real-world use of echinocandinsin an era of increasing … · 2017. 6. 12. · poster #245...
TRANSCRIPT
College of Pharmacy 2013Collge of Pharmacy 2013
BACKGROUND:Treatmentofinvasivecandidiasis(IC)israpidlydevelopingduetotheemergenceofFKS-mediatedechinocandin(echino)-resistantCandida species.Preventionofechino resistancewillrequiredevelopmentofmorepotentechinos oroptimizingcurrentechino use.Thepurposeofthisstudywastoevaluatereal-worldechinoutilizationinhospitalizedpatientswithsuspectedorconfirmedICtogaininsightintoantimicrobialstewardshipinterventions.
METHODS:Patientsadmittedtoan800-bedquaternarycarehospitalin2015-2016givenanechino wereidentified.Datafromarandomsampleofallpatientsgivenanechino wascomparedtothatofechino-treatedpatientsIC(candidemia).Areasforstewardshipinterventionsincludingspecialpopulationsandunmetmedicalneedswereidentified.
RESULTS:Fivehundredandthirteenpatientsreceived579coursesofechino therapywithamediantreatmentdurationof6days(IQR:3-12days).Ofthese,150patients(51%male)aged60±16years(ICU:64%;corticosteroids:56%)wererandomlyselectedandcomparedto59patients(47%male)aged55±16years(ICU:81%;corticosteroids:39%)withcandidemia.Globally,echinos werestarted15±19daysfromadmissionforanaveragein-hospitaldurationof6.6±5.9days.Ofthe150randomlyselectedpatients,97(65%)hadapositiveyeastculture(C.albicans:43.3%)fromanon-sterilesite(urine:51%;sputum:28%),and16hadcandidemia (11%).Patientswerecommonlyco-administeredfluconazole(31%),anotherazole(11%),oranamphotericinBproduct(10%).Oneisolatehadreducedsusceptibilitytoechinos.Inthe59patientswithcandidemia (C.albicans:45%;C.glabrata:33%),echinos werestarted12±18daysfromadmissionforanaveragein-hospitaltherapydurationof11±28days.Patientswerecommonlyco-administeredfluconazole(53%),anotherazole(12%),oranamphotericinBproduct(24%).Ninepatients(15%)withcandidemiacontinuedtorequireanechino afterdischarge.Threeisolateshadreducedsusceptibilitytoechinos.
CONCLUSIONS:Echinos arecommonlyusedinseverelyillpatientslateinthehospitalcourseduringextendedhospitalizations.Thesedataprovideimportanttargetareaswherestewardshipinterventionsarepossibletooptimizecare.
A.K.Sofjan,A.Mitchell,D.N.Shah,T.Nguyen,M.Sim,A.Trojcak,N.D.Beyda,K.W.GareyUniv.ofHoustonColl.ofPharmacy,Houston,TX,USA
• Invasivecandidiasis(IC)isassociatedwithupto50%mortality• Echinocandins (echinos)recommendedforfirst-linetreatmentofIC• Limitationsofcurrentlyavailableechinos• Dailydosing• Emergenceofechino resistancethroughFKSmutations• Potentialunderdosing withcurrentfixeddoses
• Currentantifungalusemustbeoptimizedandpotentialrole(s)ofnewantifungalagents,suchasCD101,needtobeunderstood• Novelechino (structuralanalogofanidulafungin)• Invitropotencyandspectrumofactivitysimilartootherechinos• Onceweeklydosing(half-life>80hours)• Safetywithhighdoseadministration• Significanttargettissuedistributionà targetattainment
suggestspotentialtotreatlesssusceptiblepathogensinvivo• OngoingphaseIIstudyinpatientswithIC
AmeliaK.Sofjan1441MoursundSt.Room223Houston,[email protected]:713-743-6429Fax:832-842-8383
Real-WorldUseofEchinocandins inanEraofIncreasingAntifungalResistance
ABSTRACT BACKGROUND RESULTS
CONCLUSIONS
Variable Empiricechinon =150
Definitiveechinon =60
Age, years,mean (SD) 60(16) 55(16)Male, n(%) 77(51) 28(47)ICUattimeofculture,n(%) 96(64) 48(81)Receivedcorticosteroids,n(%) 84(56) 23(39)Positiveyeastculture,n(%) 97(65) 60(100)• Candida species,n(%)
Candida albicans 42(43) 27(45)Candida glabrata 26(27) 20(33)Candida tropicalis 10(10) 8(14)Candida parapsilosis 19(20) 4(7)
• Culturesite,n(%)Urine 49(51) NASputum 27(28) NABlood 16(11) 60(100)
Isolateswithreducedsusceptibilitytoechino,n(%) 1(1) 3(5)
Concurrent antifungals,n(%)Fluconazole 46(31) 32(53)Otherazoles 16(11) 7(12)Amphotericin Bproduct 15(10) 14(24)
Poster#245
OBJECTIVE
• Asingle-centerretrospectivecohortstudy• Eligibility:adultpatientsadmittedtoan800-bedtertiarycare
hospitalbetween2015-2016givenanechino• Inclusion:• Patientsgivenempiricechino therapy(randomsample)• Allpatientsgivendefinitiveechino therapyforcandidemia
• Exclusion:prophylacticechino useintransplant&stem-cellpatients• Astewardshipauditofthepatients’recordsbyaninfectious
diseases(ID)pharmacistandanIDphysicianwasperformedto:• Evaluateeachpatient’streatmentaccordingtoICguidelinesand
clinicalexpertise• Identifyareasofunmetmedicalneed• Identifypotentialrole(s)ofnewantifungalagentssuchasCD101
Table1.Patientcharacteristics
METHODS
Funding:Cidara TherapeuticsInc.
Toidentifythegreatestunmetmedicalneedswithcurrentechinotherapybyevaluatingreal-worldechino utilizationinhospitalizedpatientswithsuspectedorconfirmedinvasivecandidiasis(IC)
513patientsreceived579coursesofechinos• Initiation:15±19daysfromhospitaladmission• 150randompatientswhoreceivedempiricechinos included
Stewardship assessmentEmpiricechinon =150
Definitiveechinon =60
Received>7daysofechino, n(%) 55(37) 37(64)
Onanechino onthelastdayofhospitalization,n(%)
44(29) 18(31)
Dischargedonanechino, n(%) 9(6) 9(16)
Dischargesettingforoutpatientechinos
• Homehealth,n 5 4• Longtermcare, n 3 3• Skillednursingfacility, n 1 2
Outpatientdurationofechino therapy,days(range)
16(2-38) 16(2-30)
Dischargedonanazole, n(%) 28(19) 14(24)
Outpatientdurationofazoletherapy,days(range)
15(5-84) 17(6-30)
Requirementforanechino duetoanazole-resistantisolate, n(%)
18(12) 34(58)
Echino-resistantCandida isolatewithpriorechino use, n(%)
1(1) 2(3)
Table2.Antimicrobialstewardshipauditofempiricordefinitiveechinocandin therapyin210patients
• Medianinpatienttreatmentduration:6days(IQR,3-12days)• 60patientswhoreceiveddefinitiveechinos forcandidemia included
• Areasofunmetmedicalneedsincurrentechino therapyweregreatestinpatientsrequiring>7daysofIVtherapy,thoseeligiblefordischarge&receivingechino attimeofdischarge,andpatientsrequiringoutpatientIVechino therapyduetoazoleresistance
• Asafeandeffective,once-weeklyechino hasapotentialroleinaddressingtheunmetneedswithcurrentechino therapy