy care. The link between clinical outcome and environ- mental contamination is further highlighted in an interesting study by Ryan et al. (2011), who used ultraviolet light to irradiate cooling coils in an air- conditioning system serving a NICU. They found the cooling coils and condensate drain to be heavily colo- nized with Gram-negative bacterial species, as were the environmental surfaces and sink traps in the NICU. However, after 6 months of ultraviolet irradi- ation, both the air-conditioning units and the environ- mental surfaces were culture negative. Furthermore, they found that patient tracheal colonization greatly reduced with the introduction of ultraviolet irradia- tion, as did the incidence of VAP. From this, they surmised that airborne Gram-negative pathogens were

being widely disseminated by the air-conditioning sys- tem and contributing to both surface contamination and patient colonization.

Given the magnitude of the HAI problem and the complexities of the systems involved, it is perhaps worth analyzing the ways in which microbes colonize the built environment (Kelley and Gilbert, 2013). Recently, researchers have sought to understand, from first principles, the microbial ecosystem that exists within hospitals, the so-called hospital microbiome (Arnold, 2014; Smith et al., 2013). In the same way that antibiotics disrupt the normal microflora of the human body, constant attempts to ‘sterilize’ the clinical environment may in fact be removing a benign microb- iome, which is capable of controlling and out-compet- ing pathogenic species, only to replacing it with a microbial ecosystem that is more harmful to patients (Arnold, 2014). The fact that a sterile ward environ- ment can become colonized with MRSA within 24 h of admitting patients (Hardy et al., 2007), illustrates just how much ‘nature abhors a vacuum’. Bacterial com- munities within indoor environments have been found to harbor microbial species not commonly found out- doors (Tringe et al., 2008). Kembel et al., (Kembel et al., 2012) found that several bacterial taxa, com- monly found in the human microbiome (including members of the families Burkholderiaceae, Pseudomo- nadaceae, and Staphylococcaceae), were abundant in indoor air, especially in mechanically ventilated rooms, but nearly absent from outdoor air. Given that these species are commonly associated with humans as com- mensals or pathogens, they concluded that humans are important dispersal vectors for bacteria that colonize the built environment. Kembel et al. (2012) also found that building attributes, such as the source of ventila- tion air, relative humidity and temperature, correlated with the composition of indoor airborne bacterial com- munities, with the highest phylogenic diversity found in the outdoor air and the lowest in rooms that were mechanically ventilated. This suggests that buildings can select for certain bacterial species, with the result that the indoor microbial ecosystem is less diverse and strongly influenced by the microflora of humans who spend as much as 90% of their lives indoors (Kelley and Gilbert, 2013). As such, it may be worth re-appraising the way that hospital buildings are designed. Reducing direct contact with the outdoor environment may not always be the best strategy for the management of bacterial pathogens (Kembel et al., 2012). By creating an indoor environment that reflects the makeup of the outdoor air, it may be possible to create a more benign hospital microbiome. This chal- lenges the assumption, held in many parts of the world, that hospitals should be sealed air-conditioned buildings, in which humidity and temperature are tightly controlled. It also presents a challenge to those seeking to minimize ventilation rates to save energy.

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However, it offers the possibility that if appropriate ventilation strategies can be identified, that move the hospital microbiome closer to that found in the out- door environment, then it may be possible to create an ecosystem which reduces the risk of patients acquiring a HAI.

Given increased emphasis on hospital hygiene in recent years, it is surprizing that the whole issue of ven- tilation and its influence on the hospital microbiome has been largely overlooked. There is mounting evi- dence that the aerial dissemination of bacteria is a widespread phenomenon within the clinical environ- ment. Yet, little is known about how this influences the microbiome as a whole, or indeed the spread of HAI. Although environmental contamination has been implicated in some outbreaks of Gram-negative bacte- rial infection (McDonald et al., 1998; Pinna et al., 2009), the full extent to which it contributes to HAI is not known. For example, one might intuitively think that heavy contamination of air ductwork systems would pose a threat to patient safety. However, because few epidemiological studies have been under- taken specifically to investigate this subject, there is lit- tle evidence to substantiate this claim. Consequently, it is difficult to make any evidence-based decisions regarding optimum strategies to control HAI. Clearly,

a better understanding of the microbial ecosystem within hospitals would be advantageous. A deeper understanding of the ways in which microbes disperse and colonize the clinical environment, together with the factors that influence this process, would provide a strong evidence base, which would be helpful in formu- lating future infection control strategies.

Acknowledgements

At the Healthy Buildings 2012 conference in Brisbane in July 2012, a debate was conducted and attended by many experts on infection control and building design. This debate explored the role of environmental con- tamination in the transmission of infection within healthcare facilities. This manuscript arises from that debate, and we are thankful to all those who contrib- uted to it. In particular, we thank the panel members, Tricia Coward, Yuguo Li, Jeremy Stamkos and Erica Stewart for their helpful contributions. This work was also supported by a Queensland University of Technol- ogy, IHBI Collaborative Research Development Grant titled, How transmissible is influenza by the airborne route? Luke Knibbs acknowledges an NHMRC Early Career (Australian Public Health) Fellowship (APP1036620).

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