Systematic Review Of Novel Disinfection Methods To Reduce .
Systematic review ofnovel disinfectionmethods to reduceinfection rates inhigh risk hospitalisedpopulationsReport prepared byCochrane Australia7 April 2017Trusted evidence.Informed decisions.Better health.
2ContentsAuthors and contributors to the protocol4Declarations of interest41.Background51.1Description of the condition and setting51.2Description of the intervention and how it might work5Ultra-violet light6Hydrogen peroxide vapour/mist6Electrolysed water6Sodium hypochlorite62.Objectives73.Methods73.1Criteria for considering studies for this review73.23.33.1.1Types of participants73.1.2Types of settings73.1.3Types of interventions73.1.4Types of comparators83.1.5Types of outcome measures83.1.6Types of studies9Search methods for identification of studies93.2.1Search terms93.2.2Bibliographic and grey literature databases93.2.3Other sourcesData collection and analysis10103.3.1Selection of studies103.3.2Data extraction and management103.3.3Assessment of risk of bias of included studies103.3.4Measures of treatment effect103.3.5Unit of analysis issues, missing data, assessment of heterogeneity and reporting bias113.3.6Data synthesis113.3.7Summary of findings tables and assessment of quality of the body of evidence114.Results114.1Results of the search11
34.2Description of studies124.2.1 Included studies124.2.2 Ongoing studies184.2.3 Excluded studies184.2.4 Studies awaiting assessment184.3 Risk of bias in included studies184.3.1 Randomised and non-randomised trials184.3.2 Time series studies194.4 Effects of interventions214.4.1 Sodium hypochlorite versus standard cleaning/disinfection214.4.2 Hydrogen peroxide vapour versus standard cleaning/disinfection274.2.3 Ultra-violet light disinfection versus standard cleaning/disinfection335.0 Discussion385.1 Summary of main results385.2 Overall completeness and applicability of the evidence385.3 Quality of the evidence395.4 Potential biases in the review process406.0 Authors’ conclusions406.1 Implications for practice406.2 Implications for research41References42References to studies included in this review42References to ongoing studies43References to studies awaiting further assessment43Other references43
4In June 2016 Cochrane Australia was contracted by the National Health and Medical Research Council(NHMRC) to design and undertake this systematic review. This review is one of several independentcontracted evidence evaluations being undertaken to update or inform new sections of the 2010Australian Guidelines for the Prevention and Control of Infection in Healthcare. The design and conductof the review was done in collaboration with the Infection Control Guidelines Advisory Committee(ICGAC) and NHMRC.Authors and contributors to the protocolSue BrennanSenior Evidence Officer responsible for leading the review. Contributed tothe design and conduct of the review (e.g. screening, data extraction, risk ofbias assessment). Wrote the protocol and systematic review report withcontributions from other authors as described.Steve McDonaldDeveloped the search strategy and conducted the search. Wrote the searchmethods and results. Critical review of the protocol and systematic reviewreport.Joanne McKenzieDeveloped the analysis plan and conducted the analysis. Wrote the analysismethods, method for reporting treatment effects and results from thetimes series analyses. Critical review of the protocol and systematic reviewreport.Allen ChengProvided expert clinical advice, especially in relation to selection of studiesfor the review, interpretation of analyses and reporting results. Wrote theimplications for clinical practice. Critical review of the protocol andsystematic review report.Sally GreenCritical review of the protocol report.Kelly AllenConducted searches of trial registers. Extracted data for time seriesanalyses.Jane ReidScreened citations and full text articles, extracted data, assessed risk ofbias assessment of included studies (critical appraisal).Declarations of interestAll authors declare they have no financial, personal or professional interests that could be construed tohave influenced the conduct or results of this systematic review.Professor Allen Cheng is a member of the Infection Control Guidelines Advisory Committee (ICGAC).
51.BackgroundThe National Health and Medical Research Council (NHMRC), in collaboration with the AustralianCommission on Safety and Quality in Health Care (the Commission), is updating the 2010 AustralianGuidelines for the Prevention and Control of Infection in Healthcare (2010 Guidelines) to ensure theGuidelines reflect the best available evidence and are current and relevant for the Australian context.This systematic review is one of several contracted evidence evaluations being undertaken to updateor inform new sections of the 2010 Guidelines. Cochrane Australia was contracted to undertake thisindependent systematic review of selected disinfectant modalities (ultra-violet light, hydrogenperoxide vapour, electrolysed water) to provide the NHMRC and the Commission with assurance thatthis revision of the Guidelines is grounded in the most up-to-date and relevant scientific evidence.1.1Description of the condition and settingThe 2010 Guideline identified healthcare-associated infections (HAIs) as the most commoncomplication affecting patients in hospital. Acquired in healthcare facilities or as a result of healthcareinterventions, these infections can cause significant morbidity for patients and are costly to the healthsystem. Infections caused by key hospital pathogens, including multiresistant organisms (MROs) andClostridium difficile are of particular concern (National Health and Medical Research Council 2010).Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococcus (VRE) areclinically significant as they are associated with increased healthcare costs and poorer patientoutcomes (McLaws 2009, Slimings 2014). While less prevalent, carbapenemase-producingEnterobacteriaceae (CPE) are resistant to antibiotics used to treat the most serious infection (so called“last resort” antibiotics), so preventing their spread is critical to ensuring ongoing availability ofeffective antibiotics (Falagas 2009, Weber 2013, Public Health England 2014, Department of Health andHuman Services Victoria 2015).1.2Description of the intervention and how it might workHealthcare-associated infections are potentially preventable, and hence the aim of the 2010 Guidelineswas “to promote and facilitate the overall goal of infection prevention and control through theimplementation of practices that minimise the risk of transmission of infectious agents” ((NationalHealth and Medical Research Council 2010), p7). Based on “the best available evidence and knowledgeof the practicalities of clinical procedures” at the time, the guideline made recommendations aboutimplementing a broad range of interventions. These interventions included standard precautions to beapplied at all times, and transmission-based precautions to be implemented “in the presence ofsuspected or known infectious agents that represent an increased risk of transmission” and in “themanagement of multi-resistant organisms (MROs) or outbreak situations” ((National Health andMedical Research Council 2010), p11).Environmental controls, including cleaning and disinfection, are used to prevent transmission ofinfectious agents to patients occurring either through direct contact with surfaces or indirect contactvia an intermediary ((National Health and Medical Research Council 2010), p21). The 2010 Guidelinesrecommend routine cleaning of surfaces with detergent solution as a standard precaution (i.e. a first-
6line approach that should be used with all patients). Disinfection is recommended in addition tocleaning as a transmission-based precaution. Its use is recommended “where the suspected orconfirmed presence of infectious agents represents an increased risk of transmission” and for themanagement of MROs (e.g. MRSA, MRGN, VRE). Unlike cleaning with detergent, disinfection involvesthe use of chemical or physical methods to kill microorganisms (including pathogens) (Rutala 2008,Therapeutic Goods Administration 2012). In Australia, claims of disinfectant properties are subject toregulation by the Therapeutic Goods Administration (TGA) and approved disinfectants are registeredafter demonstrating compliance with essential principles for quality, safety and performance(Therapeutic Goods Administration 2012).This review focuses on the use of modes of disinfection that have emerged or undergone furtherdevelopment for use in healthcare facilities subsequent to the review of evidence for the 2010Guidelines. Three novel disinfectant technologies are considered in this review: ultra-violet (UV) light,hydrogen peroxide (HP) vapour and electrolysed water. The review examines the effects (includingharms) of using each of these interventions compared to using a detergent solution (standard care),sodium hypochlorite (bleach) or both on clinical outcomes. The review also examines the effects ofsodium hypochlorite, a widely used disinfectant, compared to using a detergent solution.Ultra-violet lightUltra-violet light in the UV-C wavelength range (200 to 270 nanometers) has microbiocidal propertiesagainst multiple pathogens, including Clostridium difficile and other healthcare associated pathogens.Technologies have been developed for automated (no-touch) disinfection of hospital rooms using UVlight, and these have been suggested as an adjunct to manual application of disinfectants. Thetechnologies only disinfect areas directly in the UV light and can only be used when rooms are vacated,partly because of the potentially harmful effects of UV exposure (Leas 2015).Hydrogen peroxide vapour/mistHydrogen peroxide has microbiocidal properties against multiple pathogens, including Clostridiumdifficile. Automated (no touch) systems for producing hydrogen peroxide vapour and hydrogenperoxide dry mist are designed to disinfect by dispersing vapour or mist evenly across a room. As withUV light, the systems can only be used when rooms are vacated (Leas 2015). Rooms and ventilationsystems must be sealed to prevent exposure, and hydrogen peroxide must be monitored to ensure safelevels outside the room during disinfection and within the room before re-entering. While hydrogenperoxide has been suggested to have low toxicity, previous reviews found little or no evidence aboutthe safety of no-touch hydrogen-peroxide producing systems (Leas 2015).Electrolysed waterElectrolysed water systems pass an electric current through tap water with added salt to produceneutral electrolysed water. Electrolysed water has antimicrobial properties that have led to use inother industries (e.g. food production), where advantages are suggested to include not needinghazardous chemicals, ease of handling and low operating costs (Stewart 2014, Leas 2015).Sodium hypochloriteSodium hypochlorite (bleach) is a commonly used chlorine-based disinfectant with broad spectrumantimicrobial properties. Sodium hypochlorite may cause irritation to skin, eyes and other mucousmembranes. It can also corrode metals and discolour or stain fabrics (Leas 2015).
72.ObjectivesTo examine the effect of ultra-violet (UV) light, hydrogen peroxide (HP) vapour and/or electrolysedwater on infection rates in high risk population groups compared with standard care (cleaning withdetergent, disinfection with sodium hypochlorite, or both) on clinical outcomes.To examine the effect of disinfection with sodium hypochlorite on infection rates in high riskpopulation groups compared with cleaning with detergent on clinical outcomes.3.MethodsMethods for this review were pre-specified in the protocol for the review (Brennan 2016) and are basedon the Cochrane Handbook for Systematic Reviews of Interventions and the Cochrane Effective Practiceand Organisation of Care group (Effective Practice and Organisation of Care (EPOC) 2015). Additionalmethodological considerations pertinent to public health questions are addressed where appropriate(Armstrong 2011). The review is reported in accordance with the PRISMA statement (Liberati 2009,Moher 2009). The methods are described in full, together with documentation of any changes to theprotocol, in the accompanying Technical report. A brief outline of the approach follows.3.1Criteria for considering studies for this review3.1.1Types of participantsHigh risk population groups, defined in the 2010 Guidelines as “patients with an increased probabilityof infection due to their underlying medical condition.” ((National Health and Medical Research Council2010), p261). Examples included, patients in intensive care, oncology, haematology, burns and renalunits. Studies set on wards on which there was a known outbreak or in contact precaution rooms werealso eligible.3.1.2Types of settingsType of healthcare facility: Studies set in hospital wards (primarily acute care), including inpatientfacilities and patient rooms, were considered for inclusion in the review. Studies set in countries withhealth systems broadly comparable to those in Australia were eligible.3.1.3Types of interventionsStudies evaluating the effects of the following agents or modalities for disinfection were eligible forinclusion. Sodium hypochlorite (bleach): preparations of sodium hypochlorite, at any concentration,applied using any method and at any frequency. Automated (‘no touch’) systems or modalities of room decontamination involving ultra-violetlight (UV light devices) or hydrogen peroxide vapour (HP vapour, HP mist and other systems). Electrolysed water. applied using any method and at any frequency.Studies in which automated systems for room decontamination (UV light, HPV) were used as anadjunct to standard cleaning/disinfection were eligible if compared to the same form of standardcleaning/disinfection.
8Types of surfacesEligible studies must have involved interventions for use in patient surroundings, defined in the 2010Guidelines as “inanimate surfaces that are touched by or in physical contact with the patient andsurfaces frequently touched by healthcare workers while caring for the patient” (p262). Any high-touchsurface was eligible including hard nonporous and porous surfaces.3.1.4Types of comparatorsFor studies testing the effects of UV light, HP vapour or electrolysed water, eligible comparators werethose considered as the standard of care.For studies testing the effects of sodium hypochlorite, eligible comparators were HP disinfection, UVdisinfection, electrolysed water (as above) or cleaning/disinfection practices that were the standard ofcare (usual practice).3.1.5Types of outcome measuresPrimary outcomeHealthcare associated infection (confirmed or unconfirmed) arising from the following pathogens: Clostridium difficile (C. difficile) Methicillin-resistant Staphylococcus aureus (MRSA) Vancomycin resistant enterococcus (VRE) Acinetobacter spp. An Enterobacteriaceae (including Escherichia coli, Klebsiella sp. Enterobacter sp. and others)where a carbapenemase producing gene is detected (including MBLs and KPC) resulting in ahigh minimum inhibitory concentration (MIC) to carbapenems in vitro (based on standard labcriteria including EUCAST or CLSI) (Department of Health and Human Services Victoria 2015,Guh 2015) Extended spectrum beta lactamase (ESBL) producing organisms (includes extended-spectrumcephalosporin-resistant CPE listed above and Acinetobacter spp. (Falagas 2009).Clinical evaluation or signs of infection must have been accompanied by testing to confirm acquisitionof an MRO or C. difficile. Studies that reported outcomes in which infection and colonisation were notdistinguished (e.g. acquisition of MRSA), combined outcomes across multiple pathogens (e.g.acquisition of any MRO), or reported unconfirmed infection (e.g. clinical isolates alone), were eligible.Secondary outcomeColonisation with multi-resistant organisms (MROs) where colonisation is defined as the “sustainedpresence of replicating infectious agents on or in the body without the production of an immuneresponse or disease” ((National Health and Medical Research Council 2010), p17).Adverse effectsData on adverse effects (harms, safety) was collected and included in our review when the data werereported in included studies that measured at least one of the primary or secondary outcomes (i.e.
9infection, colonisation), or in eligible studies that explicitly aimed to examine adverse effects. Weconsidered only patient or health professional health outcomes, not broader impacts on healthservices delivery.3.1.6Types of studies Randomised trials (RTs). Non-randomised trials (NRTs). Interrupted-time-series (ITS) and repeated measures (RM) studies, including studies with datasuitable for reanalysis as a time series. Controlled before-after (CBA) studies.The types and definition of study designs eligible for inclusion are based on guidance from theCochrane Effective Practice and Organisation of Care (EPOC) group (Effective Practice and Organisationof Care 2013), and are provided in the Technical Report.Date and language restrictions. Only studies published from 2006 onwards were eligible for inclusion.Studies published in languages other than English were ineligible except for randomised trials.3.2Search methods for identification of studiesThe overall search approach was based on the search methods used for the recent Technical Briefprepared for the Agency for Healthcare Research and Quality (AHRQ) (Leas 2015). The search termsinclude concepts relevant to a second commissioned review for the 2010 guidelines (antimicrobialsurfaces), for which searching and screening was conducted concurrently.Potentially eligible studies published between 2006 and 2014 were identified from the lists of includedand excluded studies from the AHRQ report. The lists were supplemented by additional searches forthe same period for terms or concepts not covered by the AHRQ report, and by an update of the AHRQsearch for the period January 2015 to August 2016. The review considered both peer reviewedliterature, as well as unpublished literature. No language or geographic limitations were applied whensearching.3.2.1Search termsThe search strategy was developed for Embase via Ovid (used for the AHRQ report and includes allMEDLINE records). Methods for developing terms, use of filters and syntax for the search are in theTechnical Report.3.2.2Bibliographic and grey literature databasesWe searched Embase (via Ovid) for records added since January 2015 (back to 2006 for terms notcovered by AHRQ). The search strategy was translated for PubMed (limited to in-process citations andcitations not indexed in MEDLINE), the Cochrane Library and CINAHL Plus. We also searchedClinicalTrials.gov. The full search strategies for each source are provided in the Technical report,Appendix 1.
103.2.3Other sourcesWe screened all studies included in the AHRQ report plus all studies that had been excluded from theAHRQ report after full-text screen. Checks of reference lists and forward citation searches were alsouse.3.3Data collection and analysis3.3.1Selection of studiesTwo reviewers (SB, JR) independently screened citations (titles and abstracts) and full text studies forinclusion in the review against the eligibility criteria, with discussion and specialist advice from ourreview content expert (AC) and our biostatistician (JM) where disagreement arose. Citations that didnot meet the inclusion criteria were excluded and the reasons for exclusion were recorded at full-textscreening. Multiple papers from the same study were matched using trial registry numbers,bibliographic and study design details.3.3.2Data extraction and managementFor each included study, two reviewers independently extracted data using a pre-tested dataextraction and coding form. Disagreements were resolved by discussion and with advice from thereview content exper
3.2.2 Bibliographic and grey literature databases 9 . applied at all times, and transmission-based precautions to be implemented “in the presence of . Methods for this review were pre-specified in the pr otocol for the review (Brennan 2016) and are based on the .
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