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