新生兒膿毒癥課件

新生兒膿毒癥

NeonatalSepsisMostcommoncauseofneonatalmortalityindevelopingcountries.Upto20%ofneonatesdevelopsepsisand1%dieofsepsisrelatedcauses.Incidenceofsystemicinfectionis3%(India)withsepticemia(75%)andpneumonia(25%)

NNPNetwork,2005Early-onsetSepsisLate-onsetSepsisInfectionRate(%)95%ConfidenceIntervalRange*3.63:4.10to10.5

25.023.6:26.30to53.7MortalityRate(%)95%ConfidenceIntervalRange*

26.419.1:33.720to57.1

13.311.2:15.41.8to35.6*Intraunits(5ormorecases)DatafromValls-e-SokerA,etal.2009(5)Early–andLate-onsetSepsisNeoReviews,Vol.11,No.8,August2021NeonatalSepsisSepticemiaPneumoniaMeningitisArthritisOsteomyelitisUrinarytractinfection

NNPNetwork,2005NeonatalSepsisIntramuraladmissions --Klebsiellapneumoniae(32.5%) --Staphylococcusaureus(13.6%)Extramuraladmissions --Klebsiella(27.5%) --Saureus(38%)

Sankaretal.IndianjPediatr.2021;75:261-6NeonatalSepsis-DefinitionsProbable

sepsis(anyonecriteria):

-Maternalfeverorfoulsmellingamnioticfluid

-PROM(>24hrs)orgastricpolymorphs(>5hpf)

-Positivesepsisscreen(anytwocriteria)

-TotalWBCcount(<5000/mmorband/neutrophilratio>0.2)

-TotalWBCcount<1800/mm

-C-reactiveprotein(CRP)>1mg/dl,microESR>10mm-firsthour

-Radiologicalevidenceofpneumonia

NNF,IndiaNeonatalSepsis-DefinitionsCulturepositivesepsis

--Isolationofthepathogenfromblood,CSF,urineorabscess<72hoursofagePathologicalevidenceofsepsisonautopsy

NNF,IndiaNeonatalSepsis-IncidenceIncidenceofEOSis1-2cases/1000livebirths.Thisincidenceis10foldhigherintheVLBWinfants.IncidenceofearlyonsetGBShasdeclined80%from1.7cases/1000livebirths(1993)to0.34/1000livebirths(2005)duetointrapartumantibioticprophylaxis.Mortality2.6%intermand35%inVLBWinfants.SurvivorsofEOSmayhavesevereneurologicsequelaeattributabletomeningitis,hypoxemia,septicshock,PPHNetc.PuopoloKM.NeoReviews2021;9:e571-579NeonatalSepsis-ClassificationEarlyonsetsepsis(<72hours)Riskfactors:LowbirthweightFebrileillnessinthemotherwithin2weeksPTDFoulssmellingamnioticfluidPROM(>24hours)MorethanthreevaginalexamduringlaborProlongedanddifficultdeliverywithinstrumentationPerinatalasphyxia(apgar<4at1min)ordifficultresuscitation(presenceof3-treat,Presenceof2-sepsisscreen)

Aggarwaletal.IndiajPediatr.2001;68:1143-7NeonatalSepsis-ClassificationLateonsetsepsis(>72hours)usuallynosocomialorcommunityacquired)Riskfactors:NICUadmissionPoorhygieneLowbirthweightPoorcordcarePrematurityBottlefeedingInvasiveprocedureSuperficialinfection(pyoderma,umbilicalsepsis)VentilationAspirationoffeedsPuopolo,K.,NeoReviews2021,9;571-e579OrganismsCausingNeonatalEarly-onsetSepsisOrganismsCausingEarly-onsetSepsisinVeryLow-birthweightInfantsPuopolo,K.,NeoReviews2021,9;571-e579RiskFactorsforAllCausesofEarly-onsetSepsisinInfantsWeighingLessthan2000gatBirthintheEraofIntrapartumAntibioticProphylaxisPuopolo,K.,NeoReviews2021,9;571-e579RiskFactorsforEarly-onsetGBSSepsisintheAbsenceofIAPPuopolo,K.,NeoReviews2021,9;571-e579“Early〞Pathogens(firstweek)GroupBStrep(GBS)Incidenceusedtobe4-6/1000livebirths(0.4%)Now<0.1%afterprenatalscreeningguidelinesE.coliEveryfewdecadesflipsbackandforthwithGBSasmostcommoncauseGramnegativerods(esp.inurine)OccasionalSalmonellasepsisListeriamonocytogenesHerpesSimplexEnterovirus“Late〞Pathogens(~1-2weeks)GBSorgroupAstrepEnterics/EnterococcusinurineHSVEnterovirus,RSV,FluCommunityAcquired

(after4-6weeks)PneumococcusMeningococcusGABHSHaemophilusinfluenzae(HIB)notreallyaproblemanymoreSigns/SymptomsTemperatureirregularityFeverHypothermiaToneandBehaviorPoortoneWeaksuckShrillcryWeakcryIrritabilitySkinPoorperfusionCyanosisMottlingPallorPetechiaeUnexplainedjaundiceMostbythemselvesmeanlittle,butthree(ortwo)strikesandyouareOut!Signs/SymptomsFeedingProblemsVomitingDiarrheaAbdominaldistensionHypoorHyperglycemiaCardiopulmonaryTachypneaRetractionsTachycardiaforageBradycardiainfirstfewdaysoflifeHypotensionforageLowPO2Signs/SymptomsSunkenfontanelleBulgingorpulsatingfontanelleNeckstiffnessCANNOTbeusedBabiescanbebacteremicbutlookwellPresenceofa“cold〞doesnotchangeanythingPIDJApril2005StudyinIndiafoundthatanytwoofthesesignshadanalmost100%sensitivityforsepsisandover90%mortalityReducedsuckingWeakcryCoolextremitiesVomitingPoortoneRetractionsNeonatalSepsis-InvestigationsBloodculture(1mlsampleadequate)possibletodetectgrowthin24hoursusingBACTECorBACT/ALERTsystemsTotalWBCcount(<5000/mm)Band/Neutrophilratio>0.2CRP>1mg/dlorMicro-ESR>15mm/hrLP(incidenceofmeningitis0.3-3%)InEOSLPisindicatedinthepresenceof+bloodcultureorsymptomsofsepticemiaInLOS,LPshouldbedoneinallinfantspriortostartingantibioticsNeonatalSepsis-InvestigationsLPshouldnotbedoneinthefollowingcases:

--Asymptomaticbabiesinvestigatedformaternalriskfactors

--PrematurebabieswithRDS

--CriticallyillandhemodynamicallyunstablebabiesNormalCSFValuesintheNewbornTestsTermPretermCellsWBC’sPolymorphonuclearcells7(0-32)61%9(0-29)57%Protein(mg/dl)90(20-170)115(65-150)Glucose(mg/dl)52(34-119)50(24-63)CSFglucose:Bloodglucose81(44-248)74(55-105)NeonatalSepsis-InvestigationsUrinecultureshouldnotbepartofsepsisevaluationinthefirst72hoursoflife.InLOSurinecultureshouldbeobtainedbysuprapubicpunctureorcatheterization.UTIdiagnosis:>10WBC/mmina10mlcentrifugedsample>10organisms/mLincatheterizedspecimenAnyorganisminasuprapubicspecimenNeonatalSepsis-InvestigationsChestXrayincaseofrespiratorydistressorapneaAbdominalXRayifsuspectingnecrotizingenterocolitisNeonatalSepsis-Newer

DiagnosticTestsAcutephasereactantsCellsurfacemarkersGranulocytecolonystimulatingfactorCytokinesMoleculargeneticsMolcellproteomicsAcutePhaseReactantsTheseendogenouspeptidesareproducedbytheliveraspartofimmediateresponsetoinfectionorinjuryC-reactiveproteinProcalcitoninFibronectinHaptoglobinLactoferrinNeopterinOromucosoidHumanC-reactiveProteincomplexedwithPhosphocholineFiveidenticalsubunits(protomers)thatarearrangedaroundacentralporeNeoReviews,2005;6:e508-515WhatisCRP?Non-type-specificsomaticpolysaccharidefractionextractedfromStreptococcuspneumoniae.“FractionC〞asitwascalledwasprecipitatedbyseraofacutelyinfectedpatientsandseraofconvalescentpatientslosttheabilitytocauseprecipitation.Acutephasereactantproteincomposedoffiveidenticalnonglycosylatedpolypeptidesubunits.Itissynthesizedinhepatocytes,regulatedatthetranscriptionlevelbyinterleukin(IL)-6andIL-1-beta.TheexactfunctionofCRPisnotknown.CRPactivatescomplementandhasafunctionaleffectonphagocyticcellsandplayanimportantroleinthefirstlineofhostdefense.CRPmaybeakeycomponentinlipidmetabolismandcontributetothepathogenesisofatherosclerosisandmyocardialinfarction.CRPValuesintheBloodInhealthyadults:0.8mg/LIninfants:10mg/LStartswithin4-6hoursafterstimulationandpeaksaround36-48hours.Biologichalflifeis19hourswith50%reductiondailyaftertheacutephasestimulusresolves.MeasuringCRPconcentrationinCSFisunreliable.CellSurfaceMarkersandGranulocyteColonyStimulatingFactorsNeutrophilCD11bandCD64appeartobepromisingmarkers.CD64hadsensitivityof80%andspecificityof79%incultureprovensepsis.CD11bhadasensitivityof96-100%andspecificityof81-100%incultureprovensepsis.GSF,mediatorproducedbythebonemarrowfacilitatesproliferationofneutrophilsinsepsis.Aconcentrationof>200pg/mlhasasensitivityof95%andspecificityof99%.Procalcitonin(PCT)PCTisproducedbythemonocytesandhepatocytesandispropeptideofcalcitonin.PCTrises4-6hoursafterexposuretobacterialendotoxinpeakingat6-8hours.HalflifeofPCT25-30hours.ElevatedconcentrationsarefoundinRDS,IDMandhemodynamicallyunstableinfants.PCTvaluesof>2.3ng/mlandCRP>30mg/Lindicatesahighlikelyhoodoflateonsetsepsis.CRPConcentrationinSepsis

(Sensitivity,Specificity,PredictiveValues)Serialmeasurementsinearlyandlateonsetsepsisshowedthebestcutoffvalueof10mg/L(Stanford)CRPconcentrationwasnormalin30%ofallsepsisepisodes.PPVwas5%forcultureprovenearlyonsetsepsisand43%inlateonsetsepsis.GreaterelevationinCRPconcentrationswereassociatedwithhigherprobabilityofinfection.Negativepredictivevaluewashighestbothforearlyandlateonsetsepsisafterthreevalues(99.7and98.7)TwoCRPconcentration<10mg/Lobtained24hoursapartmakessepsisunlikely.Benitzetal.Pediatrics.1998;102:e41C-reactiveProtein:rateNephalometryNeoReviews,2005;6:e508-515LightscatteredisProportionaltoconcentrationofantigenFactorsThatCanInfluence

CRPValues

Modeofdelivery

Gestationalage

Typeoforganismcausingsepsis

Granulocytopenia

Surgery

Immunizations

Severeviralinfections(eg,herpessimplexvirus,rotavirus,influenza)NeoReviews,2005;6:e508-515CytokinesinSepsisCytokinesmediatecommunicationbetweencellsofthebodybybindingtospecificcellularreceptorsandtransducingsignalsintodifferenttargetcellswithbiologiceffectsthatplayaroleinthepathogenesisofsepsis.Interleukin-6(mononuclearphagocyte)hasbeenconsistentlyshowntoincreaseinearlyonsetsepsis,butsensitivityisreducedat24-48hoursastheconcentrationrapidlyfallsandbecomesundetectableat24hours(NormalplasmaconcentrationofIL6is10pg/mL)CombinedmeasurementofIL6(earlysensitive)withCRP(lateandspecific)inthefirst48hoursimprovessensitivitycomparedtoeithermarkeralone.Mehretal.pediatrInfecDisJ.2000;19:879-87CytokinesinSepsisIL8isproinflammatorycytokine(mononuclearphagocyte)thatisconsideredtobeanaccuratemarkerwithsensitivitiesrangingfrom80-91%andspecificities76-100%.AcombinationofIL8(>70pg/ml)andCRP(>10mg/L)showedasensitivityof80%andaspecificityof87%.TNFαandmedianIL6valuesweresignificantlyhigherinpatientswithsepsiscomparedtocontrols.Franzetal.Pediatrics2004;114:1-8MolecularGeneticsinSepsisPolymerasechainreaction(PCR)analysisreliesonthefactthatbacteriaspecific16SrRNAgeneisconservedinallbacterialgenomesandisausefulmethodforidentificationofbacteriainclinicalsamples.PCRassayischallengingduetosmallamountofresidualDNApresentreagentsresultinginfalsepositivity.DetectionbyPCRdoesnotyieldtheantimicrobialpatternofthepathogen.RealtimePCRcombinedwithDNAMicroArraytechnologywillallowidentificationandantimicrobialsensitivityoftheorganism.Proteomics:Significantalterationsinthelevelsofeightserumproteinswerefoundininfectedneonates.StartParenteralAntibiotic(Ab)SendCultures(reportin72hrs.)Culture-veClinicallywell(StopAb)Clinicallyill