EugénieBassèresPhD.,JulieMirandaMPH,AnneJ.Gonzales-LunaPharmD.,TravisJ.CarlsonPharmD.,TasnuvaRashidPhD.,M.JahangirAlamPhD.andKevinW.GareyPharmD.
UniversityofHoustonCollegeofPharmacy;Houston,TX
ContactInformaJon:KevinGareyUniversityofHoustonPhone:(832)-842-8386Email:[email protected]
InvitroAcJvityofEravacycline,aNewTetracyclineAnalog,andcomparatorsAgainsttheSixMostcommonlyIsolatedRibotypesofClostridioidesdifficile
ABSTRACT(edited)
SPECIFICAIM
RESULTS
CONCLUSIONS
METHODS • Eravacyclinwasmore efficient than vancomycin andmetrodinadozoleagainstthemorecommonisolatedribotypesfromourbiobank(table2)
• MICs values of ervacycline were constant in all tested ribotypes(table2)
• MIC50oferavacyclinewerelowerthanallanJbioJcscommonlyusedtotreatCDI(table3)
• LowerincreaseinMICwasobservedinmetronidazoleandvancomycinresistant strains: factor 5 for eravacycline, 8 for vancomycin, 8 formetronidazole (with one excepJon observed on one hypervirulentstrain)(table4.AandB)
• OveralleravacyclineshowspromisingoutcomesinthetreatmentofCDI
Table1.Studydesign:numberofisolatesclassifiedbyribotypeandsuscepJbilitytocommonlyusedanJbioJcs
Table2.SuscepJbiliJtesofthemostcommonlyisolatedribotyptestoeravacyclineandcomparators
Poster#2398
Tetracycline anKbioKcs have always been considered ananKbioKc class at low risk for causingClostridioidesdifficileInfecKon (CDI). A prospecKve study demonstrateddecreased occurrence of CDI in paKents with community-acquired pneumonia if their treatment regimen includeddoxycycline. Tigecycline has been shown to decrease toxinproducKon, inhibit spore formaKon, and have clinicalefficacyusedinpaKentswithsevereandsevere-complicatedCDI. However, Kgecycline is associated with mulKpletoxiciKesthatlimititsuseinclinicalpracKce. Thus,withitsfavourablesafetyprofile,eravacyclinecouldbealife-savingaddiKontotherapieseffecKveforpaKentswithCDIinneedofintravenoustherapy. AsveryliWledataexistsontheuseoferavacyclineforthetreatmentofCDI,weproposeheretoassess the in vitro suscepKbility of eravacycline versuscomparatorson contemporary clinical isolates represenKngcommon ribotypes, including isolates with decreasedsuscepKbilitytometronidazoleandvancomycin.234isolatesfromourbiobankwere selecteddivided ingroupsof37 to42 isolates per ribotype. The six most common ribotypeswereF001,F002,F014-020,F027,F106andF255asassessedby the fluorescent PCR analysis pipeline available atthewalklab.com. MICs were measured according to CLSIguidelines foreravacycline,vancomycin,metronidazoleandfidaxomicin. Eravacycline was more efficient in terms ofMICs compared to vancomycin, metronidazole andfidaxomicinagainstalltheribotypestestedincludingisolatesless suscepKble to vancomycin and metronidazole. Thesedata,forthefirstKme,showthepotenKaloferavacyclineasan agent to treat CDI and support to undergo furtherresearchtovalidatethatperspecKve.
§ Assess the in vitro suscepKbility of eravacyclinevs.comparatorsoncontemporaryclinicalisolatesrepresenKngcommonribotypesincludingisolateswith decreased suscepKbility to metronidazoleandvancomycin.
§ Bacterialisolates§ Atotalof234clinical isolates fromthesixmostcommon ribotypes. These were selected fromour biobank according to their suscepKbilityv a r i a b i l i t y a g a i n s t v a n c omy c i n a n dmetronidazole.(Table1)
§ MICs§ MICswereassessedaccordingtotheCLSIguidelinesbybrothmicrodiluKoninBHImedium.EravacyclinwasprovidedbyTetraphase,fidaxomicinprovidedbyMerck&Co.,vancomycinandmetronidazolewerepurchasedatMiliporeSigma.
Table3.MeanMICsonallsamples
Table4.MeanMICsonlesssuscepJblesamples4.Avancomycinresistantstrains4.BMetronidazoleresistantstrains
§ * The analysis on theses lines excluded the same hyper-resistant strainresistanttometronidazole(MIC≥8μg/mL),vancomycin(MIC≥8μg/mL)anderavacycline(MIC1μg/mL)
A
B
StudysponsoredbyTetraphase
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