Facility Guidance for Control of Carbapenem-resistant Enterobacteriaceae (CRE)

November 2015 Update - CRE Toolkit

National Center for Emerging and Zoonotic Infectious Diseases Division of Healthcare Quality Promotion

Facility Guidance for Control of Carbapenem- Resistant Enterobacteriaceae (CRE) November 2015 Update

This document updates CDC’s Guidance for Control of Carbapenem-resistant Enterobacteriaceae (CRE): 2012 CRE Toolkit. Unless otherwise specified, the term healthcare facility refers to all acute care hospitals and any long-term care facility that has patients who remain overnight and regularly require medical or nursing care (e.g., maintenance of indwelling devices, intravenous injections, wound care, etc.). This includes all long-term acute care hospitals and nursing homes providing skilled nursing or rehabilitation services, but generally excludes assisted living facilities and nursing homes that do not provide more than long-term custodial care. In addition, this toolkit is not intended for use in ambulatory care facilities.

Control of resistant organisms is a national problem and requires that facilities that share patients work together to prevent transmission. These efforts may be best coordinated by local public health. Facilities are strongly encouraged to participate in these regional efforts.

1 The Following Major Items Have Changed from the 2012 CRE Toolkit:

1. The CDC CRE surveillance definition has been modified.

2. The two intervention tiers have been replaced by a single tier. Not all interventions might be applicable in all settings or situations. Information is provided about situations in which specific interventions might be most important.

3. Further discussion has been added on the use of Contact Precautions in post-acute settings.

4. Information on regional interventions has been removed in order to target this document specifically to facilities. Coordinated regional approaches to prevent infections with multidrug-resistant organisms remain important; additional information on these approaches will be made available in other documents.

5. Inter-facility communication has been added to the interventions.

2 The emergence and dissemination Background of carbapenem resistance among Enterobacteriaceae in the United States CRE are Epidemiologically represents a serious threat to public health. Important for Several Reasons: These organisms cause infections that are associated with high mortality rates and • Invasive infections (e.g., they have the potential to spread widely. bloodstream infections) caused Decreasing the impact of these organisms by CRE have been associated with will require a coordinated effort involving high mortality rates (up to 40 all stakeholders including healthcare to 50% in some studies). facilities and providers, public health, and • In addition to β-lactam/ industry. This document updates the 2012 carbapenem resistance, CRE CRE Toolkit and will continue to evolve often carry genes that confer high as new information becomes available. levels of resistance to many other The current recommended approach to antimicrobials, often leaving very control transmission of these organisms in limited therapeutic options. “Pan­ healthcare facilities includes the following: resistant” CRE have been reported.

• Recognizing these organisms as • CRE have spread throughout epidemiologically important most parts of the United States and other countries and have the • Quantifying the magnitude of CRE potential to spread more widely. within the facility and regionally • Currently in the United States, • Identifying colonized and infected CRE are primarily identified patients when present in healthcare among patients with healthcare facilities exposure, but there is potential for CRE to spread outside of • Implementing interventions designed healthcare settings, given that to stop the transmission of these Enterobacteriaceae are a common organisms cause of community-associated infections.

Carbapenem resistance among Enterobacteriaceae can be due to several different mechanisms. Some CRE possess a β-lactamase (e.g., AmpC or extended- spectrum β-lactamase (ESBL)) which, when combined with porin mutations, can render an organism nonsusceptible

3 to carbapenems. Some CRE possess a carbapenemase (carbapenemase-producing CRE or CP-CRE) that directly breaks down carbapenems. Carbapenemases are often contained on mobile genetic elements that facilitate transfer of resistance among Enterobacteriaceae and other gram-negative organisms. CP-CRE were first identified in the United States from an isolate collected in 1996 and have disseminated widely since that time. All but two states (ID and ME) have reported at least one CP-CRE to the Centers for Disease Control and Prevention as of November 2015. The rapid spread of CP-CRE have made these organisms a particularly important target for prevention.

Much of the increase in CRE since 2000 has been due to the spread of CRE that produce the carbapenemase Klebsiella Klebsiella pneumoniae pneumoniae Carbapenemase (KPC). In addition to KPC, several other types of reports of Enterobacteriaceae producing carbapenemases have been identified in the OXA-48-type enzymes have also increased United States since 2009. These include the in the United States. New Delhi Metallo-β-lactamase (NDM), Verona Integron-encoded Metallo-β­ The current U.S. distribution of CRE (both lactamase (VIM), Oxacillinase-48-type CP-CRE and non-CP-CRE) appears to be carbapenemases (OXA-48), and the heterogeneous; these organisms are more Imipenemase (IMP) Metallo-β-lactamase. commonly isolated from patients in some Organisms producing these non-KPC parts of the United States, but they are not enzymes are more common in some areas of regularly found in other regions. Even in the world; in the United States, they have areas where CRE are found they may be generally been found among patients who more commonly present among patients in received medical care in countries where some healthcare settings, such as long-term organisms with these carbapenemases are acute care hospitals, than they are in others. known to be present. Beginning in 2012, Healthcare facilities should work with however, NDM has been increasingly public health to have an awareness of their reported among U.S. patients without a regional CRE epidemiology; understanding recent history of exposure to healthcare this information can help inform CRE outside of the United States. More recently, prevention efforts.

4 Interventions to control CRE are evolving the detection of carbapenemases. Only as more data and experience become one test for carbapenemase production, available. Since these organisms currently the Modified Hodge Test (MHT), is are primarily isolated from people with currently widely used in U.S. laboratories. healthcare exposures and the bulk of Although MHT has demonstrated good transmission appears to occur in these sensitivity for KPC, it has lower sensitivity settings, interventions have primarily for other carbapenemases, such as included identifying people colonized or NDM. In addition, MHT is not specific infected with CRE while in healthcare for carbapenemase production among settings and applying interventions designed some genera of Enterobacteriaceae (e.g., to minimize the risk of transmission. Enterobacter). Several other methods The specific interventions are described for detecting carbapenemases have been in detail in the next sections. Although developed, including polymerase chain the interventions described in the next reaction and the Carba NP test, but these sections are applicable to most healthcare are not currently widely used in clinical settings and most organisms meeting the laboratories in the United States. Thus, CRE defintion, facilities may choose to a definition that differentiates CP-CRE target some of the interventions to certain from non CP-CRE based on the organism’s situations (e.g., outbreaks) and certain types pattern of susceptibiltiy to antimicrobials of CRE (e.g., CP-CRE). (phenotypic definition) would have utility for surveillance and prevention. CRE Definitions In general, CRE are Enterobacteriaceae However, developing a phenotypic that are nonsusceptible (i.e., intermediate definition for CRE that differentiates or resistant) to a carbapenem. However, CP-CRE from non-CP-CRE has been as described above, carbapenem difficult because the antimicrobial nonsusceptibility among Enterobacteriaceae susceptibility profiles of these two groups can be acquired through several different overlap. The CRE definition included in mechanisms, with carbapenemase the 2012 CRE Toolkit (nonsusceptible production currently being the most to imipenem, meropenem, or doripenem concerning resistance mechanism. and resistant to all third-generation cephalosporins tested) was designed to be Differentiating CP-CRE from CRE that are more specific for CP-CRE; however, it was nonsusceptible to carbapenems due to other a complicated definition that has proven mechanisms is complicated by a number difficult to implement. Further, based on of issues, including the wide variability an assessment of the antibiograms of CRE in the capacity of U.S. clinical and public isolates submitted to CDC from six U.S. health laboratories to perform testing for metropolitan areas, that definition missed

5 a portion of KPC-producing CRE. In • At present, acceptable tests for addition, that definition has the potential detecting carbapenemases include to miss some CRE producing OXA-48­ polymerase chain reaction, MHT, β type carbapenemases, since these isolates Carba NP, metallo- -lactamase testing (e.g., MBL tests or screens). might remain susceptible to third generation As described above, the MHT cephalosporins and a number of OXA-48­ does have limitations including type-producing CRE evaluated at CDC over-calling the presence of have only been resistant to one carbapenem carbapenemases among Enterobacter (ertapenem). species and failing to identify some CRE that produce an NDM In an attempt to simplify the CRE enzyme; it is included among the definition as well as further increase the acceptable tests at this time because of its wide use. The number of ability of the definition to identify CRE available tests for carbapenemase that produce carbapenemases, CDC has is expanding; facilities using a test refined the 2012 interim CRE surveillance not included on the list above definition: should review the test performance to ensure that it has reasonable CRE are Enterobacteriaceae that are: sensitivity and specificity.

• Resistant to any carbapenem The above phenotypic definition lacks antimicrobial (i.e., minimum specificity for CP-CRE (i.e., CRE that do inhibitory concentrations of ≥4 not produce a carbapenemase will often mcg/ml for doripenem, meropenem, meet this definition), especially in areas or imipenem OR ≥2 mcg/ml for ertapenem) where CP-CRE are rare. Therefore, to guide prevention efforts, clinical and public health OR laboratories with the capacity to perform carbapenem resistance mechanism testing • Documented to produce are encouraged to test for the presence of carbapenemase carbapenemases. Ideally, U.S. laboratories should test for the presence of KPC, In addition: NDM, and OXA-48-type carbapenemases. • For bacteria that have intrinsic However, if CRE are identified from a imipenem nonsusceptibility (i.e., geographical area where other types of Morganella morganii, Proteus spp., carbapenemases are known to be common Providencia spp.), resistance to or if the patient has relevant risk factors carbapenems other than imipenem is (e.g., travel outside the United States, required. exposure to non-KPC carbapenemases), then testing for other carbapenemases should be considered.

6 Facility-Level CRE Prevention applied differently by facilities based on the underlying epidemiology of CRE Surveillance in the region including the regional Healthcare facilities should be aware of prevalence, the underlying CRE resistance whether or not CRE have been isolated mechanisms found in the area, and the from patients admitted to their facility. In type of healthcare facility involved. In addition, facilities should know whether general, standard interventions designed or not their laboratories have the capacity to prevent the transmission of multidrug­ to perform carbapenemase testing and resistant organisms (MDROs) (e.g., hand CRE screening tests. If these tests are not hygiene, Contact Precautions) should be available, facilities should identify outside implemented for most CRE (CP-CRE laboratories that can perform this testing and non-CP-CRE). However, facilities when needed. might choose to apply a wider range of interventions for CRE they judge to be Facilities should consider performing epidemiologically important, including all ongoing evaluations to quantify the CP-CRE. Some non-CP-CRE might also incidence of CRE organisms from clinical be targeted for more extensive interventions specimens, such as reviewing archived particularly during an outbreak or if the laboratory results to determine the number underlying prevalence of the organism is and/or proportion of Enterobacteriaceae high or increasing despite the application of that are CRE over a pre-specified time baseline prevention measures. The situations period (e.g., 6 to 12 months). In addition, where each intervention might be most facilities should consider collecting useful are specified more completely in the information on the basic epidemiology of next section. For more in-depth review patients colonized or infected with these of MDRO prevention, please refer to the organisms in order to understand common CDC HICPAC guidelines “Management characteristics of these individuals. This of Multidrug-Resistant Organisms in might include patient demographics, dates Healthcare Settings, 2006” (http://www.cdc. of admission, outcomes, medications, and gov/hicpac/mdro/mdro_toc.html). common exposures (e.g., wards, surgery, procedures, transfer from other healthcare If carbapenemase testing is not available, facilities, etc.) facilities should consider the possibility that any CRE that meets the phenotypic Facility-Level Prevention Strategies surveillance definition is a CP-CRE and The following briefly summarizes apply the interventions, as described below, interventions recommended to prevent accordingly. However, facilities that have CRE transmission in healthcare settings. information on the epidemiology of CRE The listed interventions might be in their region might choose to tailor the

7 range of interventions they apply based on provided. The third section outlines general these data. For all MDRO control efforts, guidance for any facility using Contact facilities should work together and with Precautions. state and local health departments in order to maximize the effect of the interventions a. Acute Care Hospitals and High- regionally. Acuity Post-Acute Care Settings

1. Hand Hygiene Acute care hospitals, long-term acute care hospitals, and ventilator units of skilled Hand hygiene is a primary part of preventing nursing facilities should generally place MDRO transmission. Facilities should patients who are colonized or infected ensure that healthcare personnel are familiar with CRE on Contact Precautions. Some with proper hand hygiene technique as well facilities might chose to not place some non- as its rationale. Efforts should be made to CP-CRE that remain susceptible to other promote staff ownership of hand hygiene antimicrobials on Contact Precautions. All using techniques like developing local (e.g., patients with CP-CRE should be placed on unit) hand hygiene champions. Further, Contact Precautions. having policies that require hand hygiene is not enough; hand hygiene adherence Proper Use of Contact should be monitored and adherence rates Precautions Includes: communicated directly to front line staff. Immediate feedback should be provided • Performing hand hygiene before to staff who miss opportunities for hand donning a gown and gloves hygiene. In addition, facilities should ensure access to adequate hand hygiene stations • Donning gown and gloves before (i.e., clean sinks and/or alcohol-based hand entering the affected patient’s room rubs) and ensure they are well stocked with • Removing the gown and gloves and supplies (e.g., towels, soap) and clear of performing hand hygiene prior to clutter. Further information on hand hygiene exiting the affected patient’s room is available at www.cdc.gov/handhygiene/. This intervention is a fundamental part of infection prevention practice and should be applied for all CRE. b. Lower-acuity Post-acute Care Settings

2. Contact Precautions In lower-acuity post-acute care settings (e.g., non-ventilator units of skilled nursing The following two sub-sections describe the facilities, rehabilitation facilities), the use use of Contact Precautions by healthcare of Contact Precautions is more challenging setting type based on the type of care and should be guided by the potential risk

8 that residents will serve as a source for Gowns and gloves might not be needed additional transmission based on their if there is minimal potential for cross- functional and clinical status and the type contamination from residents or their of care activity that is being performed. environment (e.g., setting a tray down For example, Contact Precautions should in the room, entering the room without be considered for residents colonized or contacting the resident or their immediate infected with CRE, particularly CP-CRE, environment). In addition, residents with who are ventilator-dependent (even if CRE at lower risk for transmission (as not in a ventilator unit), are incontinent described above) do not need to be restricted of stool that is difficult to contain, have from common gatherings in the facility draining secretions or draining wounds that (e.g., meals, group activities). Further work cannot be controlled. When using Contact is needed to define the risk of contamination Precautions, healthcare personnel (HCP) of HCP hands and clothing with the range should adhere to the procedures outlined in of activities performed in these settings. the section above. For other residents with CRE (CP-CRE or non-CP-CRE) who are able to perform hand hygiene, contain their stool and secretions, and are less dependent on HCP for their activities of daily living, use of gowns and gloves should be based on the type of care provided. This consists of using gowns and/or gloves when there is potential for exposure to their fluids or secretions or there is a risk of the healthcare provider contaminating their clothes, etc. Examples of when gowns and/or gloves might be used include the following:

• Bathing residents

• Assisting residents with toileting

• Changing residents’ briefs

• Changing a wound dressing

• Manipulating patient devices (e.g., urinary catheter)

9 c. All Healthcare Facilities that Use for infected or colonized patients; however, Contact Precautions CRE colonization can be prolonged (> 6 months). If surveillance cultures are used Systems should be in place to identify to decide if a patient remains colonized, patients with a history of CRE colonization more than one culture should be collected or infection at admission so that they to improve sensitivity. Regardless of can be placed on Contact Precautions. In whether surveillance cultures are performed, addition, clinical laboratories should have the presence of risk factors for ongoing an established protocol for notifying clinical carriage or ongoing CRE exposure should and/or infection prevention personnel be considered in the decision about when CRE are identified from clinical or discontinuing Contact Precautions. One surveillance cultures. recent study found that among rectal CRE carriers, predictors of rectal CRE carriage Evidence suggests that HCP may use PPE at a future healthcare encounter included incorrectly resulting in contamination exposure to antimicrobials, admission of their skin and/or clothes. HCP can from another healthcare facility, and less also contaminate themselves during than 3 months’ elapsed time since their doffing if done incorrectly. Facilities first positive CRE test. The probability of should ensure that Contact Precautions being CRE positive at the next encounter are used correctly by HCP caring for all increased to 50% if one predictor was patients with epidemiologically important present. MDROs including CRE. This should include ensuring HCP are educated Empiric Contact Precautions, in about the proper use and rationale for conjunction with surveillance cultures, Contact Precautions and that they have the can be considered for patients transferred opportunity to practice donning and doffing from high-risk settings pending results PPE and to demonstrate competency in of screening cultures. Examples include PPE use before patient contact. In addition, transferred patients from hospitals in facilities should ensure that there is a process countries or areas of the United States to monitor and improve HCP adherence where CP-CRE are common or patients to Contact Precautions. This might include transferred from facilities known to have conducting periodic surveillance on the outbreaks or clusters of CP-CRE colonized use of Contact Precautions and providing or infected patients. feedback to frontline staff about these results. 3. Healthcare Personnel Education

Currently, there is not enough evidence to HCP in all settings who care for patients make a firm recommendation about when with MDROs, including CRE, should be to discontinue use of Contact Precautions educated about preventing transmission of

10 these organisms. At a minimum this should CRE are identified from clinical and education and training on the proper use surveillance specimens to ensure timely of Contact Precaution. This intervention is implementation of control measures. a fundamental part of infection prevention This is true for both facilities with on-site practice and should be applied for all CRE. laboratories and those sending cultures off- site and is applicable primarily to all CP­ 4. Use of Devices CRE and any non-CP-CRE that are deemed epidemiologically important by the facility. Use of devices (e.g., central venous catheters, endotracheal tubes, and urinary catheters) 6. Inter-facility Communication/ puts patients at risk for device-associated Identification of CRE Patients infections and minimizing device use is an at Admission important part of the effort to decrease the incidence of these infections. Additionally, The presence of CRE infection or device use has been associated with the colonization alone should not preclude presence of CRE. Therefore, minimizing transfer of a patient from one facility to device use in all healthcare settings another (e.g., acute care to long-term care). should be part of the effort to decrease However, facilities that are transferring the prevalence of all MDROs, including patients colonized or infected with CRE CRE. In acute and long-term care settings, must notify the receiving facility of the device use should be reviewed regularly to patient’s CRE status so that appropriate ensure they are still required and devices infection prevention measures can be should be discontinued promptly when promptly implemented upon the patient’s no longer needed. For more information arrival. Additional information that might on preventing device-associated infection be communicated during patient transfers including appropriate use of devices please include the type and plan for any invasive see http://www.cdc.gov/hicpac/BSI/BSI­ devices that the patient has and the duration guidelines-2011.html and http://www.cdc. of any ongoing antimicrobial therapy. An gov/hicpac/cauti/002_cauti_toc.html. example of an inter-facility transfer form developed by the Utah Department of This intervention is a fundamental part of Health is available at: http://health.utah. infection prevention practice and should be gov/epi/diseases/HAI/resources/IC_transfer_ applied for all CRE. form.pdf

5. Laboratory Notification In addition, facilities should have a mechanism to identify patients previously Laboratories should have protocols in place identified as colonized or infected with CRE that facilitate the timely notification (i.e., at re-admission so that appropriate infection within 4 to 6 hours) of appropriate clinical control precautions can be instituted. and infection prevention staff whenever

11 This intervention is a fundamental part of actions to improve antibiotic use are in infection prevention practice and should be place can be found at http://www.cdc.gov/ applied for all CRE. getsmart/healthcare/pdfs/checklist.pdf. Both these documents and additional information 7. Antimicrobial Stewardship on antimicrobial stewardship in healthcare settings are available at http://www.cdc.gov/ Antimicrobial stewardship is another getsmart/healthcare. primary part of MDRO control and is applicable to both acute and long-term A similar set of resources for antibiotic care settings. Although the role of this stewardship implementation in nursing activity specifically for CRE has not been homes can be found at http://www.cdc. well-studied, multiple antimicrobial classes gov/longtermcare/prevention/antibiotic have been shown to be a risk for CRE -stewardship.html. colonization and/or infection. 8. Environmental Cleaning As part of an antimicrobial stewardship program, facilities should work to ensure While, the role of the environment in that antimicrobials are used for appropriate CRE transmission is not completely clear, indications and duration and that the evidence from CRE outbreaks suggests that narrowest spectrum antimicrobial that is the environment can serve as a source for appropriate for the specific clinical scenario transmission. In order to decrease the risk is used. To assist facilities in this effort, of transmission, facilities should perform CDC has identified core elements that are daily cleaning that include areas in close included in successful hospital antimicrobial proximity to the patient (e.g., bed rails, stewardship programs, including patient tray) to decrease the burden of commitment from facility leadership to organisms. In addition, CRE have been support antimicrobial stewardship activities, found in sink drains in patient rooms, designation of appropriate personnel to lead raising the possibility that equipment and the program and provide drug expertise, patient supplies could become contaminated implementation of polices and interventions if stored within the zone where splash or to support optimal antimicrobial use, aerosolization from sinks could occur. tracking and reporting of antimicrobial Surfaces around sinks should be cleaned and use and resistance rates, and education on disinfected regularly and medical equipment optimal antimicrobial prescribing practices. should not be stored in close proximity to Detailed description of these core elements sinks. is available at http://www.cdc.gov/getsmart/ healthcare/pdfs/core-elements.pdf. An Once CRE patients are discharged, terminal accompanying checklist that hospitals cleaning of CRE patient rooms should be can use to assess whether key policies and performed. Consideration should be given

12 to monitoring the cleaning process to ensure CRE colonized or infected patient. This all surfaces are adequately cleaned and recommendation might be most applicable disinfected. to CP-CRE, higher prevalence areas, and during CRE outbreaks. This intervention is a fundamental part of infection prevention practice and should be 10. Screening Contacts of CRE Patients applied for all CRE. Screening is used to identify unrecognized 9. Patient and Staff Cohorting CRE colonization as clinical cultures alone will identify only a fraction of all patients When available, patients colonized or with CRE. Generally, this testing has infected with any CP-CRE or any non- involved stool, rectal, or peri-rectal cultures CP-CRE judged to be epidemiologically and sometimes cultures of skin sites, wounds important should be housed in single or urine (if a urinary catheter is present). patient rooms. In addition, consideration A laboratory protocol for evaluating should be given to cohorting patients with rectal or peri-rectal swabs for CP-CRE CRE in specific areas (e.g., units or wards), is available at (http://www.cdc.gov/HAI/ even if in single patient rooms, and to using pdfs/labSettings/Klebsiella_or_Ecoli.pdf). dedicated staff (i.e., without responsibility Additional non-culture-based tests are also for care of non-CRE patients) to care for becoming available for use in the United them. At a minimum, dedicated staff should States that can detect the most common include the providers that provide the bulk carbapenemases. CRE screening includes of the patient’s care (e.g., nurses, nursing screening epidemiologically-linked contacts assistants) but could be expanded to include of newly identified CRE patients and other staff (e.g., respiratory therapists) active surveillance cultures. The former is particularly if there are a larger number of described in this section while the latter is CRE patients or during an outbreak. The discussed in the following section. specific staff that are dedicated may vary depending on the healthcare setting. If there If previously unrecognized carriers of are an insufficient number of single rooms, epidemiologically important CRE, including preference should be given to patients at CP-CRE, are identified, screening of patient highest risk for transmission such as patients contacts should be considered to identify with incontinence, medical devices, or transmission. This intervention would be wounds with uncontrolled drainage. most important for CP-CRE. Those patients considered contacts may vary from setting This recommendation is not meant to imply to setting; however, they usually include that one-to-one nursing is required for all roommates of the previously unrecognized CRE patients and therefore is generally CRE patient. Some facilities may also not applicable to facilities with a single choose to screen patients who might have

13 shared HCP or who were present on the consider expanding screening (e.g., point ward at the same time. prevalence survey) to determine the extent of transmission and consider conducting Point prevalence surveys might be an additional ongoing surveys to document effective way for facilities to rapidly evaluate that transmission has ceased. the prevalence of CRE in particular wards/ units and is usually conducted by screening 11. Active Surveillance Testing all patients present on the unit. This approach could be useful in situations where This process involves performing CRE a review of clinical cultures using laboratory screening of patients who might not be records identifies previously unrecognized epidemiologically linked to known CRE CRE patients have been housed on certain patients but who meet certain pre-specified wards/units or to rapidly evaluate for criteria. This could include everyone additional transmission during an outbreak. admitted to the facility, pre-specified high- Point prevalence surveys might be done risk patients (e.g., those admitted from only once if few or no additional CRE long-term acute-care facilities, patients who colonized patients are identified or might received medical care in endemic regions), be done serially if ongoing transmission is and/or patients admitted to high-risk documented. settings (e.g., intensive care units [ICUs]). This intervention might be more useful in Experience to date suggests that point areas with higher CP-CRE prevalence and prevalence surveys have generally been during CRE outbreaks. It could also be used less likely to identify additional CRE for non-CP-CRE judged epidemiologically patients when performed in response to important by the facility. Active surveillance identification of a single CRE patient testing has been used in control efforts for without documented transmission. In these several MDROs including CRE; however, in situations, due to the time it takes for the these studies, the exact contribution of this culture results on the initial CRE patient practice to subsequent decreases in CRE is to be finalized and for the survey to be not known. arranged, most or all of the patients who were present on the ward at the same time As described above, active surveillance as the index CRE patient have often been testing is based on the finding that clinical discharged. In these situations, screening cultures will identify only a minority contacts at highest risk for transmission of those patients colonized with CRE; (e.g., roommates), even if those patients unrecognized colonized patients might have been discharged or moved to not be on Contact Precautions and are a another ward, is often of higher yield. If potential source for CRE transmission. CRE transmission is identified through Surveillance testing strategies can vary initial contact screening, facilities should depending on facility and regional CRE

14 epidemiology. One approach is to focus on that further spread of the organism can be patients admitted with CRE risk factors prevented. including overnight stays in healthcare facilities in the last six to twelve months. 12. Chlorhexidine Bathing Alternatively, testing could target patients admitted to high risk settings (e.g., intensive Chlorhexidine (CHG) bathing has been care units). This testing is generally done at used successfully to prevent certain types admission but can also be done periodically of healthcare-associated infections (e.g., during admission (e.g., weekly). Point bloodstream infections) and to decrease prevalence surveys could also be used to colonization with certain MDROs, perform periodic surveillance. Patients primarily in ICUs. For CRE, it has been identified as positive by this surveillance used as part of a multifaceted intervention testing should be treated as colonized (e.g., to reduce the prevalence of CRE during placed on Contact Precautions, etc.). In an outbreak in a long-term acute care some situations (e.g., patients admitted facility. Chlorhexidine bathing with 2% from high-risk settings) patients might be liquid chlorhexidine or 2% chlorhexidine­ placed in empiric Contact Precautions until impregnated wipes has been used to bathe surveillance testing is found to be negative. patients (usually daily) while in high-risk settings (e.g., ICUs). The chlorhexidine is Regardless of whether a larger active usually not used above the jaw line or on surveillance program is undertaken, facilities open wounds. When chlorhexidine bathing should consider performing surveillance is used for a particular patient population or cultures to rule out CP-CRE in patients in a particular setting, it is usually applied to admitted following an overnight stay within all patients regardless of CRE colonization the last 6 to 12 months in a healthcare status. Some studies suggest that CHG facility outside the United States or in an bathing might not always be done area within the Unites States known to have correctly resulting in suboptimal levels of a higher prevalence of CP-CRE. If a CRE chlorhexidine on the skin. If used, facilities is identified from surveillance or clinical should ensure that it is done correctly to cultures from a patient with a history of ensure maximal effect. an overnight hospital stay outside the United States, the isolate should be sent In long-term care settings this type of an for mechanism testing to evaluate for the intervention might be used on targeted presence of carbapenemases that are not high-risk residents (e.g., residents that are regularly found in the United States. At a totally dependent upon healthcare personnel minimum this should include evaluation for activities of daily living, are ventilator- that would detect KPC, NDM, and OXA­ dependent, are incontinent of stool, or 48-type carbapenemases. This approach have wounds whose drainage is difficult to can help identify patients that harbor CRE control) or high-risk settings (e.g., ventilator with novel mechanisms of resistance so unit).

15 This intervention is likely most important as part of a plan to control CP-CRE in areas of higher prevalence including during outbreaks. It could be used for non-CP­ CRE judged epidemiologically important by the facility.

Summary

A summary of CRE prevention measures is included below.

An approach to the evaluation of newly recognized CRE colonized or infected patients is shown in Figure 1.

16 Summary of Prevention Strategies 5. Timely Notification from Laboratory For Acute and Long-Term Care When CRE are Identified Facilities 6. Communication of CRE Status for Please see text for details. Infected and Colonized Patients at Discharge and Transfer 1. Hand Hygiene • Identify known CRE patients • Promote hand hygiene at re-admission • Monitor hand hygiene adherence and provide feedback 7. Promotion of Antimicrobial Stewardship • Ensure access to hand hygiene 8. Environmental Cleaning stations 9. Patient and Staff Cohorting

2. Contact Precautions (CP) • When available cohort CRE colonized or infected patients and • Educate and train healthcare the staff that care for them even if personnel about CP including patients are housed in single rooms allowing time to practice donning and doffing • If the number of single patient • Monitor CP adherence and provide rooms is limited, reserve these rooms feedback for patients with highest risk for • No recommendations for transmission (e.g., incontinence) discontinuation of CP 10. Screening Contacts of CRE Patients Acute Care • Screen patient with epidemiologic • Place CRE colonized or infected links to unrecognized CRE patients on Contact Precautions colonized or infected patients (CP) º Empiric CP might be used for 11. Active Surveillance Testing patients transferred from high- • Screen high-risk patients at risk settings admission or at admission and Long-term Care periodically during their facility stay for CRE. Empiric CP can be • Place CRE colonized or infected considered while results of admission residents that are high-risk for surveillance testing are pending transmission on CP (as described in text); for patients at lower risk for 12. Chlorhexidine Bathing transmission use precautions based on type of care provided • Bathe patients with 2% chlorhexidine

3. Healthcare Personnel Education 4. Minimize Use of Invasive Devices

17 Figure 1: Facility Approach to Evaluation of Newly Recognized CP-CRE Colonized or Infected Patients

New CRE-colonized or CRE-infected patient identified t

• Notify appropriate personnel (i.e., clinical staff, infection prevention staff) • Notify public health (if required) t

• Place patient on Contact Precautions in single room (if available)-see discussion about use in long-term care • Reinforce hand hygiene and use of Contact Precautions on affected ward/unit • Educate healthcare personnel caring for patient about preventing CRE transmission t

• Consider screening epidemiologically-linked patient contacts (e.g., roommates) for CRE with at least stool, rectal, or peri-rectal cultures; consider review of microbiology records to identify previous cases • Consider point prevalence survey of affected unit particularly if more than one CRE patient identified t

• If screening cultures or further clinical cultures identify additional CRE- colonized or -infected patients, consider additional surveillance cultures of contacts or ongoing point prevalence surveys of affected units until no further transmission identified • Consider admission CRE surveillance cultures (i.e., active surveillance) of high- risk patients particularly in higher prevalence areas • Consider cohorting patients and staff

t

• Ensure if patient transferred within the facility that precautions are continued. Ensure, if discharged and readmitted, there is a mechanism to identify patient at readmission • Ensure if patient transferred to another facility, CRE status is communicated to accepting facility

18 Selected References

Ben-David D, Maor Y, Keller N, et al. Mody L, Krein SL, Saint S, et al. A targeted Potential role of active surveillance in the infection prevention intervention in nursing control of a hospital-wide outbreak of home residents with indwelling devices: a carbapenem-resistant Klebsiella pneumoniae randomized clinical trial. JAMA Intern Med infection. Infect Control Hosp Epidemiol 2015; 175:714-23. 2010; 31:620-6. Munoz-Price LS, Hayden MK, Lolans K, Chea N, Bulens SN, Kongphet-Tran T, et et al. Successful control of an outbreak al. Improved phenotype-based definition for of Klebsiella pneumoniae carbapenemase­ identifying carbapenemase producers among producing K. pneumoniae at a long-term CRE. Emerg Infect Dis 2015; 21:1611-6. acute care hospital. Infect Control Hosp Epidemiol 2010; 31:341-7. Guh AY, Bulens SN, Mu Y, et al. Epidemiology of carbapenem-resistant Schechner V, Kotlovsky T, Tarabeia J, et al. Enterobacteriaceae in 7 US communities, Predictors of rectal carriage of carbapenem­ 2012-2013. JAMA 2015; 314:1479-87. resistant Enterobacteriaceae (CRE) among patients with known CRE carriage at their Hayden MK, Lin MY, Lolans K, et al. next hospital encounter. Infect Control Prevention of colonization and infection by Hosp Epidemiol 2011; 32:497-503. KPC-producing Enterobacteriaceae in long­ term acute-care hospitals. Clin Infect Dis Schwaber MJ, Klarfeld-Lidji S, Navon- 2015; 60:1153-61. Venezia S, Schwartz D, Leavitt A, Carmeli Y. Predictors of carbapenem-resistant Kochar S, Sheard T, Sharma R, et al. Success Klebsiella pneumoniae acquisition among of an infection control program to reduce hospitalized adults and effect of acquisition the spread of carbapenem-resistant Klebsiella on mortality. Antimicrob Agents Chemother pneumoniae. Infect Control Hosp Epidemiol 2008; 52:1028-33. 2009; 30:447-52. Schwaber MJ, Lev B, Israeli A, et al. Lin MY, Lolans K, Blom DW, et al. The Containment of a country-wide outbreak of effectiveness of routine daily CHG bathing carbapenem-resistant Klebsiella pneumoniae in reducing KPC-producing CRE skin in Israeli hospitals via a nationally burden among long-term acute-care hospital implemented intervention. Clin Infect Dis patients. Infect Control Hosp Epidemiol 2011; 52:848-52. 2014; 35: 440-2.

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