CRE Resource Packet For Healthcare Facilities

CRE are epidemiologicallyimportant for several reasons: CRE have been associated withhigh mortality rates (up to 40to 50% in some studies). In addition to β-lactam/carbapenem resistance, CREoften carry genes that confer highlevels of resistance to many otherantimicrobials, often leaving verylimited therapeutic options.“Pan-resistant” KPC-producingstrains have been reported. CRE have spread throughout manyparts of the United States andhave the potential to spread morewidely.DefinitionsCDC has developed the following interimsurveillance definition for CRE. CRE aredefined as Enterobacteriaceae that are: Nonsusceptible to one of thefollowing carbapenems: doripenem,meropenem, or imipenem AND Resistant to all of the followingthird-generation cephalosporinsthat were tested: ceftriaxone,cefotaxime, and ceftazidime.(Note: All three of theseantimicrobials are recommendedas part of the primary or secondarysusceptibility panels forEnterobacteriaceae) Klebsiella species and Escherichia colithat meet the CRE definition area priority for detection andcontainment in all settings; however,other Enterobacteriaceae (e.g.,Enterobacter species) might alsobe important in some regions. For bacteria that have intrinsicimipenem nonsusceptibility(i.e., Morganella morganii, Proteusspp., Providencia spp.), requiringnonsusceptibility to carbapenems otherthan imipenem as part of the definitionmight increase specificity. This CRE surveillance definitionis based upon the current (M100-S222012) Clinical and LaboratoryStandards Institute (CLSI)interpretative criteria (breakpoints)for carbapenem susceptibility amongEnterobacteriaceae (Appendix A);if the older CLSI breakpoints(pre-dating M100-S20 U) are beingused to determine carbapenemsusceptibility, consideration shouldbe given to including ertapenem in theCRE definition to increase sensitivity.3

Changes in the breakpoints are shownin Appendix A. Although the use of thecurrent CLSI breakpoints offers laboratoriesa simpler and more straightforwardapproach to identifying CRE, adoptionmay be delayed by the fact that the U.S.Food and Drug Administration has not yetapproved all of these breakpoints and someautomated susceptibility panels currentlydo not include dilutions low enough to allowfor application of the lower breakpoints.Since most carbapenem resistance mediatedby carbapenemases in the United Statesis found among Klebsiella spp. and E.coli, individual facilities or public healthauthorities might choose to apply the CREsurveillance definition only to these specificEnterobacteriaceae.Definitions for CRE are complicatedby a number of factors includingthe diversity of the genera. Anotherimportant challenge to developinga standardized definition of CRE is a recent(mid-2010) change in the Clinical andLaboratory Standards Institute (CLSI)interpretative criteria (breakpoints) fordetermining susceptibility to carbapenemsamong Enterobacteriaceae. These newrecommendations lowered the breakpointsand removed the requirement for testingfor carbapenemase (e.g., modified HodgeTest) to determine susceptibility.These breakpoints were further modifiedin January 2012 (M100-S22).Klebsiella pneumonia4

Part 1: Facility-level CRE PreventionSurveillanceInpatient facilities should have an awarenessof whether or not CRE (at least E. coli andKlebsiella spp.) have ever been culturedfrom patients admitted to their facility and,if so, whether these positive cultures werecollected within 48 hours of admission.If CRE have been present, facilities shouldalso determine:Facility-level PreventionStrategiesThe following briefly summarizes anapproach to preventing CRE transmissionin healthcare settings. For a more in-depthreview, please refer to the CDC HICPACguidelines “Management of MultidrugResistant Organisms in Healthcare Settings,2006” (http://www.cdc.gov/hicpac/mdro/mdro toc.html). If there is evidence of intra-facilitytransmissionCore Measures for All Acuteand Long-term Care Facilities Which wards/units are most affectedThere are 8 core measuresfacilities should follow.Facilities that do not have this informationshould consider performing an evaluationto quantify the clinical incidence of theseorganisms, such as a review of archived labresults to determine the number and/orproportion of Enterobacteriaceae that meetthe CRE definition over a pre-specifiedtime period (e.g., 6 to 12 months).In addition, facilities should considercollecting information on the basicepidemiology of patients colonized orinfected with these organisms in orderto understand common characteristicsof these individuals. This might includepatient demographics, dates of admission,outcomes, medications, and commonexposures (e.g., wards, surgery, procedures,etc).1. Hand HygieneHand hygiene is a primary part ofpreventing multidrug-resistant organism(MDRO) transmission. Facilities shouldensure that healthcare personnel are familiarwith proper hand hygiene technique as wellas its rationale. Efforts should be made topromote staff ownership of hand hygieneusing techniques like developing local (e.g.,unit) hand hygiene champions. It is notenough to have policies that require handhygiene; hand hygiene adherence shouldbe monitored and adherence rates shouldbe fed directly back to front line staff.Immediate feedback should be providedto staff who miss opportunities for handhygiene. In addition, facilities shouldensure access to adequate hand hygienestations (i.e., clean sinks and/or alcohol-5

based hand rubs) and ensure they are wellstocked with supplies (e.g. towels, soap, etc.)and clear of clutter. Further informationon hand hygiene is available at www.cdc.gov/handhygiene/. This intervention isapplicable to both acute and long-term caresettings.2. Contact PrecautionsPatients in acute care settings who arecolonized or infected with CRE shouldbe placed on Contact Precautions. Systemsshould be in place to identify patients witha history of CRE colonization or infectionat admission so that they can be placedon Contact Precautions if not known to befree of colonization. In addition, clinicallaboratories should have an establishedprotocol for notifying clinical and/orinfection prevention personnel when CREare identified from clinical or surveillancecultures.There is not enough information for a firmrecommendation about when to discontinueContact Precautions among infectedpatients; however, CRE colonization insome patients identified during CDCinvestigations has been prolonged ( 6months). If surveillance cultures are used todecide if a patient remains colonized, morethan one culture should be collected in anattempt to improve sensitivity. One recentstudy found that among rectal CRE carriers,predictors of rectal CRE carriage at a futurehealthcare encounter included exposure toantimicrobials (especially fluoroquinolones),admission from another healthcare facility,and less than 3 months’ elapsed time sincetheir first positive CRE test.6The probability of being CRE positiveat the next encounter increased to 50%if one predictor was present. Presenceof ongoing risk factors for carriage suchas these should be considered beforediscontinuing use of Contact Precautionsin these patients. The presence of CREinfection or colonization alone shouldnot preclude transfer of a patient fromone facility to another (e.g., acute careto long-term care). Facilities shouldensure that Contact Precautions are usedcorrectly by staff caring for all patientswith epidemiologically important MDROsincluding CRE.Proper use of ContactPrecautions includes: Performing hand hygiene beforedonning a gown and gloves Donning gown and gloves beforeentering the affected patient’s room Removing the gown and gloves andperforming hand hygiene prior toexiting the affected patient’s roomEnsuring healthcare personnel (HCP) areeducated about the proper use and rationalefor Contact Precautions is an important partof this process. In addition, facilities shouldensure that there is a process to monitorand improve HCP adherence to ContactPrecautions. This might include conductingperiodic surveillance on the use of ContactPrecautions and providing feedback tofrontline staff about these results.

Preemptive Contact Precautions, oftenin conjunction with surveillance cultures,might be used on patients transferredfrom high-risk settings (see supplementalinterventions) pending results of screeningcultures. Examples include transferredpatients from hospitals in countries orareas in the United States where CREare common or patients transferred fromfacilities known to have outbreaks or clustersof CRE colonized or infected patients.In long-term care settings, ContactPrecautions are still indicated for residentsinfected or colonized with CRE; however,these might be modified to fit the inherentdifferences between acute and long-termcare facilities. Contact Precautions shouldbe used for residents with CRE who areat higher risk for transmission, includingpatients who are totally dependent uponHCP for their activities of daily living, areventilator-dependent, are incontinent ofstool, or have wounds with drainage thatis difficult to control. For other residentswho are able to perform hand hygiene,are continent of stool, are less dependenton staff for their activities of daily living,and are without draining wounds, therequirement for Contact Precautions mightbe relaxed. However, in these situationsStandard Precautions should still beobserved, including the use of gloves and/orgowns when contact with colonized/infectedsites or body fluids is possible.3. Healthcare Personnel EducationHCP in all settings who care for patientswith MDROs, including CRE, shouldbe educated about preventing transmissionof these organisms. At a minimum thisshould include information on the properuse of Contact Precautions and handhygiene. This intervention is applicableto both acute and long-term care settings.4. Use of DevicesUse of devices (e.g., central venouscatheters, endotracheal tubes, urinarycatheters) puts patients at risk for deviceassociated infections and minimizing deviceuse is an important part of the effort todecrease the incidence of these infections.Additionally, device use has been associatedwith carbapenem resistance amongEnterobacteriaceae. Therefore, minimizingdevice use in all healthcare settings shouldbe part of the effort to decrease theprevalence of all MDROs including CRE.In acute and long-term care settings, deviceuse should be reviewed regularlyto ensure they are still required and devicesshould be discontinued promptly whenno longer needed. For more informationon preventing device-associated infectionincluding appropriate use of devicesplease see www.cdc.gov/hicpac/BSI/BSIguidelines-2011.html and www.cdc.gov/hicpac/cauti/002 cauti toc.html.7

5. Patient and Staff CohortingWhen available, patients colonized orinfected with CRE should be housed insingle patient rooms and if not availablethese patients should be cohorted together.In addition, consideration should be given tocohorting patients with CRE in specific areas(e.g., units or wards), even if in single patientrooms, and to using dedicated staff to carefor them. This recommendation appliesto both acute and long-term care settings.Preference for single rooms should be givento patients at highest risk for transmissionsuch as patients with incontinence, medicaldevices, or wounds with uncontrolleddrainage.6. Laboratory NotificationLaboratories should have protocols inplace that facilitate the rapid notificationof appropriate clinical and infectionprevention staff whenever CRE are identifiedfrom clinical specimens to ensure timelyimplementation of control measures.This is true for both facilities with on-sitelaboratories and those sending culturesoff-site and is applicable to acute and longterm care settings.7. Antimicrobial StewardshipAntimicrobial stewardship is anotherprimary part of MDRO control. Althoughthe role of this activity specifically forCRE has not been well studied, multipleantimicrobial classes have been shown to bea risk for CRE colonization and/or infection.Further, restricting use of carbapenems hasbeen associated with a lower incidence ofcarbapenem-resistant Pseudomonas aeruginosain one ecological analysis. As part of an8antimicrobial stewardship program designedto minimize transmission of MDROs,facilities should work to ensure that 1)antimicrobials are used for appropriateindications and duration and 2) that thenarrowest spectrum antimicrobial thatis appropriate for the specific clinicalscenario is used. For more informationon antimicrobial stewardship in healthcaresettings please see http://www.cdc.gov/getsmart/healthcare. This intervention isapplicable to both acute and long-term caresettings.8. CRE ScreeningScreening is used to identify unrecognizedCRE colonization among epidemiologicallylinked contacts of known CRE colonizedor infected patients as clinical cultures willusually identify only a fraction of all patientswith CRE. Generally, this screening hasinvolved stool, rectal, or peri-rectal culturesand sometimes cultures of wounds or urine(if a urinary catheter is present). A laboratoryprotocol for evaluating rectal or peri-rectalswabs for CRE is available at http://www.cdc.gov/hai/pdfs/labsettings/Klebsiella or Ecoli.pdf; however, it is important to notethat this procedure has only been validatedfor E. coli and Klebsiella spp. CRE screeningof epidemiologically linked patients is aprimary prevention strategy for all healthcarefacilities; however, it is particularly importantfor healthcare facilities with CRE outbreaksor facilities that do not or only rarely admitpatients with CRE infection or colonization.This intervention is applicable to both acuteand long-term care settings.

CRE screening might include: Point prevalence surveys:Point prevalence surveys mightbe an effective way for facilitiesto rapidly evaluate the prevalenceof CRE in particular wards/units.This could be useful in a situationwhere a review of clinical culturesusing laboratory records identifiesunreported CRE patients in certainwards/units. A point prevalencesurvey is generally conducted byscreening all patients in that ward/unit. Point prevalence surveysmight be done only once if fewor no additional CRE colonizedpatients are identified or mightbe done serially if colonizationis more widespread or to follow theeffect of an intervention.S creening of epidemiolo gicallylinked patients:If previously unrecognized CREcarriers are identified, screeningof patient contacts could beconducted to identify transmissioninstead of a wider point prevalencesurvey. Those patients consideredcontacts may vary from settingto setting; however, they usuallyinclude roommates of the unrecog nized CRE patients as well aspatients who might have sharedHCP.Supplemental Measures forHealthcare Facilities with CRETransmissionThese additional measures should beconsidered when baseline core preventionpractices are not effective in reducingCRE incidence.Active Surveillance TestingThis process involves culturing patientswho might not be epidemiologically linkedto known CRE patients but who meetcertain pre-specified criteria. This couldinclude everyone admitted to the facility,pre-specified high-risk patients (e.g., thoseadmitted from long-term care facilities),and/or patients admitted to high-risksettings (e.g., intensive care units [ICUs]).Active surveillance testing has been usedin control efforts for several MDROsincluding CRE; however, the exactcontribution of this practice to decreasesin CRE is not known.As described above, active surveillancetesting is based on the finding that clinicalcultures will identify only a minorityof those patients colonized with CRE;unrecognized colonized patients mightnot be on Contact Precautions and area potential source for CRE transmission.If done, surveillance testing could be focusedon patients admitted to certain high-risksettings (e.g., ICUs, long-term acute care)or could target specific patients (i.e., patientswith risk factors, patients admitted fromhigh-risk settings like long-term acute careor transferred from areas with high CRE9

prevalence). This testing is generally doneat admission but can also be doneperiodically during admission(e.g., weekly). Patients identified as positiveby this surveillance testing should betreated as colonized (i.e., placed on ContactPrecautions, etc.). In some situations(e.g., patients admitted from high-risksettings) patients might be placed inpreemptive Contact Precautions untilsurveillance testing is found to be negative.As with screening of epidemiologicallylinked CRE contacts, the use of activesurveillance testing to control CREis applicable to both acute and long-termcare settings.Chlorhexidine BathingChlorhexidine bathing has been usedsuccessfully to prevent certain typesof healthcare-associated infections (e.g.,bloodstream infections) and to decreasecolonization with specific MDROs,primarily in ICUs. For CRE, it has beenused as part of a multifaceted interventionto reduce the prevalence of CRE duringan outbreak in a long-term acute carefacility. During chlorhexidine bathing,diluted liquid chlorhexidine (2%) or 2%chlorhexidine-impregnated wipes are usedto bathe patients (usually daily) whilein high-risk settings (e.g., ICUs). Thechlorhexidine is usually not used abovethe jaw line or on open wounds. Whenchlorhexidine bathing is used for a particularpatient population or in a particular setting,it is usually applied to all patients regardlessof CRE colonization status.In long-term care settings this type of anintervention might be used on targeted10high-risk residents (e.g., residents that aretotally dependent upon healthcare personnelfor activities of daily living, are ventilatordependent, are incontinent of stool, orhave wounds whose drainage is difficult tocontrol) or high-risk settings (e.g., ventilatorunit). In addition, chlorhexidine bathingmight be less frequent in long-term caredepending on the facility’s usual bathingprotocol.Recommendations for Facilitieswith No or Rare CREExperience with other MDROs suggeststhat it might be most effective to interveneon emerging MDROs when they first arerecognized in a facility before they becomecommon. For this reason facilities that rarely(e.g., 1 per month) or never have patientsadmitted who are colonized or infected withCRE should be aggressive about controllingthese organisms when they are identified.An example of one approach to CRE controlin these settings is shown in Appendix B.In addition, if a facility without previousCRE performs a review of archived clinicallaboratory results for CRE and identifiespreviously unrecognized CRE-colonizedor -infected patients, the facility shouldconsider point prevalence surveys ofh

carbapenem-resistant Enterobacteriaceae (CRE). 2. Improve CRE surveillance: The registry stores CRE surveillance data and has features that can help facilities track their CRE submission history. Reporting Requirements IDPH amended the Control of Communicable Diseases Code (77 Ill. Adm. Code 6