LizCraigOPATPharmacistWythenshaweHospital

Teicoplanin–therapeuticdrugmonitoring,AKIandOPAT

OPATservicesatWythenshawe•  OPATserviceestablishedin2015

•  Between500-700beddayspermonth

•  Manageavarietyofinfections

•  Multipleadministrationpathways

TeicoplaninandOPAT

•  Favourablekineticpropertiesallowoncedailyorthreetimesweeklydosing1,2

•  Consideredasuitablealternativetovancomycin3,4

•  UseincertainconditionsanindependentriskfactorforOPATfailure5

1.TarcogidSPC(Sanofi).LastupdatedontheeMC01/02/18.Accessedviawww.medicines.org.uk2.LamontE,SeatonRA,MacphersonMetal.Developmentofteicoplanindosageguidelinesforpatientstreatedwithinanoutpatientparenteralantibiotictherapy(OPAT)programme.JAntimicrobChemother2009;64:181–73.CavalcantiAB,GoncalvesAR,AlmeidaCS,BuganoDDG,SilvaE.Teicoplaninversusvancomycinforprovenorsuspectedinfection.CochraneDatabaseofSystematicReviews2010,Issue6.Art.No.:CD007022.4.SvetitskyS,etal.Comparativeefficacyandsafetyofvancomycinversusteicoplanin:systematicreviewandmeta-analysis.AntimicrobAgentsChemother2009;53:4069–79.5.ChristopherJ.A.Duncan,DavidA.Barr,AntoniaHo,EmmaSharp,LindsaySemple,R.AndrewSeaton.Riskfactorsforfailureofoutpatientparenteralantibiotictherapy(OPAT)ininfectiveendocarditis.JAntimicrobChemother.2013Jul;68(7):1650–1654

Teicoplanin–therapeuticdosing

•  Severe/deepseatedinfection–standarddosingsub-therapeutic1-3

•  Dosesofupto12mg/kgrecommendedforinfectionsincludingosteomyelitisandendocarditis2,4

•  Renallycleared–doseadjustmentrequiredinrenalimpairment1,4

•  TDMrecommendedtoensuretargetlevelsattained

•  Jul;68(7):1650–1654

1.WilsonAPR.Clinicalpharmacokineticsofteicoplanin.ClinPharmacokinet2000;39:167–832.MatthewsPC,etal.Teicoplaninlevelsinboneandjointinfections:arestandarddosessubtherapeutic?JInfect2007;55:408–133.GilbertDN,WoodCA,KimbroughRC.Failureoftreatmentwithteicoplaninat6milligrams/kilogram/dayinpatientswithStaphylococcusaureusintravascularinfection.TheInfectiousDiseasesConsortiumofOregon.AntimicrobialAgentsandChemotherapy.1991;35(1):79-87.4.TarcogidSPC(Sanofi).LastupdatedontheeMC01/02/18.Accessedviawww.medicines.org.uk

Casestudy

•  70y/ofemaleadmittedtovascularwardatWythenshaweforAAArepair•  ?mycoticaneurysm•  Commencedonteicoplanin12mg/kgandceftriaxone2gdailyfor6weeksfollowingIDspecialistreview.

•  DischargedtoOPATonday12•  Stablerenalfunctionandlevels(range20-40mg/L)untilweek4oftreatment

•  Week5;level>107mg/L.SubsequentlydevelopedAKIstage1

CaseStudy

•  107mg/Lwasapeaklevel–althoughlevelsof>30persistedfor5daysaftercessation

•  CalculatedGFRbelowthresholdfordoseadjustment;butpreviouslevelshadnotshownevidenceofaccumulation

•  Delayinprocessingofteicoplaninlevel–dosesreceivedininterim•  Riskfactors;co-prescriptionwithramipril,knownDM(dietcontrolled),?reactivationofmyeloma

Teicoplaninreview

•  Outcomesforpatientstreatedwithteicoplanininprevious12monthsexamined

•  Usedin12patientsforvarietyofindications–alltreatedwith8-12mg/kg

•  3patientsdevelopedanAKI–allhadapriorassociatedlevel>60mg/L

AKI Patient characteristics: •  Prolonged courses (4-6 weeks) •  Deep seated infections •  Co-morbidities (DM, post-transplant,

myeloma) •  Nephrotoxic medications •  Previously normal levels (ranging

20-40mg/L) and stable renal function

Teicoplaninandnephrotoxicity

•  Highthresholdfordosereductioninexistingrenalimpairment1

•  0.1%-1%incidenceofacutecreatininerise1

•  IsolatedreportsofAKI2,3

•  UseincardiacsurgicalprophylaxislinkedtoincreasedincidenceofAKI4

1.TarcogidSPC(Sanofi).LastupdatedontheeMC01/02/18.Accessedviawww.medicines.org.uk2.MHRADrugAnalysisPrints.Accessedviayellowcard.mhra.gov.uk/iDAP/3.Frye,R.F.,Job,M.L.andRosenbaum,B.J.(1992),TeicoplaninNephrotoxicity:FirstCaseReport.Pharmacotherapy:TheJournalofHumanPharmacologyandDrugTherapy,12:240-2424.OlssonDP,HolzmannMJ,SartipyU.Prophylaxisbyteicoplaninandriskofacutekidneyinjuryincardiacsurgery.JCardiothoracVascAnesth.2015;29(3):626-31

TeicoplaninTDM

•  TDMadvisedtoensureattainmentofminimumtherapeuticlevel1

•  Noprovenlinkbetweenlevelandtoxicity–limitedevidencetosuggestTDMishelpfultoavoidtoxicity2

•  Oftena“sendaway”testwithturnaroundofweeks

1.  TarcogidSPC(Sanofi).LastupdatedontheeMC01/02/18.Accessedvia

www.medicines.org.uk2.  More,etal.Nephrotoxicityofconcomitantuseoftacrolimusandteicoplanininallogeneic

hematopoieticstemcelltransplantrecipients.TransplantInfectiousDisease2014:16:329–332

Lessonslearned

•  ProlongeduseofhighdoseteicoplaninshouldbewithcautioninthosewithexistingriskfactorsforAKI

•  Considerlonghalflifeandtimetosteadystatewheninterpreting

levels•  Lowthresholdfordosereductioninrenalimpairment(GFR<80)•  MinimumofweeklyU&EsandTDMifavailable,morefrequentlyif

higherriskpatient•  Considerdosereductioniflevelstowardsupperendofdoserangeor

ifearlysignsofreducedrenalfunction

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