C.DIFFICILEINFECTION:POPULATIONPROBLEM,POPULATIONSOLUTION

SUSANM.KELLIE,MD,MPHPROFESSOREMERITA

DIVISIONOFINFECTIOUSDISEASES,UNMSOM

OBJECTIVES

1.Participantswillunderstandtheroleofantimicrobialresistanceinthespreadofnew C.difficile strains.

2.Participantswillbeabletodescribetheevidenceforantimicrobialstewardshipinthecontrolof C.difficile.

3.Participantswillbeabletodesigninterventionsforantimicrobialstewardshiptargetedfor C.difficile reduction.

TALKOUTLINE

• Thepatientexperience

• Backtobasicsinpatientsafety-variationandoverutilization

• InsightsfromtheUKintotheroleofantimicrobialstewardshipinC.difficileprevention

• High-valuetargetsinstewardship

Doctors See Gains Against ‘an Urgent Threat,’ C. DiffPaula SpanTHE NEW OLD AGE NYT FEB. 10, 2017

• Therewasnoproblemwithhisprostate,itturnedout.Butafewdayslater,Mr.Bocci developedseverediarrhea,fever andvomiting.Hegrewdehydrated.Fivedaysafterward,inahospitalemergencyroom,doctorsdiagnosedaClostridiumdifficile infection.

TomBocci’s encounterwithabacteriumhehadneverheardofbeganinApril,whenhisdoctorsuggestedatestforprostatecancer.Becausetheresultsappearedslightlyabnormal,Mr.Bocci underwentabiopsy,takingantibioticsbeforehandasastandardprecautionagainstinfection.

MOREONTHEPATIENTEXPERIENCE

• Antibioticsappearedtosquelchtheinfectionbut,ashappensin20to30percentofcases,thesymptomsreturnedwithavengeanceassoonashefinishedthedrugs.Overseveralmonths,Mr.Bocci sufferedfrommigraines,weakness,anxietyandhypertension.

• Toldtoisolatehimself,hewarnedfamilymembersnottovisithishomeinTroy,Mich.;hiswife,Wendy,movedintoasparebedroom.Helost30pounds.Afterthethirdrecurrence,“IreallythoughtIwasgoingtodie,”Mr.Bocci,now71,said.“AndsometimesIfeltIwantedto.”

THEWORDISOUTAMONGPATIENTS

• AsMr.Bocci learned,C.diffsymptomsaretoordinarydiarrheaasanukeistoahomemadefirecracker.“Peoplewhohaveopen-heartsurgeryandtakeantibiotics—andthengetC.diff— tellmethey’dratherhavethesurgeryagainthanC.diff,”saidDr.DaleGerding,whodirectstheresearchlabattheEdwardHinesJr.VeteransAffairsHospitalinChicago.

EXTENDINGOURCONCEPTSOFQUALITY

• PertheInstituteofMedicine,problemswithqualityincludeunderuse (notdoingenough),misuse (preventablecomplications)andoveruse (doingtoomuch)• Low-valuecareincludesthatforwhichthepotentialbenefitsareoutweighedbythepotentialadverseevents.• 1/3ofcaredeliveredintheUSisconsideredwasteful,healthcarewillconsume20%ofGDPby2020.

WHAT’STOOMUCH?

• Overtreatment-provisionoftreatmentsthataremorelikelytoharmthanbenefitpatients.

• Overtesting-useofteststhataremorelikelytoresultinpatientharmthanpatientbenefit

• Overdiagnosis-diagnosticlabellingofconditionsthatarenotclinicallyrelevant

Zapataetal.Editorial.Isexcessiveresourceutilizationanadverseevent?&Lipitz-SnydermanandKorenstein.Reducingoveruse-ispatientsafetytheanswer?JAMAFebruary28,2017Vol317,No.8

CHALLENGESINIDENTIFYINGANDINTERVENINGINOVERUSE

• Trackingandprioritizing• Needfordevelopedandvalidatedperformancemeasures

• Theproblemisunderappreciatedbecauseharmsaredifficulttorecognizeandmayonlyoccurafteralongcascadeofinterventionsandadverseevents

• Cliniciansmayconflateattemptstocontroloverusewith“rationing”

• Overusemaynothaveanadministrative“home”.• Littlecollectiveinstitutionalenergytoaddresstheseproblems

ANTIBIOTICSTEWARDSHIPISREADYTOGO!

• Clear-cututilizationmetricsandnationalbenchmarkingtoolshavebeendeveloped.

• Theperformancemeasureshavebeendeveloped.• HarmsareevidentandmeasurableinCDI,antibioticresistance,readmissions,andadversedrugevents

• Increasinglyacceptedbycliniciansininpatientsettings.• InstitutionalhomeinPharmacyManagementwithrequirementformultidisciplinarycommittee

• TJCandCMSrequirementscreateinstitutionalincentive,aswellasreimbursementpenaltiesforselectedHAIandreadmissions.

KEEP INTOUCHWITHPATIENTSAFETYTOMAKESURESTEWARDSHIPISAFOCUS

CDI SIR NHSN, 2008-14

SIRof1.0SIRof0.8

NATIONALACTIONPLANTARGETSFOR2020

Measure Datasource

PriorBaselineyears

Baselinedata

2013targetSIR

Progress Proposedtargetfrom2015baseline

CDI NHSN 2010-11

1.0 .70 8%↓by2014

30%↓

CDIhospitalizations

HCUP 2008 11.6per1,000discharges

30%↓ 13.6per1,000dischargesfor2012

30%↓

NEWMEXICOSIRIN2016ANNUALREPORT

Havewenotbeendoingenoughorareweoverlookingsomethingimportant?

EARLYINTUITION• C.difficile-anantimicrobialresistanceproblem

• DaleGerding.Clindamycin,Cephalosporins,Fluoroquinolones,andClostridiumdifficile–AssociatedDiarrhea:ThisIsanAntimicrobialResistanceProblem.ClinInfectDis2004;38:636-7

SUCCESSIVEWAVESOFRESISTANCEINC.DIFFICILE

• Forclindamycin,C.difficile resistanceisvariable,andriskofCDADassociatedwithaclindamycin-resistant organismisincreasedinpatientsreceivingclindamycin.

• Forthethirdgenerationcephalosporins,C.difficile resistanceisuniversal,andpresumablyanytoxigenicC.difficileorganismiscapableofcausingCDADduringcephalosporinadministration.

EFFECTSOFFLUOROQUINOLONERESISTANCEANDRESTRICTION

• HighratesofC.difficileaftergatifloxacin comparedtolevofloxacin,butbothfluoroquinoloneshadhighratesofC.difficile(34%and17%)

• C.difficileresistancetofluoroquinoloneswasdescribed,aswellasclonality

• Gaynes R,Rimland D,Killum E,etal.OutbreakofClostridiumdifficileinfectionsinalong-termnursingfacility:associationwithgatifloxacin use.Clin InfectDis2004;38:640–5.

FLUOROQUINOLONEUSETRENDSINHOSPITALS

OUTPATIENTPRESCRIBING-PERCDC

POPULATIONCONNECTIONSBETWEENFQUSEANDCDIRATES

• GlobaldispersionofthehypervirulentNAP1/Ribotype O27C.difficilestrainrevealedanassociationbetweenfluoroquinoloneresistanceandepidemicspread.

• IntheUK,CDIhasdecreasedover70%sinceitspeakrate

CORRELATIONWITHFQPRESCRIBING

OUTPATIENTPRESCRIBINGINCREASED

TRENDSINSUSCEPTIBILITIESOFC.DIFFICILE

BROAD GUIDELINESACROSSTHEHEALTHCARESYSTEM-BOLSTEREDBYCOMMUNITYDATA

• ThePHEguidancerecommendsthatsimplegenericantibioticsshouldbeusedifpossiblewhenantibioticsarenecessary.Broad-spectrumantibiotics(forexample,co-amoxiclav,quinolonesandcephalosporins)needtobereservedtotreatresistantdisease.

• https://www.nice.org.uk/advice/ktt9/chapter/evidence-context

FEATURESOFTHEUKPROGRAMME

• Guidelinesinplacewithregionalstewardshipgroupssincemid2000s

• Linknowtopayments:inApril2016,NHSEnglandlauncheda nationalprogramme toreduceinappropriateantibioticprescribing.

• DatafromMay2016 showedthetotalnumberofantibioticsprescribedbyGPswasdownby7.3%in1 year(atotalof2,696,143 feweritems)andtheuseofbroad-spectrumantibioticswasreducedby16%(areductionofover600,000 items).

• For2016/17,anew improvementandassessmentframework wasalsolaunched,whichincludesantimicrobialresistanceindicators.

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

80.0

90.0

100.0

2012 2013 2014 2015

RibotypeO27aspercentageofallstrainstestedNewMexico2012-15

https://www.cdc.gov/vitalsigns/antibiotic-prescribing-practices/index.html

MARKETANTIMICROBIALSTEWARDSHIP

• AlignStewardshipwithsubspeciality“ChoosingWisely”campaign

• Lookforwaysto“improveprescribing”

• EngagehospitalistsinPIeffortsforMOCpointsfortheircertification

EXPANDING THECONCEPTOFSTEWARDSHIP

• Thinkaboutimpactofstewardshipinotherareaseg.Protonpumpinhibitoruse,urinecultures

• PPIusedrivesC.diffratesandrecurrences

• Improperuseofculturingandculturetechniquesdrivesantimicrobialusage

PPISANDH2BLOCKERSINCREASERATEOFRECURRENCE• Meta-analysisof16observationalstudiesexaminingtheassociationbetweengastric acidsuppressants,suchasproton-pumpinhibitors(PPIs)orhistamineH2-receptorblockers(H2Bs),andrecurrentCdifficile infection.• Theyobserveda50%increaseinoddsofrecurrentCdifficileinfectionamongpatientsreceivingPPIsorH2Bscomparedwith patientsnottakinggastricacidsuppressants.• Tariqetal.[onlineMarch27,2017].JAMAInternMed.doi:10.1001/jamainternmed.2017.0212

COSTOFRECURRENTCDI:$34KPERPATIENT

Rodriguesetal.AComprehensiveStudyofCostsAssociatedWithRecurrentClostridiumdifficileInfection.ICHEFeb2017

THESTRUCTUREFORSTEWARDSHIP

Leadershipcommitment:Dedicatenecessaryhuman,financial,andITresources.

Accountability:Appointasingleleaderresponsibleforoutcomes.

Drugexpertise:Appointasinglepharmacistleadertosupportimprovedprescribing.

Act:Takeatleastoneprescribingimprovementaction,suchasrequiringreassessmentwithin48hours,tocheckdrugchoice,dose,andduration.

Track:Monitorprescribingandresistancepatterns.

Report:tostaffonprescribingandresistancepatterns,andstepstoimprove.

Educate:aboutresistanceandimprovingprescribing.NowincorporatedintoTJCMedicationManagementStandardsfor2017

http://www.cdc.gov/getsmart/healthcare/pdfs/checklist.pdf

AREASWHEREANYHOSPITALCANIMPROVEANTIMICROBIALUSE

• Rethinkthecatheter-associatedUTI

• RethinkHCAP

• Lookcriticallyatskinandsofttissueinfections

• De-escalatepromptlywhendiagnosesaremadeinpatientswithsepsis

RETHINKCAUTI

• DoIneedaurinecultureineveryhospitalizedpatientwithaFoleyandnewfever?

• Doesmyurineculturemeananything?

• DoIknowifmypatienthasaFoleycatheterandforhowlong?

EXAMPLE:TARGETINAPPROPRIATEFLUOROQUINOLONEUSE

• FQusehasbeenassociatedwithincreasedratesofMRSAandincreasedratesofC.difficile-associateddiarrhea.

• Respiratoryfluoroquinolonese.g.moxifloxacinorlevofloxacinhaveanevengreaterriskofC.difficileandareoftenusedwherealess-broadspectrumFQegciprofloxacinwouldbeadequate

• IncreasedexpendituresonFQhavebeenassociatedwithdecreasedsusceptibilityofPseudomonas toFQs.• Bhavnani SMet.al. AmJHealth-SystemPharm 200360:1962-1970.

RESULTS:INPATIENTRETROSPECTIVEREVIEWOFFQUSE

SampleanalysisfromVA2007-EleanaZamora,MD,IDfellow

Estimatedannualcost-savingswithFQappropriateuse:$33k

Interventionperiods:significantdecreasesinnosocomialC.difficile everythreemonthperiodfellowrestrictedFQ

FINDINGTHEUNNECESSARYFQS• Lookforthefollowing:• theduration oftherapywaslongerthanrecommended,

• theFQprovidedredundant antimicrobialcoverageintheabsenceofanindicationforcombinationtherapy,

• theFQprovidedinadequatecoverageofexpectedordocumentedpathogens,

• theFQwascontinueddespitenegativeevaluationforinfectioussyndromes and/oranoninfectiousconditionwasdemonstratedtoberesponsiblefortheclinicalsyndrome.

• Werneretal.Unnecessaryuseoffluoroquinoloneantibioticsinhospitalizedpatients.BMCInfectiousDiseases201111:187DOI: 10.1186/1471-2334-11-187

THEPARADOXESOFANTIMICROBIALSTEWARDSHIP

• Resistanceanywhereisresistanceeverywhere…butallresistanceislocal

• Thepreventionparadoxapplies:theincrementalimprovementinsafetyforeachindividualpatientissmall,butforthepopulation,theeffectofasaferhealthcaresystemwouldbemuchgreater.

MAKEANTIBIOTICSGREATAGAIN!

• ReflectionsfromSarahCosgrove,MD,MS,CurrentPresidentofSHEA

• Stewardshipprogramshavemovedfromjustsavingmoneytooptimizingpatientsafety

• Emergenceofnationalrequirements

BUILDINGTHEANTIMICROBIALSURVEILLANCEANDCONTROLSYSTEMINTHEUS

• CDCAntimicrobialUseModule• TJCandCMSCOPAntimicrobialStewardshipStandard• CMSupdatedregulationsforLong-TermCareFacilitiesrequireaninfectionpreventionandcontrolofficerandanantibioticstewardshipprogramthatincludesantibioticuseprotocolsandasystemtomonitorantibioticuse.

ISSUESWITHTHENEWREQUIREMENTS

• TJCwillbefocusingonareasnotalwayscoveredbystewardshipprograms:• Emergencydepartmentpatientsprescribedantimicrobials• Ambulatoryclinicpatients• Inpatientsdischargedonantimicrobials

• Nursinghomeswillrequirepharmacistreviewofthemedicalrecordduringthemonthlyreview,butfurtheractionandpracticechangesareunclear.

WHAT’SMISSINGINOURAPPROACHTOC.DIFFICILE?

• Integrationofantimicrobialstewadardshipacrossallhealthcaresettingsandintoambulatoryareas• Leveragetoimprovestewardshipinoutpatientsettings• Bettertoolsfordecision-makingatthepointofcarethatdonotundulyburdenproviders.

SCALABLEMODELFORALLHEALTHCARESETTINGS

• Individualorderreview

• Localantimicrobialsusceptibilitiesandinfectioncontroldata

• Clinicalpathwaydevelopment

• Formularyclean-up

RightAbx

available

Directionforspecificclinicalconditions,dosing

protocols

Antimicrobialtime-out,doseadjustment

Informationand

outcomesfortheprogram