AntimicrobialStewardshipwithinanOPATService

AndrewSeatonIDConsultant,QueenElizabethUniversityHospital

LeadDoctorAntimicrobialManagementTeam,NHSGGC@raseaton66

WhatistheroleofOPAT?•  ToimprovequalityandefficiencyofcareandreduceriskofharminpatientswithinfectionwhowouldotherwisebehospitalisedforIVantibiotictherapy– Infectionteaminfluenceinthebroaderpatientpopulation– Essentialcomponentofthemodernintegrated,inter-disciplinaryinfectionservice

– Moreefficientandappropriateuseofinpatientresource–partoftheAntimicrobialStewardshipstrategy

WhatOPATisnot• Analternativetothoughtfulperson-centredmedicalcare(oragooddebridement)

• Aneasyorcheapoption(longtermimplantfailure)

• Safer(thanoralRx)• Better(thanoralRxallthetime)

ANTIMICROBIALSTEWARDSHIP

Systematicapproachtosafeandeffectiveuseofantibiotics–optimising(patient)outcome,minimisingharmandpreservingfuturetherapies

AimsofanAMSProgramme

•  Optimiseantibioticuse– Route,dose,intervalandduration

•  Optimiseinfection-relatedoutcome– Survival– Speedofrecovery/Lengthofstay

•  Minimiseinappropriateantimicrobialuse

•  Minimiserisk(unintendedconsequences)– ADRs(AKIandotherantimicrobial-relatedtoxicity)

– AMR– C.difficile– Vasculardevice-relatedinfection

•  Promotecost-effectiveprescribing

OPATispartofanAntimicrobialStewardship(AMS)Strategy

•  StartSMARTthenFOCUS– Reviewtheclinicaldiagnosis+continuingneedforantibioticsat48*-72hours

– Documentaclearplanofaction:•  Stopantibioticsifthereisnoevidenceofinfection•  SwitchantibioticsfromIVtooral• Changeantibiotics:narrowerspectrumorbroaderifrequired• Continue+documentnextreview/stopdate

• OPATStartSmart-ThenFocusAntimicrobialStewardshipToolkitforEnglishHospitals,PHE,UpdatedMarch2015

KeyAMSConsiderationswithinOPAT

1.  IsIVRx(OPAT)appropriate?2. ChoiceofIVantimicrobialagent3. Monitoringandfollowup4.  IVOSTduringOPAT5. Durationoftherapy6. OPAT-AMSGovernance

1.IsIVRx(OPAT)appropriate?

StewardshipattheOPAT“gate”•  Requiresasystematicinfectionspecialistteam-ledapproach

– Correctdiagnosis(e.g.CellulitisVsVaricoseeczema)– Correctinterpretationofmicrobiology(e.g.DFI)– Propersourcecontrol(metalworkremoval,drainabscess)

– Planned(orcompleted)antibioticRx– ARETHEREIVtooralswitch(IVOS)options?

OPAT“Gate-keeping”

0%

20%

40%

60%

80%

100%

BELFAST STGEORGES

OTHER

IVOST/STOP

Accepted

OPAT2016posters:HederwickandPeirse

“Highconsequenceinfections”

•  IVRxisthecurrentmanagementstrategywhenevidencesupportingoralantibiotictherapyislackingeg– BacterialCentralNervousSystemInfection(exceptLyme,TBMeningitis)

– BacterialEndocarditis(exceptRsidedinIVDU)– S.aureusbacteraemia(first2weeks)– Boneandjointinfection?

Osteomyelitis:OVIVASTUDY•  EquipoiseinpublishedliteraturereflectedinvariationinclinicalpracticeUK/Ireland/Global

•  1054adultswithOMrandomisedtoeitherIVororalRxwithin1weekofinitiationofIVRx– PJI,otherorthopaedic,Spinal,DFI.....– SABsexcluded

•  PrimaryTreatmentsuccess(allcomers)86%@1year– Shorterhospitalisation/costsinoralRx– Lessline-relatedcomplicationsinoralRx

Scarboroughetal,ECCMID,2017

OVIVA-Importantcaveats•  PatientswithSABwereexcluded•  Ifnooral(orIV)regimenavailable-excluded•  MDRinfections(Grampositiveandnegative)andsignificantpotentialDDIslikelytohavelimitedoraloptionsandledtosomeexclusions

•  Carefullyconstructedoralregimenswithclosemonitoring(ECGs,Bloods)andotherdrugmodificationbyspecialistssupervisingRx

OralAntibioticsinBJI-Considerations

OralAntibiotic MRSA CNS BonePenetration

Biofilmactivity

QTcprolong OtherDDIs

PenicillinsClindamycinLinezolidDoxycyclineRifampicinNafusidate

Quinolones

ChloramphenicolPristinamycin(ULM)

DDI–drug-druginteractions

BJI–AntibioticDrugDrugInteractionsRIF FUSID QUIN TMP LINEZ DOXY CLINDA

RIF

FUSID

QUIN

TMP

LINEZ

DOXY

CLINDA

SubsetanalysissuggestsIVRxmaybepreferred/moreevidencerequiredwhen

•  SAB-related• Onestagerevision• Nopositivemicrobiology• Organismswheretherearelimitedoraloptions

– Pseudomonas,Cipro-RGNB– MDRGPosinfections

2.ChoiceofIVagent:TheOPAT-AMSdilemma

• AMS:Mosteffective,safeandnarrow-spectrumagentwithleastcapacityforcollateraleffects(AMR,HCAI)forspecificindication

• OPAT:AsaboveBUTchoiceanddosingofagenttooptimizeearlyhospitaldischarge/admissionavoidancemaytakeprecedenceoveranagent’sspectrumofactivity

AMSChallengesinOPAT•  Lackofdrugstabilitydataformanynarrowspectrumantimicrobials

•  Lackofnarrowspectrumantimicrobialswitheasy(oncedaily)administration– Ceftriaxone,Teicoplanin,DaptomycinandErtapenem

•  Lackofantimicrobialswithrapidspeedofadministration– Daptomycin

•  C.difficileriskofcommonlyusedOPATagents

SOMEREASSURANCE......

AntibioticChoice&AdminRouteandClostridiumdifficile(CDI)RiskinOPAT

•  CephalosporinuserestrictedinhospitalsduetohighriskofCDI......butnotinOPAT

•  DespitehigheruseofIVcephalosporinsinOPAT,UK

OPATcohortstudiessuggestmuchlowerratesof

Clostridiumdifficile(0.05per1000OPATdays)

comparedtohospitalisedpatients.Duncanetal.IntJClinPrac2012Jun;34(3):410-7OPATwithceftriaxone,areview

3.MonitoringandFollowup•  Ateachpatientencounter(includingcasediscussion/virtualwardround)thefollowingarereviewed– Thepatient’sclinicalandsocialpicture– Previousandcurrentmicrobiology,includingantibiograms– Radiologicalimagingasappropriate– Needforsurgicalintervention/sourcecontrolasappropriate– Labmarkersandantimicrobialtherapeuticmonitoring– Tolerability/effectivenessoftheantimicrobialregimen

– Opportunitiesforintravenoustooralswitchconsidered.

4.IVOSTDURINGOPAT

•  Patient-Functionalgastrointestinaltract•  Infection-Absenceofinfectionwherefewdatasupportoraltherapy(e.g.bacterialmeningitis,brainabscess,infectiveendocarditis,SAB).Clinicalimprovement

•  Organism-Susceptibletooralagent(s)•  Antibiotic-Goodoralbioavailabilityandpenetrationtoinfectionsiteatappropriateconcentrations,lackofDDIs,allergyandotherCIs(QTc)

OPATIVOSTscenarios

Scheduled/FixedDurationIV

e.g.Endocarditis,CNS,someBJI,someGNB/UTI

AnticipatedIVOST

e.g.Cellulitis,

UnplannedIVOST

e.g.Toxicityorlineinfection

OPATIVOSTscenarios

Anticipated

Basedonimprovementinclinicalsignse.g.Cellulitis,Woundinfection

IVOST?

GoodPracticeRecommendations

• SSTIshouldberevieweddailybytheOPATteamtooptimizespeedofintravenoustooralswitch.

SkinandSoftTissueInfection

OPATPatientGroupDirectionforSSTIs:empiricantibioticRx

Yes No

History of MRSA or Beta-lactam allergy?

Teicoplanin ▼

Clindamycin*

Ceftriaxone ▼

Clindamycin or

Flucloxacillin *IfBeta-lactamallergyorsensitiveMRSA

ReviewDailyToOptimiseIVOST

SomecentresareusingempiricorallinezolidsuccessfullyegLeeds,StPeters&Ashford,Surrey

Nurse-ledmanagementforOPATSSTIsComparisonofpatientspre-andpost-introductionofa

nurse-ledmanagementprotocol

§ Protocolmanagementwasassociatedwithreduceddurationofoutpatienti.v.therapy(from4to3days,P=0.02) Seaton RA et al. J Antimicrob Chemother 2005;55:764–767

DurationofOPAT(day

s)

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Year

2001 2002 2003 2004 2005 2006 2007 2008

Datashownaremedian,lowerquartileandupperquartile

SSTI:MediandurationofOPAT(days)

Seaton RA et al, IJAA, 2011

Linear time trend in log (OPAT days) Estmate 0.904 (0.886-0.922) p<0.0001

0

10

20

30

40

50

60

YearSSTI = 0

Med

ian

dura

tion

OPA

T ep

isod

es (d

ays)

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

DurationofOPATindays(median,IQR)byyearfornon-SSTIcasesbyyearofOPAT

Spearman's coefficient of rank correlation = -0.17, p < 0.0001

Barr et al IJAA, 2012

(Common)IVOSTOPATBarriersinBJI

•  Enterococcalinfection– HighdoseAmox(bonepenetration)– Linezolid(DDIs+Toxicity)

•  Staphylococcalinfection– Quinolones(QTcprolongationDDIs)– Rifampicin(DDIs,co-adminwithLinezolid)

•  BHStreptococcalinfection– Clindamycinanddoxycyclineresistance– Linezolid(DDIs+Toxicity)

NB.6ConstantineUnits=1UnitoforthopaedicTime

5.DurationofTherapy(IVandoral)

BradSpellberg

BradSpellberg

6.OPAT-AMSGovernance

SAPGGoodPracticeRecommendationsforHospitalAMSinScotland

AntimicrobialGuidelinesshouldinclude/takeintoaccount:•  DischargePlanning

– SupportearlyhospitaldischargeinsuitablepatientseitherthroughtimelyIVtooralswitchor,whenthefacilityexists,inselectedpatientgroupsthroughOPATprogrammes

•  WhereOPATprogrammesexistAMTsneedtoensurethattheyaregovernedbynationalstandardsandthattheprinciplesofAMSareadheredtosoastominimisethepotentialforinappropriatepracticeorunintendedharm.

SAPG,December2014

FromOPATtoCOPAT:TheComplexOPAntibioticTeam

Expanding(Stewardship)RoleswithinOPATteam

•  CriticalroleofAntimicrobialPharmacistindecisionsreantibioticselection

•  IncreasedfocusonshorttermIVRxandadmissionavoidance/ambulatorycare– Cellulitis– Pyelonephritis/urosepsis

•  IncreasinglycomplexMDRinfections(includingCROs)

•  Nursingstewardshipdevelopments– IVOST– Nurseeducators– Independentprescribers– Penicillinallergy

Conclusions

•  OPATisanimportantarmofAMSprogramme•  OPATpre-assessmentiscriticalmustincludeopportunitiesforstreamliningofRxincludingIVOST+stop

•  DailyreviewtooptimiseIVOSTopportunityinSSTIduringOPAT

•  CriteriaforIVOSTinBJI,Intra-abdominalinfections•  OrganisationalgovernanceandOPAToversightbyAMSprogrammeisessential

Acknowledgements

MarkGilchristOPATSteeringGroup

TraceyGuiseCarolyneHorner

FelicityDrummond

NHSGGCOPATTeamLindsaySemple,ClaireVallance,LizCollison,FionaRobb,LeeStewart,BethWhite,NeilRitchie

RiskoffailurebysurgicalprocedureandrouteofRx

Subgroup OR 95%CI Nineach

group

OMdebrided(noimplant)

0.93 (0.45,1.94) 318

OMnot

debrided(noimplant)

0.34 (0.08,1.41) 76

DAIR 1.20 (0.61,2.34) 237

Removalof

implant0.65 (0.34,1.23) 297

1stagerevision

2.16 (0.58,8.00) 87

Scarboroughetal,ECCMID,2017

RiskoffailurebyinfectingpathogenandrouteofRx

Subgroup OR 95%CI Nineach

subgroup

S.aureus 0.89 (0.49,1.59) 370

Pseudomonas n/a n/a 32

OtherGNR 1.13 (0.43,2.97) 116

Strep.species 0.54 (0.19,1.55) 81

CNS 0.56 (0.24,1.32) 189

Noneidentified 1.91 (0.77,4.75) 227

Scarboroughetal,ECCMID,2017

Riskoffailurebyplannedantibiotics(excludingrifampicin)

PlannedIVtherapy PlannedPOtherapy

Nostatisticallysignificantdifferenceinoutcomebyplannedantibioticchoice

Scarboroughetal,ECCMID,2017