【持续性肾脏替代治疗crrt英文精品课件】antibiotic dosing and crrt 2011

AntibioticDosingandCRRT2011 DepartmentofAnaesthesiaandIntensiveCarePrinceofWalesHospitalHongKong GordonChoi Importantconceptstoconsider Pk PdofantibioticsPrinciplesofCRRTProblemswithpublisheddataOurphilosophyonhowitshouldbedone RenalFailureKills Renalfailureisnotuncommon 1to25 insinglecentre 6 inmulti internationalstudy BEST Mortalityrate upto79 inthe90 s 60 inBEST DoumaCE RedekopWK VanderMeulenJHPetal JAmSocNephrol 1997 8 111 117 CosentinoF ChaffC PiedmonteM Nephrol Dial Transplant 1994 9 Suppl 4 179 182 UchinoS KellumJA BellomoRetal mJAMA 2005 294 7 813 818 Sepsisiscommoninacuterenalfailure 50 VincentJL BihariDJ SuterPM etal JAMA1995 274 639 44 UchinoS KellumJA BellomoRetal mJAMA 2005 294 7 813 818 ColeL BellomoR SilvesterW AmJRespirCritCareMed 2000 162 191 196 DelayofeffectiveantibioticequatesIncreasedmortality KumarA RobertsD WoodKE etal CritCareMed2006 34 1589 1596 Pk Pdofantibiotics RobertsJA LipmanJ ClinPharmacokinet2006 45 755 773 8 10X Pk Pdofantibiotics RobertsJA LipmanJ ClinPharmacokinet2006 45 755 773 40 100 1 5X Pk Pdofantibiotics RobertsJA LipmanJ ClinPharmacokinet2006 45 755 773 6 8X AUC24 MIC100 125 Pk Pdofantibiotics InitialDose Volumeofdistribution Vd notrelatetoclearance butpartlyduetocriticalillness renalfailure agentspecific ciprofloxacin meropenem same ceftriaxone ceftazidime renalfailure Vdfromstudieswithcriticalillnessandrenalfailure MacGowanaAPandWisebREuropeanCommitteeonAntimicrobialSusceptibilityTesting EUCAST BritishSocietyforAntimicrobialChemotherapy BSAC 2005 Fluoroquinolones EUCAST BSACclinicalMICbreakpoints Doseproteinbindingbreakpoint mg L susceptible resistant Ceftazidime2giv10 2 84 16 EnterobacteriaceaePseudomonasspp Cephalosporin EUCAST BSACclinicalMICbreakpoints MacGowanaAPandWisebREuropeanCommitteeonAntimicrobialSusceptibilityTesting EUCAST BritishSocietyforAntimicrobialChemotherapy BSAC 2005 Howdoesitwork 洗腎 washingkidney ContinuousTechniques CVVH ContinuousVenoVenousHemofiltrationCVVHD ContinuousVenoVenousHemoDialysisCVVHDF ContinuousVenoVenousHemoDiaFiltrationHVVF HighvolumeVenoVenousHemofiltration SoluteclearancebyCRRT Ingeneral hydrophilicdrug than30 ofclearancebyrenalroute Lowvolumeofdistribution 1L Kg but Ciprofloxaxin levofloxacin Lowproteinbindingbut Ceftriaxone NonrenalindicationsofCRRT Burns trauma GonzalezMA MoranchelAH DuranSetal ClinPharmacolTher1985 37 633 637ChowAT FowlerC WilliamsRRetal AntimicrobAgentsChemother2001 45 2122 2125GuenterSG IvenH BoosC BruchHPetal Pharmacotherapy2002 22 175 183 HCO1100PolyfluxGambro PoreSize 20KDa 10KDa 30KDa Urea 60 Cr 113 IL 1raMyoglobinTNF monomeric 17kDa IL 6 28kDa 40KDa 50KDa 60KDa TNF Trimeric 51kDa Vancomycin 1448Da Teicoplanin 1878Da Albumin 68kDa IgG 140kDa Sizeisimportant but ReproducedwithpermissionfromICUweb www aic cuhk edu hk web8 Importanceofproteinbinding Hemofiltration CVVH post dilution Sieving Saturatingcoefficient Thecapacityofadrugtopassthroughthehemofiltermembrane Sc C uf C pa C pv 2Sd C dialystae C pa C pv 2C uf drugconcentrationintheultrafiltrateC dialysate drugconcentrationinthedialysateC pa drugconcentrationintheplasma arterial C pv drugconcentrationintheplasma venous AUC AreaUnderCurve 0to1 CL post S Qf BloodflowrateCL pre S Qf Bloodflowrate substitutionrate Bohler KidneyIntSuppl Volume56SupplementNo 72 November1999 S 24 S 28 EquationsforcalculatingCRRTclearancefromfirstprinciples LiAm GomersallCD ChoiGetal JAntimicrobChemother 2009 64 5 929 37 CanweestimateSCbypublishedproteinbinding SC 1 proteinboundfraction GuenterS G etal Pharmacotherapy22 2 175 183 2002 MaloneR S etal Antimicrob AgentsChemother45 10 2949 2954 2001 Traunm llerF etal J Antimicrob Chemother47 2 229 231 2001 HansenE etal IntensiveCareMed27 371 375 2001 Levofloxacin Cefpirome PhillipsG JClinPharmTher23 5 353 3592002 Krohetal JClinPharmacol 36 12 1114 9 1996Matzkaetal Pharmacotherapy20 6 635 643 2000 Ceftriaxone ProteinbindinginICUCeftriaxone Freefraction JoyntGm LipmanJ GomersallCDet Al JAntimicrobChemother 47 421 2001 ReducedProteinbinding Diseasestatesbesidesuremia cirrhosisnephroticsyndromeepilepsyhepatitispregnancysevereburnstrauma DifferencesinclearanceLevofloxacin GuenterS G etal Pharmacotherapy22 2 175 183 2002 MaloneR S etal Antimicrob AgentsChemother45 10 2949 2954 2001 Traunm llerF etal J Antimicrob Chemother47 2 229 231 2001 HansenE etal IntensiveCareMed27 371 375 2001 LiAm GomersallCD ChoiGetal JAntimicrobChemother 2009 64 5 929 37 Loadingdose DesiredconcentrationxVd CalculateCRRTclearancebasedonmodeofCRRT formulaeintext Pharmacokinetic target Calculateeliminationrate concentrationx Cl tot Totalclearance Cl tot calculatedCRRT clearance non CRRTclearance Maintenanceinfusionrate eliminationrate Calculatehalf life 0 693x Vd Cl tot Calculatetimetoreach targettroughconcentration Repeatloadingdoseat calculatedtime Calculatetargetmean concentration targetAUC 24 24 Calculatedosinginterval Dose CpxCl tot f Timeabovethreshold concentration C max MIC AUC 24 MIC C max MIC ratio Repeatloadingdoseat calculateddosinginterval Loadingdose DesiredconcentrationxVd CalculateCRRTclearancebasedonmodeofCRRT TotalclearanceCl tot calculatedCRRTclearance non CRRTclearance PharmacokinteicTarget Calculateeliminationrate concentrationxCltot Maintenanceinfusionrate eliminationrate Calculatehalf life 0 693XVd Cltot CalculatetimetoreachTargettroughconcentration Repeatloadingdoseatcalculatedtime Calculatetargetmeanconcentration targetAUC24 24 Calculatedosinginterval Dose CpxCtot f Repeatloadingdoseatcalculateddosinginterval ChoiG GomersallCD TianQCritCareMed 2009Jul 37 7 2268 82 Conclusion KnowledgeofantibioticsKnowledgeofCRRTUnderstandingofpublisheddataIdeasofunderlyingdiseaseprocess organfailureApplicationofbasicprinciples Acknowledgement TianQiCharlesGomersallJeffLipmanGavinJoyntPatriciaLeungAlexLiDr So Prof Gin AmikacinNon Enterob70Kg35ml kg hr ChoiG GomersallCD TianQCritCareMed 2009Jul 37 7 2268 82 Loadingdose Desiredconcentrationx Vd 33l Desiredconcentration 8xMIC 32mg l Loadingdose 32x33 1000mg CalculateCRRTclearancebasedonmodeofCRRT formulaeintext valuesintable5 Cl HF post Qf Qd x Sd 2450 x0 62 1519ml h 25ml min Pharmacokinetic target Totalclearance Cl tot calculatedCRRT clearance non CRRTclearance 25 23 48ml min Calculatehalf life 0 693x Vd Cl tot 0 693x33000 48 467min 7 8h Calculatetimetoreachtargettroughconcentration Assumingtargettrough 1mg litwilltake5halflives forconcentrationtodropfrom32mg ltotargettrough 40h Repeatloadingdoseat calculatedtime after40h C max MIC ratio Repeatloadingdoseat calculatedtime after40h Timeabove threshold concentration C max MIC AUC 24 MIC Notrequired Notrequired Loadingdose DesiredconcentrationxVd 33l Desiredconcentration 8xMIC 32mg lLoadingdose 32x33 1000mg CalculateCRRTclearancebasedonmodeofCRRT formulaeintext valuesintable5ClHF post Qf Qd xSd 2450 x0 62 1519ml h 25ml min Totalclearance Cltot calculatedCRRTclearance non CRRTclearance 25 23 48ml min Calculatehalf life 0 693xVd Cl 0 693X33000 48 487min 7 8h CalculatetimetoreachtargettroughconcentrationAssumingtargettrough 1mg litwilltake5halflivesforconcentrationtodropfrom32mg ltotargettrough 40h Repeatloadingdoseatcalculatedtime after40h Cmax MIC MeropenemNon Enterob Entero Stahpy70Kg35ml kg hr ChoiG GomersallCD TianQCritCareMed 2009Jul 37 7 2268 82 Loadingdose Desiredconcentrationx Vd 28l Desiredconcentration 5xMIC 20mg l Loadingdose 20 x28 500mg CalculateCRRTclearancebasedonmodeofCRRT formulaeintext valuesintable5 Cl CVVH post Qf x Sd 2450 x0 95 2327ml h 39ml min Pharmacokinetic target Totalclearance Cl tot calculatedCRRT clearance non CRRTclearance 39 60 100ml min 0 1l min Calculateeliminationrate concentrationx Cl tot 20 x0 1 2mg min Maintenanceinfusionrate eliminationrate 2mg min Timeabove threshold concentration C max MIC ratio Cmax MIC AUC 24 MIC Notrequired Notrequired Loadingdose DesiredconcentrationxVd 28l Desiredconc