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Guide to the Elimination of Clostridium difficile in Healthcare Settings

About APICAPIC’s mission is to improve health and patient safety by reducing risks of infection and other adverse outcomes. The Association’s more than 12,000 members have primary responsibility for infection prevention, control and hospital epidemiology in healthcare settings around the globe. APIC’s members are nurses, epidemiologists, physicians, microbiologists, clinical pathologists, laboratory technologists and public health professionals. APIC advances its mission through education, research, consultation, collaboration, public policy, practice guidance and credentialing.

An APIC Guide

2008

Look for other topics in APIC’s Elimination Guide Series, including:

• Catheter-Related Bloodstream Infections• Catheter-Related Urinary Tract Infections• Mediastinitis• MRSA in Long-Term Care

Copyright © by 2008 APIC

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Cover photo courtesy of CDC.Micrograph of the bacterium Clostridium difficile made from an impression smear of 72hr anaerobe blood agar (1980). ISBN: 1-933013-37-0

For additional resources, please visit www.apic.org/EliminationGuides.


ASSOCIATION FOR PROFESSIONALS IN INFECTION CONTROL AND EPIDEMIOLOGY �

Table of Contents 1.Acknowledgments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

2.GuideOverview......................................................................5

3.PathogenesisandChangingEpidemiologyofClostridium difficileInfection(CDI). . . . . . . . . . . . . . . . . . 7

4.CDIinthePediatricPopulation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

5.ModesofTransmission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

6.Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

7.Surveillance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

8.FocusingonPrevention:ContactPrecautions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

9.FocusingonPrevention:HandHygiene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

10.FocusingonPrevention:EnvironmentalControl . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

11.TieredResponsetoC. difficile. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38SummaryofC. difficileTransmissionPreventionActivitiesDuringRoutine

InfectionPreventionandControlResponses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38SummaryofAdditionalC. difficileTransmissionPreventionActivitiesDuring

HeightenedInfectionPreventionandControlResponses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

12.OtherPreventiveMeasures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

13.AntimicrobialStewardshipandClostridium difficile: APrimerfortheInfectionPreventionist . . . . . . . . 43

14.UsingaSystemsApproachtotheEliminationofClostridium difficileInfection(CDI) . . . . . . . . . . . . . . 49

15.GlossaryofTerms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54

16.FrequentlyAskedQuestions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

17.References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61


� ASSOCIATION FOR PROFESSIONALS IN INFECTION CONTROL AND EPIDEMIOLOGY

Acknowledgments

ThechallengesposedbyClostridium difficilerepresentsomeofthemostdifficultandalarmingissuesconfrontinginfectionpreventionandcontrol.Theelementsinvolvedinaddressingthisproblem,aswellasthechangingepidemiologyofC. difficile,havecollided,resultinginapreventionandcontrol“perfectstorm.”Thishasalreadyimpactedthehealthandsafetyofpatients,regardlessofwhethertheyreceivecareinahospital,long-termcarefacility,outpatientsetting,ambulatorycaresetting,oraphysician’soffice.

ThedifficultiespresentedbythisorganismserveasacatalystforincreasingcollaborationamonghealthcarepersonnelandprovidersasweworktogethertominimizetheimpactofC. difficileandmaximizepatientsafety.Theprevalenceofthisorganismhighlightstheneedtocontinuestrongrelationshipsbetweeninfectionprevention,themicrobiologylaboratory,andpharmacy.

ThisguideprovidescurrentinformationregardingC. difficileanditsimpactonthepatientandthecareenvironment,andintroducesatieredapproachthatinfectionpreventionistscanuseintheirownfacilities.Specifictoolshavebeenincludedtoenablethepreventionisttoaddresstheproblemwithintherealmofaparticularsetting.TheAssociationforProfessionalsinInfectionControlandEpidemiology(APIC)acknowledgesthevaluablecontributionsfromthefollowingindividuals:

AuthorsRuthM.Carrico,PhD,RN,CICLennoxK.Archibald,MD,PhD,FRCP(Lond),

DTM&HKrisBryant,MDErikDubberke,MDLorettaLitzFauerbach,MS,CICJulietG.Garcia,MS,MT(ASCP),CICCarolynGould,MD,MScBrianKoll,MDJennieMayfield,BSN,RN,MPH,CICXinPang,MDJulioA.Ramirez,MD,FACPDanaStephensRN,CICRachelL.Stricof,MT,MPH,CICTimWiemken,MPH,CIC

ReviewersKathleenMeehanArias,MS,MT,SM,CICCandaceFriedman,MT(ASCP),MPH,CICJeffKempterMichaelOttlinger,PhDJudyPotterWilliamRutala,PhD,MPHMarionYetman,RN,BN,MN,CIC

SpecialthankstoJuliaJ.Fauerbach,interiordesigner,ShandsHealthcarebusinessassociate,M.ArchandHealthcandidate,ClemsonUniversity2009,forherartistryandknowledgeregardingphysicalelementsanddesignofthepatientroom.



Guide Overview

TheimpactofClostridium difficileInfection(CDI)hasbeenfeltacrosstheentirespectrumofhealthcareandisnowrecognizedasapathogencapableofcausinghumansufferingtoadegreematchingthatofMethicillin-resistantStaphylococcus aureus.Theseverityofdiseaseisincreasingandhasaffectedchildren,adults,andtheelderly.CDIisassociatedwithanincreasedlengthofstayinhealthcarefacilitiesby2.6to4.5daysandattributablecostsforinpatientcarehavebeenestimatedtobe$2,500to$3,500perepisode,excludingcostsassociatedwithsurgicalinterventions.IntheUnitedStates,theeconomicconsequencesrelatedtomanagementofthisinfectionexceeds$3.2billionannually.Sadly,CDIhasbeenassociatedwithanattributablemortalityrateof6.9%at30daysand16.7%atoneyear.1-6Clearly,preventingthedevelopmentandtransmissionofCDIshouldbeatoppriorityforinfectionpreventionistsinallhealthcaresettings.

AsratesofCDIcontinuetoincreasenationallyandinternationally,itisimportantthatinformationprovidedinthisguidestartatthebeginninginitsdescriptionoftheproblem,includeincrementalstepsthatidentifytargetedareasforintervention,andprovideclearguidanceforimplementation.

Theconceptsofintervention“bundling”anduseofatieredapproachrepresentanorganizedapproachtoaddresspreventionofC. difficiletransmissionapplicableinallhealthcaresettings.TheuseofatieredapproachisconsistentwiththerecommendationsfromtheHealthcareInfectionControlPracticesAdvisoryCommittee(HICPAC)andtheCentersforDiseaseControlandPrevention(CDC)regardingpreventionofmultidrug-resistantorganisms(MDROs).7

ConsiderthefollowingexamplesofCDIamongpatientsacrossthespectrumofhealthcare:

• 48-year-oldmale,treatedwithantibioticsforhealthcare-associatedinfection,developsCDIwhileaninpatientinanacutecarefacility

• 25-year-oldfemale,givenasingledoseofantibioticsassurgicalprophylaxis,developsCDIwithindaysafterreturninghome,followingasurgicalprocedureinanoutpatientsurgicalsetting

• 62-year-oldmale,developsCDIwhilearesidentinalong-termcarefacility• 51-year-oldfemale,developsCDIaftertakingacourseofantibioticsprescribedbyherprimarycare

provider• 12-year-oldfemale,developsCDIfollowingacourseofantibioticsprescribedduringtreatmentfora

chronicmedicalcondition

BeforetheincidenceofC. difficileincreasedandmorevirulentstrainsemerged,healthcareteamsoftenconsidereddiarrheaassociatedwithantimicrobialtherapyanuisance,andperhapsevenanacceptedoutcomeforpatientsreceivingantibiotics.Complacencytowardthishealthcare-associatedcomplicationcannolongerexistatanypointinthehealthcarespectrum,includingambulatorycare,acutecare,long-termcareandhomecare.TheseveremorbidityandmortalityassociatedwithC. difficileprovidestheimpetusforhealthcareproviderstointensifyeffortstowarddevelopingpreventionstrategiesthatcanbeconsistentlyappliedacrossthecontinuumofhealthcare.Althoughitisrecognizedthatfew“onesizefitsall”initiativeswork,thegoalofthisguideistobuildonevidencethat“bundling”ofactivitieshasbeeneffectiveinaddressingotherhealthcare-associatedinfections,ashasuseofatieredapproachforinterventionsguidedbyoutcomesinthespecifichealthcaresetting.

AbundledapproachtoC. difficilepreventionandcontrolattheUniversityofPittsburghincludededucation,enhancedcasefinding,expandedinfectioncontrolmeasures,theformationofaC. difficilemanagementteam,


� ASSOCIATION FOR PROFESSIONALS IN INFECTION CONTROL AND EPIDEMIOLOGY

andimplementationofanantimicrobialstewardshipprogram.8McDonaldanalyzedtheMutoandcolleagues’reportandconcludedthatthebundledapproachreflectedsuccessive,tieredinterventionsbasedondatafromtheirsurveillance.Thishighlightstheimportanceofusinglocaldatatodriveprioritysetting,andchoiceandtimingofinterventions.9AsanorganizationfocusesonCDIprevention,healthcarefacilitiesshouldevaluatetheirlocalsurveillancedataandselectappropriateinterventionsthataddresstheirparticularsituation.ElementsofaCDIbundleincludeactivitiessuchasthefollowing:

• EarlyrecognitionofCDI,throughappropriatesurveillancecase-findingmethodsandmicrobiologicidentification

• Implementationofcontactprecautions,inadditiontostandardprecautionsandpatientplacement• Establishmentandmonitoringofadherencewithenvironmentalcontrols• Handhygienemeasures• Patientandfamilyeducation• Evidence-basedmethodsforpatienttreatmentandmanagementofdisease• Antimicrobialstewardship• Educationofhealthcareworkers• Administrativesupport

Inthesectionsthatfollow,theseelementswillbediscussedatlength,followingareviewofthepathogenesisofCDI,itschangingepidemiologyandmodesoftransmission.Bundleelementsareorganizedinthesectionsoutliningroutineandheightenedinfectionpreventionandcontrolresponses.



Pathogenesis and Changing Epidemiology of Clostridium difficile Infection (CDI)

TounderstandthechainofeventsinvolvedinCDI,itishelpfultobeginwithanoverviewoftheorganismandhowitaffectsanindividual.AreviewofthepathogenesisandthechangingepidemiologyofC. difficile provideinsightintopointswherepreventiveinterventionscanbestbetargeted.

Clostridium isananaerobic,gram-positive,spore-formingbacillus.WithinthegenusClostridium,thereareanumberofspecies,includingC. tetani, C. botulinum, C. perfringens and C. difficile.Alloftheseorganismsareassociatedwithsignificantdiseaseinhumans,butthefocusofthisguideinvolvesillnessassociatedwithC. difficile.Someproducenotoxin,someproducelowlevelsoftoxin,andsomearehighlytoxigenic.

Priortothemid-1970s,developmentofpseudomembranouscolitiswasrecognizedtooccurfollowingtheuseofsomeantibiotics,especiallyclindamycinandlincomycin.Pseudomembranouscolitisisaninflammatoryconditionofthecolonthatdevelopsinresponsetotoxinsthathavebeenproducedbymicroorganisms.Thisprocessoccurswhenthenormalfloraoftheintestinaltractisdisrupted(forexample,fromtheuseofantibiotics)andtheremainingfloraprovidesanopportunityfororganismsnotimpactedbytheparticularantibiotic(s)toproliferate.InthecaseofC. difficile,thisprocessenablesC. difficiletoattachtothemucosaofthecolonandsetsthestagefortoxinproductionandresultantmucosaldisease.Toxin-producingstrainsofC. difficilecancauseillnessrangingfrommildormoderatediarrheatopseudomembranouscolitis,whichcanleadtotoxicdilatationofthecolon(megacolon),sepsis,anddeath.Figure3.1providesgraphicdemonstrationofthetransmissionandimpactofC. difficile.

ThefirstreportsestablishingClostridium difficileasthecauseofantibiotic-inducedpseudomembranouscolitiswerepublishedin1978.10,11Sincethen,CDIhasemergedasthemostcommoncauseofantibiotic-associateddiarrheaandahighlyproblematichealthcare-associatedinfection.ThedevelopmentofCDImostcommonlyhastwoessentialrequirements:(1)exposuretoantimicrobialagentsand(2)newacquisitionofC. difficilesuchasthatoccurringviafecal-oraltransmission.WhilesomepeopleexposedtothesetwofactorswilldevelopCDI,otherswillinsteadbecomeasymptomaticallycolonized.Thus,athirdfactor,possiblyrelatedtohostsusceptibilityorbacterialvirulence,isthoughttobeanotherimportantdeterminantfordevelopingdisease.12

AcquisitionofC. difficileoccursbyoralingestionofsporesthatresisttheacidityofthestomach.Thesesporesgerminateintovegetativebacteriainthesmallintestine.AlterationofthenormalcolonicflorabyexposuretoantimicrobialsprovidesanenvironmentinwhichC. difficileisabletomultiply,flourishandproducetoxinsthatcausecolitis.TheprimarytoxinsaretoxinAandB,twolargeexotoxinsthatcauseinflammationandmucosaldamage.Anexotoxinisaproteinproducedbyabacteriumandreleasedintoitsenvironment,causingdamagetothehostbydestroyingothercellsordisruptingcellularmetabolism.AlthoughevidencehassuggestedthattoxinAisthemajortoxin,C. difficilestrainsthatproduceonlytoxinBhavebeenshowntocausethesamespectrumofdiseaseasstrainsthatproducebothtoxins.13

ThemajorriskfactorsforCDIareexposuretoantimicrobials,hospitalization,andadvancedage.14NearlyallantimicrobialshavebeenimplicatedinCDI,butcertainantimicrobialclasses,suchascephalosporins,clindamycin,andfluoroquinolones,seemtocausehigherriskfordisease.Thisisprobablyrelatedtothoseantimicrobials’propensityfordisruptingnormalcolonicflorainadditiontotheantimicrobialresistancepatternsofprevalentC. difficilestrains.InrecentCDIoutbreaks,fluoroquinoloneshavebeenthemajorclassofantimicrobialsimplicatedinCDI,15-17anassociationthathasbeenattributedtohigh-levelresistancetofluoroquinolonesofthecurrentepidemicstrain.18


8 ASSOCIATION FOR PROFESSIONALS IN INFECTION CONTROL AND EPIDEMIOLOGY

Despitethefactthatexposuretomultipleantimicrobialagentsandlongercoursesoftherapyappeartoincreaseanindividual’sriskofCDI,exposuretoevenasingledoseofantimicrobialsgivenforpreoperativeprophylaxishasbeenassociatedwithCDI.19-21Severalstudiessupportrestrictionofcertainantimicrobialagentsorformularychangespromotingtheuseofnarrow-spectrumantimicrobialstoreducetheincidenceofCDIandtocontroloutbreaks.22-26Theseactivitiesformabasisforantimicrobialstewardshipprograms.

TheincubationperiodofC. difficilefollowingacquisitionhasnotbeenclearlydefined.Althoughonestudysuggestedashortincubationperiodoflessthansevendays,28theintervalbetweenexposureandonsetofsymptomsmaybelonger.29Thus,manycasesofhealthcare-associatedCDImayhavetheironsetinthecommunityafterhospitalization.AccordingtoCDIdefinitionsdevelopedforthepurposesofsurveillance,community-onsetcaseswithsymptomonsetoccurringwithinfourweeksofdischargefromahealthcarefacility(acuteorlong-term)shouldbeattributedtothatfacility.30Specificsurveillancedefinitionswillbereviewedlaterinthisguide.

Changing EpidemiologyInrecentyears,theepidemiologyofCDIhaschangeddramatically,withincreasesnotedintheincidenceofdiseaseinternationally,andreportsofCDIoutbreakswithinhealthcarefacilitiesinNorthAmericaandEuropeinvolvingmoreseverediseasethanpreviouslydescribed.IntheUnitedStates,nationalsurveillancedataindicate

Figure �.1. Transmission and Impact of C. difficile. Source: Sunenshine RH, McDonald LC. Clostridium difficile-associated disease: New challenges from an established pathogen. Cleve Clin J Med 2006;73:187–197. Reprinted with permission. Copyright © 2006 Cleveland Clinic. All rights reserved.

Pathogenesis of C difficile-associated disease

Clostridium difficile is spread via the fecal-oral route. The organiism is ingested either as the vegetative form or as hardy spores, which can survive for long periods in the environment and can traverse the acidic stomach.

C difficile reproduces in the intestinal crypts, releasing toxins A and B, causing severe in�ammation. Mucous and cellular debris are expelled, leading to the formation of pseudomembranes.

Pseudomembrane

Toxins

Monocyte

Neutrophil

In the small intestine, spores germinate into the vegetative form.

Toxin A attracts neutrophils and monocytes, and toxin B degrades the colonic epithelial cells, both leading to colitis, pseudomembrane formation, and watery diarrhea.

In the large intestine, C difficile-associated disease can arise if the normal �ora has been disrupted by antibiotic therapy

C difficile



thatthenumberofhospitaldischargeswithCDIlistedasanydiagnosisdoubledbetween2000and2003,withadisproportionateincreaseforpersonsolderthan64yearsofage(Figure3.2).4

MorerecentstatisticshaveshownamorethandoublingofthenumberofhospitaldischargeswithCDIfrom2001-2005,increasingfromapproximately149,000casesin2001toover300,000casesin2005.31SimilarincreasesinratesofCDIper10,000dischargeswerealsonoted,indicatingthatthesteepriseinCDIdischargeswasnotsimplyduetoanincreaseinnumberofhospitaldischarges.CasesofCDIintheU.S.weregeographicallydistributed,withthehighestratesintheNortheast,followedbytheMidwestandSouthernregions.Personsolderthan65yearsofagehavebeenmostaffected,withthehighestincreasesindischargerateswithCDI,representingovertwo-thirdsofpatientswithCDI.31However,therecentchangingepidemiologyhasalsoinvolvedemergingreportsofCDIoccurringinpopulationspreviouslyatlowrisk,includingseverecasesamonghealthyperipartumwomen,andincreasingreportsinchildrenandotherhealthypeopleinthecommunitywithnorecenthealthcarecontactorantimicrobialexposure.32

DuringthistimeperiodofrisingincidenceofCDI,thereweremanyindicationsofincreasingseverity,withgreaternumbersofcomplicationsandmortalityrelatedtoCDI.ReportsofCDIoutbreaksinhospitalsinQuebec,Canada,andsubsequentlyintheU.S.,emerged,describingseverecasesassociatedwithhighernumbersofcolectomies,treatmentfailures,anddeathsthanwereeverbeforereported.15,18,27In2004,the30-dayattributablemortalityrateofnosocomialCDIinQuebechospitalswas6.9%,27comparedto1.5%amongCanadianhospitalsin1997.33AttributablemortalityistheamountorproportionofdeaththatcanbeattributedtoCDI.IntheU.S.,deathcertificatedatashowedthatmortalityratesfromCDIincreasedfrom5.7permillionpopulationin1999to23.7permillionin2004(Figure3.3).2

AhypervirulentepidemicstrainofC. difficilewasfoundtobeassociatedwiththeoutbreaksinQuebecandatleasteighthospitalsinsixU.S.states,andsubsequentlywithoutbreaksinEurope.18,27,34,35ThisepidemicstrainhasbeennamedBI/NAP1/027andproducesatypeoftoxinnotpreviouslyseeninhospitalstrains.36TheBI/NAP1/027/toxinotypeIIIstrainhasbeenfoundtoproduce16-foldhigherconcentrationsoftoxinAand23-foldhigherconcentrationsoftoxinBinvitrothantoxinotype0strains.34Anotherfeatureofthisstrainistheproductionofatoxincalledbinarytoxin,theroleofwhichisnotyetdefined;however,strainsthatproducebinarytoxinmaybeassociatedwithmoreseverediarrhea.37ThecauseoftheextremevirulenceoftheBI/NAP1/027strainmaybeacombinationofincreasedtoxinAandBproduction,binarytoxin,orotherunknownfactors.

Figure �.2. Rates of discharges from U.S. short-stay hospitals of patients with C. difficile-associated disease listed as any diagnosis by age.4

Source: McDonald LC, Owings M, Jernigan DB, 2006.

450

400

350

300

250

200

150

100

50

01996 1997 1998 1999 2000 2001 2002 2003

Dis

char

ges

per

100,

000

popu

latio

n

15–45 years46–64 years

>64 years



Asidefromitsincreasedvirulence,anotherfeaturethatmayaccountfortheproliferationofthisstrainisitshigh-levelresistancetothefluoroquinoloneclassofantimicrobials.18AlthoughBI/NAP1/027isolatesexistedpreviously,historicstrainswerelessresistanttofluoroquinolones,andtheywerenotassociatedwithoutbreaksofdisease.TheBI/NAP1/027strainhadbeendetectedinatleast38U.S.statesasofNovember2007(seewww.cdc.gov/ncidod/dhqp/id_Cdiff_data.html)(Figure3.4),insevenCanadianprovinces,38andhasledtooutbreaksintheUnitedKingdomandotherpartsofEurope.34,39

Figure �.�. States with BI/NAP1/027 strain of C. difficile (n = 38), November 2007. Source: CDC, (www.cdc.gov/ncidod/dhqp/id_Cdiff_data.html).

Figure �.�. Yearly C. difficile-related mortality rates per million population in the U.S. 1999 to 2004.2

Source: Redelings MD, Sorvillo F, Mascola L, 2007.

25

20

15

10

5

0

1999 2000 2001 2002 2003 2004

5.7

7.38.2

12.2

16

23.7


ASSOCIATION FOR PROFESSIONALS IN INFECTION CONTROL AND EPIDEMIOLOGY 11

CDI in the Pediatric Population

Atpresent,thereismuchwedonotknowaboutCDIinchildren,butwedoknowthatCDIismuchlesscommoninchildrenthaninadults,andthatfrom2%to70%ofinfantsmaybeasymptomaticallycolonizedwithC. difficile,includingcolonizationwithtoxigenicstrains.40,41Ratesofcolonizationdecreasewithage,fallingtoabout6%atagetwoyears,whileinchildrenolderthantwo,colonizationratesaresimilartothoseinadults(approximately3%).Infantsmayacquirecolonizationearlyinthefirstweekoflife.42StudiesexaminingriskfactorsforC. difficilehavefailedtoshowaconsistentassociationbetweenmodeofdeliveryorreceiptofformulaversusbreastmilk.However,nosocomialacquisitionoftheorganismiswell-describedinNeonatalIntensiveCareUnits(NICU),andC. difficilecontaminationoftheNICUenvironmenthasbeendemonstrated.43

Moststudieshavefailedtoshowanepidemiologicassociationbetweencolonizationanddiseaseininfantslessthanoneyearofage.Forexample,inoneSwedishstudy,C. difficile wasisolatedwithequalfrequencyinhealthychildrenoneweektooneyearofage(17%)andinchildrenlessthansixyearswithdiarrhea(18%).44Inastudyofoutpatientchildren,C. difficilewasisolatedfrom7%ofpatientswithdiarrheaand15%ofhealthycontrols.ChildrenwithC. difficile wereyoungerthanchildrenwithouttheorganism(meanage8.2to9.8months);priorantibioticexposurewasnotedinonly22%.59Inanotherstudy,toxinBwasidentifiedin4.2%of618childrenwithdiarrheaandinanequivalentnumberofhealthycontrols.46

SimilarfindingshavebeennotedinmostcontrolledstudiesofNICUpatients.C. difficiletoxinwasrecoveredfromthestoolsof55%ofpatientsinoneNICU,butsignsofentericdisease,includingnecrotizingenterocolitis,occurredwithequalfrequencyinbothtoxin-positiveandtoxin-negativeinfants.47SporadiccasereportssuggestthatsevereCDIoccasionallyoccursininfants,especiallythosewithunderlyingintestinalpathology.

TheaccuratediagnosisofCDIinyoungchildreniscomplicatedbythefactthatcommonlyusedtestssuchastheenzymeimmunoassay(EIA)fortoxinAandBmaylackspecificityinthisagegroup.Between2004and2006,ahospitalinGeorgianotedanincreaseinC. difficiletoxin-positivestoolsinprematureinfants.Fiveinfantswerediagnosedwithnecrotizingenterocolitis.Retestingof26frozenstoolspecimensbyEIAattheCentersforDiseaseControlandPrevention(CDC)confirmedtoxininonlyfivespecimens.C. difficilecouldnotbeisolatedincultureinanyspecimen,althoughotherClostridiaspecieswerefoundin50%ofsamples.(L.CliffordMcDonald,CDC,personalcommunication).

YoungchildrenwhoarecolonizedwithC. difficilewithoutsymptomsneverthelessrepresentareservoirfortransmissionofdiseasetoothers.A19-year-oldwomandevelopedCDIintheimmediatepost-partumperiod.Althoughhersymptomsresolvedwithmetronidazoletreatment,shedevelopedthreerecurrences.HerasymptomaticinfantwasacarrieroftheidenticalstrainofC. difficileisolatedfromthemother, suggestingtheinfantwasthesourceofthemother’srecurrentdisease.48

TheemergenceofB1/NAP1/027maybechangingtheepidemiologyofCDIinchildren.B1/NAP1/027hasbeenassociatedwithseverediseaseinbothadultandpediatricpatientswithoutrecentexposuretohealthcarefacilities,andinsomecases,withoutrecentantimicrobialuse.In2005,theCDCreportedcasesofsevereCDIinpopulationspreviouslyatlowriskfordisease,includinghealthychildrenwithnorecentantibioticuse.32Afive-yearretrospectivestudyperformedatatertiarycarechildren’shospitalrevealedanincreaseinthenumberofchildrenseenintheEmergencyDepartmentwithcommunity-associatedCDI;43%lackedahistoryofrecentantibioticuse.49



ThereremaingapsinourknowledgeaboutthepathogenicityofC. difficileininfants,thespectrumofdiseaseinchildrenduetotheepidemicstrainB1/NAP1/027,andthemostappropriatediagnostictoolstoconfirmCDIinpediatricpatients.Judicioustestingandprospectivesurveillanceusingconsistentdefinitionsisessentialtobetterunderstandingthediseaseinthispopulation.

GuidelinespublishedbytheSocietyforHealthcareEpidemiologyofAmerica(SHEA)in1995discouragedtestingofstoolsfrominfantslessthanoneyearofageforC. difficile.TheNationalHealthcareSafetyNetwork(NHSN)surveillancedefinitionforCDIdoesnotdiscriminatebetweenadultandpediatricpatientsexcepttoexcludeNICUpatients.Otherpatientslessthanoneyearofagearenotspecificallyexcluded,althoughitremainsdifficulttodifferentiateincidentalcolonizationfromtrueCDIinthispopulation.Giventhechangingepidemiologyofdiseaseinotherpopulationspreviouslyatlowriskfordisease,additionalguidanceforcliniciansiswarranted.SystematicevaluationofCDIinyoungchildren,includingNICUpatients,isessentialtobetterunderstandingtheepidemiologyofdiseaseinthispopulation.

GuidelinesforthediagnosticevaluationforCDIinchildrenhavebeenproposed(L.CliffordMcDonald,AdHocClostridium-difficileSurveillanceWorkingGroup,personalcommunication).Pendingadditionalinformation,itseemsprudenttorestrictroutinetestingforC. difficileinchildrenlessthanoneyearofage.Whentestingisperformed,morethanonediagnosticapproachshouldbeutilized.Forexample,acultureand/ortoxintestingshouldbeperformedinadditiontoothertests.Retentionofmicrobiological,surgicalandautopsyspecimensforadditionaltestingbypublichealthauthoritiesorcenterswithspecialexpertisemaybeusefulforconfirmingthediagnosis,ordetectingepidemicstrains.Investigationofsuspectedclustersofinfectionsisessential.

Becauseasymptomaticcolonizationdecreaseswithage,testingforC. difficile shouldbeconsideredinchildrenonetotwoyearsofagewithdiarrheaandrecentantibioticexposure,especiallyaftermorecommonpathogenshavebeenexcluded.

Childrenolderthantwoyearsofagewithdiarrheaandahistoryofrecentantimicrobialusemaybetestedinthesamemannerasolderchildrenandadults.Becausediseasehasbeenconfirmedinhealthychildrenwithoutrecentantibioticexposure,testingforC.difficile maybeconsidered,butotherdiagnosesaremorelikely.


ASSOCIATION FOR PROFESSIONALS IN INFECTION CONTROL AND EPIDEMIOLOGY 1�

Modes of Transmission

WhenconsideringthemodesoftransmissionforC. difficile,itisimportanttonotethesekeyconcepts:• C. difficilecansurviveinthehospitalenvironmentandonhospitalsurfaces.Astheorganismstrivesto

protectitselffromundesirableenvironmentalconditions,itassumesitssporeform.• Patientsand/orhealthcareworkerscantransmitand/oracquireC. difficilefromcontactwithcontaminated

surfaces,includingcontaminationwithbothvegetativecellsandspores.• Transmissionoccursviaafecal-oralroute,soanyactivitythatmayresultinmovementoftheorganisminto

themouthmustbeaddressedaspartofpreventionactivities.

Survival of C. difficile in the Healthcare EnvironmentClostridium difficileisafastidiousanaerobeandthevegetativecelldiesrapidly,generallywithin24hours,outsidethecolon.50,51ThiswouldleadonetobelievethatC. difficileisnotahighlytransmissibleorganism.However,C. difficileproducessporesthatcanpersistintheenvironmentformanymonthsandarehighlyresistanttocleaninganddisinfectionmeasures.50,51Thesporesmakeitpossiblefortheorganismtosurvivepassagethroughthestomach,resistingthekillingeffectofgastricacid,wheningested.Afteringestion,thesporescangerminate,producetoxinsandcausedisease.Therefore,boththevegetativeandsporeformsofC. difficileareimportantintermsofenvironmentalcleaninganddisinfection.

Transmission of C. difficile to Patients from the Healthcare EnvironmentThetwomajorreservoirsofC. difficileinhealthcaresettingsareinfectedhumans(symptomaticorasymptomatic)andinanimateobjects.Patientswithsymptomaticintestinalinfectionarethoughttobethemajorreservoir.52

TheleveltowhichtheenvironmentbecomescontaminatedwithC. difficile sporesisproportionaltotheseverityofdiseaseinthepatient.6However,asymptomaticcolonizedpatientsshouldalsobeconsideredasapotentialsourceofcontamination.56PatientcareitemssuchaselectronicthermometersandcontaminatedcommodeshavealsobeenimplicatedinthetransmissionofCDI.53

TransmissionofC. difficiletothepatientviatransienthandcarriageonhealthcareworkers’handsisthoughttobethemostlikelymodeoftransmission.ReductionofCDIratesassociatedwiththeuseofglovesprovidesstrongsupportfortheimportanceofhandcarriage.54AlcoholisnoteffectiveinkillingC. difficilespores,butCDIrateshavenotbeenfoundtoincreaseasuseofalcohol-basedhandrubs(ABHR)increase.IfahospitalisexperiencinganoutbreakorincreasinginfectionrateswithC. difficile,itcanbebeneficialforhealthcareworkerstowashtheirhandswithsoapandwaterexclusivelywhencaringforpatientswithknownCDI.55

Transmission Via Patient Care ActivitiesThereareanumberofpatientcareactivitiesthatprovideanopportunityforfecal-oraltransmissionofC. difficile.Someoftheseactivitiesinclude:

• Sharingofelectronicthermometersthathavebeenusedforobtainingrectaltemperatures(handlesmaybecontaminatedwithC. difficileeventhroughprobesarechangedandprobecoversused)

• Oralcareororalsuctioningwhenhandsoritemsarecontaminated• Administrationoffeedingsormedicationwithcontaminatedhands,foodormedication• Emergencyproceduressuchasintubation


1� ASSOCIATION FOR PROFESSIONALS IN INFECTION CONTROL AND EPIDEMIOLOGY

• Poorhandhygienepractices• Ineffectiveorinconsistentdisinfectionofpatientcareequipment• Sharingofpatientcareitemswithoutappropriatedisinfection• Ineffectiveenvironmentalcleaning

Theseexamplesservetoidentifythebroadarrayofactivitiesthatcouldresultinfecal-oraltransmissionofC. difficile. Therefore,whenpreventionstrategiesaredesigned,itisimportantthattransmissionopportunitiessuchasthesebeconsideredandobservationofpatientcareactivitiesbeperformed,inanefforttoidentifypreviouslyunrecognizedorunsuspectedpotentialmodesoftransmission.



Diagnosis

C. difficileinfection(CDI)shouldbesuspectedinanypatientwithdiarrheaorabdominalpainwithrecentantibioticorhealthcareexposures.52SevereCDIhasalsorecentlybeenreportedin“low-risk”populations,forexample,peoplewithoutrecentantibioticorhealthcarefacilityexposures,andCDIshouldbeconsideredinanypatientwithdiarrhealastinglongerthanthreedayswithfeverorabdominalpain.32Reviewthesurveillancedefinitionsprovidedlaterinthisguide.CDIismostcommonlyconfirmedwithalaboratory-basedassay,andthereareadvantagesanddisadvantagesforalllaboratory-basedmethodsfordetectingC. difficile oritstoxins.Therefore,itisessentialtobefamiliarwiththemethodusedatyourfacility.

Who Should be Tested and How Frequently?ItisrecommendedtoonlytestforC. difficileinpatientswhoaresuspectedofhavingCDI,forexample,patientsexperiencingdiarrhea.52,57ItisrecommendedtoNOTscreenasymptomaticpatientsorperforma“testofcure”inpatientswhohaverespondedtotherapy.52,57Thereareseveralreasonsfortheserecommendations.Allnon-culturelaboratory-basedassaysfordetectingC. difficileoritstoxinshavebeendevelopedandvalidatedtodiagnoseCDIonlyinsymptomaticpatients.Therearenumerousreasonstobelievethesensitivity(thelikelihoodthatsomeonewiththediseaseorconditionwillhaveapositivetestresult),specificity(thelikelihoodthatsomeonewhodoesnothavethediseaseorconditionwillhaveanegativetestresult),andpositivepredictivevalue(thelikelihoodthatsomeonewhotestspositiveactuallyhasthediseaseorcondition)oftheseassaysarelowerinasymptomaticpatients,resultinginmorefalse-positiveandfalse-negativeresults.Inaddition,thisinformationprovidesnoclinicallyusefulinformationandmayresultinpatientharm.

ItisnotrecommendedtoplaceasymptomaticpatientscolonizedwithC. difficile inContactPrecautions.Thiscanleadtodecreasedpatientsatisfactionaswellasanincreaseinhealthcarecostsassociatedwithplacingthepatientinaprivateroomandtheunnecessaryuseofgownsandgloves.Somereportsquestiontheimpactofisolationonpatientsafety,duetootheradverseeventssuchasfalls,decreasedmonitoring,andmedicalerror.

PersistentlypositivetestresultsattheendoftreatmentarenotpredictiveofaC. difficilerelapse,andapositivetestresultinanasymptomaticpatientmayresultinunnecessarytreatmentwithantimicrobials,whichcanincreasethepatient’sriskofdevelopingCDIinthefuture.59Testingasymptomaticpatientsalsotakesnursingandmicrobiologytimetocollectandtestthestool,plusthecostofthetestitself.

Acommonquestionishowoftenapatientwithdiarrheashouldbetestediftheinitialtestsarenegative,duetoconcernsoflowsensitivityofthetests.Somestudieshavedemonstratedthatanadditional10%ofpatientswillhaveapositivetestifrepeattestingisperformed.52ItisimportanttonotethattheprevalenceofCDIislowerinpatientswithapreviousnegativetest.WhentheprevalenceofCDIdecreases,thepositivepredictivevalueofthetestdecreasesaswell,increasingthelikelihoodthatapositivetestwillbeafalse-positivetest.Theincreaseinfalse-positivetestsandlowyieldofadditionaltestingdoesnotsupporttheroutineuseofrepeattestingasacost-effectivemeasure.52Collection and Transport of Stool for C. difficile TestingOnlywateryorloosestoolshouldbecollectedandtestedtoestablishthediagnosisofCDI.Specimensshouldbesubmittedinaclean,watertightcontainer.Transportmediaisnotnecessary,andmayincreasethefalsepositiverateofsometests.59Specimensshouldbetransportedassoonaspossibleandstoredat2˚to8˚Cuntiltested.



Storageatroomtemperaturedecreasesthesensitivityofsometests,presumablyduetotoxininactivation.60Repeatfreezingandthawingofthespecimenshouldalsobeavoidedforthesamereason.60

Laboratory Tests for Diagnosing CDIAsCDIisatoxinmediateddiseaseandonlyC. difficileisolatescapableofproducingtoxinareabletocauseCDI,mostdiagnostictestsinvolvethedetectionofC. difficile toxinAand/ortoxinB(Table6.1).Thecellcytotoxicityassay,whichdetectsthecytopathiceffectoftoxinBonculturedcelllines,isconsideredthegold-standardclinicallaboratoryassayforthediagnosisofCDI.52However,somehavereportedasensitivityofthisassayaslowas67%comparedtocultureforC. difficile.52TheprimaryadvantageofthisassayisitismoresensitivethanimmunoassaysfortoxinAand/orB.Disadvantagesofthisassayincludeaprolongedturn-aroundtimeof48to72hours,andthatitisnecessarytobeabletomaintaincellculturesinorderforalaboratorytoperformthisassay.

Enzymeimmunoassays(EIA)fortoxinsAand/orBhavebecomethemostwidelyusedlaboratory-basedmethodsfordiagnosingCDIintheUnitedStatesbecauseoftheirlowcost,easeofuse,andrapidturn-aroundtime.SomeassaysdetectonlytoxinA,whereasothersdetectbothtoxinsAandB.Thisisanimportantdistinction.TherearesomestrainsofC. difficilethatproduceonlytoxinB.ThesestrainsarecapableofproducingthesamespectrumofillnessasstrainsthatproducebothtoxinsAandB.52ThesestrainsaremissedbyEIAsthatonlydetecttoxinA.AlthoughthereareseveraladvantagesofEIAscomparedtocellcytotoxicityassaysasmentionedabove(lowercost,easeofuse,andrapidturn-aroundtime),thesensitivityoftheseassaysrangefrom63%to94%,withaspecificityof75%to100%comparedtocellcytotoxicityassays.52

Glutamatedehydrogenase(GDH)isaproteinproducedbyC. difficile,andassaysareavailabletodetectGDHinstool.Initially,itwasthoughtthatthisassaywasspecificforC. difficile, butitwassubsequentlydemonstratedthatotherbacterialstrainscancross-reactwiththisassay.52Theseassaysarerelativelylow-costandrapid.NewerassaysforGDHhaveasensitivityof85-95%andspecificityof89-99%.62ThisassayisnotspecificforC. difficileand

Laboratory Test Advantages Disadvantages

Toxinenzymeimmunoassay(EIA) Inexpensive.Rapid.

Lesssensitivethancellcytotoxicityassay.SomeonlytestfortoxinA.

Cellcytotoxicityassay MoresensitivethantoxinEIAassays.

Notalllaboratoriesabletoperformthetest.48-72hoursforresults.

Glutamatedehydrogenaseassay Rapid.Inexpensive.Sensitive.Canbeusedasinitialscreen.

Notspecific(detectsnon-toxigenicC. difficileandotherbacteria).

StoolcultureforC. difficile Mostsensitivetest.ProvidesC. difficileisolates.

Notspecific(detectsnon-toxigenicC. difficile).Laborintensive.Cantakemorethan72hoursforresults.

Table �.1. Comparison of different laboratory-based diagnostics tests for CDI.



detectssomestrainsofC. difficile thatdonotproducetoxin(andareunabletocausedisease);thereforethisassayshouldnotbeusedalonetodiagnoseCDI.52

BecauseofthehighnegativepredictivevalueofGDHassays,severalinvestigatorshavestudiedtheGDHassayasascreeningtest.61,62,63StoolwithanegativeGDHassayisreportedassuchandnofurthertestingisperformed.StoolpositiveforGDHisthentestedfortoxinwithacellcytotoxicityassay.StoolpositivebythecellcytotoxicityassayisdiagnosticforCDI;stoolnegativebythecellcytotoxicityassayisreportedasnegative.Thetwo-stepapproachisabletorapidlyidentifypatientswithoutCDI(negativeGDHassay),whileutilizingthemoresensitivecellcytotoxicityassaytoidentifypatientswithCDI.Thisapproachmayalsobemorecost-effectivethanuseofthecellcytotoxicityassayalone.63

Undertheproperconditions,stoolcultureisthemostsensitivelaboratorymethodfordetectingC. difficile.However,becauseoftheexpenseandtimerequiredforculture,itisrarelyperformedintheU.S.CharacteristiccolonymorphologyandgramstainappearanceareoftensufficientforidentifyingC. difficile.C. difficile isolatesshouldbetestedfortoxinproductiontoestablishthediagnosisofCDIbecauseasmanyas25%ofC. difficileisolatesdonotproducetoxinandareincapableofcausingCDI.52Stoolcultureisnecessarytoperformmolecularfingerprinting,andisthereforeausefultoolinevaluatingoutbreaks,sourcesofinfectionandcontrolmeasures.

Molecular TypingThereareseveralmoleculartypingtechniquesforC. difficile,butthesearenotroutinelyavailableoutsideofresearchlaboratories.Duetotherelianceontoxinassays,culturesforC. difficilearenotroutinelyperformedtodiagnoseCDI,andisolatesareinfrequentlyavailableformoleculartyping.Whilemoleculartypingisnecessaryforin-depthepidemiologicalstudiesofC. difficile andishelpfulwhenchangesinCDIepidemiologyoccur,itisnotnecessaryforroutinepatientcare.

Non-laboratory Based TestsCDIisthecauseofmorethan90%ofcasesofpseudomembranouscolitis(PMC)andcanbediagnosedwithdirectvisualizationofpseudomembranesbysigmoidoscopyorcolonoscopy.SomepatientsmaynothavePMCidentifiedbydirectvisualization,buthaveevidenceofPMConhistopathology.AlthoughconsidereddiagnosticforCDI,PMCisidentifiedinonly50%ofcasesofCDI.64

AbdominalCTscansarehelpfultosuggestthediagnosisofCDIifcolitisisidentifiedinapatientwithabdominalpainorileus.However,thesescansshouldnotbereliedupontoruleinorruleoutthediagnosisofCDIduetotheirpoorsensitivityandspecificity.65,66AbdominalCTscanfindingsalonealsodonotcorrelatewithseverityofCDI.65,66



Surveillance

Surveillanceisdefinedastheongoing,systematiccollection,analysis,interpretationanddisseminationofdataregardingahealth-relatedevent,usedtoreducemorbidityandmortalityandtoimprovehealth.Surveillancemayinvolveprocessmeasures(e.g.,handhygiene,adherenceratestospecificprotocols,etc.)oroutcomemeasuressuchasinfectionrates,deathrates,lengthsofstay,orcostsofcare.Outcomemeasuresareparticularlyimportanttoevaluatetheeffectivenessofinfectionpreventioneffortsandidentifyingindicationsforchange.7

Theessentialcomponentsofahealthcaresurveillancesystemare:• Standardizeddefinitions• Identificationandmonitoringofpopulationsatriskforinfection• Statisticalanalysis(calculationofratesusingappropriatenumeratorsanddenominators,trendanalysis

usingcontrolchartstoidentifyhigh-incidenceareasandtomonitortrends)• Feedbackofresultstotheprimarycaregivers7

• Feedbacktomanagers,directors,andtoseniorleadership,includingadministratorsandeventheboardofdirectorsortrustees

Ataminimum,everyhealthcarefacilityshouldhavetheabilitytoidentifyclustersofinfections,knowhowtoconductasystematicepidemiologicinvestigationtodeterminecommonalitiesinpersons,placesandtime,anddevelop,implementandevaluatepreventionmeasures.ForC. difficile,thiscanbeaccomplishedthroughmonitoringofclinicaldisease,orbyusingaproxymeasure,laboratory-basedsurveillanceindicator.

Case Definitions for Clinical CDI SurveillanceStandardizedcasedefinitionsarecriticaliftheinformationisgoingtobeusedtocompareoneunitorfacilitywithanother,tomonitortrendsovertime,ortoevaluatetheeffectivenessofinterventionstoreduceinfections.30ThedefinitionsproposedbyMcDonaldetal.aresummarizedhereandrecommendedforsurveillancepurposes.30Itisimportanttorememberthatsurveillancedefinitionsarenotnecessarilythesameasclinicaldefinitionsandmaynotbeappropriateforclinicaldecision-makingandtreatment.

AcaseofCDIisdefinedasanindividualpatientwiththesymptomofdiarrhea(unformedstoolthatconformstotheshapeofaspecimencollectioncontainer)ortoxicmegacolon(abnormaldilationofthelargeintestinedocumentedradiologically)withoutotherknownetiologyinwhich:

1. thepatienthasadiarrhealstoolsamplepositiveforC. difficiletoxinAand/orB,oratoxin-producingC. difficile

OR2. pseudomembranouscolitisisfoundduringsurgeryorendoscopically OR3. pseudomembranouscolitisisseenduringhistopathologicalexamination.30

Healthcare Facility-onset, Healthcare Facility-associated CDIAhealthcarefacilityisdefinedasanyacutecare,long-termacutecareorotherfacilityinwhichskillednursingcareisprovidedandpatientsareadmittedatleastovernight.30



Apatientclassifiedashavinghealthcare facility-onset, healthcare facility-associated CDIisdefinedasapatientwhodevelopsdiarrheaorCDIsymptomsmorethan48hoursafteradmissiontoahealthcarefacilityandfulfillscriterion1,2,or3definedabove.30TheNationalHealthcareSafetyNetwork(NHSN)hasfurtherclarifiedthistobethethirdcalendardayafteradmission.

Healthcarefacility-onset,healthcarefacility-associatedCDIisalso defined as a patient who develops diarrhea or CDI symptoms less than 48 hours after discharge from a healthcare facility and fulfills criterion 1, 2, or 3 defined above.

Community-onset, Healthcare Facility-associated CDIApatientclassifiedashavingcommunity-onset, healthcare-facility associated CDIisdefinedasapatientwithCDIsymptomonsetinthecommunityor48hoursorlessafteradmissiontoahealthcarefacility,providedthatsymptomonsetwaslessthanfourweeksafterthelastdischargefromahealthcarefacility.30

Community-associated CDIApatientclassifiedashavingcommunity-associated CDIisdefinedasapatientwithCDIsymptomsonsetinthecommunity,or48hoursorlessafteradmissiontoahealthcarefacility,providedthatsymptomonsetwasmorethan12weeksafterthelastdischargefromahealthcarefacility.30

Indeterminate or Unknown CDIApatientwhodoesnotfitanyoftheabovecriteriawouldbedefinedashavingindeterminate or unknown CDI.30

Recurrent CDIApatientwithrecurrentCDIisdefinedasonewithanepisodeofC. difficilethatoccurseightweeksorlessaftertheonsetofapreviousepisodethatresolvedwithorwithouttherapy.Table7.1showstheseorganizeddefinitions.

Case Type Definition

Healthcarefacility-onset,Healthcarefacility-associated(HO-HCFA)

CDIsymptomonsetmorethan48hoursafteradmission(thirdcalendarday).

Community-onset,healthcarefacility-associated(CO-HCFA)

CDIsymptomonsetinthecommunity,orwithin48hoursfromadmission,providedsymptomonsetwaslessthanfourweeksafterthelastdischargefromahealthcarefacility.

Community-associated(CA-CDI)

CDIsymptomonsetinthecommunity,orwithin48hoursafteradmissiontoahealthcarefacility,providedsymptomonsetwasmorethan12weeksafterthelastdischargefromahealthcarefacility.

Indeterminateorunknownonset CDIcasepatientwhodoesnotfitanyoftheabovecriteria.

RecurrentCDI EpisodeofCDIthatoccurseightweeksorlessaftertheonsetofapreviousepisode,providedthesymptomsfromthepriorepisoderesolved.

Table �.1. Surveillance definitions for C. difficile infection.



Figure7.1providesavisualtimelinethatmaybeofassistanceinapplyingthedefinitions.Casepatientswithsymptomonsetduringthewindowofhospitalizationmarkedbyanasterisk(*)wouldbeclassifiedashavingcommunity-onset,healthcarefacility–associateddisease(CO-HCFA),ifpatientwasdischargedfromahealthcarefacilitywithintheprevious4weeks;wouldbeclassifiedashavingindeterminatedisease,ifthepatientwasdischargedfromahealthcarefacilitybetweentheprevious4-12weeks;wouldbeclassifiedashavingcommunity-associatedCDI(CA-CDI),ifthepatientwasnotdischargedfromahealthcarefacilityintheprevious12weeks;ifsymptomonsetmorethan48hoursafteradmission;wouldbeclassifiedashaving,healthcarefacility–onset,healthcarefacility–associatedCDI(HO-HCFA).30

Forsurveillancepurposes:1. Asymptomaticpatientwithanadditionalpositivetoxinassaywithintwoweeksorlessafterthelast

specimentestedpositiveisacontinuationofthesameCDIcaseANDnotanewcase.2. Asymptomaticpatientwithanadditionalpositivetoxinassaywithintwotoeightweeksafterthelast

specimentestedpositiveisarecurrent CDIcaseANDnotanewcase.3. Asymptomaticpatientwithanadditionalpositivetoxinassaymorethaneightweeksafterthelast

specimentestedpositiveisanew CDIcase.30

Conducting SurveillanceDependingonthepurposesofsurveillance,alloronlysomeoftheaboveCDIcasedefinitionsmaybeappropriateforuse.30BecauseinpatientstayinahealthcarefacilityisarecognizedriskfactorforCDI,the initial purpose of surveillance in a healthcare facility should be to first track and compare healthcare facility-onset, healthcare facility-associated CDI.

Surveillanceshouldbefacility-wideandalinelistmaintainedinaretrievabledatabasefile,suchasMicrosoftExcel,MicrosoftAccess,SPSS(StatisticalPackagefortheSocialSciences),oranothersuchelectronicmeans.Thedatabaseshouldincludeatleastthefollowing:

• Patientidentification(nameoruniqueidentifier,suchasmedicalrecordnumber)• Dateofbirth• Admissiondate• Patientlocation(unitandroom)atthetimeofstoolcollection• CDIsymptomonsetdate(e.g.diarrhea)• Stoolcollectiondate• Dischargedate

Otherinformationmayalsobecollected,includingelementssuchasunderlyingdiagnosis,treatment(e.g.antibiotics),procedures(e.g.endoscopy,surgicalinterventions),oradditionalcircumstancesthatmayhaveled

Admission Discharge

48 h 4 weeks 8 weeksSymptom onset

(*) HO-HCFA CO-HCFA Indeterminate CA-CDI

Figure �.1. Timeline for definitions ofTimeline for definitions of Clostridium difficile infection (CDI) exposures.Source: Adapted from McDonald LC, Coignard B, Dubberke E, et al., 2007. Copyright © 2007, Society of Healthcare Epidemiology of America.


ASSOCIATION FOR PROFESSIONALS IN INFECTION CONTROL AND EPIDEMIOLOGY 21

toexposureoracquisitionrisks.Inaddition,itmaybehelpfultonoteif/whenapreviousadmissiontookplace,residenceorlocationpriortoadmission(transferfromanotherhealthcarefacility,includinglong-termcarefacility),anddischargestatus(death,dischargetoextended/long-termcare,residence,etc.).

CDI RatesDenominatorforCalculationofCDIRates30

• Ratesshouldbeexpressedasnumberofcasepatientsperreportingperiod(usuallypermonth)per10,000patientdays.

• Thecalculationofthisrateis(numberofCDIcasepatientspermonth/numberofinpatientdayspermonth)x10,000=rateper10,000inpatientdays.

• Thisratereflectstheper-daypatientriskforCDIandisusefulacrossdifferenttypesofhealthcarefacilitieswithvaryinglengthsofpatientstay.

• Thisratecanbeusedforcomparingfacility-wideCDIrateswithotherorganizationsaswellasforcomparingdifferentunits,wardsand/orserviceswithinagivenhealthcarefacilityinwhichunit-specific/ward-specific/service-specificdenominatorsareavailable.

Expression of CDI Rates for Feedback to Caregivers and Comparative PurposesControl charts

ControlchartsmaybecreatedtodisplaythenumberofCDIcasesorratesfortheentirehealthcarefacility,and/orbyunit/ward/service.

• TheX-axisisthesurveillancetimeperiod(month).• TheY-axisisthenumberofCDIcasesorCDIrate.• Controlchartsareusefultodetermineiftherateofahealthcarefacilityand/orunit/ward/serviceisoutof

range,andtomonitortrends.• Controlchartscanbeusedtodemonstratedifferentaspectsofsurveillance,usingaseparatechart

foreachofthefollowing:healthcarefacility-onset,healthcarefacility-associated;community-onset,healthcarefacility-associated;community-associated;indeterminate;orrecurrentCDI.Theemphasisshouldbeonprovidinginformationandthemonitoringofoutcomesrelevanttothefacilityandthecommunity.

• Controlchartscanbepostedonindividualpatient-careunitsandusedduringeducationalin-servicessostaffcanunderstandwhatthechartsreflectandalsoseetheresultsofinterventionsputintoplacetoreduceCDIrates.AnexampleofacontrolchartisprovidedinFigure7.2.

• TheuseofcontrolchartsisavaluabletoolinmonitoringratesofCDIaswellasprovidingvisualrepresentationofwhenratesareinoroutofstatisticalcontrol.

UsingthecontrolchartshowninFigure7.2,whentherateofCDIexceedsthreestandarddeviations,thiscanbeatriggerforimplementationofheightenedinterventionsusingatieredapproach.Theappropriateuseofcontrolchartsandidentificationoftriggerstoguideinterventionsisanimportanttopicofdiscussionintheinfectionpreventionandcontrolcommittee.Forexample,aninitialuseofthreestandarddeviationsfromthemeanmaybetheplacetostartwithregardtothattrigger.Astimegoesonandratesmoveclosertozero,thecommitteemaychoosetoadjustthetriggersorelecttoexploreotherrulesforspecialcausemonitoring.

Formoreinformationregardingcontrolcharts,refertotheworkdonebyJ.C.BenneyaninICHEandareviewofstatisticalprocesscontrolbyAmininQuality Management in Health Care.67-69



Other monitoring toolsTheinfectionpreventionistmayalsofindothertypesofchartsorfigurestobehelpfulwhenmonitoringratesaswellastemporaldocumentingofinterventions.Figure7.3demonstratesarun chartdevelopedusingEpiGraphics(availablefromAPIC).

Runchartsshowtherateovertime,andenabletheinfectionpreventionisttoaddtextboxesdescribingspecificinterventionsandwhentheywereperformed.Chartssuchasthiscanbeofhelpwhenprovidingacomprehensiveoverviewofactivitiesandoutcomestogroupssuchasmedicalstaff,administration,andaccreditationsurveyors.

Anepidemic curve(epicurve)canbeusedtopresentagraphicdepictionofthenumberofcasesofillnessbythedateofillnessonset.Anepicurvecanprovideinformationonthepatternofspread,magnitudeoftheevent,outliercases,andtimetrend.

Laboratory-based Surveillance for C. difficileLaboratory-basedsurveillancemayalsobeconsideredasasimplifiedoptionorproxymeasureratherthanconductingsurveillanceforclinicaldiseasewithchartreview.ThisshouldbeperformedsolelyinconjunctionwithlaboratoriesthatonlytestunformedstoolsamplesandlaboratoriesthatdonotperformscreeningculturesortoxinassaysforcolonizationwithC. difficile,allofwhicharediscouraged.

Figure �.2. Control chart example.



Laboratory-basedsurveillancecanbeconductedfortheentirefacilityorbyspecificunit/location.Thedenominatorshouldbepatientdaysfortheentirefacilityorbyspecificunit/location,respectively.

Inanefforttoensurethatapatienthasbeeninthefacilityforaminimumof48hours,withoutreviewingthemedicalrecordfortheexacttimeofadmissionanddateandtimeofonset(asisdoneforclinicaldiseasesurveillance),acaseoflaboratory-basedhealthcarefacility-onsetdiseaseshouldbelimitedtothosepatientswithC. difficilefirstdetectedonoraftercalendardaythreeafteradmission(morethan48hoursafteradmission).

Bymaintaininganongoinglinelistofpositivepatients,incidentorrecurrentdiseasecanalsobeascertained.AneworincidentcaseisdefinedasanewpatientwithC. difficileoroneinwhomthelastpositivespecimenwasobtainedmorethaneightweeksafterapreviouspositive.Arecurrentcaseisdefinedasapatientwithapositivespecimenobtainedmorethantwoweeks,butlessthanorequaltoeightweeksafterapreviouspositivespecimen.Ifapatienthasanotherpositivespecimenwithintwoweeks,thisisconsideredacontinuationoftheinfectionandshouldnotbecountedagain.

IncidentcasesofCDIshouldbemonitoredfortheentirefacilityorbyspecificlocationstodetecttrendsandpossibleoutbreaks.Recurrentdiseaseshouldbemonitoredtoevaluatetheeffectivenessoftreatment.ControlchartscanbecreatedinthesamemannerasdescribedaboveforclinicalCDI,butshouldbeclearlytitledtoreflectthattheinformationisbaseduponlaboratory-basedsurveillancedata.

TheCentersforDiseaseControlandPreventionwillbeincorporatingalaboratory-basedC. difficilemoduleintotheNationalHealthcareSafetyNetworkforhospitalswantingtomonitorandcomparetheirC. difficilerates.

Figure �.�. Example of a run chart with text boxes noting interventions.



Focusing on Prevention: Contact Precautions

Earlyrecognitionofpatientswhoaresuspectedtohave,orwhoarediagnosedwith,CDIisthefirststepinpreventingthespreadofthisepidemiologicallysignificantorganism.C. difficilecanbespreadbydirectandindirectcontactwiththepatientorthepatient’senvironment,andtherefore,patientswiththisorganismshouldbeplacedonContactPrecautionsasrecommendedintheHICPAC/CDCGuidelineforIsolationPrecautions.7AdherencetothecomponentsofContactPrecautionswillhelptobreakthechainofinfection.FecalincontinenceandanincreasedpotentialforextensiveandprolongedenvironmentalcontaminationmakepatientswithCDIasignificantthreatfordisseminationandtransmissionofthedisease.ThefollowingcomponentsofContactPrecautionsshouldbeobservedforallpatientssuspectedof,ordiagnosedwith,CDI.

1. Patient PlacementPatientsshouldbeassignedtoaprivateroomwithabathroomthatissolelyforusebythatpatient.Whenprivateroomsareoflimitedavailability,patientswhoarefecallyincontinentshouldpreferentiallybeassignedtothoseprivaterooms.Ifaprivateroomisnotavailable,theinfectioncontrolteamshouldassesstherisksandworkwiththepatientcareteamtodeterminethebestpatientplacementoptions(e.g.,cohortwithanotherpatientdiagnosedwithCDIandnootherdiscordantorganisms,orkeepingthepatientwithanexistingroommate).IfbothpatientshaveCDIandarecohorted,oncethediarrheastopsforoneperson,thatpatient,ifpossible,shouldbetransferredtoacleanroom.70

Inmanycaresettings,suchasrehabilitationprograms,long-termcareinstitutionsorresidentialsettings,privateroomsmaynotbeavailable.Thecareteamneedstodetermineifaroomshouldbeclosedofftootherpatients.Theteamshouldhaveadministrativesupporttotakethisadditionalprecautionarystep.Inthemulti-patientroomsettingwhereisolationinasinglepatientroomisnotpossible,otheractivitiesmaybeconsidered,includingtheuseofatleastathree-footspatialseparationbetweenbedstoreducetheopportunitiesforinadvertentsharingofitemsbetweentheinfected/colonizedpatientandotherpatients.Itmaybeprudenttodrawaprivacycurtainbetweenpatientstopromoteseparation.Somefacilitiesuseavisualqueue,suchascoloredtapeplacedonthefloor,inordertoidentifyareaswhererestrictedaccessanduseofadditionalprecautionsareneeded.

2. Personal Protective Equipment (PPE)Barrierprecautionsarecriticaltopreventtransmissionfromthepatienttothehealthcareworkerandthentoanotherpatient.PPEmustbedonnedbeforegoingintotheroomorcubicleanddiscardedbeforeexitingthepatient’sroom/cubicle.VisittheCDCwebsite(www.cdc.gov/ncidod/dhqp/ppe.html)foravideoandpostersillustratingproperPPEdonningandremovalprocedures,entitled“GuidancefortheSelectionandUseofPersonalProtectiveEquipment(PPE)inHealthcareSettings.”

a. GlovesGlovesmustbedonnedbeforeenteringtheroomandwornbyallhealthcareprovidersduringpatientcareandwhenincontactwiththepatient’senvironment.Glovesshouldalsobechangedaccordingtostandardrecommendationsforglovesutilization(e.g.,ifheavilycontaminatedortorn),andremoved/discardedasthehealthcareproviderleavestheroom.Contactwiththepatientandthepatient’senvironmentcanexposethehealthcareworkertovegetativeClostridium difficileanditsspores.High-touchsurfaces(e.g.,bedrails,lightswitches,faucets)areaknownsourceofC. difficilespores.C. difficilemayalsobefoundatmultipleskinsitesofpatientswithCDI,includinggroin,chest,abdomen,forearm,andhands,andcouldbetransferredtothecareprovider’shands.Thiscolonizationcanpersistafterthecessationofdiarrhea.71

b. GownsHealthcareworkersshoulddonandweargownsandgloveswhenenteringaroomtoprovidecaretoapersononContactPrecautions.Theuseofglovesalonemaybeaseffectiveinpreventingtransmission



astheuseofglovesandgownstogether.72However,untilconclusivedataisgenerated,gownsshouldcontinuetobewornwithglovesforallinteractionsthatmayinvolvecontactwiththepatient,contaminatedequipment,orpotentiallycontaminatedareaswithinthepatient’senvironment.

ProtectiveequipmentandpersonalitemssuchasclothinganduniformsmaybecomecontaminatedaftercareofapatientcolonizedorinfectedwithaninfectiousagentsuchasC. difficile.Althoughcontaminatedclothinghasnotbeenimplicateddirectlyintransmission,thepotentialexistsforsoiledgarmentstotransferinfectiousagentstosuccessivepatients,andinlightoftheseverityofCDI,liberaluseofPPEisappropriate.73

3. Patient Transport WhenapatienthasCDI,patienttransportationandmovementoutsidetheroomorcubicleshouldbelimitedtomedicallynecessarypurposes.Patientsshouldbetaughttoperformhandhygienepriortomovementfromtheirroom.Thesestrategiescanhelpcontainandlimitsheddingintotheenvironment.AccordingtotheHICPACIsolationGuideline,thetransportershouldremoveanddiscardcontaminatedPPEandperformhandhygienepriortotransportingpatientsonContactPrecautions.CleanPPEshouldbedonnedtohandlethepatientatthetransportdestination.Thepatient’sisolationstatusshouldbecommunicatedtothereceivingunitpriortotransport,sothatunitpersonnelareabletoaccommodatethespecialneedsofthatpatient.

4. Patient Care Equipment, Instruments, Devices and the Environment C. difficilecontaminatespatientcareequipmentanddevicesthroughfecalsheddingorthroughthecontaminatedhandsofpatientorhealthcareprovider.TheabilityofC. difficiletosurviveonenvironmentalsurfacesdemandsadherencetorecommendedmeasurestopreventcross-contamination.OngoingtransmissionofC. difficilemaybeamarkerforpooradherencetoenvironmentaldecontaminationandotherinfectionpreventionmeasures.Theinfectioncontrolteamshouldobservepersonnelandmeasureadherencetoappropriatehealthcarepractices,especiallywhenongoingtransmissionoccurs,inordertoidentifyanybreachesininfectionpreventionpractice.

C. difficilesporescanpersistformonthsinthehealthcareenvironmentandbetransmittedtopatientsduringthistime.Fecalcontaminationofsurfaces,devices,andmaterials(e.g.,commodes,bathingtubs,andelectronicrectalthermometers)55mayprovideareservoirfortheC. difficilespores,whichleadstotransmission.High-touchsurfacesandequipmentmustbethoroughlycleanedanddisinfectedtoremoveand/orkillspores.Useofanindividualbedsidecommodeforeachpatientreducestheriskoftransmissionofinfectiousagents.Whenabedsidecommodeisused,thestaffmustuseappropriatePPEandemptywasteinamannerthatpreventssplashing.Thecommodemustalsobecleanedanddisinfectedafterwasteisdiscarded.

Eachhealthcarecaresettingshouldhaveaplantocleananddisinfectsurfaceswhenfecalcontamination(e.g.,uncontrolleddiarrhea)hasoccurred.Personnelshouldbesuretocleananddisinfectallpatientcareequipmentthathasbeencontaminated.Reusableequipmentmustbecleanedanddisinfectedbetweenpatients.Wheneverpossible,eachpatientshouldbeassignedhisorherownequipmenttominimizecross-contamination.

5. Discontinuing Contact PrecautionsItiscurrentlyrecommendedthatContactPrecautionsmaybediscontinuedwhenthepatientnolongerhasdiarrhea.7Becauseofcontinuedenvironmentalcontaminationandpatientskincolonization,someexpertsrecommendcontinuingcontactprecautionsfortwodaysafterdiarrheastops.74ThisisoneexampleofheightenedresponseactivitiesandwillbediscussedinmoredetailinthesectionaddressingatieredapproachtoCDItransmissionprevention.

6. Assessing Adherence to Isolation PrecautionsAssessingadherencewithisolationprecautionsisanimportantelementinprevention.Figure8.1providesanexampleofatoolusedtomonitoradherence.Thistoolisalsoavailableatwww.apic.org/eliminationguides.



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Focusing on Prevention: Hand Hygiene

PreventionofCDIdemandsmeasurement,assessment,andevaluationofcurrenthandhygienepractices.C. difficiletrumpsallotherhealthcare-associatedinfectionsforthepolarizedapproachesregardingthebesthandhygienepracticestopreventtransmission.UnderstandingoftheincidenceofCDIinyoursetting,barrierstoperformanceofhandhygiene,andenvironmentalcleanlinesswillhelpyourteamselecttherightepidemiologically-driveninterventionstopreventtransmissionofthisorganism.

AccordingtotheCDCHICPAChandhygieneguidelines,healthcareproviderhandsarefrequentlycontaminatedwithC. difficile followingpatientcontact.WearingglovescansignificantlyreducethespreadofC. difficile inhospitals.Currentinformationontheneedtousetraditionalhandwashing,ascomparedtousingalcoholhandrubs,isconflicting.Commonantimicrobialagents(includingalcohols,chlorhexidine,hexachlorophene,iodophors,PCMX,andtriclosan)forhandwashingarenotactiveagainstspores.Thebenefitofhandwashingwithsoapandwateristhephysicalremovalanddilutionofsporesfromthehands,ratherthanthekillingofspores.54

Afterglovesareremoved,healthcareproviders’handsshouldbewashedwithanon-antimicrobialoranantimicrobialsoapandwater,ordisinfectedwithanalcohol-basedhandrub.76Hospitalsusingalcohol-basedhandrubsastheirprimarymeansofhandhygienehavenotseenincreasesintheincidenceofCDIassociatedwiththeirintroduction. TheincreasedincidenceofCDInotedinnumeroushospitalshasbeenattributedtotheintroductionoftheepidemicC. difficilestrainNAP1andnotduetoincreaseduseofalcoholbasedhandrubs.77However,duringoutbreaksorevidenceofon-goingtransmissionofC. difficile-relatedinfectionsinaninstitution,washinghandswithanon-antimicrobialorantimicrobialsoapandwaterafterremovingglovesandotherpersonalprotectiveequipment(PPE)isprudent.

Inanintensivecareunitstudythatcharacterizedhealthcareworkers’(HCW)encounterswithpatientsandcorrelatedthattotheirhandhygienecompliance,itwasnotedthathandhygienecompliancewasthelowestafterbriefencountersoflessthantwominutes.Theobserversnotedthatbriefencountersmadeupasubstantialportionofthecontactandhealthcareworkershadopportunitiesforhandhygieneduringallbriefencounters.TheauthorsconcludedthatHCWeducationandtrainingshouldincludespecialemphasisonthepotentialforhandcontaminationevenduringbriefencounters,andshouldstresstheimportanceofhandhygiene.InlightofhypervirulentstrainsandtheincreasingincidenceofCDIandotherepidemiologically-significantorganisms,thosemissedopportunitiespresentarealriskoftransmission.77

• SeveralresourcesforhandhygieneeducationalmaterialsareprovidedinTable9.1.AnexampleprovidedbyAPICisshowninFigure9.1.(Thesematerialsarealsoavailableatwww.apic.org/eliminationguides).

Teaching patient hygiene including hand hygiene and bathingFamilies,visitorsandpatientsshouldbepartnersinpreventingCDI.Therehavebeenseveralnationalinitiativesencouragingpatientstotakeanactiveroleintheircare.Aninformedpatientpromotesunderstandingoftheircare.Educationshouldinclude:

• ExplanationoftheinfectioncausedbyC. difficile• Reviewofthespectrumofdiseaseandre-occurrences• Discussionofhowtheorganismisspread• Descriptionofwhatthepatientcandotohelpreducethespreadofthedisease• EducationofpatientsandtheirfamiliesaboutvisitorswhomaybeathighriskforacquiringC. difficile, such

asindividualsonantibiotics,orwhoareimmunosuppressed,andhelpingthemdecideabouttheirvisitations



WHO Guidelines on Hand Hygiene in Health Care (Advanced Draft): A Summary. WorldHealthOrganization;2005.Availableathttp://www.who.int/patientsafety/events/05/HH_en.pdfandhttp://www.who.int/gpsc/tools/en/

IHI How-to Guide: Improving Hand Hygiene “A Guide for Improving Practicesamong Health Care Workers.” ThisguidewasacollaborateeffortbetweentheCentersforDiseaseControlandPrevention(CDC),theAssociationforProfessionalsinInfectionControlandEpidemiology(APIC),andtheSocietyofHealthcareEpidemiologyofAmerica(SHEA),andhasbeenendorsedbyAPICandSHEA.ValuableinputalsowasprovidedbytheWorldHealthOrganization’sWorldAllianceforPatientSafetythroughtheGlobalPatientSafetyChallenge.(Thisdocumentisinthepublicdomainandisavailableonwww.IHI.org.ItmaybeusedorreprintedwithoutpermissionprovidedappropriatereferenceismadetotheInstituteforHealthcareImprovement).

Hand Hygiene for Health Care Settings. OntarioMinistryofHealthandLong-TermCare/PublicHealthDivision/ProvincialInfectiousDiseasesAdvisoryCommittee;May2008.ToreviewtheHandHygieneFactSheetwithsupportingevidencegoto:http://www.health.gov.on.ca/english/providers/program/infectious/pidac/fact_sheet/fs_handwash_010107.pdf

APIC http://www.apic.org/AM/Template.cfm?Section=Search&section=Brochures&template=/CM/ContentDisplay.cfm&ContentFileID=298http://www.preventinfection.org/Content/NavigationMenu3/InformationCenter/HandHygiene/default.htm

TheJoint Commissionhasbeenworkingwithleadinginfectionpreventionandcontrolorganizationsandhandhygieneexpertstodevelopaneducationalmonographtoguidethefieldinmeasuringadherencetohandhygieneguidelines.Themonographwillofferguidanceonsettingmeasurementgoalsandwillexploretheprosandconsofthethreemajorapproachestomeasuringhandhygiene.Themonographwillcontainextensiveresources,includingorganization-specificexamplesofmeasurementtoolsandlinkstohelpfulwebsites.Themonographisexpectedtobeavailableinfallof2008andwillbepostedontheAPICwebsite.

CDC’s Hand Hygienesitecontainspostersandeducationalprogramsaswellasaninteractiveeducationalprogram.http://www.cdc.gov/Handhygiene/

John Boyce and St. Raphael’ssiteprovidesaPowerPointpresentationforeducatingstaffandhandhygienemonitoringtools.http://www.handhygiene.org/

Henry the Handprovidescampaignslidesandprogramstouseindevelopingalocalhandhygienecampaignandincreasingcompliance.http://www.henrythehand.com/

Soap and Detergent AssociationEducationalmaterialsarepresentedonthissite.http://www.cleaning101.com/newsroom/2005_survey/handhygiene/

Table �.1. Resources for hand hygiene educational materials.



Figure �.1. Sample hand hygiene educational material. Source: APIC.


�0 ASSOCIATION FOR PROFESSIONALS IN INFECTION CONTROL AND EPIDEMIOLOGY

• DescriptionofhowtopreventtransmissionofC. difficile,includingContactPrecautions,StandardPrecautions,andhandhygiene

• Identifyingstepsthatpatientsandfamilycantaketocleantheirenvironmentathome

AsuccessfulpatientandfamilyeducationprogramcangaincooperationwithfollowingContactPrecautionswhileinthehospital.79Handhygiene,especiallyhandwashing,willbecriticalinminimizingthespread.Nursingstaffshouldassistthepatientinhandhygieneifthepatientcannotdoit,especiallyaftertoiletingandbeforeeating.Nursingstaffshouldeducatethefamilyabouttheriskfactorsfortransmission.

PatienteducationshouldincludetheimportanceofbothhandhygieneandshoweringtoreducethebioburdenofC. difficileontheirskin.Ifapatientisunabletoshower,bedbathsshouldbeperformed,withthestaffassistingasneeded.Acleanhospitalgown/clothingshouldbedonnedafterbathingorshowering.Freshbedlinensarealsoimportant,sincethepatientmaycontinuallyshedthebacteriaanditsspores,creatingheaviercontaminationonusedlinens.

Table9.2isasamplehandoutthatcanbeusedforpatient/familyeducationregardingC. difficile.(Thistableisalsoavailableatwww.apic.org/eliminationguides).

Patient and Family Education Regarding Clostridium difficile Infection (CDI)What is Clostridium difficile? Clostridium difficile is a bacterium that causes diarrhea as well as more serious intestinal conditions such as colitis, aninflammationofthebowel.

What is Clostridium difficile infection? Clostridium difficileisthemostcommoncauseofinfectiousdiarrheainhealthcarefacilities.Themainsymptomsincludewaterydiarrhea,fever,andabdominalpainortenderness.Clostridium difficile infectionmayoccurasanundesirableconsequencewhenantibioticsaretakentotreataninfection.Whentreatingthatinfection,someofyourgoodbowelbacteriaarealsokilledtherebyallowingthebacteriathatarenotkilledbytheantibioticstogrow.OneofthesebacteriathatareresistanttomanyantibioticsisClostridium difficile.WhenClostridium difficilemultiplies,itproducestoxinsorsubstancesthatcandamagethebowelandcausediarrhea.Clostridium difficileinfectionresultsindiarrhearequiringspecifictreatmentanditcansometimesbequitesevere.Inseverecases,surgeryresultinginremovalofaportionoftheintestinesmaybeneeded.

Who can develop Clostridium difficile infection? Clostridium difficile infection,alsoknownasCDI,usuallyoccursduringorafter theuseofantibiotics.Those individualshavingseriousillness,theelderly,orthoseinpoorgeneralhealthareatincreasedriskofdevelopingCDI.

How is Clostridium difficile infection diagnosed? Ifyouareonantibiotics,orhaverecentlytakenantibiotics,andyoudevelopwaterydiarrheaandfever,yourdoctormaysuspectClostridium difficileasacauseofthosesymptoms.Asampleofyourstool(feces)willbecollectedandsenttothelaboratoryforanalysis.ThelaboratorywilltestthestooltoseeifClostridium difficiletoxinsarepresent.Oneormorestoolsamplesmaybecollected.

How is Clostridium difficile infection treated? YourdoctormayprescribeaspecifictypeofantibioticthattargetsandkillsClostridium difficile.Treatmentusuallyconsistsofantibioticstakenforabout10days.

How do people get Clostridium difficile infection? Peopleingoodhealthusuallydon’tget C. difficile infection.Peoplewhohaveotherillnessesorconditionsrequiringprolongeduseofantibioticsandtheelderlyareatgreaterriskofacquiringthisdisease.WhenapersonhasClostridium difficileinfection,

Table �.2. Patient and family education.


ASSOCIATION FOR PROFESSIONALS IN INFECTION CONTROL AND EPIDEMIOLOGY �1

thegermsinthestoolcansoilsurfacessuchastoilets,handles,bedpans,orcommodechairs.Whentouchingtheseitems,thehandsofthepatientaswellasthehandsofhealthcareworkersandfamilymemberscanbecomesoiledwithClostridium difficile.Thesesoileditemsandhandscanbeinvolvedinmovingtheorganismtoothersurfacesandotherpeople.ThisiswhyanindividualwithClostridium difficileinfectionisplacedinisolationwheninahealthcaresetting.

What type of isolation is used for Clostridium difficile infection? IfyouhaveClostridium difficilediarrhea,youwillbemovedtoaprivateroomuntilyouarefreefromdiarrhea.Youractivitiesoutsidetheroomwillberestricted.Everyonewhoentersyourroommustweargownandgloves.EveryoneMUST cleantheirhandsafterprovidingcaretoyouortouchingyourenvironment.Youshouldalsopayattentiontocleaningyourhandsregularlyandshoweringorbathingtoreducetheamountofbacteriaonyourskin.Yourroomwillalsobecleanedregularlyandallequipmentdisinfectedbeforeitisremovedfromyourroom.

What should I do to prevent the spread of C. difficile to others?Ifyouareinfectedyoucanspreadthediseasetoothers.However,onlypeoplethatarehospitalizedoronantibioticsarelikelytobecomeill.Forsafetyprecautionsyoumaydothefollowingtoreducethechanceofspreadtoothers:

• washhandswithsoapandwater,especiallyafterusingtherestroomandbeforeeating;• cleansurfacesinbathrooms,kitchensandotherareasonaregularbasiswithhouseholddetergent/disinfectants

Should special practices be done when I go home? HealthypeoplelikeyourfamilyandfriendswhoarenottakingantibioticsareatverylowriskofdevelopingClostridium difficile infection.However,itisprudentforeveryonetocleantheirhandsregularlyandmaintainahygienicenvironment,especially the bathroom area. Cleaning of the environment can be done using your regular germicide or you can use asolutionofchlorinebleachandwater.Ifyouusethissolution,mix1partchlorinebleach(unscented)with9partstapwater.Changethesolutiondailyandbesuretoprotectyourselffromsplashesorspraysofthesolutionintoyourfaceandeyes.Youmightwanttowearprotectiveglovessothebleachsolutiondoesnotcomeintocontactwithyourskin.

What else should I know about cleaning the house environment?Useacleanclothandsaturateitwiththegermicideorbleachsolution.Usefrictionwhencleaningsurfacesthenallowthesurfacetoairdry.Ifthereissoilonthesurface,removeitthenuseanewclothsaturatedwiththegermicideinordertodisinfectthesurface.Payspecialattentiontoareasthatmayhavesomeintocontactwithfecessuchasthecommodeandsink.Whenlaunderingitems,rinseclothingorfabricthathasbeensoiledwithstool,thenuseyourregularlaundryprocesses.Usethehotwatercycleanddetergent.Ifyouwanttoaddsomechlorinebleach,thatwillassistwithkillingofthegerms.Drytheitemsinthedryer.Thereisnoneedtoinitiatespecialprecautionswithdishesandeatingutensils.

What about cleaning of hands?Havingcleanhandsisthemostimportantthinganyofuscandotopreventillness.Whenperforminghandhygiene(anothertermforcleaninghands),itcanbedoneusingtraditionalsoapandwaterhandwashingorusinganalcohol-basedsolution.SinceClostridium difficileisanorganismfoundinfeces,useoftraditionalhandwashingispreferred.

Whenwashingyourhands,firstwetyourhandswithwaterthanapplysoapinthepalm.Rubhandstogethertakingcaretocoverallsurfacesofthehandsaswellasbetweenthefingers.Rubforatleast15seconds,thenrinsewithwater.Pathandsdryinsteadofrubbingasthismaypreventdamagetotheskinofthehandsandchapping.Ifalcohol-basedhandrubsareused,putasmallamountofthesolution(aboutthesizeofanickel)inthepalmofonehandthenrubthesolutionoverbothhandsandbetweenfingersuntilthesolutiondries.Thereisnoneedtorinsehandsafterward.

Performhandhygieneafterusingthetoilet,aftertouchingdirtysurfacesoritems,beforeeating,beforepreparingmeals,andanytimeyourhandsarevisiblysoiledor“feel”dirty.Teachthisimportantpracticetoothersincludingchildren.

What other information is important for me to know?Itisveryimportantthatyoutakeallyourmedicationasprescribedbyyourdoctor.Youshouldnotuseanydrugsfromthedrugstorethatwillstopyourdiarrhea(e.g.,Imodium)asthismayresultintheClostridium difficiletoxinsstayinginsideyourcolonandcausingmoresevereillness.If your diarrhea persists or comes back, contact your doctor.

FormoreinformationonClostridiumdifficileinfection,gototheCentersforDiseaseControlandPreventionwebsitewww.cdc.gov/ncidod/dhqp/id_CdiffFAQ_general.



Focusing on Prevention: Environmental Control

Theenvironmentmustberecognizedasacriticalsourceofcontamination,anditplaysasignificantroleinsupportingthespreadofinfection.BecauseC. difficileisshedinfeces,anysurface,item,ormedicaldevicethatbecomescontaminatedwithfecescanactasasourceforthesporesand,therefore,beinvolvedininfectiontransmission.50,51

C. difficilesporescanexistforfivemonthsonhardsurfaces.50,51Inonestudy,sporeswerefoundin49%oftheroomsoccupiedbypatientswithCDIand29%ofthetimeinroomsofasymptomaticcarriers.80Theheaviestcontaminationisonfloorsandinbathrooms.74

Othersitesthatcanbecontaminatedincludeelectronicthermometers,bloodpressurecuffs,bedrails,callbuttons,tubefeedings,flow-controldevicesforIVsandtubefeedings,bedsheets,commodes,toilets,scales,telephones,TVcontrols,lightcontrols,andwindowsillsinthepatientroom.Aslevelsofenvironmentalcontaminationincrease,thelevelofhandcontaminationofhealthcarepersonnelalsoincreases.ThegreatertheincidenceofCDI,thegreatertheopportunityfortransmission,sointerventionsshouldbetiedtosurveillanceresults.

Disinfectantscommonlyusedinhealthcaresettingsincludequaternaryammoniumsandphenolics,neitherofwhicharesporicidal81,82Somedisinfectantsmayactuallyencouragesporulation(thechangingoftheorganismfromthevegetativestatetotheprotectedsporestate).Thetermhypersporulationhasbeenusedtodenotethepropensityofthebacteriumtomovefromthevegetativeformtothesporeformwithincreasedrapidity.Thetermhasalsobeenusedtonotethatcontactwithsomegermicidesstressthebacterium,soitmorereadilytransitionstothesporeform.Therefore,thetermhypersporulationmaybeunderstoodasthepropensityoftheorganismtomorereadilymovefromthevegetativeformtothesporethanoccursunderusualconditions.AlthoughmanyEPA-registeredgermicideskillthevegetativeC. difficile,onlychlorine-baseddisinfectantsandhigh-concentration,vaporizedhydrogenperoxidekillspores.Currently,therearenoEPA-registeredsporicidalagentsacceptableforuseasageneralsurfacedisinfectant.83-85

ThisinformationmightleadonetobelievethattheenvironmentsofallpatientswithCDImustorshouldbecleanedwithahypochloritesolution.Butthereareanumberofproblemsassociatedwithuseofasodiumhypochloritesolution(hereafterreferredtoasbleach),includingcorrosionandpittingofequipmentandothersurfacesovertime,andemployee-relatedconcernssuchasthetriggeringofrespiratorydifficultiesinworkersusingthesolutions.Therefore,theuseofbleachshouldbelimitedtooutbreaksituationsasrecommendedbytheCDC.Cleaninganddisinfectionactivitiesusingthephysicalmotionsofcleaninganduseoftheroutinegermicideremovesanddilutessporeconcentrationandisacceptableintheabsenceofanoutbreak.

Ingeneral,surfacesshouldbekeptclean,andbodysubstancespillsshouldbemanagedpromptly,asoutlinedinCDC’s“GuidelinesforEnvironmentalInfectionControlinHealth-CareFacilities.”86Thisdocumentcanbeaccessedatthewebsitewww.cdc.gov/ncidod/hip/enviro/guide.htm.DisinfectantproductswithEPAregistrationcanbeusedforroutinecleaninginhealthcaresettings.Activecleaninginvolvestheremovalanddilutionofdirtandcontamination.Cleaningiscriticalforoptimaldisinfectiontooccur.

AstheCDCenvironmentalguidelineindicates,hypochlorite-baseddisinfectantshavebeenusedwithsomesuccessforenvironmentalsurfacedisinfectioninthosepatient-careareaswheresurveillanceandepidemiologyindicateongoingtransmissionofC. difficile.Theuseofa10%sodiumhypochloritesolutionmixedfreshdaily(oneparthouseholdchlorinebleachmixedwithninepartstapwater)hasbeenassociatedwithareductioninCDIin


ASSOCIATION FOR PROFESSIONALS IN INFECTION CONTROL AND EPIDEMIOLOGY ��

somesettings.81CommunicationfromtheEnvironmentalProtectionAgency(EPA)hassuggestedthatuseofapH-adjustedbleachsolutionmadebymixingoneparthouseholdbleach(5.25%-6%),ninepartswaterandonepartvinegar(5%aceticacid),mayprovideanevengreaterimpactonC. difficile(J.Kempter,EnvironmentalProtectionAgency,2008,personalcommunication).

Awordofcautiontotheinfection-preventionteamwhentheyevaluateadisinfectant’sclaimsofefficacy;besuretoclarifywhattheclaimsmean.Forexample,aproductmayclaimtokillC. difficileandbereferringtothevegetativecells,notthespores.Vegetativecellsarereadilykilledbymostdisinfectants.Cleaninganddisinfectingagentsshouldbereviewedandapprovedbyinfectionpreventionandcontrolcommitteestoassurethechemicalsmeetthestandardsandareeffectivefortheintendeduse.

Ifusinga10%sodiumhypochloritesolution,thereareseveralkeypointstoremember:• Commerciallyavailablesolutionscontainadetergentbase,whichishelpfulincleaningaswellas

disinfecting.• Evaluatetheuseofcommerciallyavailablesolutionswithinyourfacility.Somehypochloriteproductsare

availableinareadytousesolution.Thismaybeatime-savingprocessthatminimizesdilutionerror,butitmayalsobeachallengeforstorageandprovetobemorecostly.

• Makingamixtureofbleachandwaterwillprovideonlythedisinfectant,notthedetergentbase.Therefore,atwo-stepprocessmaybeneededifcleaningistobeperformedpriortodisinfection.

• Ifableachandwatermixtureismade,useonlychlorinebleachwithoutthescentadditive,asthisreducestheresultantpartspermillion(ppm)ofavailablechlorine.

• Ableachandwatersolutionshouldprovideatleast4,800ppmofavailablechlorine.• Thereisadifferencebetweenagermicidalbleach(6.15%hypochlorite),alaundrybleach(6.0%

hypochlorite),andadiscountedbleach(5.25%orlesshypochlorite).• Acontacttimeofoneminuteforthehypochlorite(bleachandwater)solutionshouldprovideadequate

disinfectionfornon-poroussurfaces.Thisisaccomplishedbyathoroughwettingofthesurfacewiththehypochloritesolution,thenallowingittoairdry.(Rutala,APIC2008).

Contact TimeContacttimereferstotheamountoftimenecessaryforthegermicidetocomeintocontactwiththeorganismandresultinasignificantreductioninthenumberofmicro-organisms.Thisusuallymeansa3logarithmic(3log)reductioninthenumberoforganisms.ItisthiskillclaimthatmustbesubmittedtotheEPAinorderforagermicidetoreceiveapprovalasacceptableforuseinhealthcaresettings.

Whenapplyingtheconceptofcontacttimeinthehealthcareenvironment,itisvitalfortheinfectionpreventionisttoknowthecontacttimeoftheselectedgermicideandhowtoapplythisknowledge.Germicidescommonlyusedinthehealthcaresettinghaveacontacttimeof10minutes,althoughsomehaveashortercontacttime.Thismeansthatthesurfacebeingdisinfectedshouldcomeintocontactwiththegermicide(staywetaftercleaning)for10minutes(orlessaccordingtothespecificsofthegermicide)inordertoreducetheamountoforganismsby3logs(99%).Thiscanbestbeaccomplishedbyusingthebucketmethodofcleaning,wherethegermicideismixedwiththeappropriateamountofwaterinaccordancewithmanufacturer’srecommendationsandplacedinacleanbucketorcontainer.Acleanclothisusedduringcleaning,andthecleaningprocessprohibitsthedirtyclothfromreturningtothebucketorcontainerofcleangermicide.Thegermicidesolutionmustbechangedperiodicallytoensureitseffectiveness,andbucketsorcontainersarewashedanddisinfectedregularly,inadditiontobeinginspectedforcracks.Thepracticesusedduringcleaninganddisinfectionshouldbeclearlyoutlinedinpolicyformatandobservationusedtoevaluateadherence.


�� ASSOCIATION FOR PROFESSIONALS IN INFECTION CONTROL AND EPIDEMIOLOGY

Germicidalwipeshavebecomeanimportantadditiontoenvironmentalcleaning,buttheymustbeusedappropriatelytobeeffective.Wipesaremadeofamaterial,orsubstrate,thatletsthemabsorbthegermicideinwhichtheyarepackagedandallowsthatgermicidetobedistributedontothesurfaceduringthecleaninganddisinfectionprocess.

GermicidalwipesareregisteredwiththeEPAandthegermicidehasaspecificcontacttimeaspartofthatEPAapprovalprocess.Thismeansthatthewipemustenabletheusertowetthesurfacebeingdisinfectedforthecontacttimenotedonthelabelinordertodestroytheorganismsonthesurfacebeingcleaned.Therefore,itisimportanttousewipesfortherighttypeofjob.Forexample,onecurrentlyavailablegermicidalwipehasacontacttimeof30secondsforsomebacteria(includingC. difficile)andoneminuteforsomeviruses.Tomaintainawetsurfaceforthatcontacttime,thatwipeisappropriatefordisinfecting20squarefeet.Forinfectionpreventionists,itisimportanttoknowthecontacttimeforthegermicide,aswellastheabilityofthewipetomaintaincontacttimeforthetaskinwhichitwillbeused.Ifwipesareusedtocleanthehigh-touchsurfacesinapatientroom,multiplewipeswilllikelyneedtobeusedtoaccomplishthattask,duetothenumberofsurfacestobedisinfected.Healthcarepersonnel,includingenvironmentalservicesstaff,mustbetrainedtousethewipesappropriately.Theinfectionpreventionistmustbeinvolvedinselectionoftherighttypeofwipetoperformthedesiredjobs.

Monitoring Environmental CleaningConsistencywithrecommendedcleaninganddisinfectionproceduresshouldberoutinelymonitored.Allsurfacesanditemsnearthepatientshouldbeincludedinthisprocess.Achecklistwillhelptheworkertoconfirmthateachcriticalareahasbeencleanedanddisinfected—however,theworkermustfollowthelistandcheckoffeachitemasthecleaninganddisinfectionprocessiscompleted.

• Checkliststhatdelineaterecommendedpracticesforafacilityandroutineroundstoevaluatepracticeswillassistthecareteaminidentifyingopportunitiesforimprovement.Workingwithunitandspecialtyspecificgroupstodevelopchecklistsandmeasurestosupportadherencewithenvironmentalcleaningactivitieswillhelpimproveadherence.Table10.1showsachecklistusedamonghealthcarefacilitiesinNewYorktoassessenvironmentalcleaning.Table10.2showsachecklistusedwhenC. difficileisinvolvedandenvironmentalcleaningpracticeshavebeenaltered.Figure10.1depictsapatientroomthathasnotyethadhigh-touchsurfacesidentified.Figure10.2depictsapatientroomandidentifieshigh-touchsurfacesthatneedtobetargetedforspecificpatientenvironments.(Thesechecklistsandfiguresarealsoavailableathttp://www.apic.org/eliminationguides)

Notethatinsomesettings,somepatientcareequipmentsuchasinfusionpumpsandventilatorsarecleanedbynursesorspecialequipmenttechnicians.Adaptationoftheseexamplesshouldincludelocalpractices.

ThereisnoneedforroutineenvironmentalbiologicalsamplingforC. difficile. Itisimportantfortheteamtoselecttheappropriateenvironmentaldisinfectant.Non-compliancewithprotocolswillusuallybedetectedbyongoingtransmissionoftheorganism.Ifongoingtransmissionisnoted,thenathoroughcleaninganddisinfectionoftheenvironmentmustbedone.



ENVIRONMENTAL CHECKLIST -

Hospital:_____________________________________

Date:________________________________________

Unit:_________________________________________

Room:________________________________________

Time:________________________________________

Instruction Component Yes No N/A

At start, perform hand hygiene.

Put on PPE.

Disinfect high-touch surfaces: Door knobs/handles

Door surface

Bed rails

Call button

Phone

Overbed table & drawer

Countertop

Light switches

Furniture

Arms of patient chair

Seat of patient chair

All other miscellaneous horizontal surfaces

Window sills

Bedside commode

Medical equipment (e.g., IV controls)

Spot clean walls with disinfectant cloth

Disinfect: BATHROOM, including:

Bathroom door knob

Toilet horizontal surface/seat

Toilet lever/flush

Faucets (at sink)

Bathroom handrails

Sink

Tub/shower

Mirror

Damp dust: Overhead light (if the bed is empty)

TV & stand

Clean: Lights

Clean floor: Dust mop tile

Wet mop tile

Replace as needed: Hand sanitizer

Paper towels

Soiled curtains

For terminal cleaning, damp dust: Bed frame

Mattress

Remake bed with clean linen

Replace as needed: Pillows, mattresses, pillow

covers, mattress covers

Other: Empty trash & replace liner

Discard dust cloths.

Change mop heads after each isolation room.

Remove PPE before exit.

Perform hand hygiene.

Any significant areas not mentioned above (please describe):

This room looks clean and ready for use:

Sign-off by environmental services employee cleaning the room:______________________________________________

Sign-off by TBD, based on your hospital process for cleaning room:_______________________________________________

Table 10.1 - Environmental Checklist for Daily Cleaning

FOR DAILY CLEANING - ROOM OBSERVATIONS: Please review a sample of 5 patients per week (1 patient per day)

Table 10.1. Environmental checklist using sodium hypochlorite for daily cleaning.



Clostridium difficile ENVIRONMENTAL CHECKLIST USING SODIUM HYPOCHLORITE

Hospital: _____________________________________

Date:________________________________________

Unit:_________________________________________

Room:________________________________________

Time:________________________________________

Instruction Component Yes No N/A

At start, perform hand hygiene. N/A

Put on PPE. N/A

Disinfect w/ hypochlorite-based disinfectant, high-touch

surfaces. Door knobs/handles

Door surface

Bed rails

Call button

Phone

Overbed table & drawer

Countertop

Light switches

Furniture

Arms of patient chair

Seat of patient chair

All other miscellaneous horizontal surfaces

Window sills

Bedside commode

Medical equipment (e.g., IV controls)

Spot clean walls with disinfectant cloth

Disinfect w/ hypochlorite-based disinfectant: BATHROOM, including:

Bathroom door knob

Toilet horizontal surface/seat

Toilet lever/flush

Faucets (at sink)

Bathroom handrails

Sink

Tub/shower

Mirror

Damp dust: Overhead light (if the bed is empty)

TV & stand

Clean: Lights

Clean floor: Dust mop tile

Wet mop tile

Replace as needed: Hand sanitizer

Paper towels

Soiled curtains

For terminal cleaning, damp dust: Bed frame

Mattress

Remake bed with clean linen

Replace as needed: Pillows, mattresses, pillow

covers, mattress covers

Other: Empty trash & replace liner

Discard dust cloths. N/A

Change mop heads after each isolation room. N/A

Remove PPE before exit. N/A

Perform hand hygiene. N/A

Any significant areas not mentioned above (please describe):

This room looks clean and ready for use:

Sign-off by Environmental Services employee cleaning the room:______________________________________________

Sign-off by TBD, based on your hospital process for cleaning room:_______________________________________________

Table 10.2 - ENVIRONMENTAL CHECKLIST USING SODIUM HYPOCHLORITE FOR DAILY CLEANING

FOR DAILY CLEANING - ROOM OBSERVATIONS: Please review a sample of 5 patients per week (1 patient per day) with known or suspected C. difficile.

Table 10.2. Environmental checklist using sodium hypochlorite for daily cleaning when C. difficile is involved.



Figure 10.1. Picture of a patient’s room for use in training individuals regarding room cleaning.

Figure 10.2. Picture of room noting some high touch surfaces and items.



Tiered Approach to CDI Transmission Prevention

ThepriorsectionshavefocusedonexpandingknowledgeregardingCDIandthemanyquestionsastothemosteffectiveandefficientwaytoeliminatetransmissionwhilecontinuingtoprovidecareforallpatientsinacomplexhealthcareenvironment.Understandingthosechallengesandconstraints,theCDCfirstintroducedtheideaofatieredapproachtoaddresstheuniqueaspectsofmultidrug-resistantorganismsaspartofthe2006guidelinesforpreventingtransmissionofMDROs.

Followingthatlead,thisguideoutlinessomeofthetransmission-preventionactivitiesthatshouldbeundertakenaspartofroutineinfectionpreventionandcontrolresponsestoC. difficile.Inthepagesthatimmediatelyfollowtheseroutineactivities,thenexttierofheightenedactivitiesareprovided.Routineandheightenedactivitieshavebeenseparatedsotheyclearlydemonstratewhenandhowtoinitiateamoreintenseresponsetopatientoutcomesspecifictoasinglehealthcaresetting.Thesetieredactivitiesarerelevanttoavarietyofhealthcaresettingsandstresstheuseoflocaldatatoguidedecision-making.

Summary of C. difficile Transmission Prevention Activities During Routine Infection Prevention and Control Responses

Early Recognition of CDI Surveillance

• Performfacility-widesurveillanceforCDI.• Calculatehealthcare-onset/healthcare-associatedCDIratesforeachpatientcareareaaswellasan

aggregateorganization-widerate.• ProvideCDIdataandinterventionstokeyindividualsandgroupssuchastheinfectioncontrolcommittee,

administration,medicalstaff,nursingstaff,andpharmacyandtherapeuticscommittee.• Monitorforanincreasedrateofcolectomies.• NetworkwithotherareainfectionpreventionistsasameansofassessingtheimpactofCDIacrossthe

community.• CommunicateopenlywithlocalhealthdepartmentregardingCDIrates.

Microbiologic identification

• WorkwithmicrobiologylabtoensurerapidreportingoftestresultsforCDI,includingweekendsandholidays.• Ensurethereisaprocessforprovidingresultstothepatientcareareasoisolationprecautionscanbe

initiatedpromptly.

Implementation of Contact Precautions for Patients with CDI

• UseStandardPrecautionsforallpatients,regardlessofdiagnosis.• PlacepatientswithCDIonContactPrecautionsinprivateroomswhenavailable.Preferenceforprivate

roomsshouldbegiventopatientswhohavefecalincontinence.• Ifaprivateroomisnotavailable,cohortpatientswithCDI;however,patientsinfectedwithotherorganisms

ofsignificance(i.e.,MRSA,VRE,Acinetobacter)shouldnotbehousedwithpatientswhoarenot.• Usededicatedequipment(i.e.,bloodpressurecuff,thermometer,stethoscope).• Putongownandglovesuponentrytothepatient’sroom.



• Changeglovesimmediatelyifvisiblysoiled,andaftertouchingorhandlingsurfacesormaterialscontaminatedwithfeces.

• Removegownandglovesbeforeexitingtheroom.• Ifcohortingisused,changegownandglovesandperformhandhygienepriortotouchingthenextpatient.• RoutinelycheckavailablesuppliesforContactPrecautionstoensurethatadequateselectionandamounts

arereadilyavailable.Thismaybestoccurbyassigningspecificresponsibilityforthetaskofcheckingandrestockingsuppliesonaregularbasis.

• DiscontinueContactPrecautionswhendiarrhearesolves.ConsiderincreasingthedurationofIsolationPrecautionsinepidemicsituations,orwhenongoingtransmissionissuspected.RefertothesectionoutliningSummaryofAdditionalC. difficileTransmissionPreventionActivitiesDuringHeightenedInfectionPreventionandControlResponses.

• DonotisolateasymptomaticcarriersofC. difficile.

Environmental Controls

• UseEPA-approvedgermicideforroutinedisinfectionduringnon-outbreaksituations.• Ensurethatpersonnelallowappropriategermicidecontacttime.• Ensurethatpersonnelresponsibleforenvironmentalcleaninganddisinfectionhavebeenappropriatelytrained.• Forroutinedailycleaningofallpatientrooms,addressatleastthefollowingitems:

o Bed,includingbedrailsandpatientfurniture(i.e.,bedsideandover-the-bedtablesandchairs)o Bedsidecommodeso Bathrooms,includingsink,floor,tub/shower,toileto Frequentlytouchedorhigh-touchsurfacessuchaslightswitches,doorknobs,callbell,monitorcables,

computertouchpads,monitors,andmedicalequipment(e.g.,intravenousfluidpumps)• Disinfectallitemsthataresharedbetweenpatients(e.g.,glucosemeters,infusionpumps,feedingpumps).• Monitoradherencetocleaninganddisinfectionprocessesbypersonnelresponsibleforenvironmentalcleaning.

Hand Hygiene

• Performhandhygieneuponremovalofgownandglovesandexitingthepatient’sroom.• Usealcohol-basedhandrubsforhandhygieneduringroutineinfectionpreventionandcontrolresponsesto

C. difficile.• Handwashingisthepreferredmethodforhandhygienewhenhandsarevisiblysoiled.• Assesshandhygienecompliancetoaddressobstaclestoperformance.

Antimicrobial Stewardship

• Implementaprogramthatsupportsthejudicioususeofantimicrobialagents.• Theprogramshouldincorporateaprocessthatmonitorsandevaluatesantimicrobialuseandprovides

feedbacktomedicalstaffandfacilityleadership.

Patient Education

• ShareinformationregardingC. difficileanditstransmissionwithpatientsandtheirfamilies.• Instructpatientsandfamiliesonhandhygieneandpersonalhygiene.• Instructpatientsandfamiliesregardingtheimportanceofdailybathingandprovideassistanceasneeded.

Healthcare Workers Education

• Provideongoingeducationregardingmodesofinfectiontransmission,ratesofCDI,andinfectionpreventioninterventionswithpatientcarestaff.



• Expandcapacitythroughdevelopmentofinfectioncontrolliaisonorlinkswithpatientcarestaffandutilizetheirassistanceinmonitoringadherencetopreventivepracticessuchasisolation,handhygiene,andenvironmentalcleanliness.

Administrative Support

• Shareratesandinfectionpreventioninterventionswithseniorleadership.• Includeseniorleadershipincommunicationsregardingadherencemonitoring.• Communicateexpectationofsupportandaccountabilityregardingpreventionactivitiestokeyleadership

andprovideconcreteexamplesofwaystheycansupportinfectionpreventionandcontrol.

Summary of Additional C. difficile Transmission Prevention Activities During Heightened Infection Prevention and Control Responses AheightenedlevelofinterventionsshouldbeimplementedwhenthereisevidenceofongoingtransmissionofC. difficile,anincreaseinCDIrates,and/orevidenceofchangeinthepathogenesisofCDI(e.g.,increasedmorbidity/mortalityamongpatientswithCDI),despiteroutinepreventiveactivities.

Early Recognition of CDI Surveillance

• PerformpatientcareroundstoidentifypatientswhohavediarrheathatmayberelatedtoCDI.• InitiateContactPrecautionsforallsymptomaticpatientsinwhomCDIissuspected(e.g.,patientswith

diarrheaofunknownorigin).IfinitialtestingisnegativeforC. difficile, discontinueisolation.• ConsiderexpandingsurveillancetoincludeothercategoriesofCDIpatients,suchascommunity-onset,

healthcare-associated.• Increaseactivecommunicationwiththelocalhealthdepartmentandotherinfectionpreventionistsinyour

community.

Microbiologic identification

• DiscussaCDIrateincreasewithmicrobiologystaff,andevaluatealterationsintestingmethodsthatmayhaveimpactedresults.

Implementation of Contact Precautions for Patients with CDI• ConsidertheutilityofanadditionalCDIsigninordertoensureawarenessofallstaff,includingpersonnel

responsibleforcleaningtheenvironment,astheywillneedtouseanalternativecleaningsolutionandprocess.Ifused,thesignmustprotecttheprivacyofthepatientandnotrevealthediagnosis.

• Evaluatethecurrentsystemforpatientplacement.• ConsiderplacingallpatientswithdiarrheainContactIsolationuntilCDIisruledout(asopposedto

waitingforpositivetestresultstoinitiateisolation).• Increasemonitoringofadherencetoisolationprecautionsandhandhygiene.• Holdanopenforumwithpatientcarestafftoidentifybarrierstoinfectionpreventionpractices(e.g.,

interruptioninisolationsupplies,lackofprivaterooms).• ContinueContactPrecautionsevenwhendiarrhearesolves.Considerextendingisolationuntilpatient

discharge.



Environmental Controls• Use10%sodiumhypochloritefordisinfectingthepatient’sroomandallequipmentusedinthatroom.

Verifycompatibilityoftheequipmentwiththebleachsolution.• Use10%sodiumhypochloritefordailydisinfectionaswellasdischargedisinfectionfortheroomofthe

patientwithCDI.• Ifthereisevidenceofongoingtransmission,considerexpandingtheuseof10%sodiumhypochloritefor

disinfectionofallpatientroomsandequipment.• Ensurethatstaffmembersunderstandhowtousethesodiumhypochlorite(bleach)solutionandallow

adequatecontacttime.• Ensurethatpersonnelresponsibleforenvironmentalcleaninganddisinfectionhavebeenappropriately

trainedandareusingthecorrectPPE.• Usebleachwipesasanadjuncttoenvironmentalcleaninganddisinfection;trainstaffontheiruse,

includinginstructiononhowlargeanareacanbedisinfectedwithasinglewipeandpotentialadverseeffectsoftheproduct,suchasstaining,corrosion,anddamagetoequipment.

• Monitorandenforceadherencetocleaninganddisinfectionprocessesbypersonnelresponsibleforenvironmentalcleaning.

Hand Hygiene• Ensurecompliancewithappropriatehandhygieneuponremovalofgownandglovesandexitingthe

patient’sroom.• Enforcehandwashingasthepreferredmethodforhandhygieneduringthisheightenedresponse.• Assesshandhygienecompliancetoaddressobstaclestoperformance.• Ensurethatalcohol-basedhandrubsareavailableforuseaspartofacomprehensivehandhygiene

program.

Antimicrobial Stewardship• Aprogramthatsupportsthejudicioususeofantimicrobialagentsshouldbeinplace.• EvaluatetheuseofantimicrobialsamongpatientsidentifiedwithCDIandprovidefeedbacktomedical

staffandfacilityleadership.

Patient Education• ShareinformationregardingC. difficileanditstransmissionwithpatientsandtheirfamilies.• Instructthemregardinghandhygiene,andmonitorforadherence.

Education of Healthcare Workers• Provideongoingeducationtoclinicians,healthcareprovidersandancillarypersonnel(e.g.,environmental

services)regardingCDIratesandtheirchangingresponsibilitiesinlightoftheincreasedrates.

Administrative Support• Shareratesandinterventionswithseniorleadershipandclearlyoutlinetheactivitiesneededtodemonstrate

administrativesupport.• SharecostsassociatedwithCDIandthefinancialimpactonthefacility.



Other Preventive Measures

DespitethemyriadofpublisheddataontheincreasingmorbidityandmortalityratesassociatedwithC. difficiletransmissioninU.S.healthcareinstitutions,andtheimportanceofhandwashingandbasicinfectioncontrolpracticesinpreventingthisadverseevent,nationaldatapublishedbytheCDCindicateincreasingseculartrendsofC. difficile infectionanddiseaseinU.S.healthcareinstitutionsoverthepastdecade.Thisrealityhasbroughttotheforefrontthequandaryofwhetherotherpreventiveeffortsarerequiredinadditiontoexistinginfectioncontrolpracticesandprocedures.Inthecurrenteraofmanagedcare,additionalpreventiveeffortsneedtobefocusedonareaswherethereisatleastamodicumofevidenceofpotentialeffectiveness.

Therearedataonthreeadditionalareasofprevention:

1. Antimicrobial Stewardship BecauseanyantimicrobialcanpotentiallyinduceC. difficiledisease,stewardshipprogramsthatpromotejudicioususeofantimicrobialsshouldbeencouragedandcomplementinfectioncontroleffortsandenvironmentalinterventions.87,88IntermsofCDIprevention,antimicrobialstewardshipcaninvolverestrictionofantibioticsassociatedwithCDIatthatinstitution(s)and/ordecreasingunnecessaryantimicrobialuseandisdiscussedelsewhereinthisguide.

2. ProbioticsThesearenaturallyoccurring,livebacteriathatarelargelynon-pathogenic.TherationalefortheiruseinpreventingC. difficilediseaseisbasedonthehypothesisthattheywouldrestoreequilibriumtothegastrointestinalflorathathavebeenalteredbypriorantimicrobialexposureandthusprotectagainstcolonizationorovergrowthwithC. difficile.ProbioticsthathavebeenconsideredforpreventionofC. difficilediseaseincludevariousbacteria(Bifidobacterium,agram-positiveanaerobethatiscommonlyfoundinthecolon;Lactobacillus spp., Enteroccus faecium),andyeasts(Saccharomyces boulardii, S. cerevisiae).Theyarecommonlyavailableaslyophilizedcapsulesorintheformofafermenteddrink.SullivanandNord89havesuggestedthatS. boulardiiwassomewhateffectiveinpreventingrecurrentC. difficileinfection.However,studiesoftheutilityofprobioticsinpreventingC. difficilediseaseinpatientsreceivingantimicrobialagentshaveshownnoreductionsintheincidenceofC. difficiledisease.Todate,thereisinsufficientevidence-baseddatatosupportroutineclinicaluseofprobioticstopreventortreatC. difficiledisease.

3. Decolonization Todate,therearenodatathatsupporttheuseofvancomycinormetronidazoleinasymptomaticindividualswhoarecolonizedwithC. difficile inanattempttoridthepatientoftheorganism;suchuseoftheseantimicrobialsdoesnotwork.Moreover,theeffectivenessofvancomycinandmetronidazoleinpreventingC. difficilediseaseinpatientswhoarereceivingotherantimicrobialshasnotbeenshown.

Inconclusion,untilthereisfurtherpublishedevidenceontheutilityofprobiotics,vaccines,anddecolonizationmodalities,thebasisofeffectivepreventionofC. difficileinfectionanddisease,forthetimebeing,willrestlargelyonanintegratedinfectioncontrolprogramthatincludesthefollowing:(a)enforcementofhandhygiene,(b)appropriateuseofstandardandcontactprecautions,(c)maintenanceofahighstandardofenvironmentalcleanliness,and(d)anantimicrobialstewardshipprogram.



Antimicrobial Stewardship and Clostridium difficile Infection: A Primer for the Infection Preventionist

Antimicrobialstewardshipisanaspectofinfectionpreventionandcontrolthatmaybeanewadditiontothejobresponsibilitiesoftheinfectionpreventionist.ThediscussionofantimicrobialuseanditsimpactonpatientsinallhealthcaresettingsandantimicrobialstewardshipprogramswillbesolelywithinthecontextofC. difficileinfection(CDI).Theterm“antimicrobialstewardship”isusedinplaceof“antibioticstewardship,”sincedevelopmentofastewardshipprogramideallyincludesantiviralandantifungalagentsinadditiontoantibiotics;henceuseofthebroaderterm.Theterm“antibiotics”isusedmostofteninthisdiscussion,whereasthosearetheagentsmostrelevantwhenaddressingC. difficileinfection.

Role of Antibiotic Use in the Occurrence of CDISinceCDIisseenalmostexclusivelyasacomplicationofantibioticuse,thedevelopmentofahealthcarefacilityprogramtoensureappropriateantibioticuseisconsideredanimportantinterventionforthecontrolofCDI24,90,91Figure13.1representsthedifferentphasesofC. difficileinfectionofthecolon,startingwithanormalcolonicenvironment(phaseA),throughthedevelopmentofpseudomembranouscolitis(phaseD).Tounderstandthecriticalrolethatantibioticuseplaysinthedevelopmentofpseudomembranouscolitis,thedifferentstepsinthepathogenesisofCDIwillbereviewed.

Normal Colonic Flora Thenormalgastrointestinalfloraisanimportantdefensemechanismagainstintestinalpathogens.Someofthenormalfloraisattachedtoreceptorsinthecolonicepithelialcells,whileotherbacteriaarepresentinthelumenof

Figure 1�.1. Phases of the pathogenesis of C. difficile colitis.



thegut(Figure13.1,phaseA).InorderforC. difficiletocolonizethegut,thenormalfloraneedstobedisrupted.Duetothediversenumberofbacterialspeciesinthehumancolon,ithasbeendifficulttoidentifywhichparticularorganismsareresponsiblefortheprotectiveeffectagainstC. difficile.TheexactmannerbywhichanintactgutfloraprotectsagainstC. difficilecolonizationisnotcompletelyunderstood,butseveralmechanismshavebeenproposed.C. difficileneedstoattachtoreceptorsinthehumangutcells,butaslongasthereceptorsareoccupiedbynormalgutflora,C. difficilestrainsreachingthegutmucosawillhavenoplaceforattachment.

Besidespreventingcolonizationbycompetingforattachmentsites,thenormalfloramaypreventcolonizationbydeprivingC. difficilefromessentialnutrients.ThenormalfloramayalsoantagonizeC. difficilethroughproductionofsubstancesthatinhibitorkillC. difficile.AntibioticsmayfavorC. difficilenotonlybyalteringthecolonicflora,butalsobyalteringthecolonicmicroenvironmentbychangingthelocalproteincompositionoramountoflocalmucusproduction.

C. difficile ColonizationPatientsadmittedtoahealthcarefacilityarelikelytocomeincontactwithfacilitystrainsofC. difficile. EventhoughC. difficilemayreachthecolonicenvironment,itwillnotbeabletobecomeestablishedaspartoftheintestinalfloraandcolonizetheintestinesaslongasthepatienthasanormalflora.ThepatientwithanormalgutfloraisgenerallyresistanttoC. difficilecolonization.ItisconsideredthatC. difficiledoesnothaveanadvantageoversusceptibleorganismsinregardtosurvivalmechanismsinthepatient’scolonicmicrofloraenvironment.Oncethemicrofloraenvironmentisdisruptedbyantibioticuse,thepatientisplacedatriskforcolonization(Figure13.1,phaseB).

Thepropensityofaparticularantibiotictoalterthegutfloraisdefinedasantibioticcollateraldamage.Theextentofcollateraldamagedependsuponaseriesofantibioticfactorssuchasthespectrumofactivity,theamountoftheantibioticthatreachesthecolonicenvironment,andthebactericidalactivityoftheantibioticundertheanaerobicconditionsofthecolon.Otherconsiderationsthatwillaffecttheextentofcollateraldamageincludetheantibioticdose,therouteofadministration,eliminationbythebile,andthepresenceofantibioticmetabolitesinthegut.Antibioticcollateraldamageisforthemostpartduetothekillingofnormalcolonicflora,butantibioticsmaycausecollateraldamagebyalteringothercolonicfactorsbeyondbacteriathatmayplayanimportantroleinlocaldefensemechanismsagainstC. difficile.

C. difficile Toxin ProductionNotallstrainsofC. difficileproducetoxins.Thetoxigenicstrainsprimarilyproducetwotypesoftoxins:AandB.Thetoxinsneedtoattachtoreceptorsintheepithelialcellstobeabletopenetratethecells(Figure13.1,phaseC).TheabsenceofintestinalreceptorsfortoxinsAandBinneonatesmayexplainwhyneonatesareprotectedagainstCDI.

Bothtoxinspossesscytotoxicactivity.RecentoutbreaksofsevereCDIinU.S.hospitalshavebeencausedbyahighlytoxigenicstrainthatproducesabout15to20timestheamountoftoxinsAandBasusualstrains.ThestrainwascharacterizedbymoleculartechniquesastoxinotypeIII,NorthAmericanPFGEtype1(NAP1).

C. difficile Colitis Aftercolonizationanddevelopmentoftoxins,thetoxinsattachtocellreceptorsandpenetratethecellsinthecolon.C. difficiletoxinsinducecelldeathbypromotingcellapoptosis.Apoptosisisanaturalprocessofself-destructionincertaincellsthataregeneticallyprogrammedtohavealimitedlifespanoraredamaged.Epithelialcellsareshedfromthebasementmembraneintothelumen,leavingashallowcoloniculcer.Whitebloodcellsandotherinflammatorycells,aswellasserumproteinsandmucus,flowoutwardfromtheulcer,creatingthetypicalC. difficile-associatedcolonicpseudomembrane(Figure13.1,phaseD).



Antimicrobial Stewardship as a Component of C. difficile Prevention ActivitiesTheworstpossibleclinicalscenarioforhealthcare-associated,healthcare-onsetCDIwouldberepresentedbyapatientwhoisadmittedtothehospitalwithoutaninfection,withnormalgastrointestinalflora,whoafterseveraldaysofhospitalizationdiesduetointra-abdominalsepsisasaconsequenceofC. difficilefulminantcolitis.Figure13.2depictsthedifferentstepsintheclinicalcourseofthistypeofpatientfromthetimeofhospitalizationuntilthepatientdeath.Thefigurealsodepictsanorganizedandsystematicapproachtothestrategiesthatcanbeappliedfortheprevention,control,andtreatmentofhealthcare-associated,healthcare-onsetCDI.ImprovingtheuseofantibioticsinthehealthcaresettingbydevelopingandimplementingalocalantimicrobialstewardshipprogramisacriticalcomponentinseveralstepsintheprocessesinvolvingC. difficilepreventionactivities.

Role of Antimicrobial Stewardship in Prevention of ColonizationAllantibioticsproducedisruptionofthecolonicflora,butantibioticsarenotequalintheircapabilityofcausingcollateraldamageofthepatient’sgastrointestinalflora.TwoelementsneedtobeconsideredwhenevaluatingtheriskforCDIproducedbyaparticularantibiotic(Figure13.3).Oneisthelevelofriskproducedbyaparticularantibiotic.Inthisregard,someantibioticswillplacethepatientatlow,intermediate,orhighriskfordevelopmentofCDI.TheotheristhenumberofdaysthatthepatientwillbeatriskfordevelopmentofCDI.Daysatriskforcolonizationoccurduringthetimethatthepatientisreceivingantibiotictherapy,anduptofiveto10daysafterdiscontinuationofantibiotics.

Forexample,apatientwhoreceivesanarrowspectrumantibioticforlessthanoneday,suchasonedoseofafirst-generationcephalosporinforsurgicalprophylaxis,willbeconsideredtohavealowlevelofriskandashortdurationofrisk(Figure13.3,pointA).Ifthesamepatientisgivensurgicalprophylaxiswithanunnecessarybroadspectrumantibiotic,thelevelofriskcanmovefromlowtohighwithoutanyadditionalclinicalbenefitfromthatunnecessaryantibiotic(Figure13.3,pointB).Extensionofsurgicalprophylaxiswithafirstgenerationcephalosporinfor

Figure 1�.2. Activities to prevent and manage C. difficile infection in healthcare settings.



multipledosesthatcontinuebeyondthedayofsurgerywillalsoincreasetheriskofCDIbyextendingthenumberofdaysthatthepatientwillbeatrisk(Figure13.3,pointC).

Eventhoughallantibiotictherapy,appropriateorinappropriate,willproducecollateraldamageandplacethepatientatriskforCDI,theprolongedinappropriateuseofbroad-spectrumantibioticsisacriticaldeterminantofcollateraldamagethatshouldbeprevented.Thistypeofcollateraldamagewillplacethepatientathighriskforalongdurationoftime(Figure13,3,pointD).

Themostcommoninappropriateantibioticusethatwillplaceapatientatahighlevelandprolongeddurationofriskisthecontinuationofbroad-spectrumantibioticsaftertheetiologyofinfectionhasbeenidentifiedandthepathogenissusceptibletoanarrowerspectrumantibiotic.Forexample,inapatientwithaprolongedICUstaywhodevelopedaventilator-associatedpneumonia(VAP),itwouldbeappropriatetostartempirictherapywithabroad-spectrumregimentocoverthepossibilityofresistantgram-positiveaswellasgram-negativebacteria.

IfrespiratoryorbloodculturesidentifyaMethicillin-susceptibleStaphylococcus aureus(MSSA)astheetiologyofVAP,thecontinuationoftheinitialbroad-spectrumcoverageshouldbeconsideredinappropriate.Inthisclinicalscenario,antibiotictherapyshouldbede-escalatedtoaregimenthattargetsMSSA,suchasnafcillinorcefazolin.Initialempiricbroad-spectrumtherapyinhospitalizedpatientsatriskofinfectionsduetoresistantorganismsshouldalwaysbefollowedbyde-escalationoftherapyifresistantorganismsarenotidentifiedastheetiologyofinfection.Sincelackofde-escalationisacommonreasonforinappropriateantibioticuse,theantibioticstewardshipprogramshoulddevelopstrategiestopreventthecollateraldamageassociatedwithlackofappropriatede-escalationofantibiotictherapy.

Theantibioticprogramshouldintervenetocorrectotherpoorantibioticpracticesthatareassociatedwithcollateraldamage,suchastheuseofantibioticsdirectedtotreatbacterialcolonizationorcontamination,aswellastheuseofantibioticsinpatientswithoutdocumentedinfections.

Role of Antimicrobial Stewardship in Prevention of InfectionOnceapatientiscolonizedwithC. difficile,thepatientmayprogresstodevelopC. difficilecolitis,ormayremaincolonizedwithoutdevelopingdisease.LackofdiseasemaybeduetocolonizationwithaC. difficilestrainthatdoesnotproducetoxins.Inthisclinicalscenario,oncethepatientiscolonizedwithanon-toxigenicstrain,the

Figure 1�.�. Patient’s level of risk and duration of risk for CDI, according to antibiotic use.



patientwillbeprotectedfromcolonizationwithatoxigenicstrain.Itisconsideredthattheinitialstrainmayoccupyreceptorsthatbecomeunavailabletothenewstrain.Theuseofmetronidazoleinapatientcolonizedwithanon-toxigenicC. difficilestrainmayfavordevelopmentofC. difficilecolitisbykillingthenon-toxigenicstrainandallowingcolonizationandinfectionduetoatoxigenicstrain.

IthasbeensuggestedthatC. difficilemaychangeitsabilitytoproducetoxinswhenitisincontactwithcertainantibiotics.InvitroexperimentsindicatethatC. difficileincontactwithantibioticsmaybeabletoexpressmoretoxins.Intheory,apatientalreadycolonizedwithC. difficilewhoisstartedonantibioticsmaybeatincreasedriskofdiseasebythedirecteffectoftheantibioticonC. difficile.Thishasimplicationsfortheantibioticstewardshipprogram,sinceavoidanceofunnecessaryantibioticusemaybeanimportantstrategytopreventC. difficileinfectiononceapatientisalreadycolonized.

NotallstrainsofC. difficilehavethesamecapabilitiestoproducetoxinsandcolitis.FulminantcolitisismorefrequentwhenapatientisinfectedwiththehypervirulentNAP1strain.SincethisparticularC. difficilestrainisresistanttofluoroquinolones,theuseoffluoroquinolonesmayaltergutfloraandproduceselectivepressureinfavoroftheNAP1strain.AntimicrobialstewardshipregardingfluoroquinolonesisimportantinareaswheretheNAP1strainispresent.

ApositivetestforC. difficiletoxininthestoolisnotbyitselfindicationforantibiotictherapy.ApatientwhoisasymptomaticbuthasapositiveC. difficiletestshouldbeconsideredacarrier,andantibiotictherapyisnotindicated.Theinappropriateuseofmetronidazoleorvancomycinmayfavordevelopmentofdiseaseinapatientwhoisonlyacarrier.SincethepresenceofnormalgutfloramayinhibittoxinproductionbyC. difficile,theinappropriateuseofbroad-spectrumantibioticsmayfavortoxinproductionanddevelopmentofdiseaseinapatientwhoisonlycolonizedwithC. difficile.

Role of Antimicrobial Stewardship in Treatment of InfectionOnceapatientisdiagnosedashavingCDI,antimicrobialstewardshipisimportanttoachieveoptimalmedicaltherapy.ThisisrepresentedintheC. difficilePreventionActivities(Figure13.2)asthefourthlevelofintervention.TherearethreestrategiesthatcanbeconsideredforthemanagementofapatientwithC. difficilecolitis:1)killingofC. difficile,2)blockingtoxin,and3)restoringnormalflora.

KillingofC. difficileinthecoloncanbeachievedwiththeuseoforalmetronidazoleorvancomycin.Inpatientstreatedwithoralmetronidazole,thestoolmetronidazolelevelsdecreaseascolonicinflammationimproves,whenthepatientmovesfromliquidstoolstomoreformedstools.Oralvancomycinmaintainssimilarconcentrationsthroughouttherapy.Inpatientswithanileus,asignificantdelayinthepassageofantibioticsfromthestomachtothecolonmayoccur.Whenintravenoustherapyisnecessary,metronidazolecanbeusedsinceitisexcretedbythebileandbytheinflamedcolonicmucosa,achievingfecallevelssufficienttotreatCDI.Ontheotherhand,intravenousvancomycinisnotexcretedintothecolonandcannotbeusetotreatCDI.Iforalvancomycincannotbeused,vancomycinenemasareanalternativetokillC. difficileinthecolon.Evenwhenappropriatemetronidazoleorvancomycintherapyisused,relapseofCDIisexpectedtooccurin10%to25%ofpatients.

BlockingC. difficiletoxininthecolonwiththeanion-bindingresinscolestipolandcholestyraminehasbeeninvestigated,butthisstrategyisnoteffectiveasprimarytherapyforCDI.Thetoxinsmaybeblockedbyadministrationofintravenousimmunoglobulin,sincecommerciallyavailableintravenousformulationcontainsantibodiestotoxinAandB.Thisapproachisconsideredforpatientswithseveredisease.

RestorationofthenormalcolonicmicroenvironmentisofparamountimportanceinthemanagementofCDI.Acriticalstepintherestorationofnormalcolonicfloraisanevaluationofthepatienttodetermineifcurrentantibiotic



therapycouldbediscontinued.Insomepatients,continuationofantibiotictherapywillbenecessarytocompletetreatmentofadefinedinfection.Inthesecases,theantimicrobialteam,consideringthetypeofinfection,cansuggestcontinuationoftherapywithanantibioticthatproducesminimalcollateraldamageofthegastrointestinalflora.

Inanattempttorestorecolonicmicroenvironment,theoraladministrationofmicroorganismswithbeneficialproperties,orprobiotics,hasbeeninvestigatedinpatientswithCDI.ThetheoreticalbenefitsofprobioticsinpatientswithCDImayincludethesuppressionofC. difficilegrowth,thebindingofprobioticstoepithelialcellswithnoreceptorsavailableforC. difficilebinding,improvementofintestinalbarrierfunction,andfavorablemodulationofthelocalimmunesystem.SincethedatafromclinicalstudiesofprobioticsinpatientswithCDIisinconclusive,probioticsarenotconsideredcurrentstandardofcareinthemanagementofpatientswithCDI.

Inanefforttorestorenormalcolonicflora,theadministrationoftheentirefecalflorafromahealthyindividual,anapproachreferredtoasfecaltransplant,hasbeeninvestigated.Althoughthedataarelimitedtocaseseries,fecaltransplanthasbeenusedsuccessfullytotreatrelapsingCDI.

Elements of an Antimicrobial Stewardship Program Thegoalofanantimicrobialstewardshipprogramistooptimizetheuseoftherightdrug,fortherightpurpose,andfortherightdurationinanefforttopromotejudicioususeoftheantimicrobialagent.Discussionofwhatconstitutesaneffectivestewardshipprogramisbeyondthescopeofthisdocument,butthebasicsincludeelementssuchas:

1. writtenguidelinesforuseofspecificantimicrobialsthathavebeendevelopedusingevidenceasabasisandinvolveinputfromclinicians

2. accuratemicrobiologicresultsandpromptreportingofthoseresults3. antibiogramscompiledanddisseminatedinamannerthatenablesclinicianstoselecttheappropriate

agent(s)forempirictherapy4. systemsthatminimizeopportunitiesforinappropriatedurationoftherapy5. processesthatactivelysupportde-escalationoftherapytoamorenarrowspectrumagent6. feedbackonadherencetoguidelines,and7. monitoringofsystemsthatsupportthetotalprogram

Theseexamplesarebutafewoftheimportantelementsforaneffectiveantimicrobialstewardshipprogramandservetodemonstratethescopeofactivitiesanddepthofadministrativesupportnecessaryforsuccess.

ConclusionsCDIisincreasinginincidenceandseverityinhealthcaresettings.InfectionsduetoC. difficileareassociatedwithincreasedpatientmorbidityandmortality.Itisdeeplydisturbingthatpatientsadmittedtoahealthcarefacilityforanon-infectiousdiseasecandieduringhospitalizationduetoaninfectionproducedbyC. difficile.ConsideringthecriticalrolethatantibioticuseplaysinthepathogenesisofCDI,itisimportantforhospitalstoimplementanantimicrobialstewardshipprogramwithafocusonCDIprevention,control,andtreatment.AcombinationofoptimalinfectionpreventionandcontrolactivitiesandantibioticcontrolisnecessarytopreventthetransmissionofC. difficileanddevelopmentofCDI.

Tomaintainacomprehensiveapproachtooptimizinguseofantimicrobialagents,itisimportantthattheinfectionpreventionistunderstandsthecomponentsofanantimicrobialstewardshipprogramandtheorganizationalsupportnecessaryforitssuccess.



Using a Systems Approach to Eliminate Clostridium difficile Infection

Ashealthcareknowledgeincreasedexponentiallyoverthepast50years,healthcaredeliveryintheU.S.evolvedintosilosofcare,withgroupsofspecializedworkersprovidinghighlyspecializedservicesandinformationsystems.Manyofthesesystemscouldnotcommunicateorsharedatawithoneanother,increasingthepaperworkburdenandaddingmoretasksforalreadyover-burdenedhealthcareworkers(HCW).Healthcarehastraditionallylackedstandardizedperformancemeasures,andactivitiestoimprovequalityandefficiencyarefrequentlyisolatedwithinalargersystem.Insituationswhereperformancegoalsareestablished,agoalof80%complianceisoftenconsideredacceptable.Comparedtonon-healthcareindustries,however,healthcaregoalsappearwoefullyinadequate—aperformancelevelof80%inotherindustrieswouldmeanthat36millioncheckswouldbedrawnonthewrongaccounteveryday;9millioncreditcardtransactionswouldcontainerrors,andtherewouldbea1,000-foldincreaseinaviationdeaths.

OnefactorcomplicatingthehealthcaresystemintheU.S.isthatitisevent-based.Inotherwords,theoccurrenceofanevent(e.g.,apositivestooltoxinassayforC. difficile)triggersotherworkactions(e.g.,theinitiationofContactPrecautions).Theseeventsarefrequentlydisconnectedfromthetriggeringeventandfromoneanother.

TheInstituteofMedicine(IOM)identifiedseriousandwidespreadproblemsthroughouttheU.S.healthcaresystemalmost10yearsago.Initslandmarkreport,To Err is Human: Building a Safer Health System,theIOMnotedthatasmanyas98,000patientsdieeveryyearasaresultofmedicalerrors.92Themajorityoftheseerrorsdonotresultfromindividualorevenagroup’scarelessness,butratherfromfaultysystems,processes,andconditionsthateitherfailtopreventmistakesorleadpeopletomakethem.

TheIOMrecognizedthatbuildingasaferhealthcaresystemmeantdesigningprocessesofcaresothatpatientsaresafefromaccidentalinjury.Italsorecognizedthattheworkofotherhigh-riskindustrieshasprovidedexperienceandtoolswhichcanbeusedtoimprovehealthcaresystems.

In2005,theIOMpublishedanotherseminalreport,Building a Better Delivery System: A New Engineering/Health Care Partnership.93Thisreportnotedthatsystemsengineeringtoolshavebeenusedtorevolutionizethequalityandperformanceoflarge-scaleindustriesliketelecommunications,transportation,andmanufacturingcompanies,andsuggestedthatthesetoolscanalsobeusedtoimprovethehealthcaresystem.

A Review of Systems Engineering Systemsengineeringisthedesign,implementation,andcontrolofinteractingcomponentsorsubsystemstoproduceasystemthatmeetstheneedsofusersandparticipants.Allsystemsconsistofinterrelated,interdependentparts,orsubsystems.Thesesubsystemsareasetofinteractingobjectsorpeoplethatbehaveinwaysindividualswouldnot,andtheinteractionofthesesubsystemsisresponsibleforthesystem’scharacteristics.

Asystem’sgoalistomeetspecificperformanceobjectives.Thetwobroadcategoriesofperformanceobjectivesareservice(availability,reliability,quality,etc.)andcost(thedegreetowhichcostscanbecontrolledorreduced).Mathematicalandanalyticalmethodsallowmeasurementofsystemperformanceandcanalsoimprovetheoperationofexistingsystemsandtheirsub-systems.The2005IOMreportreviewsanddiscussessystemsdesign



andanalysistoolswhichmaybeusefulinmeasuringhealthcaresystemperformance,includingconcurrentengineeringandqualityfunctiondeployment,queuingmethods,discrete-eventsimulation,supply-chainmanagement,andothers.93

Onefrequentlyusedmethodfordevelopingstreamlinedandefficientsubsystemsistheprocessflowmodel.Processflowidentifiesallthestepsandtasksintheidealstate;thesearethencomparedtotheexistingprocess.Agapanalysisenablesidentificationofpotentialbottlenecksandencouragestheconsiderationofeveryimprovementopportunity.Theworkteam,composedofrepresentativesfromalldisciplinesinvolvedintheprocess,visualizestheidealprocessandworkstoturnthatvisionintoareality.Oneofthemostimportantquestionstoaskwhenperformingprocessevaluationis“why?”Inotherwords,whydowedothisthewaywedo?Thisquestionhelpsidentifystepsnecessarytothetask,versusthosethataredonebecausethey’vealwaysbeendonethatway.

ThefollowingsectionsreviewkeyprocessesineliminatingC. difficile fromasystemsperspective,andidentifyissuestoconsiderwhenmappingtheidealprocessflow.

Using a Process Flow Model to Eliminate Clostridium difficile Infection TransmissionThesysteminthiscaseiscomprisedofalloftheworktasksandresourcesrequiredtoprevent,control,andeliminatethetransmissionofC. difficile.Thedesiredperformancethresholdisthatnocasesofhospital-acquiredCDIwilloccur.However,preventingC. difficilerequiresseveralsubsystems,orprocesses,includingsurveillance,promptdiagnosisandtreatment,initiationandmaintenanceofContactPrecautions,andenvironmentalcleaninganddisinfection.

SurveillanceIfthemedicalrecordiselectronic,itmaybepossibletoworkwithIT/IStodevelopanautomatedC. difficilequeryusingrecentlypublishedsurveillancedefinitions.30Thesurveillancedefinitionsprovidetheprogrammingrulesforthequery.Ifroomorwarddatafrompreviousadmissionsisinthehospitaldatabase,anautomatedquerywouldenablesurveillanceforcommunity-onset,healthcarefacility-associated(CO-HCFA)casesaswellashealthcarefacilityonset,healthcarefacility-associated(HCFO-HCFA)cases.Developinganautomatedquerywouldallowmoretimetobeallocatedtopreventioneffortsandlesstimespentreviewingandcollectingdata.

Prompt Diagnosis and Treatment of High-risk Patients

What triggers C. difficile testing? HavingahighindexofsuspicioninpatientswithriskfactorsforCDI(prioruseofantimicrobialsorantineoplasticagentswhichimpactgutflora;increasingage;previoushospitalizationwithin30days;residentofalong-termcarefacility)isessentialforearlydetection.

1. Ifantibioticsareordered,givethoughttoactivitiesthatenhancetheindexofsuspicion.Oncesuchmethodmightbetoplaceastickeratthefrontofthechartwiththemessage:“AntibioticsareariskfactorforthedevelopmentofClostridium difficileinfection(CDI).ConsiderevaluatingforCDIifpatientdevelopsdiarrheawhilereceivingantibioticsorhasreceivedantibioticswithinthepast60days.”a. Ifthemedicalrecordiselectronic,theabovemessagecouldbeautomaticallygeneratedatthetimethe

antibioticisenteredintothecomputerizedorderentrysystem(COE)andsenttotheattendingortreatingphysician’se-mailorcomputerizedtasklist.EntryintotheCOEcouldalsotriggeraflagonthenursingcareplantoremindstafftoevaluatethepatientfordiarrhea.



b. Anorderforantibioticscouldtriggerasearchofthemicrobiologydatabase;ifthepatienthasapreviouspositivetoxinassay,anelectronicmessagenotifyingoftheCDIhistoryandrecommendingrepeattestingifthepatienthasnewonsetofdiarrheaisautomaticallysenttophysiciansandthenursingcareplan.

2. AfieldinthecomputerizedI&Osheetcouldbededicatedtoliquidstooloutput.Ifthepatientisreceivingantibioticsandanumberotherthan0isenteredintothediarrheafield,amessageisautomaticallytriggeredtoencouragethephysiciantoconsiderC. difficiletesting.

How often does the microbiology or reference laboratory perform C. difficile toxin assays?Manylaboratoriesbatchtestsandrunthemonceortwiceaweek.Dependingonthevolumeofassays,itmaybefeasibletoincreasethefrequencyoftoxinassaytesting.

If the toxin assay is positive, are appropriate staff members notified immediately (infection prevention, treating physician, nursing staff)? Is the microbiology laboratory able to call in the results if positive? Who should be called? Can that person be reached 24/7/365?

1. Iftherecordiselectronic,anautomatedmessagecouldbesenttotheattending/treatingphysician,infectionpreventionist,andnursingstaffatthetimethemicrobiologylaboratoryentersapositiveresultintothecomputer.

2. Haveadesignatedfieldintherecordforisolationcategoryandflagallisolationpatients.Maketheflagvisibletootherpatientcaredepartmentssothattheisolationcategoryisknownatthetimeofschedulingproceduresandtests.

How much time elapses from when the result of the toxin assay is available to when the physician writes an order for metronidazole? How much time elapses from when the order is written to when the patient receives the first dose of metronidazole?

1. Ifthenotificationsystemisautomated,theautomatedmessagecouldcontainafieldforthemedicationorder,e.g.,“PatienthavingdiarrheaandstoolispositiveforC. difficile.Doyouwanttoordermetronidazolenow?”

2. Ifthephysicianclicksyes,theorderwouldbeautomaticallyenteredintotheCOE,triggeringothermessages.

Initiation and Maintenance of Contact Precautions

Who initiates Contact Precautions, and why? Requiringaphysicianorderwasnecessarywhenpay-for-performancewasthestandardforreimbursement.Today,healthcarefacilitiesnegotiatereimbursementschedulesbasedonDRG,andaphysician’sordermaynotbenecessary.AuthorizingstaffcaringforpatientswithCDItoinitiateisolationshouldshortenthetimerequiredtoisolatethatpatient.

How much times elapses from when the test result is available to when the isolation sign is placed on the door?IfCDIisstronglysuspected(priorantibioticuse,liquidstools,etc.)oriftheunithasmorethanoneHCFO/HCFAcaseatatime,nursingstaffmaywanttoinitiateContactPrecautionswhenthestoolissentfortoxinassay,ratherthanwaitfortheresult.



How are isolation supplies obtained?1. Ifanisolationcartsystemisused,necessarysupplies(gowns,disposablestethoscope,disposableBPcuff,

thermometer,disinfectantwipes)aredeliveredwiththecart.2. Ifelectronic,anautomatedorderforisolationsuppliesissenttoCentralSupply(CS)whenapositivetest

resultisenteredbymicrobiology.

Are isolation supplies (gowns, gloves, etc.) readily available? Who is responsible for re-filling isolation carts or wall-mounted racks with necessary supplies? If isolation supplies are needed, can they be obtained in a timely manner?

1. Verifythatre-stockingsuppliesonaregularscheduleisincludedinthetasklistoftheindividualassignedtodoit.

2. Useavisualcue,e.g.,aredarrowatadesignatedlevelonthewall-mountedisolationrack,tohelpstaffeasilyrecognizewhensuppliesaregettinglow.Whenthelevelofgownsfallsbelowtheredarrow,therackshouldbere-stocked.

3. Ifaparticularitem,suchasgowns,forexample,isfrequentlyinshortsupply,thenursingunitandCSshouldevaluateunitparlevelsforthatitem.

4. Ifshortagesoccuronmorethanoneunit,CSmayneedtoevaluateparlevelshouse-wide.5. Determineanaveragenumberofisolationgownsusedperpatient,perday.NotifyCSdailyofthenumber

ofisolationpatientsontheunit.Anautomatedreportwithnumbersofisolationpatientsperunit,perdayshouldbepossibleifisolationstatuscanbeflaggedinthepatient’srecord.Sendtheautomatedreportdaily,sothatCScanrestockbasedontheactualnumberofisolationpatientsratherthanafixedparlevel.

6. Keepextra“isolationpacks”containingisolationsign,gowns,stethoscope,etc.,inthecleansupplyroom.7. Keepextragownsinthecleansupplyroom.

If the facility requires hand hygiene with soap and water following contact with a CDI patient, how is staff from other units or departments notified of the patient’s CDI status?

1. Apictureofableachbottleonthedoorcouldbeusedtoindicatethatsoapandwatermustbeusedforhandhygiene.

2. Awordofcaution:Bleachshouldnotbeusedonthehands,sorecognizethepotentialforaccesstobleachandmisinterpretationofthebleachbottlesign,andbuildinappropriatetrainingandmonitoring.

Environmental Cleaning and Disinfection

If bleach is used to clean the rooms of C. difficile patients, how is housekeeping notified?a. Havethehousekeeperscheckdailywiththechargenurseforthelistofroomsneedingbleachorplacea

pictureofableachbottleonthedoor.

Toensureefficientandeffectivecleaninganddisinfection,thereareotherquestionsthatneededtobeaddressedaswell.

• Arecleaningsupplies(prepackagedwipes,spraybottlesandcloths,impregnatedcloths,etc.)readilyavailabletostaffforcleaningequipmentthatcannotbededicated?

• Whoisresponsibleformaintainingthesupply?• Whoisresponsibleformonitoringandreplacingdatedsupplies,e.g.,pre-mixedquaternaryammonium?



• Arecleaningsupplieskeptwithportableequipment(bedscales,EKGmachines,x-ray,ultrasound,etc.)sothatstaffcaneasilycleananddisinfectbetweenpatients?

• Whoisresponsibleformaintainingthesupply?• Whoisresponsibleformonitoringandreplacingdatedorpre-mixedsupplies?

EliminatingthespreadofCDIrequirestheeffortsofawiderangeofhealthcaredepartmentsandpersonnel.Systemsengineeringprovidestoolswhichwillallowthedevelopmentofefficientprocessesandcommunicationofinformationforitscontrol.Systemsengineeringwillalsoenableongoingevaluationofthoseprocesses,whilecontinuallylookingforwaystoimprovethem.Havingefficientcaremodelsandautomatingprocessesthatintegrateisolationtaskswheneverpossiblewilleliminatesomeoftheadded-onstepsthatisolatingpatientsrequires.Thisinturnwilldecreasethelikelihoodthataparticularstepintheprocessisover-lookedorforgotten.Ultimately,healthcareworkerswillhavemoretimetodowhattheywantanddobest—spendtimewiththeirpatients.



Glossary of Terms

BI/NAP1/027 Strain:AhypervirulentepidemicstrainofC.difficilefoundtobeassociatedwiththeoutbreaksinQuebec,theU.S.,andEurope.TheBI/NAP1/027strainhasbeenfoundtoproduce16-foldhigherconcentrationsoftoxinAand23-foldhigherconcentrationsoftoxinBinvitro.Anotherfeatureofthisstrainistheproductionofatoxincalledbinarytoxin,theroleofwhichisnotyetdefined;however,strainsthatproducebinarytoxinmaybeassociatedwithmoreseverediarrhea.ThecauseoftheextremevirulenceoftheBI/NAP1/027strainmaybeacombinationofincreasedtoxinAandBproduction,binarytoxin,orotherunknownfactors.

CDAD:Clostridium difficile-associateddisease.ThistermisbeingreplacedbythetermClostridium difficileInfection(CDI).

CDI:Clostridium difficileInfection.

Clostridium difficile: Ananaerobic,gram-positive,spore-formingbacillus.

Community-associated CDI:CDIsymptomonsetinthecommunity,or48hoursorlessafteradmissiontoahealthcarefacility,providedthatsymptomonsetwasmorethan12weeksafterthelastdischargefromahealthcarefacility.

Community-onset, healthcare facility-associated CDI:CDIsymptomonsetinthecommunity,or48hoursorlessafteradmissiontoahealthcarefacility,providedthatsymptomonsetwaslessthanfourweeksafterthelastdischargefromahealthcarefacility.

Exotoxin:Aproteinproducedbyabacteriumandreleasedintoitsenvironment,causingdamagetothehostbydestroyingothercellsordisruptingcellularmetabolism.

Fecal transplantation/fecal slurry:AsomewhatcontroversialprocedureusingaslurryofhumanfecesandsalinesolutiontoregrowhealthybacteriaintheintestinaltractofanindividualexperiencingCDIthathasbeenrefractorytotraditionaltherapy.Theprocessinvolvesobtainingdonorfecesfromanotherfamilymember,usuallyaspouse,andtransplantingitintotheillindividualvianasogastrictube.

Healthcare facility-onset, healthcare facility-associated CDI:DevelopmentofdiarrheaorCDIsymptomsmorethan48hoursafteradmissiontoahealthcarefacilityandfulfillscriterionforthecasedefinitionofCDI.

Hypersporulation:Thepropensityofthebacteriumtomovemorereadilyfromthevegetativeformtothesporethanoccursundernormalcircumstances.Hypersporulationcanbeinducedbycontactwithsomegermicides.

Hypochlorite solution:AsolutioncapableofkillingthebacterialsporesofC. difficileinconcentrationslargerthan4,800partspermillion(ppm)availablechlorine.Thisistypicallyasolutionofonepartunscentedchlorinebleachandninepartswater,yieldinga10%hypochloritesolution.Thesesolutionsarecommerciallyavailableandcontainadetergent,inadditiontothehypochloritesolution.

Probiotics:Naturally-occurring,livemicroorganismsthatareadministeredtoconferahealthbenefittoahost.TherationalefortheiruseinpreventingC. difficilediseaseisbasedonthehypothesisthattheywouldrestoreequilibriumtothegastrointestinalflorathathasbeenalteredbypriorantimicrobialexposureandthusprotect



againstcolonizationorovergrowthwithC. difficile.Todate,thereisinsufficientevidence-baseddatatosupportroutineclinicaluseofprobioticstopreventortreatC. difficiledisease.

Pseudomembranous colitis:Aninflammatoryconditionofthecolonconsistingofacharacteristicmembranewithadherentplaquesassociatedwithseveresymptoms,includingprofusewaterydiarrheaandabdominalpain.TheconditionisconsideredpathognomonicforClostridium difficile infection.

Recurrent CDI:AnepisodeofCDIthatoccurseightweeksorlessaftertheonsetofapreviousepisodethatresolvedwithorwithouttherapy.

Spore:Thedormantstagesomebacteriawillenterwhenenvironmentalconditionscausestresstotheorganismornolongersupportitscontinuedgrowth.C. difficilesporesarehighlyresistanttocleaninganddisinfectionmeasures,andthesporesalsomakeitpossiblefortheorganismtosurvivepassagethroughthestomach,resistingthekillingeffectofgastricacid.

Systems engineering:Thedesign,implementation,andcontrolofinteractingcomponentsorsubsystems,withthegoalbeingtoproduceasystemthatmeetstheneedsofusersandparticipants.

Toxic megacolon:Alife-threateningcomplicationofintestinalconditions,characterizedbyadilatedcolonwithseverecolitisandsystemicsymptomssuchasfever,tachycardia,orshock.

Vegetative C. difficile:Theactivelygrowingandmetabolizingstateofthebacteria.



Frequently Asked Questions

1. What is the incubation period for C. difficile?TheincubationperiodforC. difficilefollowingacquisitionhasnotbeenclearlydefined.Althoughonestudysuggestedashortincubationperiodoflessthansevendays,theintervalbetweenexposureandonsetofsymptomsmaybelonger.Thus,manycasesofhealthcare-associatedCDImayhavetheironsetinthecommunityafterhospitalization.

2. If the patient is on antibiotics, is there a way to prevent them from developing C. difficile colitis?Atpresent,thereisnoprophylaxisforC. difficile.Themosteffectivepreventionactivityisthroughantimicrobialstewardshipprogramstargetedtothespecificorganism(s),andtoquicklyde-escalatetherapy(narrowthespectrum)andpromotetheshortestdurationoftherapywhileadequatelytreatingtheinfection.

3. When should a patient with C. difficile be removed from contact isolation?Underroutinecircumstances,apatientwithCDIcanberemovedfromisolationwhenthediarrhearesolves.IfthereisanoutbreakorevidenceofongoingC. difficiletransmission,theinfectionpreventionistrecognizesthatevenafterthediarrhearesolves,thepatientmaycontinuetoshedC. difficile,sothepreventionistmayconsiderextendingcontactisolationuntilthepatientisdischarged.Aheightenedresponsemightalsoincludeanothermethodforextendingisolation,suchascontinuingContactPrecautions,untilthepatientiswithoutdiarrheafortwodays,followedbyshoweringorbathingofthepatient,provisionofcleanlinen,thenthoroughcleaningoftheroom.

4. We are currently using a germicide that kills C. difficile in the vegetative state. Is that good enough?C. difficileisaspore-former,andeventhoughitmayinitiallybeinthevegetativestateinthestool,soonafteritencountersstressfulenvironmentalconditions,itwilltrytoprotectitselfandtransformintoasporewhichremainsintheenvironmentuntilitisremovedordies,andmayormaynotreturntoavegetativestateatanytime.ManygermicideskillthevegetativeformofC. difficile,andaresuitableforuseduringnon-outbreaktimes.Somegermicidesinducehypersporulation,resultinginanincreasedsporeburdenintheenvironment,soifanoutbreakoccursand/orthereisevidenceofongoingpatient-to-patienttransmission,heightenedresponsesarenecessary.Theyshouldincludechangingthegermicidetoa10%sodiumhypochloritesolutionuntiltheoutbreakortransmissionisundercontrol.

5. Can bleach wipes be used to effectively clean frequently touched surfaces in rooms of patients suspected of having, or diagnosed with, C. difficile Infection? If so, what criteria should be used to select the product?

Germicidalwipesprovidinga10%sodiumhypochloritesolutionprovidingatleast5000partspermillionofchlorinearegoodadjunctstocleaningwhenithasbeendeterminedthattheroutinegermicideisnolongeradequateforthecircumstances.Effectiveness,cost,andeaseofuseareusuallythebiggestissueswhendecidingtouseagermicidalwipe.Lookathowthewipesarepackaged(individuallyorinapop-upcontainer).Aretheybigenoughforthejob?Readthedirectionsandlookatthesizeandwetnessofthewipe,anddoatesttocheckcontacttimeandthenumberofsurfacesthatneedtobewiped.Thiscanhelpyoudecideifawipewillmeetyourneeds,andifso,howmanyareneededforeachtask.Onceyouhaveanideaofuse,youcancalculatecosts.Checkotheraspectsofthewipesthatmayimpacthowtheyareused.Forexample,iftheusercannottolerateordoesnotlikethesmell,heorshemaybelessinclinedtouseit.Whenyouaretestingyourgermicidalwipe,leavetheroom,returningshortlyaftertodeterminewhetheraresidualodormaynegativelyimpactuse.Involvethosewhowillbeusingthewipesinthesetestsaswell.

6. How do we determine if diarrhea is due to C. difficile or from another cause?ThebestwaytoruleoutC. difficileasacausefordiarrheaistoperformanappropriatetest.IfdiarrheacontinuesandthereisstillconcernthatC. difficilemaybethecause,itisuptotheorderingcliniciantousehisorherbestjudgmentastowhetherornotthepatientshouldbeassumedtohaveCDI,andtoimplementisolationandtreatment.



7. Can bleach be used in the pediatric setting?Yes,ahypochloritesolutioncanbeusedinthepediatricsettingbut,asinallsettings,bleachhasacharacteristicodor,butthisodorisgenerallyinnocuousandbleachvaporsalonegenerallydonotcauseirritation.(Directexposuretospraysormistsofbleachproductsisadifferentissueandpotentiallycancauseirritation.)However,duringuse,bleachcaninteractwithsoilstoformmalodorousvaporsthatpeoplemightfindobjectionableorpossiblyirritating.Peoplewithpreexistingcompromisedlungfunctionmaybeparticularlysensitivetosuchvapors(e.g.asthma,obstructivelungdisease,heartconditions).Bleachshouldnotbemixedwithothercleaningproductssincemixingwithcertaintypesofproductscanformirritatingorharmfulvapors.Exposuretofumesfromimpropermixingisinfrequentandrarelyproducesserioushealtheffects,inpartbecausethefumescompelpeopletoleavetheareapreventingsignificantexposure.Exposuremightbemoreseriousifapersonisunabletoleavetheareaifimpropermixingoccurs.Careshouldbetakentoallowforadequateventilation,regardlessofthesetting.Commercialformulationsmayeasesomeoftheodorissues,butthoseusingtheproductsshouldbeinvolvedindeterminingtheeffectoftheodoranditsimpactonbothuserandpatient.Aswithallchemicals,hypochloritesolutionsmustbestoredinasecuremannersochildrenorotherunauthorizedpersonnelcannotaccesstheproduct.

8. Can bleach be used to clean the OR setting?Yes,butcaremustbetakentoavoidcontactwithitemssuchassurgicalinstruments,whereascorrosionanddamagemayoccurfollowinglong-termuse.Somecommerciallyavailablepreparationshavebeenformulatedtominimizethiscorrosiveeffect.

9. Is there a benefit to mixing a bleach solution over purchasing one pre-mixed?OnlyEPAregisteredproductsarereviewedforefficacy,purityandshelflife.EPAreviewestablishesstandardsforproductmanufacturinganddistributingtobetterensureproductquality,concentrationandefficacy.

Whenyouwanttocleanwithagermicide,itisimportantthatthegermicidehaveadetergentbasethatpromotestheremovaloforganicandinorganicmatter.Mixingsodiumhypochloritewithwaterdoesnotprovidethatdetergent.Ifitisdesiredtocombineadditionalcleaningagentsordetergentswiththegermicide,apre-mixedproductshouldbeused.Detergentshouldnotbeaddedtosodiumhypochloritedilutedinwatertoavoidthepotentialreleaseofhazardousfumes(seequestion7).Inaddition,somedetergentswilldestroyallorpartofthehypochloritesothatthedesiredantimicrobialbenefitwillnotbeachieved.InsteadoneshouldpurchaseaproperlyformulatedproductthathasbeenapprovedbytheEPAforproductsafetyandefficacy.Theseproductscanreducethetimerequiredforcleaninganddisinfectingbycombiningbothactivitiesintoonestepandreducetheoverallcostbyreducingtheamountoflaborrequired.

10. We do not restrict use of alcohol-based hand rubs for healthcare workers providing care for patients with CDI. Is this incorrect?

ThisisasatisfactorystrategytouseunlessyouhavebeenunabletocontrolyourcasesofCDI.Weknowthatalcohol-basedhandrubsdonotkilltheC. difficilesporesandthathandwashingservestophysicallyremovethenwashawayspores.WhenapatienthasCDI,theyhavediarrheaforsometimeuntiltreatmenthelpsresolvetheinfection.Therefore,itcanbereasonablyanticipatedthatfeceswillhavecontaminatedtheenvironment,anditislikelythatthehealthcareworkerwillcomeintocontactwithfeceswhilecaringforthepatient.Consequently,handwashingmakessense,butuseofalcohol-basedhandrubsshouldalsobeavailableduringroutinecareofpatientswithCDI.Wealsoknowthathandhygienecompliancegoesdownifalcohol-basedhandrubsareremoved,makingitcounterproductivetowhatwewishtoaccomplish.Tothatend,thefewsimplerulesforthiscomplexsituationinclude:

• performhandhygienebetweenallpatientcontactandimmediatelyafterremovalofPPE• washwithsoapandwaterasthepreferredhandhygienemethodifhandsarevisiblysoiled• providealcohol-basedhandrubsasanadditionalmethodtoperformhandhygieneforhealthcarepersonnel



11.What are the potential benefits and risks of the use of loperamide and opiates in the control of diarrhea in patients?

IntermsofdiarrheacausedbyC. difficile, itisimportanttorememberthatthereisatoxininvolvedanduseofanti-motilityagentsmaybeharmfultothepatient.Themostappropriateuseforloperamide,opiates,orothertherapiesthatservetominimizediarrheacomesafterthecausehasbeenidentified,andthedesireistonowminimizedehydration.AlthoughdehydrationmaycertainlyoccurwithCDI,themostimportantthingforthesepatientsistostartonappropriatetreatmentandcorrecttheinfection.Wheninfectioniscorrected,thediarrheawillresolve.

12. Is there a benefit to the use of disposable bedpans?Thisquestionimpliesthatuseofdisposablebedpansmaybeofgreaterbenefitinpreventingtransmissionthanistheuseofbedpansthataredisinfectedbetweenpatientsorbetweenuses.BedpansorcommodesmustbedesignatedforsoleusebythepatientwithCDI.Oncethatpatientnolongerneedsthisitem,itshouldbedisposedof(ifdisposable)orcleaned,thendisinfectedifitismadeofmaterialdesignedtobereused.Thesimpleuseofadisposablebedpandoesnotimplyincreasedpatientsafety.Thesystemsandprocessesofcarethatmakeitdifficultforcontaminatedequipmenttobesharedbetweenpatientsrepresentthegreateropportunityforpatientsafety.Handlingthebedpanpresentsthelikelihoodofhandcontaminationbythehealthcarepersonnelandthepatient,sohandhygieneremainsacriticalintervention.

13. Is there value in tracing previous locations of patients with CDI in the facility and then terminally cleaning the area?

Althoughtracingapatient’smovementmaybeanelementusedduringanepidemiologicstudy,whenconsideringthisquestioninthecontextofCDI,themoreusefulapproachistoensurethattherearesystemsinplaceforconsistentenvironmentalcleaningthroughoutthefacility.Theterm“terminalcleaning”seemstohavemanydefinitions,butwhenwehearthatterm,itisgenerallyusedtodescribethemorein-depthcleaningthatisdonefollowingpatientdischargeifitinvolvesapatientroom,orcleaningdoneattheendofthedayorendofaprocedureinareassuchastheoperatingsuite.Terminalcleaningshouldinvolvethecleaninganddisinfectionofallitemsandsurfacesintheroomandmayalsoincludethechangingofitemsthatmayremainintheroom(e.g.,cubiclecurtains)iftheyaresoiled.Therefore,thereshouldalreadybeasysteminplacethatsupportsconsistentterminalcleaningbypersonnelwhohavebeentrainedintheprocessandhavebeendeemedcompetenttoperformthatprocess.Theideathatterminalcleaningwouldbepartofapatienttracingsystemiscounterintuitivetothesystemsapproach.RoutinecleaningmethodsshouldimpacttheburdenofC. difficile,andterminalcleaningshouldmoveclosertowarderadicationoftheorganismintheenvironment.

14. What is the environmental transmission risk of CDI in long-term care facilities?Theriskoftransmissionwithinaspecificenvironmentsuchasalong-termcarefacilityhasnotbeenquantified,buttheriskfactorsinvolvedinCDIdevelopmentandtransmissionarelargelythesame,regardlessofthesetting.Inthelong-termcaresetting,emphasiswouldcertainlybeplacedonantimicrobialstewardship,handhygiene,andstandardandcontactprecautions.Thesearethesameelementsemphasizedinmostsettings.Althoughthereisno“onesizefitsall”foraCDIpreventionprogram,theelementsinallsuchprogramsshouldbefairlyconsistent.

15. What is the impact of ventilation and air pressure gradients on control of CDI?ThereisnoevidencethatC. difficilesporesareairborne,thereforeventilationandairpressuregradientsarenotelementsrequiringspecificactions.InhalationofC. difficilesporesisunlikelytocauseinfection.However,aerosolizationofsporesorvegetativebacteriumthatcomesintocontactwiththemouthorcontaminateshandsthattouchthemouthmayactasamodeoftransmission.ThisfurthersupportstheconceptsofStandardPrecautionsanduseofpersonalprotectiveequipmentandpracticesthatpreventcontactwithpatientbodyfluids.Airborneordropletprecautionsarenotindicated.Contactprecautionsandstandardprecautionsaretheappropriateactivitiestopreventtransmission.



16. What is the infectious potential of patients who have had interventions such as colectomy?Followingcolectomy,theareaofpseudomembranouscolitishasbeenremovedbuttheorganismscontinuetobepresentintheremainingareasofthecolon.Therefore,precautionsshouldcontinueasforallpatientswithCDI.Ifthepatienthasacolostomy,thestooldrainingintothecolostomybagshouldbeconsideredasourceofcontamination.ContactPrecautionsshouldcontinueuntilthediarrhearesolvesoruntilstoolconsistencythatcanbeexpectedviaacolostomyhasresumed.Inaddition,ifthepatienthasrectaldrainageviaamucousfistula,precautionsshouldcontinueuntilthatdrainagehasstopped.

17. What is the risk of transmission by asymptomatic carriers?Surveillancetesting,ora“testofcure,”shouldnotbedoneonasymptomaticpatients.NotallC. difficileisalikeinthatsomearenon-toxinproducers,andsomeproducethehypervirulenttoxin.Ifasymptomaticindividualsaretested,notonlyaretheysubjecttothesensitivityandspecificityconstraintsofthetesting,weareleftnotknowingwhattheresultsmean.Anindividualwithoutsymptoms(i.e.,diarrhea)isnotthoughttobealikelytransmitterofC. difficile.

18. What are the benefits of single rooms with their own toilets for the prevention and control of C. difficile?AprivateroomandtoiletaretwoofthemostcriticalactionsthatshouldbetakenaspartoftheCDItransmissionpreventionprogram.SeparatingdiarrheapatientsfromothersandprovidingthemwiththesoleuseofatoiletaretwovitalinterventionsthatdisablethechainofCDItransmission.

19. Do hyper-spreaders exist, and if so, who are they?Thereiscurrentlynoevidenceregardinghyper-spreaders.However,ifwelookattheconceptwithinthepresentationsandtransmissionofotherinfections,suchasSARS,theideaisthatthereareindividualswhoareseriouslyillandpresentwithpronouncedclinicalsymptoms.Thismakesitconceivablethatindividualswithprofounddiarrheamaycontaminatetheenvironmentatagreaterdegreethanothers.ItisalsoimportanttorecognizethatthehypervirulentstrainsofC. difficilearenotmoretransmissible;therefore,animportantelementintransmissionpreventioninvolvesearlyrecognitionofindividualswithCDI,followedbyrapidandearlyimplementationofContactPrecautions.

20. Is there a relationship between CDI rates and nurse-patient ratios?ThereisnospecificevidenceofarelationshipbetweenCDIratesandnurse-patientratios,althoughwecanlearnfrompriorresearchthatdemonstratestheeffectofstaffingandtheresultantdeclineinadherencewithbasicinfectionpreventionmeasures,suchashandhygieneandenvironmentalcleanliness.BecausethedevelopmentofCDIismultifacetedandinvolvesanumberofdifferentcomponents,includingantimicrobialusage,handhygiene,environmentalcleanliness,andContactPrecautions,itiseasytoseethatnurse-patientratioisnottheonlyconcern.PreventingthedevelopmentandtransmissionofCDIisanexcellentrepresentationoftheneedforasystemsapproach.Notonesingleprocessisresponsibleforthetransmission,andthereforenosingleprocessorinteractioncanbeentirelyresponsibleforprevention.

21. How many stool specimens should be sent for C. difficile diagnosis?Determiningtheapproachfortestingideallyoccursasacollaborativediscussionbetweenclinicians,microbiologistsandinfectionpreventionists.Therearecurrentlynodatatoguidetheestablishmentofasetnumberofstoolsamplesthatshouldbesentfortestingonanygivenpatient.Therefore,establishmentoflocalpolicyshouldbemadeusingthebestavailableinformationandwithinthesupportingsystemsandcapabilitiesofthefacility.Despitethelackofdatatoguidedecision-makingsurroundingthisissue,somefacilitieshaveimplementedthefollowingstepsasameansofdevelopingpolicydevelopment:

• WhentestingapatientforC. difficile, onlyloose,waterystoolspecimenswillbeevaluatedbymicrobiology.Formedstoolsampleswillbediscardedandnotevaluated.

• OnlyonestoolsampleforC. difficilewillbeevaluatedbymicrobiologyduringa24-hourperiod.Additionalsampleswillbediscardedandnotevaluated.



• TestingforC. difficileconsistsofonesamplesenteachdayfortwoconsecutivedays.Ifbothspecimensarenegative,nofurthertestingwillbeconductedunlesstheclinicalcourseofthepatientchanges.IfthefirsttestispositiveforC. difficile,nofurthertestingwillbedone.

• Testsofcurewillnotbeperformed.

Thesearenothardandfastrules,butaresimplyacombinationofactivitiesusedatsomefacilities.Theinfectionpreventionistisencouragedtodiscussthisissuewiththeinfectionpreventionandcontrolcommitteetodeterminelocalstrategy.

22. Should I handle endoscopes differently after being used on a patient with CDI?Thereisnoneedtoalteryourmethodsforreprocessingofendoscopesifyourprocessesareconsistentwithcurrentrecommendations.TheMulti-societyGuidelineforReprocessingFlexibleGastrointestinalEndoscopes,publishedin2003,aswellasinformationprovidedintheHICPACSterilizationandDisinfectionguideline,canserveasresources.Certainlyerrorsinreprocessingofsemi-criticalitemsplacepatientsatrisk,soyourprocessshouldincludestepstomonitorandevaluateadherencetotheprocess.

23. I have seen a number of skin care items and fecal management systems. Do they have a role in the prevention of C. difficile transmission?

Maintainingtheintegrityofthepatient’sskinisalwaysapatientcaregoal.PatientswithCDIwillhaveliquidstools,soskincaremaybeaprimarynursingcaregoal.UseofasystemthatservestominimizeenvironmentalandhandcontaminationmayalsohavearoleinpreventingtransmissionofC. difficileinhealthcaresettings.



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CommitteeonQualityofHealthCareinAmerica,InstituteofMedicine,2001.Crossing the Quality Chasm: A New Health System for the 21st Century. Availableathttp://www.nap.edu/catalog.php?record_id=10027#toc.

WangMC,HyunJK,HarrisonMI,ShortellSM,FraserI.RedesigningHealthSystemsforQuality:LessonsfromEmergingPractices.Journ Qual Patient Safety 2006;32:599-611.

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For links to references and resources, please visit www.apic.org/EliminationGuides.

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