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        Establishing a Research Agenda for Preventing Transmission of Multidrug-Resistant Organisms in Acute-Care Settings in the Veterans Health Administration
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        Establishing a Research Agenda for Preventing Transmission of Multidrug-Resistant Organisms in Acute-Care Settings in the Veterans Health Administration
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(See introductory commentary by Livorsi et al, pages 186–188.)

Transmission of multidrug-resistant organisms (MDRO) is a major contributor to the emergence of antibacterial resistant pathogens in healthcare settings. Transmission can occur through contact with contaminated environmental surfaces and other fomites or via the hands of healthcare workers. Numerous interventions have been implemented to target transmission prevention including hand hygiene surveillance and education, active surveillance, isolation of colonized or infected patients, patient cohorting, enhanced environmental cleaning, and the use of antimicrobial surfaces. Interventions can be generally divided into horizontal interventions that target the transmission of any organisms, such as hand hygiene, and vertical interventions that target a specific organism (eg, active surveillance and decolonization for methicillin-resistant Staphylococcus aureus [MRSA]).Reference Wenzel and Edmond 1

The Veterans Health Administration (VHA) has been a leader in transmission prevention within acute-care settings. A notable example is the 2007 MRSA directive that mandated that all acute-care units adopt a specific bundle of interventions to prevent the transmission of MRSA.Reference Jain, Kralovic and Evans 2 The bundle consists of nasal surveillance testing for MRSA for all patients on admission, in-hospital transfer and discharge; contact precautions (CP) for MRSA colonized or infected patients; hand hygiene; and a change in the institutional culture that included institutional leadership with ground-level innovation along with hiring an MRSA coordinator at each facility. The implementation of this bundle has been associated with reduced MRSA acquisition and infection along with marked reduction in hospital-onset gram-negative bacteremia.Reference Goto, O’Shea and Livorsi 3 In 2012, the VHA followed the example of the MRSA directive with a Clostridium difficile initiative that includes environmental management, hand hygiene, CP for the duration of diarrheal symptoms, and cultural transformation.Reference Evans, Kralovic, Simbartl, Jain and Roselle 4 Most recently, similar guidance for control of carbapenem-resistant Enterobacteriaceae (CRE) was released by the MDRO Prevention Office of the VHA National Infectious Diseases Service in September 2014, which was updated in January 2017. Given that the VHA is the largest integrated healthcare system in the United States and has a strong history of MDRO prevention and control, it is ideally positioned to further the generalizable knowledge around optimal control of MDRO transmission in both acute-care and long-term care settings.

In September 2016, a multidisciplinary group of investigators gathered to review the existing literature and outline a research agenda for transmission prevention in VHA. While the research targets were specifically designed to guide health services researchers in VHA, these suggested targets should be broadly useful in other settings including integrated healthcare systems outside the United States. A summary of the existing knowledge base, research recommendations and how needs fit within the VA Quality Enhancement Research Initiative (QUERI) 6-step model are provided in Table 1.Reference Stetler, Mittman and Francis 5

TABLE 1 Proposed Veterans Healthcare Administration (VHA) Research Agenda for Transmission Prevention Research

NOTE. QUERI, Quality Enhancement Research Initiative; HAI, hospital-associated infection; MDRO, multidrug-resistant organism; CP, contact precautions; MRSA, methicillin-resistant Staphylococcus aureus; CRE, carbapenem-resistant Enterobacteriaceae; CDI, Clostridium difficile infection, VHA, Veterans Health Administration; ICU, intensive care unit.


Hand Hygiene

Hand hygiene is the cornerstone of infection prevention efforts and the quintessential horizontal intervention. It is included in almost all infection control bundles from the central-line–associated bloodstream infection (CLABSI) bundle to the VHA MRSA bundle.Reference Jain, Kralovic and Evans 2 , Reference Marschall, Mermel and Fakih 6 Yet despite all the attention, hand hygiene compliance remains dismal, with the best estimates of compliance ranging from 34% to 57%.Reference Kingston, O’Connell and Dunne 7 Hand hygiene initiatives can be broken down into 2 major components: surveillance and interventions. Specific interventions are listed in Table 1.


Surveillance of hand hygiene practice is the cornerstone of hand hygiene programs, and audit and feedback of accurate compliance rates are the most basic components of hand hygiene improvement. However, the difficulty in hand hygiene surveillance can be summarized in this quote from Dr Mark Chassin, President and Chief Executive Officer of The Joint Commission: “It’s interesting that a number of the hospitals were misled by faulty data to believe that they were doing as well as, say, 85%, at baseline rather than (a more accurate) 48%.”Reference Berman 8 Given that the Joint Commission could not attain compliance rates above 82% under study conditions and no longer requires a specific hand hygiene target be met in their National Patient Safety Goals, an evidence-based hand hygiene compliance target or “safe threshold” is needed in acute-care, critical-care, and long-term care settings. Thus, the processes that go into hand hygiene surveillance need critical analysis and innovative studies. First, the current gold standard for measuring hand hygiene compliance is direct observation, which has inherent biases such as the Hawthorne effect.Reference Chen, Vander Weg, Hofmann and Reisinger 9 Research related to best practices for direct observation, including multicenter VA studies, is appearing; however, much more research is needed to insure that infection prevention and control teams have accurate hand hygiene surveillance data.Reference Yin, Reisinger and Vander Weg 10 Some call for automated systems, but more technological developments and research are needed to fully realize the potential of this type of surveillance, including randomized control or quasi-experimental studies to validate the systems and cost-effectiveness studies.Reference Ward, Schweizer, Polgreen, Gupta, Reisinger and Perencevich 11 Critical analysis is also needed regarding defining hand hygiene opportunities—the denominator of hand hygiene compliance rates. For example, hand hygiene might not be necessary prior to donning gloves.Reference Rock, Harris, Reich, Johnson and Thom 12 Thus, eliminating this opportunity or others might reduce the denominator for calculating compliance rates and focus the attention of the clinical staff and administrative oversight on the most critical hand hygiene opportunities. Additional attention is needed in developing optimal surveillance methods for non–acute-care settings, including outpatient clinics.

Hand hygiene improvement interventions

Beyond audit and feedback, the existing World Health Organization, Centers for Disease Control and Prevention (CDC), and VHA hand hygiene bundles have been shown to increase hand hygiene compliance in acute-care settings.Reference Schweizer, Reisinger and Ohl 13 These bundles have included education, reminders, administrative support, and access to alcohol-based hand rub and have typically been evaluated using single-center quasi-experimental studies. Novel and sustainable interventions are still needed and might include long-acting hand hygiene preparation. Any evaluation of long-acting agents would need to include qualitative evaluation to understand how implementation might impact overall behavior. Evaluation of existing bundle components and novel interventions should occur using cluster-randomized trials or well-designed multicenter quasi-experimental studies using factorial designs to determine the least number of components required to maintain compliance over established safe thresholds without overburdening clinical staff. Intervention studies could include longer postintervention observational periods to determine which interventions most effectively sustain compliance rates above safe thresholds. Interventions that sustain compliance may differ from those that initially increase compliance.

Active Surveillance

Active surveillance, obtaining screening tests of patients not known to be colonized or infected with a specific organism, has played an integral role in the control of MDRO for decades. Active surveillance and subsequent isolation and/or decolonization of patients carrying a single pathogen of interest is the prototypical vertical intervention.Reference Wenzel and Edmond 1 Passive surveillance, which typically relies on clinical cultures, misses or delays the detection of the majority of patients who could potentially spread the pathogen to uncolonized patients.Reference Perencevich, Fisman, Lipsitch, Harris, Morris and Smith 14 Yet the role of active surveillance has not been without controversy, particularly after the 2006 CDC Healthcare Infection Control and Prevention Advisory Committee guidelines suggested that facilities could choose to apply active surveillance in a targeted fashion.Reference Siegel, Rhinehart, Jackson and Chiarello 15 Early evidence supported a role for active surveillance in national control efforts for MRSA in the Netherlands and other countriesReference Bootsma, Diekmann and Bonten 16 , in regional vancomycin-resistant enterococci control,Reference Ostrowsky, Trick and Sohn 17 and in numerous outbreak settings. However, more recent clinical trials have been less supportive when active surveillance was combined with delayed implementation of CP for VRE and MRSAReference Huskins, Huckabee and O’Grady 18 or when compared to universal decolonization.Reference Huang, Septimus and Kleinman 19

In the VHA, active surveillance has played a central and successful role in the MRSA bundle adopted in 2007Reference Jain, Kralovic and Evans 2 but was not included in the subsequent C. difficile infection (CDI) bundle. The VHA CRE bundle recommended targeted screening of high-risk patients or patients sharing a room with CRE-positive patients based on individual facility’s risk assessment. Specific recommendations are provided in Table 1. Potential targets for future study include (1) establishing organism-specific (eg, CRE) and setting-specific (eg, intensive care unit [ICU]) thresholds for cost-effectiveness of active surveillance, (2) developing and validating prediction-rule guided active surveillance, (3) exploring and studying the inclusion of active surveillance or targeted active surveillance into existing CDI and CRE VHA directives, and (4) completing implementation-effectiveness studies of MRSA/S. aureus screening plus decolonization bundles in surgical and nonsurgical settings.

Isolation Measures

Isolation measures include CP and patient cohorting. Contact precautions require healthcare workers to wear gowns and gloves when entering patient rooms and caring for patients. Cohorting requires that patients colonized or infected with an MDRO be placed in the same unit, together in a shared room, or in single-occupancy rooms. Contact precautions can be implemented universally for all patients,Reference Harris, Pineles and Belton 20 selectively as guided by active surveillance interventions as used in the VHA MRSA directive, or passively for patients known to be currently or historically infected with select MDROs. Some facilities also use syndrome-based CP (ie, isolation of patients with draining wounds or uncontrolled diarrhea). The additional benefit of gowns when added to gloves has not been well established, and recent studies have supported potential benefits of universal gloving strategies.Reference Yin, Schweizer, Herwaldt, Pottinger and Perencevich 21

Recently, the utility of CP, particularly when combined with active surveillance programs, has been questioned.Reference Morgan, Wenzel and Bearman 22 Despite this, CDC guidance has remained unchanged on this issue, and most infection control programs in the United States continue to utilize CP.Reference Siegel, Rhinehart, Jackson and Chiarello 15 , Reference Morgan, Murthy and Munoz-Price 23 Continued utilization of CP will require additional large-scale studies to establish the benefits, potential harms, and costs associated with targeted or universal implementation for endemic (eg, MRSA) and emerging (eg, CRE) pathogens. Existing studies have been predominantly performed in ICU settings and the utility of CP in non-ICU and long-term care settings is understudied. Additionally, the utility of CP independent of other, often bundled interventions, such as cohorting and enhanced environmental cleaning, needs to be investigated.Reference Fitzpatrick and Perencevich 24

Enhanced Environmental Cleaning Interventions

Until recently, the focus of infection control has been on the individual patient and not the environment surrounding the patient. However, it is well recognized that pathogens can be transmitted from porous (eg, textiles) or hard surfaces (eg, tables) directly or indirectly via contaminated hands of healthcare workers or patients.Reference Samore, Venkataraman, DeGirolami, Arbeit and Karchmer 25 Thus, daily environmental cleaning and disinfection and terminal cleaning (ie, at patient discharge) are important components in transmission prevention.

Few studies have examined the risks and benefits of daily environmental cleaning while the MDRO-colonized or infected patient remains in the room. Given that most healthcare worker contacts with the environment occur during this period, additional studies are needed to outline the risks of environmental contamination during this period and the methods for monitoring and reducing the risk through daily or more frequent cleaning or disinfection. Novel technologies, such as antimicrobial textiles (eg, privacy curtains or surgical scrubs) and antimicrobial surfaces (eg, copper coatings), have been evaluated as methods for continuous cleaning with mixed success.Reference Anderson, Addison and Lokhnygina 26 Reference Schweizer, Graham, Ohl, Heilmann, Boyken and Diekema 30

The current focus on environmental cleaning and disinfection has been on terminal cleaning at patient discharge based on the recognition that patients who inhabit a room whose prior room occupant carried an MDRO might be at higher risk for acquiring the same pathogen.Reference Martinez, Ruthazer, Hansjosten, Barefoot and Snydman 31 Terminal cleaning methods include surface cleaning using chemical disinfectants (eg, quaternary ammonium or bleach) and no-touch automated systems (eg, disinfecting ultraviolet [UV-C] light and hydrogen peroxide vapor). The effectiveness and cost-effectiveness of these technologies are currently being evaluated and would benefit from more in-depth comparative effectiveness studies.Reference Anderson, Chen and Weber 32

Technologies for monitoring environmental cleaning and disinfection have been evaluated including fluorescent UV surface markers and adenosine triphosphate bioluminescence. However, frequency of monitoring, intensity of monitoring (ie, number of surfaces tested), and the implementation of monitoring bundles have not been adequately evaluated. A recent review highlighted the importance of contextual factors, and further studies, particularly outside acute-care facilities, are needed.Reference Han, Sullivan, Leas, Pegues, Kaczmarek and Umscheid 33 Finally, while environmental cleaning technologies have been linked to reduced environmental bioburden, few studies have been able to link interventions to improved clinical outcomes such as reductions in MDRO infections. The reasons include rarity of outcomes and many potential confounders in the pathway between a contaminated environment and clinical infection, including unit-level hand hygiene compliance and patient comorbidity. Thus, without large and cost-prohibitive cluster-randomized trials, a definitive link between environmental cleaning and improved clinical outcomes may never be established. Mathematical models that incorporate the best estimates of intervention benefits and other important parameters, such as hand hygiene compliance, are likely our best hope in estimating the effectiveness and cost-effectiveness of old and new technologies.Reference Barnes, Morgan, Harris, Carling and Thom 34 , Reference Nelson, Jones and Leecaster 35


This work was supported in part by funding from the VA Health Services Research and Development (HSR&D) Service Center of Innovation (COIN) conference supplement for (“Setting the Clinical Research Agenda for MDROs in VA,” grant no. CIN 13-412), and VA Quality Enhancement Research Initiative CARRIAGE Program (grant no. IP1 HX001993-01A1). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the US government. All authors report no conflicts of interest or financial disclosures relevant to this article.


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