新生儿脓毒症.ppt

新生儿脓毒症,NeonatalSepsis,Mostcommoncauseofneonatalmortalityindevelopingcountries.Upto20%ofneonatesdevelopsepsisand1%dieofsepsisrelatedcauses.Incidenceofsystemicinfectionis3%(India)withsepticemia(75%)andpneumonia(25%)NNPNetwork,2019,EarlyandLate-onsetSepsis,NeoReviews,Vol.11,No.8,August2019,NeonatalSepsis,SepticemiaPneumoniaMeningitisArthritisOsteomyelitisUrinarytractinfectionNNPNetwork,2019,NeonatalSepsis,Intramuraladmissions-Klebsiellapneumoniae(32.5%)-Staphylococcusaureus(13.6%)Extramuraladmissions-Klebsiella(27.5%)-Saureus(38%)Sankaretal.IndianjPediatr.2019;75:261-6,NeonatalSepsis-Definitions,Probablesepsis(anyonecriteria):-Maternalfeverorfoulsmellingamnioticfluid-PROM(24hrs)orgastricpolymorphs(5hpf)-Positivesepsisscreen(anytwocriteria)-TotalWBCcount(0.2)-TotalWBCcount1mg/dl,microESR10mm-firsthour-RadiologicalevidenceofpneumoniaNNF,India,NeonatalSepsis-Definitions,Culturepositivesepsis-Isolationofthepathogenfromblood,CSF,urineorabscess15mm/hrLP(incidenceofmeningitis0.3-3%)InEOSLPisindicatedinthepresenceof+bloodcultureorsymptomsofsepticemiaInLOS,LPshouldbedoneinallinfantspriortostartingantibiotics,NeonatalSepsis-Investigations,LPshouldnotbedoneinthefollowingcases:-Asymptomaticbabiesinvestigatedformaternalriskfactors-PrematurebabieswithRDS-Criticallyillandhemodynamicallyunstablebabies,NormalCSFValuesintheNewborn,NeonatalSepsis-Investigations,Urinecultureshouldnotbepartofsepsisevaluationinthefirst72hoursoflife.InLOSurinecultureshouldbeobtainedbysuprapubicpunctureorcatheterization.UTIdiagnosis:10WBC/mmina10mlcentrifugedsample10organisms/mLincatheterizedspecimenAnyorganisminasuprapubicspecimen,NeonatalSepsis-Investigations,ChestXrayincaseofrespiratorydistressorapneaAbdominalXRayifsuspectingnecrotizingenterocolitis,NeonatalSepsis-NewerDiagnosticTests,AcutephasereactantsCellsurfacemarkersGranulocytecolonystimulatingfactorCytokinesMoleculargeneticsMolcellproteomics,AcutePhaseReactants,TheseendogenouspeptidesareproducedbytheliveraspartofimmediateresponsetoinfectionorinjuryC-reactiveproteinProcalcitoninFibronectinHaptoglobinLactoferrinNeopterinOromucosoid,HumanC-reactiveProteincomplexedwithPhosphocholine,Fiveidenticalsubunits(protomers)thatarearrangedaroundacentralpore,NeoReviews,2019;6:e508-515,WhatisCRP?,Non-type-specificsomaticpolysaccharidefractionextractedfromStreptococcuspneumoniae.“FractionC”asitwascalledwasprecipitatedbyseraofacutelyinfectedpatientsandseraofconvalescentpatientslosttheabilitytocauseprecipitation.Acutephasereactantproteincomposedoffiveidenticalnonglycosylatedpolypeptidesubunits.Itissynthesizedinhepatocytes,regulatedatthetranscriptionlevelbyinterleukin(IL)-6andIL-1-beta.TheexactfunctionofCRPisnotknown.CRPactivatescomplementandhasafunctionaleffectonphagocyticcellsandplayanimportantroleinthefirstlineofhostdefense.CRPmaybeakeycomponentinlipidmetabolismandcontributetothepathogenesisofatherosclerosisandmyocardialinfarction.,CRPValuesintheBlood,Inhealthyadults:0.8mg/LIninfants:10mg/LStartswithin4-6hoursafterstimulationandpeaksaround36-48hours.Biologichalflifeis19hourswith50%reductiondailyaftertheacutephasestimulusresolves.MeasuringCRPconcentrationinCSFisunreliable.,CellSurfaceMarkersandGranulocyteColonyStimulatingFactors,NeutrophilCD11bandCD64appeartobepromisingmarkers.CD64hadsensitivityof80%andspecificityof79%incultureprovensepsis.CD11bhadasensitivityof96-100%andspecificityof81-100%incultureprovensepsis.GSF,mediatorproducedbythebonemarrowfacilitatesproliferationofneutrophilsinsepsis.Aconcentrationof200pg/mlhasasensitivityof95%andspecificityof99%.,Procalcitonin(PCT),PCTisproducedbythemonocytesandhepatocytesandispropeptideofcalcitonin.PCTrises4-6hoursafterexposuretobacterialendotoxinpeakingat6-8hours.HalflifeofPCT25-30hours.ElevatedconcentrationsarefoundinRDS,IDMandhemodynamicallyunstableinfants.PCTvaluesof2.3ng/mlandCRP30mg/Lindicatesahighlikelyhoodoflateonsetsepsis.,CRPConcentrationinSepsis(Sensitivity,Specificity,PredictiveValues),Serialmeasurementsinearlyandlateonsetsepsisshowedthebestcutoffvalueof10mg/L(Stanford)CRPconcentrationwasnormalin30%ofallsepsisepisodes.PPVwas5%forcultureprovenearlyonsetsepsisand43%inlateonsetsepsis.GreaterelevationinCRPconcentrationswereassociatedwithhigherprobabilityofinfection.Negativepredictivevaluewashighestbothforearlyandlateonsetsepsisafterthreevalues(99.7and98.7)TwoCRPconcentration70pg/ml)andCRP(10mg/L)showedasensitivityof80%andaspecificityof87%.TNFandmedianIL6valuesweresignificantlyhigherinpatientswithsepsiscomparedtocontrols.,Franzetal.Pediatrics2019;114:1-8,MolecularGeneticsinSepsis,Polymerasechainreaction(PCR)analysisreliesonthefactthatbacteriaspecific16SrRNAgeneisconservedinallbacterialgenomesandisausefulmethodforidentificationofbacteriainclinicalsamples.PCRassayischallengingduetosmallamountofresidualDNApresentreagentsresultinginfalsepositivity.DetectionbyPCRdoesnotyieldtheantimicrobialpatternofthepathogen.RealtimePCRcombinedwithDNAMicroArraytechnologywillallowidentificationandantimicrobialsensitivityoftheorganism.Proteomics:Significantalterationsinthelevelsofeightserumproteinswerefoundininfectedneonates.,StartParenteralAntibiotic(Ab)SendCultures(reportin72hrs.),Culture-ve,Clinicallywell(StopAb),Clinicallyill(ContAbx7-100),Culture+ve,Pneumonia,Sepsis(ContAbx7-100),Meningitis,Osteomyelitis(ContAbx3-6wks),CRPGuidedDecisionforEarlyOnsetSepsis,NeoReviews,2019;6:e508-515,CRPGuidedDecisionforLateOnsetSepsis,NeoReviews,2019;6:e508-515,AntibioticTherapy,Earlyonsetsepsis:-AmpicillinandGentamicinorCefotaximeHospitalacquiredinfection:-Vancomycin/Oxacellin/Cefotaxime(6070%ofGmnegativeorganismsareresistant)MRSA:-Vancomycin/Ciprofloxacin/AmikacinEnterococus:-AmpicillinandGentamicinPsuudomonas:-Piperacilli-tazobactamwit