Airborne Hydrogen Peroxide

Transcription

1 Literature Review and Practice Recommendations: Existing and emerging technologies used for decontamination of the healthcare environment Airborne Hydrogen Peroxide Version: 1.1 Date: December 2016 Review: December 2019

2 DOCUMENT CONTROL SHEET Key Information: Title: Existing and emerging technologies used for decontamination of the healthcare environment: Airborne Hydrogen Peroxide Date Published/Issued: December 2016 Date Effective From: December 2016 Version/Issue Number: 1.1 Document Type: Literature Review Document status: Final Author: Name: D. Scott, F. Hansraj Role: Healthcare Scientists (Health Protection) Division: HPS Owner: Infection Control Approver: Annette Rankin Approved by and Date: December 2016 Contact Name: Infection Control Team Tel: Version History: This literature review will be updated in real time if any significant changes are found in the professional literature or from national guidance/policy. Version Date Summary of changes Changes marked 1.1 December 2016 Addition of categories for recommendations. No changes made to the content of the literature review. 1.0 May 2015 Final for publication Version 1.1. December 2016 Page 2 of 28

3 Contents Topic... 4 Background... 4 Aim... 5 Objectives... 5 Research Questions... 5 Methodology... 6 Search Strategy... 6 Exclusion Criteria... 6 Screening... 7 Critical Appraisal... 7 Results... 7 Research Questions... 8 Discussion Recommendations for Clinical Practice Implications for Research Conclusion Appendix 1: MEDLINE Search (2014) Appendix 2: MEDLINE Search (2016) References Version 1.1. December 2016 Page 3 of 28

4 Topic The use of airborne hydrogen peroxide (HP) for decontamination of the healthcare environment. Background Current microbiological and epidemiological evidence indicates that contaminated surfaces in hospital settings can contribute to the transmission of nosocomial pathogens. 1 In particular, there appears to be a risk of pathogen acquisition from prior room occupants for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Clostridium difficile and Acinetobacter baumannii. 2 Accordingly, existing research implies that improved surface cleaning and disinfection can reduce healthcare-associated infections. 3 Manual processes for terminal cleaning are frequently sub-optimal, suggesting that automated decontamination processes might offer an opportunity to improve cleaning efficacy and consistency. 4 There are two major airborne HP systems currently in use for environmental decontamination: HP vapour devices that vaporise a solution of % HP, and aerosolised HP systems that dispense a dry aerosol of 3 7 % HP with or without the addition of silver ions. 5 Automated mobile airborne HP devices can be placed in patient rooms following discharge as an adjunct to terminal cleaning. However, airborne HP systems are suggested as a supplement to, rather than a replacement for, standard discharge cleaning measures due to the requirement of physical removal of dirt from surfaces. 6 The advantages of airborne HP devices include greater laboratory sporicidal activity over UV light devices, bactericidal effectiveness throughout an enclosed space including surfaces not in direct line-of-sight (unlike UV light systems), and the lack of need to arrange furniture and equipment preexposure to allow maximal disinfection. 7 However, airborne HP systems require a longer decontamination cycle than UV light systems, necessitating that patients rooms are unavailable to admission for a longer time period. 6 Their main disadvantages also include the requirement to disable HVAC (heating, ventilation and air conditioning) systems, substantial set-up costs for equipment, the necessity to remove staff and patients from the room before disinfection, and the need to physically remove dirt and debris before use. 7 It has been reported that airborne HP systems are capable of substantially reducing the number of environmental C. difficile spores, indicating their applicability for the terminal cleaning of rooms following the discharge of patients under contact precautions. 8 The NHSScotland National Infection Prevention and Control Manual 9 currently recommends the use of a disinfectant solution at a dilution of 1,000 parts per million (ppm) available chlorine for routine and terminal room cleaning under transmission-based precautions. This review intends to assess the evidence base on the Version 1.1. December 2016 Page 4 of 28

5 appropriateness of using airborne HP decontamination systems for both routine cleaning and terminal (or discharge) cleaning in the healthcare environment. Aim To review the evidence base for using airborne hydrogen peroxide (HP) for decontamination of the healthcare environment. Objectives To provide a generic description of airborne HP decontamination systems, including the proposed or actual mechanism of action and the procedure for use. To assess the scientific evidence for effectiveness of airborne HP decontamination systems. To explore practical and safety considerations related to the use of airborne HP decontamination systems. To explore the costs associated with airborne HP decontamination systems. To produce a concise evidence summary for airborne HP to assist the Equipment and Environmental Decontamination Steering Expert Advisory Group in making practical recommendations on the use of airborne HP decontamination systems for NHS Scotland. Research Questions The following research questions will be addressed: 1. Are airborne HP decontamination systems currently in use in UK healthcare settings? 2. What is the actual or proposed mechanism of action of airborne HP decontamination systems? 3. What is the procedure for using airborne HP decontamination systems? 4. What is the scientific evidence for effectiveness of airborne HP for decontamination of the healthcare environment? 5. Are there any safety considerations associated with using airborne HP decontamination systems in the healthcare setting? 6. Are there any practical or logistical considerations associated with using airborne HP decontamination systems in the healthcare setting? 7. What costs are associated with using airborne HP decontamination systems in the healthcare setting? Version 1.1. December 2016 Page 5 of 28

6 8. Have airborne HP decontamination systems been assessed by the Rapid Review Panel? Methodology Search Strategy The following databases and websites were searched to identify relevant academic and grey literature: MEDLINE CINAHL EMBASE NHS Evidence ( Health Technology Assessment (HTA) database ( Database of Abstracts of Reviews of Effects (DARE) ( National Patient Safety Agency (NPSA) ( National Institute for Health and Care Excellence (NICE) ( Medicines & Healthcare products Regulatory Agency (MHRA) ( Rapid Review Panel (RRP): product evaluation statements ( Search terms were developed and adapted to suit each database/website. Initial literature searches were run between 24/06/2014 and 01/07/2014. For the update, the literature search was performed on 08/08/2016. Different search strategies were applied in each year. See Appendix 1 for an example of the search run in the MEDLINE database in 2014 and Appendix 2 for an example of the updated search conducted in Exclusion Criteria Academic and grey literature was excluded from the review on the basis of the following exclusion criteria: Article was released before 2004 Article was not published in the English language Article does not concern airborne hydrogen peroxide (HP) decontamination systems in the healthcare environment (off-topic) Article is an opinion piece, a non-systematic review or a conference abstract Article does not present evidence compatible with the McDonald-Arduino evidentiary hierarchy 10 Version 1.1. December 2016 Page 6 of 28

7 Article concerns a study that did not have an appropriate comparison in the form of Screening standard cleaning methods There was a two-stage process for screening the items returned from the literature searches. In the first stage, the title/abstract was screened against the exclusion criteria by the lead reviewer. Items that were not excluded at the screening stage progressed to the second screening stage. In the second stage of the screening process, the full text of remaining items was screened against the exclusion criteria by the lead reviewer. Items that were not excluded at the second screening stage were included in the review. Critical Appraisal Critical appraisal of the studies included in this review and considered judgement of the evidence was carried out by the lead reviewer using the Scottish Intercollegiate Guidelines Network (SIGN) methodology. 11 The McDonald-Arduino evidentiary hierarchy was used as a framework for assessing the evidence. 10 Results The search found 326 articles. After the first stage of screening this was reduced to 90 articles, and after the second stage there were eight articles to critically appraise The update search retrieved a further 98 articles, of which 21 passed the first stage of screening, and three were critically appraised The 11 included studies used two different types of airborne HP disinfection: 10 studies used HP vapour and two studies used aerosolised HP 12;22 (one study compared HP vapour with aerosolised HP 22 ). Four of the 11 studies were conducted in the United Kingdom (UK), 13;16;18;19 three studies took place in the United States of America (USA), 14;15;21 two studies were situated in France, 12;22 one study was conducted in the Netherlands, 17 and another study was set in Australia. 20 All of the studies included a comparison with terminal cleaning methods. These included the use of sodium hypochlorite solution at varying concentrations of available chlorine (e.g. 1,000 ppm and 2,000 ppm), quaternary ammonium compound disinfectants or neutral ph detergents. Many of the studies were funded by the manufacturers of the airborne HP systems and, in a few instances, the funding bodies were also involved in the design and execution of the projects. It is important to bear this in mind when evaluating the findings. Four of the 11 studies monitored the effect of airborne HP on the incidence of healthcareassociated infections or patient acquisition of nosocomial pathogens. 14;15;20;21 By contrast, seven of Version 1.1. December 2016 Page 7 of 28

8 the studies evaluated the impact of airborne HP on the reduction of environmental bioburden. 12;13;16-19;22 There were a range of airborne HP disinfection systems available that exhibited effectiveness against various comparison groups. Of the four studies that demonstrated greater levels of effectiveness than terminal room cleaning with hypochlorite solution, two studies used aerosolised HP disinfection devices 12;22 and three studies used HP vapour systems 15;17;22 (one study compared both aerosolised HP and HP vapour systems with hypochlorite solution 22 ). Two other studies observed that terminal cleaning with hypochlorite solution exhibited similar effectiveness to HP vapour devices. 16;18 Of the five studies that demonstrated greater levels of effectiveness than terminal room cleaning with quaternary ammonium disinfectants or detergents, all studies used HP vapour disinfection. 13;14;19-21 Research Questions Are airborne HP decontamination systems currently in use in UK healthcare settings? There is no mention of airborne HP decontamination systems in the NHSScotland National Cleaning Services Specification. 23 The NHSScotland National Infection Prevention and Control Manual 9 recommends that, should airborne HP decontamination systems be considered for adoption in NHSScotland, a formal assessment of the cost, benefit, potential hazards and user safety should be undertaken. The National Patient Safety Agency (NPSA) Revised Healthcare Cleaning Manual 24 and the Association of Healthcare Cleaning Professionals (AHCP) Revised Healthcare Cleaning Manual 25 both feature sections on airborne HP decontamination systems alongside other new technologies for environmental disinfection. They summarise that the use of airborne HP systems for disinfection of patient rooms is increasing, although there is currently insufficient evidence to confirm their cost-effectiveness for routine cleaning. These findings suggest that airborne HP decontamination systems are not widely in use within UK healthcare settings. Version 1.1. December 2016 Page 8 of 28

9 What is the actual or proposed mechanism of action of airborne HP decontamination systems? HP is an oxidising agent, responsible for the production of free radicals that are capable of damaging microbial DNA and cell constituents. 26 There are a number of different methods of airborne HP decontamination, 5 two of the most commonly used being: Hydrogen peroxide vapour Aerosolised hydrogen peroxide The HP vapour system manufactured by Bioquell produces vapour from a 30 % HP solution. These vapour particles are less than 1 micron in size, allowing the vapour to disperse effectively. At the end of the process, the HP vapour is catalytically broken down into water and oxygen. 27 The aerosolised HP system Sterinis produces a dry mist by aerosolising a solution of 5 % HP, consisting of < 50 ppm silver ions, < 50 ppm phosphoric acid, < 1 ppm gum arabic, and 95 % biosmotic water. The aerosol is stabilised using silver ions and other chemicals to avoid aggregation before the drops reach the target. 12;28;29 The particles are electrically charged, ranging in diameter from 8 to 12 microns, and are able to circulate freely in the air as a dry aerosol disinfectant with access to all surfaces. 12 This airborne HP system is alternately referred to as dry mist HP. 12 Holmdahl et al. 29 compared HP vapour and aerosolised HP systems and found that a key difference was the peak HP concentration, which was twice as high in HP vapour systems than in aerosolised HP systems, while the total HP concentration was also seen to be higher for HP vapour. What is the procedure for using airborne HP decontamination systems? Airborne HP disinfection systems should only be used as a supplement to standard terminal cleaning, as biological soiling of surfaces will reduce the effectiveness of decontamination. 30 HP is hazardous to human health, so it can only be used in areas which have been vacated by people and, in some instances such as the use of HP vapour, properly sealed prior to the disinfection process. 31 This increases the time required for disinfection and the subsequent costs, since airborne HP must only be applied in rooms that have been vacated. The time required for a cycle of airborne HP disinfection is proportional to the size of the area to be disinfected. 30 The HP vapour system produced by Bioquell consists of four portable units: a generator unit to produce HP vapour; an aeration unit to break down the HP vapour catalytically after the exposure period; an instrumentation module which measures the concentration of HP, as well as the temperature and relative humidity of the room; and a control computer situated outside the room. 13 The generator unit is used to vaporise 30 % liquid HP at 130 o C and the vapour produced is delivered via a dual axis vapour distribution system that ensures high kinetic energy and even Version 1.1. December 2016 Page 9 of 28

10 distribution throughout the room. 13 After decontamination has been completed, aeration units inside the room catalytically convert the HP vapour into water and oxygen. 13;32 The time required to complete the process depends upon the size of the room, the process typically taking 90 minutes for a single room. 31 The HP vapour system manufactured by Steris produces an aqueous solution of HP while controlling the temperature and humidity levels within the room. 33 It operates as a dry system, reducing the relative humidity inside the room so that condensation does not form on surfaces. 34 The HP vapour is degraded to oxygen and water in the aeration process, leaving behind no chemical residues behind. 33 The aerosolised HP system Sterinis consists of a robot that can be pre-programmed to dispense the required concentration of HP needed for full disinfection. 12 The time taken to disinfect a room depends on the volume of the room. The system uses Sterusil, a mixture of HP (5 %), silver ions (< 50 ppm) and phosphoric acid (< 50 ppm). 32;35 The device needs to be placed in the corner of the room as instructed by the user manual. According to the manufacturers, the technology uses the processes of ionisation and nucleation to allow the small electrically charged droplets, which have a particle size of approximately 8 to 12 microns, to bond to micro-organisms on surfaces or in the environment. 35 As with other airborne HP systems, disinfection may only take place within vacant rooms. In the study by Barbut et al. 12 it was not deemed necessary to seal the rooms, although the doors and windows were closed. 12;32 What is the scientific evidence for effectiveness of airborne HP for decontamination of the healthcare environment? One cohort study, 14 a cross-over study, 22 six before-and-after studies, 12;13;15;17;18;21 two interrupted time series 19;20 and a non-randomised trial 16 evaluated the efficacy of airborne HP for decontamination of the healthcare environment. It was demonstrated that this intervention could reduce environmental surface contamination and decrease the incidence of healthcare-associated infections. As detailed in the methodology, the McDonald-Arduino evidentiary hierarchy 10 was used as a framework for assessing the evidence relevant to this research question. Level V Demonstration of reduced microbial pathogen acquisition (colonisation or infection) by patients via non-outbreak surveillance testing and clinical incidence: Manian et al. 15 compared standard methods of terminal isolation room cleaning with the use of HP vapour and its impact on Clostridium difficile infection rates, using a before-and-after study. This study monitored the number of cases of C. difficile-associated diarrhoea (CDAD) before (using standard cleaning methods) and during the intervention periods (using HP vapour) and showed a Version 1.1. December 2016 Page 10 of 28

11 37 % reduction in CDAD rates following its introduction. However, it is worth noting that this was a single-centre study so the findings may not be transferable to other hospitals. It is also worth noting that this study took place in the USA, where infection control practices may differ to those in the UK: most notably, the use of quaternary ammonium compounds for terminal cleaning. Horn and Otter 21 undertook a before-and-after study (USA) in which patient room decontamination was provided using HP vapour on the discharge of all patients with Clostridium difficile infection (CDI), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) or extended-spectrum beta-lactamases (ESBL) producing Gram-negative bacteria. After the 12-month baseline period, in which non-specified standard discharge cleaning was performed, rates of nosocomial infections were measured over the following 24 months. Over the intervention period, there was a decrease in CDI from 1.38 to 0.90 cases per 1,000 patient-days (p = 0.009), a decrease in VRE from 0.21 to 0.01 (p < 0.001), and a decrease in ESBL producing bacteria from 0.16 to 0.01 (p = 0.001). There was also a decrease in MRSA, although this reduction was not statistically significant (p = 0.188). The authors concluded that using HP vapour for disinfection was more effective than standard discharge cleaning. However, the standard cleaning practices in use were not specified and may not represent current practice within NHSScotland. Improvements in hand hygiene were judged by the authors to be likely to have contributed to the reduction in infection rates and, therefore, this is a probable confounding factor. One of the authors is employed part-time by Bioquell, the manufacturer of a HP vapour system. For this reason, there is the possibility of investigator bias due to financial interests. Passaretti et al.14 compared the risk of acquiring multidrug resistant organisms (MDROs) in patients admitted to a room decontaminated using HP vapour compared to a room disinfected using standard methods. This was a prospective cohort intervention study comparing acquisition rates of MDROs. Patients in the HP vapour cohort were significantly less likely to acquire any MDROs than the patients in the standard cleaning cohort, even after adjustment for confounding factors; essentially HP vapour used in addition to standard cleaning reduced the risk of MDRO acquisition by 64 %. This reduction of MDRO acquisition was largely due to patients in the HP vapour cohort being five times less likely to acquire VRE than the standard cleaning cohort; reductions in the rates of MRSA, MDR-Gram-negative rods and C. difficile were not statistically significant. Comparison of the cohorts indicated that over an 18-month period 28 MDRO transmissions were likely to have been prevented by the use of HP vapour in three units. HP vapour decontamination also decreased levels of environmental contamination, particularly in rooms with multiple MDROs. However, it is worth noting that this study took place in a single institution, so the results are not necessarily amenable to generalisation. It is also significant that this study was conducted in the USA, which may have led to different infection control practices, including the use of quaternary ammonium cleaning products as part of a terminal clean. The Version 1.1. December 2016 Page 11 of 28

12 authors also note that there were other infection prevention initiatives ongoing at the time of the study. In addition, Bioquell (the manufacturers of a HP vapour system) contributed to the study design, collection of data and the writing of the report, increasing the risk of investigator bias. Mitchell et al. 20 conducted an interrupted time series in a public hospital (Australia) that introduced a combination of HP vapour for single rooms (n = 1363) and HP wipes for shared rooms (n = 349), after discharge of patients either colonised or infected with MRSA. Following a baseline period of 12 months, in which terminal discharge room cleaning was provided using neutral ph detergent (n = 1917), airborne HP was utilised by in-house hospital cleaning staff for a further period of 24 months. After the intervention was introduced, the incidence of MRSA acquisition reduced from 9.0 to 5.3 per 10,000 patient-days (p < 0.001). Meanwhile the incidence of MRSA bacteraemia also reduced from 0.16 to 0.11 per 10,000 patient-days, although this change was not statistically significant (p = 0.58). The authors concluded that using HP vapour and HP wipes in combination was more effective than detergent cleaning alone. Detergent cleaning is not recommended practice for discharge cleaning of MRSA-contaminated patient rooms in NHSScotland; thus, it does not make a suitable comparator. In addition, the study combines multiple intervention components, so it is not possible to determine whether this impact was solely due to the use of HP vapour or HP wipes. A number of potential confounders were recognised: additional MRSA screening, changing antimicrobial consumption, staff feedback on terminal cleaning, and quicker laboratory methods of MRSA isolation. However, hand hygiene compliance was consistent throughout the study duration. Level IV Demonstration of reduced microbial pathogen acquisition (colonisation or infection) by patients via outbreak surveillance testing and clinical incidence: No evidence identified. Level III Demonstration of in-use bioburden reduction that may be clinically relevant: Otter et al. 19 assessed the efficacy of terminal cleaning and HP vapour for the decontamination of environmental surfaces in the ward side-room of a patient with an extensive history of MRSA, Gram-negative rods (GNRs) and VRE infection and colonisation. The rate of environmental recontamination following HP vapour decontamination was also assessed. Terminal cleaning reduced the number of sites with MRSA from 60 % to 40 % and, for GNRs, from 30 % to 10 %. HP vapour reduced the number of sites with MRSA to 3.3 % and no GNRs were isolated. VRE was isolated from 6.7 % of sites before and after cleaning but was not isolated from any sites after HP disinfection. The patient remained colonised with MRSA during and after both experiments, so HP vapour decontamination did not lead to the decolonisation of the patient through removal of the environmental reservoir. This might have been due to the intrinsic colonisation of the patient leading to recontamination of the environment immediately after cleaning occurs. However, the GNRs seen in the environment did not match the species infecting or colonising the patient, so it is Version 1.1. December 2016 Page 12 of 28

13 unlikely that the patient was the source of the GNRs. It is worth noting that only 15 sample sites were used for the environmental sampling and that only one patient was included in the study. Terminal cleaning was conducted using quaternary ammonium compounds a product that is not currently recommended by the NHS in Scotland. Level II Demonstration of in-use bioburden reduction effectiveness: Otter et al. 17 compared the effect of a terminal clean using 2,000 ppm hypochlorite solution with the use of HP vapour to remove environmental reservoirs of multidrug resistant GNRs during an outbreak. In this study, 10 of 21 areas yielded GNRs after a terminal clean; however, no GNRs were found after the use of HP vapour. The study also looked at acquisition rates of MDROs and found no new cases until at least 3 months after HP vapour disinfection had taken place. This would indicate that HP vapour was more effective at removing GNRs from surfaces than a terminal clean with hypochlorite solution, and that the chain of transmission was broken during the outbreak. However, this study used a before-and-after study design, whereas a cohort design might have allowed a more appropriate comparison to be made. No rationale was provided for the use of hypochlorite with 2,000 ppm available chlorine over the concentration of 1,000 ppm currently recommended in NHS Scotland. In addition, there were a limited number of sample sites used and the study took place on a single site in a hospital in the Netherlands, so the results cannot be generalised. Barbut et al.12 compared the efficacy of an aerosolised (or dry mist ) HP system with a hypochlorite solution containing 5,000 ppm available chlorine for eradicating C. difficile spores. There were 31 rooms included in this study; 15 rooms were treated with HP and 16 rooms were treated with hypochlorite. Before cleaning, C. difficile spores were detected in 21 % of surface samples and 74 % of rooms. After disinfection, the percentage of samples showing environmental contamination decreased in both arms; spores were detected in 12 % of samples from the hypochlorite-treated rooms and 2 % of the HP-treated rooms. The decrease in the percentage of contaminated samples was significantly greater in the HP group (91 %) than in the hypochlorite group (50 %). The percentage of rooms with at least one sample positive for C. difficile in the hypochlorite disinfection arm was 69 % before treatment and 50 % after treatment. In the HP disinfection arm, the percentage of rooms with at least one sample positive for C. difficile was 80 % before treatment and 20 % after treatment. This demonstrates that the aerosolised HP system had a greater efficacy for the removal of C. difficile than 5,000 ppm hypochlorite. This study took place in two university hospitals in France. The study was financially supported by Sterinis (the manufacturer of the HP system used). The company also provided the reagents, equipment and contributed to the costs of consumables, potentially leading to a conflict of interest. No rationale was provided for the use of hypochlorite with 5,000 ppm available chlorine rather than the concentration of 1,000 ppm currently recommended in NHSScotland. Version 1.1. December 2016 Page 13 of 28

14 French et al. 13 compared terminal cleaning and HP vapour decontamination of a hospital environment using the presence of MRSA as an outcome measure. Using matched sites, 90 % of 248 sites had MRSA before terminal cleaning and 66 % had MRSA after terminal cleaning. 72 % of 85 sites had MRSA before HP vapour disinfection and 1.2 % of sites had MRSA after HP disinfection. These results indicated that HP vapour was more effective at removing environmental MRSA than standard terminal cleaning. However, a few points are important to bear in mind: firstly, this study took place in 2004 and HP vapour technology has changed significantly since then, in terms of the equipment available and the time taken for decontamination to take place. Secondly, standard terminal cleaning used a solution of detergent sanitiser containing 5 15 % non-ionic surfactant and 5 15 % cationic surfactant, diluted at a ratio of 1:500, which is not in line with current guidance in Scotland. The study was funded by Bioquell, a company that also declares an involvement in the conception, design and execution of the project. There is no mention of the rooms being cleaned before HP vapour decontamination took place, despite current guidance stating that this could impact on the results observed. Doan et al. 16 investigated and compared the effectiveness of HP vapour with standard hypochlorite cleaning using 1,000 ppm available chlorine to decontaminate rooms contaminated with C. difficile 027. The clinical effectiveness was measured using standardised median log 10 reductions in colony counts and, based on this measurement, the chlorine releasing agent was found to be as effective as HP vapour. However, despite standardised techniques, each room started at different baseline counts of C. difficile spores and, even with a standardised inoculation density, it was not possible to control how many C. difficile spores germinated and how many bacteria grew. This variability in results was compensated for in the statistical analysis by using median values and standardised reduction. Blazejewski et al. 22 embarked upon a randomised cross-over study in a university hospital (France) that randomly allocated patient rooms to either HP vapour (n = 93) or aerosolised HP/peracetic acid (n = 89) for disinfection, after standard terminal cleaning using quaternary ammonium compounds, detergent and a sodium hypochlorite solution. A total of 24 environmental microbiological samples were collected per room, from eight high-touch surfaces, at three time points: after patient discharge, after standard cleaning, and after HP disinfection. Standard terminal cleaning reduced environmental bacterial load (p < 0.001) without affecting MDRO contamination (p = 0.371). But HP reduced environmental MDRO contamination from 6 % to 0.5 % (p = 0.004), although no significant difference was found between HP vapour and aerosolised HP/peracetic acid. The authors concluded that both HP systems were more effective at reducing environmental contamination than standard terminal cleaning. The prevalence of MDRO within the patient rooms was relatively low (8%); therefore, the sample size (which was calculated assuming a prevalence of %) may not have been large enough to detect a statistically significant difference Version 1.1. December 2016 Page 14 of 28

15 between the two HP systems. In addition, Bioquell and Anios donated the airborne HP systems for the trial. Although neither company had any role in the data analysis or reporting, Bioquell did contribute to the study design. This raises the possibility of investigator bias due to financial interests. Level I Laboratory demonstration of bioburden reduction efficacy: Lawley et al. 18 used C. difficile spores as an outcome measure to evaluate hypochlorite solution with 10,000 ppm available chlorine in relation to 3 % and 10 % HP vapour provided by Sigma and Bioquell. They demonstrated that C. difficile spores were inactivated by 10,000 ppm hypochlorite as well as 10 % HP vapour. They also investigated the time dependency involved in the use of HP vapour, demonstrating that prolonged exposure was required to achieve a six-log reduction of bacterial spores (20 minutes at 10 %). To summarise the evidence, it can be concluded that there is low- to moderate-quality evidence to support the use of airborne HP decontamination as an adjunct to standard cleaning procedures in the healthcare environment. In accordance with SIGN methodology, the cohort study constituted level 2+ evidence (well-conducted controlled analytic studies with a low risk of confounding, bias, or chance and a moderate probability that the relationship is causal). In contrast, the cross-over studies, before-and-after studies and interrupted time series were all designated level 3 evidence (uncontrolled analytic studies). Are there any safety considerations associated with using airborne HP decontamination systems in the healthcare setting? Chlorine-releasing agents are considered easy-to-use and the least expensive environmental disinfection method available. However, they do feature a number of limitations such as the release of irritating vapours and toxic gases which may affect the eyes and respiratory tracts of healthcare workers at high concentrations (i.e. 10,000 ppm available chlorine), and personal protective equipment is recommended for this reason. Sodium hypochlorite-based products can be corrosive to various materials and potentially cause damage to environmental surfaces. In addition, the disinfection process must be performed manually, which can be time-consuming, with the quality of disinfection depending on the staff member performing the procedure. This has led to a renewed interest in alternative methods of environmental decontamination. 12;16;36 HP appears to have low levels of toxicity and, as it degrades into oxygen and water, it is compatible with most materials. Monitoring units are able to measure the residual concentrations of HP and ensure that exposure is appropriate. 12;30 Johnston et al. 37 found HP vapour to be safe and environmentally-compatible for decontaminating areas such as biological safety cabinets and Version 1.1. December 2016 Page 15 of 28

16 microbiology containment laboratories. Passaretti et al. 14 have also reported no safety, equipment, or material compatibility concerns. Ernstgard et al. 38 tested the effects of exposure to HP vapour in humans. The key limitation of this study was that only 11 people were included. In this study, no exposure-related effects on pulmonary function were observed. Similarly, there were no exposure-related effects on markers of inflammation or coagulation. Mild irritation of the upper respiratory airways was observed when people were exposed to HP vapour at 2.2 ppm, though no effects were observed at 0.5 ppm. There were no effects on lung function or inflammatory markers at either exposure level. Manian et al. 15 state that they found HP vapour to be safe with no instances of vapour leaking outside the sealed rooms during the decontamination process. During their intervention, there were no significant adverse reactions attributed to HP vapour in either patients or healthcare workers. Barbut et al. 12 compared an aerosolised HP disinfection system with a hypochlorite clean and found that the HP-based formulations had greater material compatibility, while also being less toxic to human beings and the environment. The aerosolised HP system also had an advantage over HP vapour systems in that, while disinfection still needs to take place in a vacant room, there is no need to seal the room. Are there any practical or logistical considerations associated with using airborne HP decontamination systems in the healthcare setting? Airborne HP decontamination offers a number of benefits compared to standard cleaning with hypochlorite. Automated HP systems are not subject to user error in the way that manual cleaning may be. The quality of manual cleaning can vary and has been shown to be suboptimal, not least because manual cleaning is limited to areas that are easily accessible. 32;39 Airborne HP can reach sites that would be inaccessible for cleaners, such as cracks, crevices or other hard-to-reach surfaces. 30;39;40 Airborne HP can also be used to decontaminate electrical equipment which may be damaged by the use of cleaning liquids. 40 Equipment that may be missed in standard decontamination can be collected together in a room and effectively decontaminated at the same time using airborne HP. 16 HP systems are able to ensure adequate contact times between the disinfectant and environmental sites, ensuring the application of correct disinfectant concentrations. These are key issues for the effectiveness of the disinfection process, and can be achieved more successfully by using pre-programmed robots rather than relying on cleaning personnel. 30;39;40 There a number of practical and logistical considerations with using airborne HP systems. One key limitation is the need to remove debris and organic matter from all surfaces so that the HP is not prevented from accessing micro-organisms. 40 Pottage et al. 34 found that biological soiling reduced Version 1.1. December 2016 Page 16 of 28

17 the efficacy of airborne HP decontamination. Their study demonstrated that the presence of organic matter resulted in a slower inactivation of bacteriophage using HP vapour decontamination and that this was exacerbated as the concentration of organic matter increased. This highlights the importance of effective cleaning prior to gaseous disinfection especially in the hospital setting where infective agents are likely to be suspended in body fluids. Therefore, it is recommended that surfaces are manually cleaned with appropriate disinfectants prior to the deployment of airborne HP decontamination. The use of all airborne HP decontamination systems require the area to be vacated for the duration of the decontamination process. 14 If a hospital ward needs to be decontaminated, then the whole ward needs to be moved to alternative accommodation which is a major undertaking and depends on the availability of additional space. 40;41 If HP vapour is used then all heating, ventilation and air conditioning ducts in the area to be decontaminated must be sealed, along with any doors. 14;42 The airborne HP systems require a team of trained personnel to operate the specialised machinery. 16;41 Airborne HP decontamination is relatively time-consuming, even if it is limited to rooms rather than wards. This is due to the need for an effective initial clean, followed by the use of airborne HP decontamination and aeration processes, and then monitoring of the environment to ensure that it is safe to re-enter. This entails a longer process than a standard clean. 40;41 If it could be applied without the need to wait for a deep clean to take place, the process would be easier, less timeconsuming and more cost-effective for healthcare use. 41 Another key issue to be considered when using airborne HP decontamination is the rapid rate of recontamination with pathogens that occurs as soon as patients are readmitted. 27 Best et al. 40 highlighted this issue in their study investigating the effectiveness of airborne HP against C. difficile infection (CDI). They found that the rate of CDI influenced how long the enhanced antimicrobial effectiveness of airborne HP lasted, and depended on whether the ward it was used in was in an outbreak or non-outbreak setting. Their results demonstrated that airborne HP may be a useful decontamination method for a hospital ward with a high incidence of CDI. What costs are associated with using airborne HP decontamination systems in the healthcare setting? Airborne HP systems are significantly more expensive than the hypochlorite solutions used in standard cleaning. Doan et al. 16 compared the cost-effectiveness of HP vapour and a chlorinereleasing agent. Their studies demonstrated that the chlorine-releasing agent cost per use and per month, compared with per use and 1, per month for HP vapour. They concluded that HP vapour was more effective at reducing spore counts than the chlorinereleasing agent but was also more expensive. They found that there was insufficient evidence for the cost-effectiveness of HP over traditional hypochlorite based cleaning. Version 1.1. December 2016 Page 17 of 28

18 Best et al. 40 report that the cost of using airborne HP amounted to about 7,000 per ward, including staff costs and materials, and therefore may only be justifiable in some cases, e.g. following an outbreak. The requirement for areas to be vacated while they are being decontaminated using airborne HP systems incurs additional costs and can potentially lead to delays in bed availability. 14 Another factor to consider in terms of the cost of airborne HP decontamination is the rapid rate of recontamination seen to take place. 41 Have airborne HP decontamination systems been assessed by the Rapid Review Panel? The Rapid Review Panel 43 (RRP) is a panel of UK experts established by the Department of Health to review new technologies with the potential to aid in the prevention and control of healthcareassociated infections. The RRP has reviewed a number of airborne HP disinfection products between 2005 and 2008: 2005: Sterinis (Related Life Sciences Ltd) 2007: Bioquell Hydrogen Peroxide Vapour System (Bioquell) 2008: Vaporised Hydrogen Peroxide (Steris) The aerosolised HP system Sterinis was assessed in 2005 and awarded a recommendation 4 status. The RRP has since altered their recommendation system to encompass 4a and 4b categories: Not a significant improvement on equipment/materials/products already available which claim to contribute to reducing health care associated infection; no further consideration needed. (R4a) Unlikely to contribute to the reduction of health care associated infection; no further consideration needed. (R4b) A HP vapour system produced by Bioquell was assessed in 2007 and awarded a recommendation 1 status: Basic research and development, validation and recent in use evaluations have shown benefits that should be available to NHS bodies to include as appropriate in their cleaning, hygiene or infection control protocols. (R1) A HP vapour system produced by Steris was assessed in 2008 and awarded a recommendation 2 status: Basic research and development has been completed and the product may have potential value; in use evaluations/trials are now needed in an NHS clinical setting. (R2) Version 1.1. December 2016 Page 18 of 28

19 Discussion This systematic review incorporated the results of 11 studies into its findings. The quality of included studies was predominantly of level 3 (low-quality) evidence; however, there was one study classified as level 2+ (moderate-quality) evidence. The study design of choice was a before-and-after study, an interrupted time series or a cohort study. They primarily concerned either in-use bioburden reduction (level III) or reduced microbial pathogen acquisition in a nonoutbreak setting (level V). The findings identified by the review were used to develop the following recommendations for clinical practice. Recommendations for Clinical Practice This review makes the following recommendations based on an assessment of the extant professional literature on airborne hydrogen peroxide (HP) systems for environmental decontamination: Airborne HP systems can be used as an adjunct to manual cleaning when performing terminal room decontamination. (Grade C recommendation) The use of airborne HP systems for environmental decontamination should only be adopted following completion of a manual clean as residual dirt can reduce efficacy. (Grade D recommendation) Prior to an airborne HP system being considered, an assessment of the area to be decontaminated must be undertaken to ensure the area can be sealed and the use of HP made safe. (Grade D recommendation) Airborne HP systems must only be used in an area which has been cleared of all patients and staff. No entry to the decontamination area is allowed once the decontamination process has commenced. (Grade D recommendation) Consideration must be given to whether airborne HP will interact with the fire alarm system and, if so, ensure that local estates are involved to isolate the fire alarm system. (Grade D recommendation) Airborne HP systems in use must be maintained in good working order and a system of programmed maintenance in place with documented evidence. (Good Practice Point) Version 1.1. December 2016 Page 19 of 28

20 Airborne HP may be considered for cleaning of the environment and/or equipment where ongoing transmission of an organism has occurred and the environment and/or equipment is considered the route of transmission. (Good Practice Point) Airborne HP systems should not be used for routine cleaning. (Grade D recommendation) If fumigation is the recommended decontamination process (e.g. disinfection of Ebolacontaminated equipment), then HP should be considered. (Good Practice Point) The use of airborne HP cleaning does not reduce the importance of general cleaning routinely and between patients. (Good Practice Point) All users of airborne HP systems, whether an NHS Board employee or an external contractor, must be trained in the product use and potential hazards of the system, and have assurance of product safety. (Good Practice Point) A Standard Operating Procedure (SOP) must be established and detail processes of when and how airborne HP cleaning is used regardless of the provision of use by NHS Boards or external contractors. (Good Practice Point) Validation processes must be in place by NHS Boards and external contractors following decontamination to ensure the healthcare environment is clean. (Good Practice Point) Version 1.1. December 2016 Page 20 of 28

21 Implications for Research The review identified several gaps in the literature in relation to airborne HP decontamination systems. Many of the relevant studies identified could not be included in this review as they did not make a suitable comparison in the form of standard cleaning as recommended for NHSScotland in the National Infection Prevention and Control Manual. 9 These studies variously compared the use of airborne HP disinfection with sodium hypochlorite at a range of concentrations, quaternary ammonium compound disinfectants, or the use of detergent only. Future studies assessing the clinical effectiveness of airborne HP systems for decontamination should include suitable comparison groups to enable the results to be transferable to clinical practice within NHSScotland. It was also notable that several of the studies combined multiple infection control interventions with the use of airborne HP disinfection, such as the simultaneous introduction of airborne HP and HP wipes, the provision of staff feedback on terminal cleaning, and additional screening for colonised patients. Ideally, studies that evaluate the effectiveness of airborne HP decontamination systems should exclude other infection control interventions in order to minimise the risk of confounding factors producing a spurious result. Finally, very few studies thus far have evaluated the cost-effectiveness of airborne HP decontamination systems. Of the few that have, the majority have primarily considered the capital costs of the necessary equipment and the cost of manual labour to operate the devices, in comparison against the costs of disinfectants used for traditional cleaning. It can be seen from these studies that a comprehensive cost-effectiveness evaluation for the use of airborne HP decontamination systems in NHSScotland would be timely. Version 1.1. December 2016 Page 21 of 28

22 Conclusion The contribution of environmental contamination in healthcare settings to the cross-transmission of nosocomial infections has been thoroughly demonstrated: firstly, by interventional studies in which improved surface cleaning has reduced the incidence of HAIs; 1 and secondly, by observational studies which have evidenced the higher risk of pathogen acquisition in patients admitted to rooms where the prior occupant was known to be infected or colonised. 2 Airborne hydrogen peroxide (HP) decontamination systems provide an example of a novel technology that may supplement standard cleaning practices and potentially further reduce the transmission of nosocomial pathogens. This review aimed to provide a concise evidence summary outlining: the evidence of effectiveness for, the practical and safety considerations of, and the costs associated with, the use of airborne HP decontamination systems. The review found that there was a larger quantity of evidence supporting the use of HP vapour systems than aerosolised HP systems, although this evidence was of low- to moderate-quality. Nine of the eleven studies demonstrated that using airborne HP systems after standard cleaning was more effective than standard cleaning alone. For four of these studies, airborne HP was more effective than hypochlorite while for five of the studies, airborne HP was more effective than quaternary ammonium disinfectants or detergents. The two other studies showed that airborne HP systems were similar in effectiveness to hypochlorite solution. However, the studies often lacked a concurrent control group and frequently combined multiple infection control interventions within a single study. In addition, the standard cleaning measures adopted did not always reflect current best practice recommended for use in NHSScotland. To ensure staff and patient safety, it is recommended that all personnel should be cleared from the room before use and that the room should be closed to entry for the duration. There is a risk that airborne HP systems can interfere with the normal operation of heating, ventilation and air conditioning systems. Consideration should be given to whether airborne HP devices will interact with these systems and, if so, measures should be implemented to disable them. There has also been little in the way of cost-effectiveness evaluations of airborne HP systems in the UK. The Rapid Review Panel (RRP) has evaluated three airborne HP disinfection systems: one that uses aerosolised HP and two that use HP vapour. Both HP vapour devices were assigned a recommendation grade of 1 or 2. This classification advises that the product has either shown benefits that should be available to NHS bodies or that the product may have potential value, and that in-use evaluations are needed in an NHS clinical setting. The only aerosolised HP device was categorised with a grade 4: a product that does not show a significant improvement over the alternatives currently available. Version 1.1. December 2016 Page 22 of 28