Guidance For Control Of Carbapenem-Resistent .
Facility Guidance for Controlof Carbapenem-resistantEnterobacteriaceae (CRE)November 2015 Update - CRE ToolkitNational Center for Emerging and Zoonotic Infectious DiseasesDivision of Healthcare Quality Promotion
Facility Guidance for Control of CarbapenemResistant Enterobacteriaceae (CRE)November 2015 UpdateThis document updates CDC’s Guidance for Control of Carbapenem-resistantEnterobacteriaceae (CRE): 2012 CRE Toolkit. Unless otherwise specified, the termhealthcare facility refers to all acute care hospitals and any long-term care facility thathas patients who remain overnight and regularly require medical or nursing care (e.g.,maintenance of indwelling devices, intravenous injections, wound care, etc.). Thisincludes all long-term acute care hospitals and nursing homes providing skilled nursing orrehabilitation services, but generally excludes assisted living facilities and nursing homes thatdo not provide more than long-term custodial care. In addition, this toolkitis not intended for use in ambulatory care facilities.Control of resistant organisms is a national problem and requires that facilities that sharepatients work together to prevent transmission. These efforts may be best coordinated bylocal public health. Facilities are strongly encouraged to participate in these regional efforts.1
The Following Major Items Have Changed from the 2012CRE Toolkit:1. The CDC CRE surveillance definition has been modified.2. The two intervention tiers have been replaced by a single tier. Not all interventionsmight be applicable in all settings or situations. Information is provided aboutsituations in which specific interventions might be most important.3. Further discussion has been added on the use of Contact Precautions in post-acutesettings.4. Information on regional interventions has been removed in order to target thisdocument specifically to facilities. Coordinated regional approaches to preventinfections with multidrug-resistant organisms remain important; additionalinformation on these approaches will be made available in other documents.5. Inter-facility communication has been added to the interventions.2
The emergence and disseminationof carbapenem resistance amongEnterobacteriaceae in the United Statesrepresents a serious threat to public health.These organisms cause infections that areassociated with high mortality rates andthey have the potential to spread widely.Decreasing the impact of these organismswill require a coordinated effort involvingall stakeholders including healthcarefacilities and providers, public health, andindustry. This document updates the 2012CRE Toolkit and will continue to evolveas new information becomes available.The current recommended approach tocontrol transmission of these organisms inhealthcare facilities includes the following: Recognizing these organisms asepidemiologically important Quantifying the magnitude of CREwithin the facility and regionally Identifying colonized and infectedpatients when present in healthcarefacilities Implementing interventions designedto stop the transmission of theseorganismsBackgroundCRE are EpidemiologicallyImportant for Several Reasons: Invasive infections (e.g.,bloodstream infections) causedby 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” CRE have been reported. CRE have spread throughoutmost parts of the United Statesand other countries and have thepotential to spread more widely. Currently in the United States,CRE are primarily identifiedamong patients with healthcareexposure, but there is potentialfor CRE to spread outside ofhealthcare settings, given thatEnterobacteriaceae are a commoncause of community-associatedinfections.Carbapenem resistance amongEnterobacteriaceae can be due to severaldifferent mechanisms. Some CRE possessa β-lactamase (e.g., AmpC or extendedspectrum β-lactamase (ESBL)) which,when combined with porin mutations,can render an organism nonsusceptible3
to carbapenems. Some CRE possess acarbapenemase (carbapenemase-producingCRE or CP-CRE) that directly breaksdown carbapenems. Carbapenemases areoften contained on mobile genetic elementsthat facilitate transfer of resistance amongEnterobacteriaceae and other gram-negativeorganisms. CP-CRE were first identified inthe United States from an isolate collectedin 1996 and have disseminated widely sincethat time. All but two states (ID and ME)have reported at least one CP-CRE to theCenters for Disease Control and Preventionas of November 2015. The rapid spreadof CP-CRE have made these organisms aparticularly important target for prevention.Much of the increase in CRE since 2000has been due to the spread of CRE thatproduce the carbapenemase Klebsiellapneumoniae Carbapenemase (KPC). Inaddition to KPC, several other types ofcarbapenemases have been identified in theUnited States since 2009. These include theNew Delhi Metallo-β-lactamase (NDM),Verona Integron-encoded Metallo-β lactamase (VIM), Oxacillinase-48-typecarbapenemases (OXA-48), and theImipenemase (IMP) Metallo-β-lactamase.Organisms producing these non-KPCenzymes are more common in some areas ofthe world; in the United States, they havegenerally been found among patients whoreceived medical care in countries whereorganisms with these carbapenemases areknown to be present. Beginning in 2012,however, NDM has been increasinglyreported among U.S. patients without arecent history of exposure to healthcareoutside of the United States. More recently,4Klebsiella pneumoniaereports of Enterobacteriaceae producingOXA-48-type enzymes have also increasedin the United States.The current U.S. distribution of CRE (bothCP-CRE and non-CP-CRE) appears to beheterogeneous; these organisms are morecommonly isolated from patients in someparts of the United States, but they are notregularly found in other regions. Even inareas where CRE are found they may bemore commonly present among patients insome healthcare settings, such as long-termacute care hospitals, than they are in others.Healthcare facilities should work withpublic health to have an awareness of theirregional CRE epidemiology; understandingthis information can help inform CREprevention efforts.
Interventions to control CRE are evolvingas more data and experience becomeavailable. Since these organisms currentlyare primarily isolated from people withhealthcare exposures and the bulk oftransmission appears to occur in thesesettings, interventions have primarilyincluded identifying people colonized orinfected with CRE while in healthcaresettings and applying interventions designedto minimize the risk of transmission.The specific interventions are describedin detail in the next sections. Althoughthe interventions described in the nextsections are applicable to most healthcaresettings and most organisms meeting theCRE defintion, facilities may choose totarget some of the interventions to certainsituations (e.g., outbreaks) and certain typesof CRE (e.g., CP-CRE).CRE DefinitionsIn general, CRE are Enterobacteriaceaethat are nonsusceptible (i.e., intermediateor resistant) to a carbapenem. However,as described above, carbapenemnonsusceptibility among Enterobacteriaceaecan be acquired through several differentmechanisms, with carbapenemaseproduction currently being the mostconcerning resistance mechanism.Differentiating CP-CRE from CRE that arenonsusceptible to carbapenems due to othermechanisms is complicated by a numberof issues, including the wide variabilityin the capacity of U.S. clinical and publichealth laboratories to perform testing forthe detection of carbapenemases. Onlyone test for carbapenemase production,the Modified Hodge Test (MHT), iscurrently widely used in U.S. laboratories.Although MHT has demonstrated goodsensitivity for KPC, it has lower sensitivityfor other carbapenemases, such asNDM. In addition, MHT is not specificfor carbapenemase production amongsome genera of Enterobacteriaceae (e.g.,Enterobacter). Several other methodsfor detecting carbapenemases have beendeveloped, including polymerase chainreaction and the Carba NP test, but theseare not currently widely used in clinicallaboratories in the United States. Thus,a definition that differentiates CP-CREfrom non CP-CRE based on the organism’spattern of susceptibiltiy to antimicrobials(phenotypic definition) would have utilityfor surveillance and prevention.However, developing a phenotypicdefinition for CRE that differentiatesCP-CRE from non-CP-CRE has beendifficult because the antimicrobialsusceptibility profiles of these two groupsoverlap. The CRE definition included inthe 2012 CRE Toolkit (nonsusceptibleto imipenem, meropenem, or doripenemand resistant to all third-generationcephalosporins tested) was designed to bemore specific for CP-CRE; however, it wasa complicated definition that has provendifficult to implement. Further, based onan assessment of the antibiograms of CREisolates submitted to CDC from six U.S.metropolitan areas, that definition missed5
a portion of KPC-producing CRE. Inaddition, that definition has the potentialto miss some CRE producing OXA-48 type carbapenemases, since these isolatesmight remain susceptible to third generationcephalosporins and a number of OXA-48 type-producing CRE evaluated at CDChave only been resistant to one carbapenem(ertapenem).In an attempt to simplify the CREdefinition as well as further increase theability of the definition to identify CREthat produce carbapenemases, CDC hasrefined the 2012 interim CRE surveillancedefinition:CRE are Enterobacteriaceae that are: Resistant to any carbapenemantimicrobial (i.e., minimuminhibitory concentrations of 4mcg/ml for doripenem, meropenem,or imipenem OR 2 mcg/ml forertapenem)OR Documented to producecarbapenemaseIn addition: 6For bacteria that have intrinsicimipenem nonsusceptibility (i.e.,Morganella morganii, Proteus spp.,Providencia spp.), resistance tocarbapenems other than imipenem isrequired. At present, acceptable tests fordetecting carbapenemases includepolymerase chain reaction, MHT,Carba NP, metallo-β-lactamasetesting (e.g., MBL tests or screens).As described above, the MHTdoes have limitations includingover-calling the presence ofcarbapenemases among Enterobacterspecies and failing to identifysome CRE that produce an NDMenzyme; it is included among theacceptable tests at this time becauseof its wide use. The number ofavailable tests for carbapenemaseis expanding; facilities using a testnot included on the list aboveshould review the test performanceto ensure that it has reasonablesensitivity and specificity.The above phenotypic definition lacksspecificity for CP-CRE (i.e., CRE that donot produce a carbapenemase will oftenmeet this definition), especially in areaswhere CP-CRE are rare. Therefore, to guideprevention efforts, clinical and public healthlaboratories with the capacity to performcarbapenem resistance mechanism testingare encouraged to test for the presence ofcarbapenemases. Ideally, U.S. laboratoriesshould test for the presence of KPC,NDM, and OXA-48-type carbapenemases.However, if CRE are identified from ageographical area where other types ofcarbapenemases are known to be commonor if the patient has relevant risk factors(e.g., travel outside the United States,exposure to non-KPC carbapenemases),then testing for other carbapenemasesshould be considered.
Facility-Level CRE PreventionSurveillanceHealthcare facilities should be aware ofwhether or not CRE have been isolatedfrom patients admitted to their facility. Inaddition, facilities should know whetheror not their laboratories have the capacityto perform carbapenemase testing andCRE screening tests. If these tests are notavailable, facilities should identify outsidelaboratories that can perform this testingwhen needed.Facilities should consider performingongoing evaluations to quantify theincidence of CRE organisms from clinicalspecimens, such as reviewing archivedlaboratory results to determine the numberand/or proportion of Enterobacteriaceaethat are CRE over a pre-specified timeperiod (e.g., 6 to 12 months). In addition,facilities should consider collectinginformation on the basic epidemiology ofpatients colonized or infected with theseorganisms in order to understand commoncharacteristics of these individuals. Thismight include patient demographics, datesof admission, outcomes, medications, andcommon exposures (e.g., wards, surgery,procedures, transfer from other healthcarefacilities, etc.)Facility-Level Prevention StrategiesThe following briefly summarizesinterventions recommended to preventCRE transmission in healthcare settings.The listed interventions might beapplied differently by facilities based onthe underlying epidemiology of CREin the region including the regionalprevalence, the underlying CRE resistancemechanisms found in the area, and thetype of healthcare facility involved. Ingeneral, standard interventions designedto prevent the transmission of multidrug resistant organisms (MDROs) (e.g., handhygiene, Contact Precautions) should beimplemented for most CRE (CP-CREand non-CP-CRE). However, facilitiesmight choose to apply a wider range ofinterventions for CRE they judge to beepidemiologically important, including allCP-CRE. Some non-CP-CRE might alsobe targeted for more extensive interventionsparticularly during an outbreak or if theunderlying prevalence of the organism ishigh or increasing despite the application ofbaseline prevention measures. The situationswhere each intervention might be mostuseful are specified more completely in thenext section. For more in-depth reviewof MDRO prevention, please refer to theCDC HICPAC guidelines “Managementof Multidrug-Resistant Organisms inHealthcare Settings, 2006” (http://www.cdc.gov/hicpac/mdro/mdro toc.html).If carbapenemase testing is not available,facilities should consider the possibilitythat any CRE that meets the phenotypicsurveillance definition is a CP-CRE andapply the interventions, as described below,accordingly. However, facilities that haveinformation on the epidemiology of CREin their region might choose to tailor the7
range of interventions they apply based onthese data. For all MDRO control efforts,facilities should work together and withstate and local health departments in orderto maximize the effect of the interventionsregionally.provided. The third section outlines generalguidance for any facility using ContactPrecautions.1. Hand HygieneAcute care hospitals, long-term acute carehospitals, and ventilator units of skillednursing facilities should generally placepatients who are colonized or infectedwith CRE on Contact Precautions. Somefacilities might chose to not place some nonCP-CRE that remain susceptible to otherantimicrobials on Contact Precautions. Allpatients with CP-CRE should be placed onContact Precautions.Hand hygiene is a primary part of preventingMDRO 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. Further,having policies that require hand hygieneis not enough; hand hygiene adherenceshould be monitored and adherence ratescommunicated directly to front line staff.Immediate feedback should be providedto staff who miss opportunities for handhygiene. In addition, facilities should ensureaccess to adequate hand hygiene stations(i.e., clean sinks and/or alcohol-based handrubs) and ensure they are well stocked withsupplies (e.g., towels, soap) and clear ofclutter. Further information on hand hygieneis available at www.cdc.gov/handhygiene/.This intervention is a fundamental part ofinfection prevention practice and should beapplied for all CRE.2. Contact PrecautionsThe following two sub-sections describe theuse of Contact Precautions by healthcaresetting type based on the type of care8a. Acute Care Hospitals and HighAcuity Post-Acute Care SettingsProper 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 roomb. Lower-acuity Post-acute Care SettingsIn lower-acuity post-acute care settings(e.g., non-ventilator units of skilled nursingfacilities, rehabilitation facilities), the useof Contact Precautions is more challengingand should be guided by the potential risk
that residents will serve as a source foradditional transmission based on theirfunctional and clinical status and the typeof care activity that is being performed.For example, Contact Precautions shouldbe considered for residents colonized orinfected with CRE, particularly CP-CRE,who are ventilator-dependent (even ifnot in a ventilator unit), are incontinentof stool that is difficult to contain, havedraining secretions or draining wounds thatcannot be controlled. When using ContactPrecautions, healthcare personnel (HCP)should adhere to the procedures outlined inthe section above. For other residents withCRE (CP-CRE or non-CP-CRE) who areable to perform hand hygiene, contain theirstool and secretions, and are less dependenton HCP for their activities of daily living,use of gowns and gloves should be basedon the type of care provided. This consistsof using gowns and/or gloves when thereis potential for exposure to their fluids orsecretions or there is a risk of the healthcareprovider contaminating their clothes, etc.Examples of when gowns and/or glovesmight 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)Gowns and gloves might not be neededif there is minimal potential for crosscontamination from residents or theirenvironment (e.g., setting a tray downin the room, entering the room withoutcontacting the resident or their immediateenvironment). In addition, residents withCRE at lower risk for transmission (asdescribed above) do not need to be restrictedfrom common gatherings in the facility(e.g., meals, group activities). Further workis needed to define the risk of contaminationof HCP hands and clothing with the rangeof activities performed in these settings.9
c. All Healthcare Facilities that UseContact PrecautionsSystems should be in place to identifypatients with a history of CRE colonizationor infection at admission so that theycan be placed on Contact Precautions. Inaddition, clinical laboratories should havean established protocol for notifying clinicaland/or infection prevention personnelwhen CRE are identified from clinical orsurveillance cultures.Evidence suggests that HCP may use PPEincorrectly resulting in contaminationof their skin and/or clothes. HCP canalso contaminate themselves duringdoffing if done incorrectly. Facilitiesshould ensure that Contact Precautionsare used correctly by HCP caring for allpatients with epidemiologically importantMDROs including CRE. This shouldinclude ensuring HCP are educatedabout the proper use and rationale forContact Precautions and that they have theopportunity to practice donning and doffingPPE and to demonstrate competency inPPE use before patient contact. In addition,facilities should ensure that there is a processto monitor and improve HCP adherenceto Contact Precautions. This might includeconducting periodic surveillance on theuse of Contact Precautions and providingfeedback to frontline staff about theseresults.Currently, there is not enough evidence tomake a firm recommendation about whento discontinue use of Contact Precautions10for infected or colonized patients; however,CRE colonization can be prolonged ( 6months). If surveillance cultures
Enterobacteriaceae (CRE): 2012 CRE Toolkit. Unless otherwise speciied, 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.). his
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and carbapenem) 2005, Portugal missing K.pneumoniae (resistant to carbapenem) 2005, New Zealand missing MRSA 2014, Australia missing S.pneumoniae (resistant to penicillin) 2014, Iceland missing K.pneumoniae (resistant to carbapenem) 2014. Includes resistant and intermediate data Source: ES
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2 Guidance for Preventing Transmission of Carbapenem -Resistant Enterobacteriaceae (CRE) in Acute and Long -Term Care Hospitals INTRODUCTION AND PURPOSE The Wisconsin Division of Public
The CRE Toolkit is designed to aid health care workers with carbapenem-resistant Enterobacteriaceae prevention, detection and treatment across the continuum of health care. This group would include . MHT has variable accuracy in detecting carbapenemases other than KPC. (9, 12-14) In the 2015 CLSI
