Management and Outcome of Sepsis in Term and Late Preterm Infants

17/9/2015
Managementandoutcomeofsepsisintermandlatepreterminfants
OfficialreprintfromUpToDate
www.uptodate.com2015UpToDate
Author
MorvenSEdwards,MD
SectionEditors
LeonardEWeisman,MD
SheldonLKaplan,MD
DeputyEditor
CarrieArmsby,MD,MPH
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Aug2015.|Thistopiclastupdated:Jul13,2015.
INTRODUCTIONSepsisisanimportantcauseofmorbidityandmortalityamongnewborninfants.Althoughthe
incidenceofsepsisintermandlatepreterminfantsislow,thepotentialforseriousadverseoutcomes,including
death,isofsuchgreatconsequencethatcaregiversshouldhavealowthresholdforevaluationandtreatmentfor
possiblesepsisinneonates.Theapproachdiscussedbelowisconsistentwithguidelinespublishedbythe
AmericanAcademyofPediatrics(AAP)andtheCenterforDiseaseControl(CDC)[1,2].
Thetreatmentandoutcomeofsepsisintermandlatepreterminfantswillbereviewedhere.Theepidemiology,
clinicalfeatures,diagnosis,andevaluationofsepsisintermandlatepreterminfants,neonatalsepsisinpreterm
infants,themanagementofwellappearinginfantsatriskforgroupBstreptococcalinfection,andtheevaluationof
febrileorillappearingnewbornsarediscussedseparately:
(See"Clinicalfeatures,evaluation,anddiagnosisofsepsisintermandlatepreterminfants".)
(See"Clinicalfeaturesanddiagnosisofbacterialsepsisinthepreterminfant".)
(See"Treatmentandpreventionofbacterialsepsisinthepreterminfant".)
(See"ManagementoftheinfantwhosemotherhasreceivedgroupBstreptococcalchemoprophylaxis".)
(See"Evaluationandmanagementoffeverintheneonateandyounginfant(youngerthanthreemonthsof
age)",sectionon'Neonates(0to28days)'.)
(See"Approachtothesepticappearinginfant".)
TERMINOLOGYThefollowingtermswillbeusedthroughoutthisdiscussiononneonatalsepsis:
Neonatalsepsisisaclinicalsyndromeinaninfant28daysoflifeoryounger,manifestedbysystemicsigns
ofinfectionandisolationofabacterialpathogenfromthebloodstream[3].Aconsensusdefinitionfor
neonatalsepsisislacking[4].(See"Clinicalfeatures,evaluation,anddiagnosisofsepsisintermandlate
preterminfants",sectionon'Diagnosis'.)
Terminfantsarethosebornatagestationalageof37weeksorgreater.
Latepreterminfants(alsocallednearterminfants)arethosebornbetween34and36completedweeksof
gestation[5].(See"Latepreterminfants".)
Preterminfantsarethosebornatlessthan34weeksofgestation[5].
Neonatalsepsisisclassifiedaccordingtotheinfant'sageattheonsetofsymptoms:
Earlyonsetsepsisisdefinedastheonsetofsymptomsbefore7daysofage,althoughsomeexpertslimit
thedefinitiontoinfectionsoccurringwithinthefirst72hoursoflife[6].
Lateonsetsepsisisdefinedastheonsetofsymptomsat7daysofage[6].Similarlytoearlyonset
sepsis,thereisvariabilityinitsdefinition,rangingfromanonsetat>72hoursoflifeto7daysofage[6,7].
SUPPORTIVECARESymptomaticinfantsshouldbetreatedinacaresettingwithfullcardiopulmonary
monitoringandsupport,becausetheclinicalcourseoftheseinfantscandeterioraterapidly.Althoughthereareno
datademonstratingtheimportanceofsupportivecaremeasuresinneonateswithsepsis,itisgenerallyaccepted
thatthefollowingsupportivemeasuresarecriticalcomponentsofmanagement:
http://www.uptodate.com/contents/managementandoutcomeofsepsisintermandlatepreterminfants?topicKey=PEDS%2F5046&elapsedTimeMs=0&sou
1/22
17/9/2015
Maintainingadequateoxygenationandperfusion(see"Oxygenmonitoringandtherapyinthenewborn")
Preventionofhypoglycemiaandmetabolicacidosis(see"Managementandoutcomeofneonatal
hypoglycemia")
Maintenanceofnormalfluidandelectrolytestatus(see"Fluidandelectrolytetherapyinnewborns")
Severelyillpatientsmayrequireventilatory,volume,and/orvasopressorsupporttomaintainadequateoxygenation
andperfusion.(See"Mechanicalventilationinneonates"and"Etiology,clinicalmanifestations,andevaluationof
neonatalshock".)
ONGOINGDIAGNOSTICEVALUATION
OtherdiagnosticconsiderationsIninfantswithsuspectedsepsis,additionaltestingforotherconditionsmay
bewarrantedbasedonclinicalsignsandsymptoms(table1).Itisoftendifficulttodifferentiateneonatalsepsis
fromotherdiseaseshowever,giventhemorbidityandmortalityofneonatalsepsis,empiricantibiotictherapy
shouldbeprovided(afterculturesareobtained)toinfantswithsuspectedsepsispendingdefinitiveculturebased
diagnosis.Alternativediagnosesshouldbeentertainedwhenaninfantwithsuspectedsepsishasnegative
cultures.(See"Clinicalfeatures,evaluation,anddiagnosisofsepsisintermandlatepreterminfants",sectionon
'Differentialdiagnosis'.)
LumbarpunctureIfnotdoneduringtheinitialevaluation,alumbarpuncture(LP)shouldbeperformedin
infants,wheneverpossible,withcultureprovenorculturenegativeclinicalsepsis.Clinicalsignssuggesting
meningitiscanbelackingandbloodculturemaybenegativeininfantswithmeningitis.(See"Bacterialmeningitis
intheneonate:Clinicalfeaturesanddiagnosis".)
ANTIBIOTICTHERAPY
WhomtotreatThedecisiontostartantibiotictherapyisbasedonassessmentofriskfactors,clinical
evaluation,andlaboratorytests.Indicationsforempiricantibiotictherapyinclude(see"Clinicalfeatures,
evaluation,anddiagnosisofsepsisintermandlatepreterminfants",sectionon'Evaluationandinitial
management'):
Illappearance(see"Approachtothesepticappearinginfant")
Concerningsymptoms,includingtemperatureinstability,orrespiratory,cardiocirculatory,orneurologic
symptoms(see"Clinicalfeatures,evaluation,anddiagnosisofsepsisintermandlatepreterminfants",
sectionon'Clinicalmanifestations')
Cerebrospinalfluid(CSF)pleocytosis(whitebloodcell[WBC]cellcountof>20to30cells/microL)(table2)
(see"Bacterialmeningitisintheneonate:Clinicalfeaturesanddiagnosis",sectionon'InterpretationofCSF')
Confirmedorsuspectedmaternalchorioamnionitis(see"Clinicalfeatures,evaluation,anddiagnosisof
sepsisintermandlatepreterminfants",sectionon'Maternalriskfactors')
Positiveblood,urine,orCSFculture(see"Clinicalfeatures,evaluation,anddiagnosisofsepsisintermand
latepreterminfants",sectionon'Bloodculture')
InitialempirictherapyTheinitialchoiceofparenteralantimicrobialsforsuspectedsepsisintermandlate
pretermneonatesisbasedontheinfant'sage,likelypathogens,thesusceptibilitypatternsoforganismsina
particularnursery,andthepresenceofanapparentsourceofinfection(eg,skin,joint,orboneinvolvement)(table
3).
EarlyonsetsepsisTherecommendedempiricregimenforsuspectedearlyonsetsepsisinatermorlate
preterminfantisampicillin150mg/kgperdoseintravenously(IV)every12hoursandgentamicin4mg/kgperdose
IVevery24hours[7,8].Wegenerallyobtainbaselinerenalfunctiontests(ie,bloodureanitrogenandcreatinine
levels)attheinitiationoftreatmentwithgentamicin.Serumgentamicinlevelsshouldbeobtainedininfants
receivingafullcourseofantibiotics,butarenotrequiredifatreatmentcourseofonly48hoursisanticipatedand
2/22
17/9/2015
renalfunctionisnormal[3,7].
Thecombinationofampicillinandgentamiciniseffectiveintreatingmostcommonpathogensthatcauseearly
onsetsepsis,includinggroupBStreptococcus(GBS),Listeria,Enterococcus,andmostisolatesofEscherichia
coli(E.coli)(table4)[1,9].
Inanationalsurveillancestudy(2006to2008),94percentofallisolatesinneonatesweresusceptibletothe
combinationofpenicillinandgentamicin[10].Ina10yearreviewfromasinglecenter,90percentofearlyonset
sepsispathogensintermandlatepreterminfantsweresusceptibletoampicillinand/orgentamicin[11].Amongsix
infantswithearlyonsetS.aureusbacteremiathatwasnotsusceptibletoampicillinandgentamicin,therewereno
complicationsbeforeorafterantibiotictherapywasadjustedbaseduponantibioticsusceptibility.
Ampicillinandgentamicinarepreferredoverampicillinandathirdgenerationcephalosporin(eg,cefotaxime)based
uponthefollowing:
Theregimenofampicillinandathirdgenerationcephalosporinisnotmoreeffectivethanthecombinationof
ampicillinandgentamicin[12].
Theemergenceofcephalosporinresistantgramnegativeorganisms(eg,Enterobactercloacae,Klebsiella,
andSerratiaspecies)canoccurwhencefotaximeisusedroutinely[1,13].
AmpicillinandgentamicinaresynergisticintreatinginfectionscausedbyGBSandListeriamonocytogenes.
CephalosporinsarenotactiveagainstL.monocytogenes.
Inalargecohortstudy,infantswhoreceivedampicillinpluscefotaximehada1.5foldincreaseinmortality
comparedwiththosetreatedwithampicillinplusgentamicin(4.2versus1.9percent,adjustedoddsratio1.5,
95%CI1.41.7)[12].
Ceftriaxoneishighlyboundtoalbuminandappearstodisplacebilirubin[14,15].Althoughdisplacementof
freebilirubinbyceftriaxonehasnotbeenreported,avoidanceofceftriaxoneinneonatesatriskforacute
bilirubinencephalopathyisrecommended[1].(See"Clinicalmanifestationsofunconjugated
hyperbilirubinemiaintermandlatepreterminfants",sectionon'Neurologicmanifestations'.)
Theadditionofathirdgenerationcephalosporintotheregimenofampicillinandgentamiciniswarrantedforinfants
withsuspectedmeningitisandcriticallyillneonateswithriskfactorsassociatedwithampicillinresistantinfections
(ie,prolongedruptureofmembranesand/orprolongedantenatalmaternalampicillintreatment).
LateonsetsepsisThechoiceofempirictherapyforlateonsetsepsisdependsuponwhethertheinfantis
admittedfromthecommunity,andthusisatlowerriskforinfectioncausedbyamultidrugresistantpathogen,oris
hospitalizedsincebirthandthusatahigherrisk.
AdmittedfromthecommunityNeonatesadmittedfromthecommunityareatlowerriskforinfection
causedbyamultidrugresistantpathogenthanareinfantswhoremainhospitalizedsincebirth.Thecombinationof
ampicillinandgentamicinorampicillinandcefotaximeareregimensforempirictreatmentofsepsiswithoutan
apparentfocusofinfectioninthissetting(table3)[6].
Ampicillinandgentamicinisgenerallythepreferredregimenhowever,localantibioticresistancepatternsmustbe
considered.Thedosingforampicillinis75mg/kgperdoseintravenouslyeverysixhoursthedosingofgentamicin
is4mg/kgperdoseintravenouslyevery24hours[7,8].Wegenerallyobtainbaselinerenalfunctiontests(ie,blood
ureanitrogenandcreatininelevels)attheinitiationoftreatmentwithgentamicin.Serumgentamicinlevelsshould
beobtainedininfantsreceivingafullcourseofantibiotics,butarenotrequiredifatreatmentcourseofonly48
hoursisanticipatedandrenalfunctionisnormal[3,7].
Inanationalsurveillancestudy(2006to2008),96percentofisolatesfromlateonsetbacteremiaweresusceptible
tothecombinationofamoxicillinandgentamicin[10].Theadditionofathirdgenerationcephalosporintoan
ampicillinandgentamicinregimeniswarrantedforneonateswithsuspectedmeningitis.(See'Special
3/22
17/9/2015
circumstances'below.)
HospitalizedsincebirthInfantswhocontinuetobehospitalizedsincebirthareathigherriskfor
multidrugresistantorganisms,andthereforevancomycinissubstitutedforampicillin(table3).Forinfants>7days
oflife,thedosingofvancomycinisdependentonpostmenstrualage(PMA)[8]:
30to37weeksPMA15mg/kgperdoseevery12hours
>37weeksPMA15mg/kgperdoseevery8hours
SpecialcircumstancesAlternativeregimensbaseduponspecificclinicalcircumstancesincludethe
following(table3):
SuspectedmeningitisWhenlumbarpuncturesuggestsmeningitis,cefotaximeshouldbeincludedinthe
regimentoprovideanextendedspectrumforentericgramnegativerodsandforoptimalactivityintheCSF
againstpneumococci.Treatmentofbacterialmeningitisinneonatesisdiscussedindetailseparately.(See
"Bacterialmeningitisintheneonate:Treatmentandoutcome",sectionon'Empiricaltherapy'.)
SuspectedpneumoniaEmpiricregimensfortreatmentofinfantswithapulmonaryfocusofinfectioninclude
ampicillinandgentamicin,ampicillinandcefotaxime,vancomycinandcefotaxime,orvancomycinand
gentamicin.Treatmentofpneumoniainneonatesisdiscussedindetailseparately.(See"Neonatal
pneumonia",sectionon'Treatment'.)
Ifthereisafocusofinfectioninvolvingthesofttissues,skin,joints,orbones(inwhichcaseS.aureusisa
likelypathogen),vancomycinshouldbesubstitutedforampicillin[16].Inatoxicappearinginfant,nafcillin
shouldalsobeadded.
Ifintravascularcatheterrelatedinfectionisaconcern,treatmentshouldbeinitiatedwithvancomycinand
gentamicintoprovideempiriccoverageforcoagulasenegativestaphylococci,S.aureus,andgramnegative
bacteria.
Ifinfectionisthoughttoarisefromthegastrointestinaltract(eg,anaerobicbacteria),clindamycinoranother
suitableagent,suchasmetronidazole,shouldbeaddedtothetherapeuticregimentoimprovecoveragefor
thesepathogens.
CultureprovensepsisInneonateswithcultureprovensepsis,theusualcourseoftherapyis10days
[1,3,13,17,18].Longertreatmentcoursesmaybewarrantedifaspecificfocusofinfectionisidentified(eg,
meningitis,osteomyelitis,orsepticarthritis).Antimicrobialtherapyshouldbealteredbaseduponthesusceptibility
profileofthepathogenisolated.
PathogenspecifictherapyGuidelinesforthetreatmentofthemostcommoncausativeorganismsof
neonatalsepsisare(table3):
GroupBstreptococcusThedrugofchoiceforGBSispenicillin.Thus,whenGBSisidentified,and
resolutionofbacteremiaisdocumentedbyarepeatbloodcultureand,ininfantswithmeningitis,theCSFissterile,
werecommenddiscontinuinggentamicinandcontinuingtherapywithpenicillinGalone(table5AB).(See"Group
Bstreptococcalinfectioninneonatesandyounginfants",sectionon'Definitivetherapy'.)
EscherichiacoliInpatientswithEscherichiacoli(E.coli)sepsissensitivetoampicillinwhohave
improvedclinicallyandinwhommeningitishasbeenexcluded,ampicillinmonotherapyisadministeredfora10
daycourse.
ForpatientswithampicillinresistantE.coli,thechoiceofdefinitivetherapyisbaseduponthesusceptibilityprofile.
Cefotaximeisoftenemployediftheisolateissusceptible.
OthergramnegativebacilliNonmeningealinfectionscausedbyE.coli,Klebsiella,Proteus,
Salmonella,orShigellashouldbetreatedwithasingleagent,basedupontheantimicrobialsusceptibilityprofile.
4/22
17/9/2015
AntimicrobialtreatmentforinfectionscausedbyEnterobacter,Serratia,orPseudomonasshouldbeselectedbased
uponthesusceptibilityprofileoftheorganism.
Infectionscausedbymultidrugresistantgramnegativebacilli,includingthosecausedbyextendedspectrumbeta
lactamaseproducingorganisms,orthosewithhyperproductionofbetalactamases,shouldbetreatedwith
meropenem.
ListeriamonocytogenesThecombinationofampicillinandgentamicinisusedforinitialtherapy.
TreatmentwithbothagentsismoreeffectivethanampicillinaloneinvitroandinanimalmodelsofListeria
infection.CephalosporinsarenotactiveagainstL.monocytogenes.Durationoftherapyusuallyis10days.(See
"Treatment,prognosis,andpreventionofListeriamonocytogenesinfection",sectionon'Antibioticregimens'.)
StaphylococcusspeciesDirectedtherapyforinfectioncausedbystaphylococciisdeterminedbythe
sensitivityoftheisolatetospecificantibioticagents:
S.aureusVancomycinor,inatoxicappearinginfant,vancomycinplusnafcillinshouldbeemployedforS.
aureusinfectionuntilthesusceptibilityprofileisavailable.Theregimenthenshouldbeadjustedaccordingto
thesusceptibilityprofile:
MethicillinsusceptibleS.aureus(MSSA)TreatmentofMSSAinfectionshouldbecompletedwith
nafcillin.CefazolinisanalternativefortreatmentofmostMSSAinfectionsoutsidethecentralnervous
system(CNS)andnotinvolvingendocarditis.(See"Staphylococcusaureusbacteremiainchildren:
Managementandoutcome".)
MethicillinresistantS.aureus(MRSA)Treatmentshouldbecompletedwithvancomycin.(See
"MethicillinresistantStaphylococcusaureusinchildren:Treatmentofinvasiveinfections",sectionon
'Treatmentofneonates'.)
CoagulasenegativestaphylococciCoagulasenegativestaphylococcalinfectionsrequiretreatmentwith
vancomycin.
ProbablebutunprovensepsisIninfantswithanegativebloodculturebutaclinicalstatusthatremains
concerningforasystemicinfection(eg,ongoingtemperatureinstabilityongoingrespiratory,cardiocirculatory,or
neurologicsymptomsnotexplainedbyotherconditionsorlaboratoryabnormalitiessuggestiveofsepsis),
antibiotictherapycanbeextendedforaslongasatotalof5to10days.
After48hours,theempiricregimenisalteredbaseduponwhetherornotmeningitishasbeenexcluded:
Ifmeningitishasbeenexcluded,theampicillinregimencanbechangedto75mg/kgevery12hours.
Iflumbarpuncturehasnotbeenperformed,ampicillinshouldbecontinuedatameningiticdose.
Managementofinfantswithcerebrospinalfluid(CSF)pleocytosisand/orpositiveCSFcultureisdiscussed
separately.(See"Bacterialmeningitisintheneonate:Treatmentandoutcome".)
Alternativediagnosesshouldalsobeentertainedwhenaninfantwithsuspectedsepsishasnegativecultures
(table1).Antibioticsshouldbediscontinuedwhenanotherdiagnosisisestablished.(See"Clinicalfeatures,
evaluation,anddiagnosisofsepsisintermandlatepreterminfants",sectionon'Differentialdiagnosis'.)
InfectionunlikelyEmpiricantibioticsareinitiatedinmanyinfantswithmaternalriskfactors,abnormal
laboratoryvalues,and/ormildtomoderatesymptomsthatsubsequentlyresolve.Sepsisisunlikelyintheseinfants
iftheyremainwellandthebloodcultureissterileat48hours.Empiricantibiotictherapyshouldbediscontinued
after48hoursintheseneonates[1,19].
ResponsetotherapyInmostcases,symptomaticinfantswithprovensepsisimproveclinicallywithin24to48
hours.
Ininfantswithbacteremia,arepeatbloodcultureshouldbeobtainedafter24to48hoursoftherapytodocument
5/22
17/9/2015
sterility.Failuretosterilizethebloodstreamsuggeststhattheantimicrobial(s)chosenarenotactiveagainstthe
infectingpathogenorthatthereisanunrecognizedfocusofinfection.Consultationwithapediatricinfectious
diseasespecialistmaybewarranted.
ADJUNCTIVETHERAPIESThefollowingadjunctiveimmunotherapeuticinterventionshavebeenstudiedin
neonatalsepsis,butshouldNOTberoutinelyadministeredastheyhavenotbeenshowntoconclusivelyimprove
outcomes[17,18,20]:
Intravenousimmunoglobulin(IVIG)infusions[21,22]
Granulocytetransfusions[23]
Granulocyteandgranulocytemacrophagecolonystimulatingfactor(GCSFandGMCSF)[24,25]
Pentoxifylline[26]
Lactoferrin[27]
PREVENTIONTheprimaryinterventiontopreventneonatalsepsisistheuseofintrapartumantibiotic
prophylaxis(IAP)inmotherswithgroupBstreptococcal(GBS)colonizationandotherriskfactors.AlthoughIAP
hasresultedinadecreaseintheincidenceofearlyonsetGBSinvasiveneonatalinfection,ithasnothadasimilar
impactontherateoflateonsetGBSdisease.(See"NeonatalgroupBstreptococcaldisease:Prevention"and
"GroupBstreptococcalinfectioninneonatesandyounginfants",sectionon'Epidemiology'.)
Comprehensivepreventionofneonatalsepsiswillrequireamultiinterventionalprogramincludingeffective
maternalvaccination,reductioninpretermdelivery,andlimitedexposureofterminfantstopotentialpathogens.
(See"VaccinesforthepreventionofgroupBstreptococcaldisease".)
OUTCOMEOverallmortalityintermandlatepreterminfantswithneonatalsepsisisapproximately2to4
percent[12,28].Mortalityestimatesvarydependingongestationalageoftheinfant(lowergestationalageis
associatedwithhighermortality),pathogen(E.coliisassociatedwithhighermortalitythanGBS),andsepsis
definition(lowermortalityratestendtobereportedifinfantswithculturenegativeclinicalsepsisareincluded
comparedwithcasesofcultureprovensepsisonly).
MortalityratesforGBSsepsisinterminfantsaftertheintroductionofIAPandroutineuseofempiricalantibiotic
therapyrangefrom2to3percentforearlyonsetdiseaseand1to2percentforlateonsetdisease.Theriskof
mortalityishigherininfantswithbirthweightlessthan2500g,absoluteneutrophilcountlessthan1500
cells/microL,hypotension,apnea,andpleuraleffusion[29].(See"GroupBstreptococcalinfectioninneonatesand
younginfants",sectionon'Outcome'.)
TheriskofmortalityisparticularlyhighinneonateswithearlyonsetsepsiscausedbyE.coli.Estimatedmortality
ratesfortermneonateswithE.colisepsisare6to10percent[9,28,30].
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"and
"BeyondtheBasics."TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgrade
readinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.These
articlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.Beyond
theBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewritten
atthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortable
withsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
"patientinfo"andthekeyword(s)ofinterest.)
Basicstopics(see"Patientinformation:Sepsisinnewbornbabies(TheBasics)")
SUMMARYANDRECOMMENDATIONS
6/22
17/9/2015
Althoughtheincidenceofsepsisintermandlatepreterminfantsislow,thepotentialforseriousadverse
outcomes,includingdeath,isofsuchgreatconsequencethatcaregiversshouldhavealowthresholdfor
evaluationandtreatmentforpossiblesepsis.(See'Introduction'above.)
Supportivecareforsymptomaticinfantsisdeliveredinanintensivecaresettingtoensureadequate
oxygenation,perfusion,andmaintenanceofnormalfluidandelectrolytebalance,especiallyinseverely
affectedpatients.(See'Supportivecare'above.)
Indicationsforempiricantibiotictherapyincludeanyofthefollowing:
Illappearance(see"Approachtothesepticappearinginfant")
Concerningsymptoms,includingtemperatureinstability,orrespiratory,cardiocirculatory,orneurologic
symptoms(see"Clinicalfeatures,evaluation,anddiagnosisofsepsisintermandlatepreterminfants",
sectionon'Clinicalmanifestations')
Cerebrospinalfluid(CSF)pleocytosis(whitebloodcell[WBC]cellcountof>20to30cells/microL)
(table2)(see"Bacterialmeningitisintheneonate:Clinicalfeaturesanddiagnosis",sectionon
'InterpretationofCSF')
Confirmedorsuspectedmaternalchorioamnionitis(see"Clinicalfeatures,evaluation,anddiagnosisof
sepsisintermandlatepreterminfants",sectionon'Maternalriskfactors')
Positiveblood,urine,orCSFculture(see"Clinicalfeatures,evaluation,anddiagnosisofsepsisinterm
andlatepreterminfants",sectionon'Bloodculture')
Werecommendsuspectedneonatalsepsisbetreatedinitiallywithempiricantibiotictherapy(table3)that
providesbroadcoverageforthemostlikelypathogens(groupBStreptococcus[GBS]andgramnegative
entericorganisms,includingEscherichiacoli[E.coli])(table4)(Grade1B).
Theempiricregimenforearlyonsetsepsiswithoutanapparentfocusconsistsofampicillinand
gentamicin.(See'Earlyonsetsepsis'above.)
Empiricantibioticregimensforlateonsetsepsiswithoutanapparentfocusareasfollows(see'Late
onsetsepsis'above):
Forneonatesadmittedfromthecommunity,wesuggestampicillinandgentamicin.
Forinfantswhocontinuetobehospitalizedfrombirth,wesuggestvancomycinandgentamicin.
Empiricantibioticregimensforsuspectedneonatalsepsis(earlyorlateonset)withcertainspecial
circumstancesareasfollows(see'Specialcircumstances'above):
Ifthereisconcernofmeningitis,wesuggestaddingcefotaximetotheregimen.(See"Bacterial
meningitisintheneonate:Treatmentandoutcome",sectionon'Empiricaltherapy'.)
Ifthereisconcernforpneumonia,wesuggestaregimenofampicillinandcefotaximeor
vancomycinandcefotaxime.
Ifthereisafocusofinfectioninvolvingthesofttissues,skin,joints,orbones(inwhichcaseS.
aureusisalikelypathogen),wesuggestsubstitutingvancomycinor,intoxicappearinginfants,
vancomycinplusnafcillinforampicillin.
Ifintravascularcatheterrelatedinfectionisaconcern,wesuggestvancomycinandgentamicin.
Ifanintestinalsourceforsepsisissuspected,wesuggestaddingclindamycin,orothersuitable
antibioticsuchasmetronidazole.
Antibiotictherapyisalteredbaseduponisolationofthecausativeagentanditsantimicrobialsusceptibility
7/22
17/9/2015
pattern.(See'Pathogenspecifictherapy'above.)
Ininfantswithcultureprovensepsis,theusualcourseoftherapyis10days.Longertreatmentiswarrantedif
aspecificfocusofinfectionisidentified(eg,meningitis,osteomyelitis,orsepticarthritis).(See'Culture
provensepsis'above.)
Inwellappearinginfantswithnegativeculturesafter48hours,empiricantibiotictherapyshouldbe
discontinuedassepsisisunlikelyintheseinfants.(See'Infectionunlikely'above.)
Mostinfantswithcultureprovensepsisimproveclinicallywithin24to48hoursafterappropriateantibiotic
treatmentisstarted.Theresponsetoantibiotictherapyisassessedbyarepeatbloodculture24to48hours
afterinitiationofantibiotictherapy.Failuretosterilizethebloodstreamsuggestseitherthatthe
antimicrobial(s)chosenarenotactiveagainsttheinfectingpathogenorthatthereisanunrecognizedfocusof
infection.(See'Responsetotherapy'above.)
Themortalityofneonatalsepsisinterminfantsislessthan10percent.(See'Outcome'above.)
Theprimaryinterventiontopreventneonatalsepsisistheuseofintrapartumantibioticprophylaxisinmothers
withdocumentedGBScolonization,apreviousbirthofaninfantwithGBSdisease,orGBSbacteriuriaduring
thecurrentpregnancy.(See"NeonatalgroupBstreptococcaldisease:Prevention".)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
REFERENCES
1. PolinRA,CommitteeonFetusandNewborn.Managementofneonateswithsuspectedorprovenearly
onsetbacterialsepsis.Pediatrics2012129:1006.
2. VeraniJR,McGeeL,SchragSJ,DivisionofBacterialDiseases,NationalCenterforImmunizationand
RespiratoryDiseases,CentersforDiseaseControlandPrevention(CDC).PreventionofperinatalgroupB
streptococcaldiseaserevisedguidelinesfromCDC,2010.MMWRRecommRep201059:1.
3. Edwards,MS,Baker,CJ.SepsisintheNewborn.In:Krugman'sInfectiousDiseasesofChildren,11thed,
Gershon,AA,Hotez,PJ,Katz,SL(Eds),Mosby,Philadelphia2004,p.545.
4. WynnJL,WongHR,ShanleyTP,etal.Timeforaneonatalspecificconsensusdefinitionforsepsis.Pediatr
CritCareMed201415:523.
5. RajuTN,HigginsRD,StarkAR,LevenoKJ.Optimizingcareandoutcomeforlatepreterm(nearterm)
infants:asummaryoftheworkshopsponsoredbytheNationalInstituteofChildHealthandHuman
Development.Pediatrics2006118:1207.
6. AmericanAcademyofPediatrics.GroupBstreptococcalinfections.In:RedBook:2015Reportofthe
CommitteeonInfectiousDiseases,30thed,KimberlinDW(Ed),AmericanAcademyofPediatrics,2015.
p.745.
7. RaoSC,AhmedM,HaganR.Onedoseperdaycomparedtomultipledosesperdayofgentamicinfor
treatmentofsuspectedorprovensepsisinneonates.CochraneDatabaseSystRev2006:CD005091.
8. Medications.In:GuidelinesforAcuteCareoftheNeonate,22ndEd,AdamsJM,FernandesCJ.(Eds),
BaylorCollegeofMedicine,Houston,TX2014.p.89.
9. StollBJ,HansenNI,SnchezPJ,etal.Earlyonsetneonatalsepsis:theburdenofgroupBStreptococcal
andE.colidiseasecontinues.Pediatrics2011127:817.
10. MullerPebodyB,JohnsonAP,HeathPT,etal.Empiricaltreatmentofneonatalsepsis:arethecurrent
guidelinesadequate?ArchDisChildFetalNeonatalEd201196:F4.
11. MaayanMetzgerA,BarzilaiA,KellerN,KuintJ.Arethe"goodold"antibioticsstillappropriateforearly
onsetneonatalsepsis?A10yearsurvey.IsrMedAssocJ200911:138.
12. ClarkRH,BloomBT,SpitzerAR,GerstmannDR.Empiricuseofampicillinandcefotaxime,comparedwith
ampicillinandgentamicin,forneonatesatriskforsepsisisassociatedwithanincreasedriskofneonatal
death.Pediatrics2006117:67.
8/22
17/9/2015
13. AmericanAcademyofPediatrics.EscherichiacoliandotherGramnegativebacilli(septicemiaand
meningitisinneonates).In:RedBook:2015ReportoftheCommitteeonInfectiousDiseases,30thed,
KimberlinDW(Ed),AmericanAcademyofPediatrics,ElkGroveVillage,IL2015.p.340.
14. GulianJM,DalmassoC,GonardV.Interactionofbetalactamantibioticsonbilirubinalbumincomplex:
comparisonbythreemethods,totalbilirubin,unboundbilirubinanderythrocyteboundbilirubin.
Chemotherapy199036:91.
15. MartinE,FanconiS,KlinP,etal.Ceftriaxonebilirubinalbumininteractionsintheneonate:aninvivo
study.EurJPediatr1993152:530.
16. FortunovRM,HultenKG,HammermanWA,etal.CommunityacquiredStaphylococcusaureusinfectionsin
termandneartermpreviouslyhealthyneonates.Pediatrics2006118:874.
17. NizetV,KleinJO.Bacterialsepsisandmeningitis.In:InfectiousdiseasesoftheFetusandNewbornInfant,
7thed,RemingtonJS,etal(Eds),WBSaunders,Philadelphia2010.p.222.
18. GerdesJS.Diagnosisandmanagementofbacterialinfectionsintheneonate.PediatrClinNorthAm2004
51:939.
19. PolinRA,WatterbergK,BenitzW,EichenwaldE.Theconundrumofearlyonsetsepsis.Pediatrics2014
133:1122.
20. CohenWolkowiezM,BenjaminDKJr,CapparelliE.Immunotherapyinneonatalsepsis:advancesin
treatmentandprophylaxis.CurrOpinPediatr200921:177.
21. INISCollaborativeGroup,BrocklehurstP,FarrellB,etal.Treatmentofneonatalsepsiswithintravenous
immuneglobulin.NEnglJMed2011365:1201.
22. OhlssonA,LacyJB.Intravenousimmunoglobulinforsuspectedorproveninfectioninneonates.Cochrane
DatabaseSystRev20153:CD001239.
23. PammiM,BrocklehurstP.Granulocytetransfusionsforneonateswithconfirmedorsuspectedsepsisand
neutropenia.CochraneDatabaseSystRev2011:CD003956.
24. SchiblerKR,OsborneKA,LeungLY,etal.Arandomized,placebocontrolledtrialofgranulocytecolony
stimulatingfactoradministrationtonewborninfantswithneutropeniaandclinicalsignsofearlyonsetsepsis.
Pediatrics1998102:6.
25. CarrR,ModiN,DorC.GCSFandGMCSFfortreatingorpreventingneonatalinfections.Cochrane
DatabaseSystRev2003:CD003066.
26. PammiM,HaqueKN.Pentoxifyllinefortreatmentofsepsisandnecrotizingenterocolitisinneonates.
CochraneDatabaseSystRev20153:CD004205.
27. PammiM,AbramsSA.Orallactoferrinforthetreatmentofsepsisandnecrotizingenterocolitisinneonates.
CochraneDatabaseSystRev2011:CD007138.
28. WestonEJ,PondoT,LewisMM,etal.TheburdenofinvasiveearlyonsetneonatalsepsisintheUnited
States,20052008.PediatrInfectDisJ201130:937.
29. PayneNR,BurkeBA,DayDL.CorrelationofclinicalandpathologicfindingsinearlyonsetneonatalgroupB
streptococcalinfectionwithdiseaseseverityandpredictionofoutcome.PediatrInfectDis19987:836.
30. EscobarGJ,LiDK,ArmstrongMA,etal.Neonatalsepsisworkupsininfants>/=2000gramsatbirth:A
populationbasedstudy.Pediatrics2000106:256.
Topic5046Version21.0
9/22
17/9/2015
GRAPHICS
Differentialdiagnosisofneonatalsepsis
Distinguishing
features
Diagnosis
Diagnostictests
Othersystemicneonatalinfections
Viralinfections:
Herpessimplexvirus
Mucocutaneousvesicles,CSF
ViralcultureHSVPCR
pleocytosis,elevatedCSF
protein,thrombocytopenia,
hepatitis
Enteroviruses
Fulminantsystemicdisease,
ViralcultureEVPCR
myocarditis,hepatitis,
encephalitis
Parechovirus
Cytomegalovirus
Encephalitis/meningitis,rash
HPeVPCR(availablethrough
onpalmsandsoles
CDC)
Thrombocytopenia,
periventricularintracranial
calcifications,microcephaly,
ViralcultureCMVPCR
sensorineuralhearingloss,
chorioretinitis
Influenzaviruses
Respiratorysymptoms,
rhinorrhea,gastrointestinal
Viralcultureinfluenzaspecific
antigendetectionor
symptoms
immunofluorescenceassay
Respiratorysymptoms,
rhinorrhea,cough,apnea,
pneumonia
ViralcultureRSVspecific
antigendetectionor
immunofluorescenceassay
Spirochetalinfections
Skeletalabnormalities
RPRorVDRL
Syphilis
(osteochondritisand
periostitis),pseudoparalysis,
Respiratorysyncytial
virus
persistentrhinitis,
maculopapularrash
(particularlyonpalmsandsoles
orindiaperarea)
Parasiticinfections:
Congenitalmalaria
Anemia,splenomegaly,
jaundice
Detectionofparasitemiaon
bloodsmear
Toxoplasmosis
Intracranialcalcifications
(diffuse),hydrocephalus,
T.gondiiserology
chorioretinitis,mononuclear
CSFpleocytosis,elevatedCSF
protein
Fungalinfection
Persistenthyperglycemia,
IsolationofCandidainblood,
Candidiasis
thrombocytopenia,multiorgan
urineorCSFculture
http://www.uptodate.com/contents/managementandoutcomeofsepsisintermandlatepreterminfants?topicKey=PEDS%2F5046&elapsedTimeMs=0&so
10/22
17/9/2015
failure
Noninfectiouscausesoftemperatureinstabilityinneonates
Alteredenvironmental
temperature
Transientnoothersystemicsymptomsresolveswithsimple
nonpharmacologicmeasures
Dehydration
Clinicalhistoryofpoorfeedingorfluidlosses(eg,vomitingand/or
diarrhea)
Neonatalabstinence
Historyofmaternaldruguse
syndrome
sweating,sneezing,nasal
stuffiness,andyawning
CNSinsult(eg,anoxiaor
Historyofperinatalasphyxia
Abnormalneuroimaging
hemorrhage)
focalneurologicfindingsor
seizures
studies
Hypothyroidism
Hypotonia,lethargy,
hypothermia,largefontanels
AbnormalT4orTSHlevelon
newbornscreen
Congenitaladrenal
Ambiguousgenitalia(females),
Abnormal17a
hyperplasia
adrenalinsufficiencyandsalt
wasting(hyponatremia,
hyperkalemia,dehydration)
hydroxyprogesteronelevelon
newbornscreen
Positivedrugscreeningtests
Noninfectiouscausesofrespiratoryandcardiocirculatorysymptomsinneonates
Transienttachypneaofthe
newborn
Onsetofsymptomswithintwo
hoursafterdeliverysymptoms
CXRfindingsincludeincreased
lungvolumes,mild
usuallyresolvewithin24hours
cardiomegaly,prominent
vascularmarkings,fluidinthe
interlobarfissures,andpleural
effusions
Respiratorydistress
syndrome
Mostcommoninpreterm
infantsrareinterminfants
CXRfindingsincludelowlung
volumeanddiffuse
onsetofsymptomswithinfirst
fewhoursafterdelivery,
progressivelyworsensoverfirst
reticulogranulargroundglass
appearancewithair
bronchograms
48hoursoflife
Meconiumaspiration
Pneumothorax
Historyofmeconiumstained
amnioticfluidrespiratory
distressoccursimmediately
InitialCXRmayshowstreaky,
lineardensitiesasthedisease
progresses,thelungsmay
afterbirth
appearhyperinflatedwith
diffusepatchydensities
Asymmetricchestrise,
CXRwillusuallydetect
decreasedbreathsoundson
affectedsidehypotension(in
casesoftension
symptomaticpneumothoraces
pneumothorax)
Congenitalanomalies
(includingtracheal
esophagealfistula,choanal
Oftenoccurwithother
congenitalanomaliesincluding
VACTERLandCHARGE
CDHisoftendiagnosedby
routineantenatalultrasound
screeningpostnatalCXR
atresia,anddiaphragmatic
associationschoanalatresiais
showsherniationofabdominal
11/22
17/9/2015
hernia)
characterizedbynoisylabored
contentsintohemithoraxTEF
breathingwhilefeeding
isdiagnosedwithupper
gastrointestinalseriesand/or
bronchoscopy
Neonatalabstinence
syndrome
Cardiacarrhythmias(eg,
supraventricular
tachycardia)
Abruptonsetandtermination
ofrapidheartrate
AbnormalECG
Congenitalheartdisease
Infantswithductaldependent
lesionsmayinitiallylack
symptomsthendevelop
cyanosisandrapidclinical
Abnormalhyperoxiatest
abnormalechocardiography
deteriorationasthePDAcloses
inthefirstfewdaysoflife
Noninfectiouscausesofneurologicsymptomsinneonates
Hypoglycemia
Commonininfantswhoare
largeforgestationalageand/or
infantsofdiabeticmothers
Abnormalbloodglucoselevel
Hypercalcemia
Increasedneuromuscular
Abnormalserumcalciumlevel
irritabilityandseizures
associatedwithprematurity,
maternaldiabetes,and
perinatalasphyxia
Hypermagnesemia
Generalizedhypotonia,
respiratorydepressionand
apneatypicallyresultsfrom
maternaltreatmentwith
magnesiumsulfate
Abnormalserummagnesium
level
CNSinsult(eg,anoxiaor
hemorrhage)
Historyofperinatalasphyxia
focalneurologicfindingsor
seizures
studies
CongenitalCNS
malformations(eg,
hydrocephalus)
Abnormalheadcircumference
studies
Neonatalabstinence
syndrome
Inbornerrorsofmetabolism
Otherwiseunexplainedacid
Positivenewbornscreenfor
basedisorders,
hyperammonemia,
hypoglycemia,hematologic
abnormalities,liver
dysfunction,andrenaldisease
inbornerrorsofmetabolism
12/22
17/9/2015
Pyridoxinedeficiency
Refractoryseizures
Abnormalplasmapyridoxal5
phophatelevel
HSV:herpessimplexvirusPCR:polymerasechainreactionCSF:cerebralspinalfluidHPeV:human
parechovirusEV:enterovirusCMV:cytomegalovirusRSV:respiratorysyncytialvirusRPR:rapid
plasmareaginVDRL:venerealdiseaseresearchlaboratoryCNS:centralnervoussystemT4:thyroxine
TSH:thyrotropinCXR:chestradiographTEF:tracheoesophagealfistulaCDH:congenitaldiaphragmatic
herniaVACTERL:malformationsofthevertebrae,anus,cardiacstructures,trachea,esophagus,renal
system,andlimbsCHARGE:colobomaoftheirisorchoroid,heartdefect,atresiaofthechoanae,
retardedgrowthanddevelopment,genitourinaryabnormalities,andeardefectsECG:electrocardiogram
PDA:patentductusarteriosus.
Adaptedfrom:NizetV,KleinJO.Bacterialsepsisandmeningitis.In:Infectiousdiseasesofthefetusand
newborninfant,7thed,RemingtonJS,etal(Eds),ElsevierSaunders,Philadelphia2010.
Graphic100409Version1.0
13/22
17/9/2015
Characteristicsofcerebrospinalfluidintermandpretermneonates
withoutbacterialmeningitis
Age
Mean
WBC/mm 3
(rangeor
90th
percentile)
ANC/mm 3
orpercent
PMNs
(range)
Mean
protein
(mg/dL)
(rangeor
SD)
Mean
glucose
(mg/dL)
(rangeor
SD)
Termneonatesevaluatedinthenurserysetting
0to24hours
5(0to90)
3/mm 3(0to70)
63(32to240)
51(32to78)
0to10days
(n=87) [2]
8.2(0to32)
61.3percent
90(20to170)
52(34to119)
0to32days
(n=24) [3]
11(1to38)
21percent(0to
100)
NR
NR
(n=135)* [1]
Termneonatesevaluatedintheemergencydepartmentsetting
0to7days
(n=17) [4]
15.3(1to130)
4.4/mm 3(0to
65)
80.8(30.8)
45.9(7.5)
0to7days
8.6(90 th
NR
106.4(90 th
NR
(n=118) [5]
percentile:26)
percentile:153)
1to28days
(n=297) [6]
6.1(0to18)
NR
75.4(15.8to
131)
45.3(30to61)
0to30days
(n=108) [4]
7.3(0to130)
0.8/mm 3(0to
65)
64.2(24.2)
51.2(12.9)
8to14days
3.9(90 th
NR
77.6(90 th
NR
(n=101) [5]
percentile:9)
percentile:103)
8to14days
(n=33) [4]
5.4(0to18)
0.1/mm 3(0to
1)
69(22.6)
54.3(17)
15to22days
(n=107) [5]
4.9(90 th
percentile:9)
NR
71(90 th
percentile:106)
NR
15to21days
7.7(0to62)
0.2/mm 3(0to
59.8(23.4)
46.8(8.8)
(n=25) [4]
2)
22to28days
(n=141) [5]
4.5(90 th
percentile:9)
NR
68.7(90 th
percentile:85)
NR
22to30days
(n=33) [4]
4.8(0to18)
0.1/mm 3(0to
1)
54.1(16.2)
54.1(16.2)
Pretermorlowbirthweightneonates
0to28days
(n=30 ) [2]
9(0to29)
57.2percent
115(65to150)
50(24to63)
0to32days
7(0to28)
16percent(0to
NR
NR
(n=22 ) [3]
100)
[7]
14/22
17/9/2015
Verylowbirthweightneonates [7]
<1000g
0to7days
(n=6)
3(1to8)
11percent(0to
50)
162(115to222)
70(41to89)
8to28
days
(n=17)
4(0to14)
8percent(0to
66)
159(95to370)
68(33to217)
29to84
days
(n=15)
4(0to11)
2percent(0to
36)
137(76to269)
49(29to90)
0to7days
(n=8)
4(1to10)
4percent(0to
28)
136(85to176)
74(50to96)
8to28
days
(n=14)
7(0to44)
10percent(0to
60)
137(54to227)
59(39to109)
29to84
days
(n=11)
8(0to23)
11percent(0to
48)
122(45to187)
47(31to76)
1000to1500g
WBC:whitebloodcellcountANC:absoluteneutrophilcountPMNs:polymorphonuclearleukocytesSD:
standarddeviationNR:notreportedCSF:cerebrospinalfluid.
*CSFobtainedfromtermneonateswithoutanyobviouspathology.
CSFobtainedfromhospitalizedneonatesathighriskforinfection(eg,unexplainedjaundice,prolonged
ruptureofmembranes,maternalfever,etc)infectionexcludedbysterilecultures(CSF,blood,urine)and
lackofclinicalevidenceofbacterialorviralinfection.
CSFobtainedintheemergencydepartmentduringevaluationforpossibleinfectioninfectionwas
excludedbysterilecultures(CSF,blood,urine,andnegativepolymerasechainreactionforenterovirus).
OnlytwoinfantshadCSFWBC>30/mm 3:one<7daysofagewith130WBC/mm 3,andone15to21
daysofagewith62WBC/mm 3.
Includes29preterminfantsand1infantwhowas2190gat40weeks'gestation.
Includesallinfantswithbirthweight<2500g.
References:
1. NaidooBT.Thecerebrospinalfluidinthehealthynewborninfant.SAfrMedJ196842:933.
2. SarffLD,LynnH,PlattMD,etal.Cerebrospinalfluidevaluationinneonates:Comparisonofhigh
riskinfantswithandwithoutmeningitis.JPediatr197688:473.
3. PappuL.CSFcytologyintheneonate.AmJDisChild1982136:297.
4. AhmedA.Cerebrospinalfluidvaluesinthetermneonate.PediatrInfectDisJ199615:298.
5. ChadwickSL,WilsonJW,LevinJE,MartinJM.Cerebrospinalfluidcharacteristicsofinfantswho
presenttotheemergencydepartmentwithfever:establishingnormalvaluesbyweekofage.
PediatrInfectDisJ201130:e63.
6. ByingtonCL,KendrickJ,ShengX.Normativecerebrospinalfluidprofilesinfebrileinfants.JPediatr
2011158:130.
7. RodriguezAF,KaplanSL,MasonEO.Cerebrospinalfluidvaluesintheverylowbirthweightinfant.
JPediatr1990116:971.
15/22
17/9/2015
Suggestedantimicrobialregimensinthemanagementofneonatal
sepsisintermandlatepreterminfants
Antibioticregimen
Empirictherapy
Earlyonset(<7days)
AmpicillinANDgentamicin
Lateonset(7days):Admittedfromthe
community
Lateonset(7days):Hospitalizedsincebirth
GentamicinANDvancomycin
Specialcircumstances:
Suspectedmeningitis
Ampicillin,gentamicin,ANDcefotaxime
Suspectedpneumonia
Alternatives:
AmpicillinANDcefotaxime,OR
VancomycinANDcefotaxime,OR
VancomycinANDgentamicin
Suspectedinfectionofsofttissues,skin,
joints,orbones(S.aureusisalikely
VancomycinorvancomycinANDnafcillin
pathogen)
Suspectedintravascularcatheterrelated
infection
VancomycinANDgentamicin
Suspectedinfectionduetoorganisms
foundinthegastrointestinaltract(eg,
anaerobicbacteria)
Ampicillin,gentamicin,ANDclindamycin
Alternatives:
Ampicillin,gentamicin,ANDmetronidazole
OR
PiperacillintazobactamANDgentamicin
Pathogenspecifictherapy
GroupBStreptococcus
PenicillinG
Escherichiacoli:Ampicillinsensitive
Ampicillin
Escherichiacoli:Ampicillinresistant
Cefotaxime
Alternative:
Meropenem
Multidrugresistantgramnegativebacilli
(includingESBLproducingorganisms)
Meropenem
Listeriamonocytogenes
MethicillinsusceptibleS.aureus(MSSA)
NafcillinORcefazolin
MethicillinresistantS.aureus(MRSA)
Vancomycin
Coagulasenegativestaphylococci
Vancomycin
16/22
17/9/2015
ESBL:extendedspectrumbetalactamase.
References:
1. EdwardsMS,BakerCJ.Bacterialinfectionsintheneonate.In:PrinciplesandPracticeofPediatric
InfectiousDiseases,4thed,LongSS,PickeringLK,ProberCG(Eds),ElsevierSaunders,
Philadelphia2012.p.538.
2. NizetV,KleinJO.Bacterialsepsisandmeningitis.In:InfectiousdiseasesoftheFetusand
NewbornInfant,7thed,RemingtonJS,etal(Eds),ElsevierSaunders,Philadelphia2010.p.222.
3. AmericanAcademyofPediatrics.GroupBstreptococcalinfections.In:RedBook:2015Reportof
theCommitteeonInfectiousDiseases,30thed,KimberlinDW(Ed),AmericanAcademyof
Pediatrics,2015.p.745.
4. AmericanAcademyofPediatrics.EscherichiacoliandotherGramnegativebacilli(septicemiaand
meningitisinneonates).In:RedBook:2015ReportoftheCommitteeonInfectiousDiseases,
30thed,KimberlinDW(Ed),AmericanAcademyofPediatrics,ElkGroveVillage,IL2015.p.340.
17/22
17/9/2015
Commonbacterialagentscausingneonatalsepsisinterminfants
Bacterialspecies
Frequencyof
isolation
Early
onset
Lateonset
GroupBStreptococcus
+++
+++
Escherichiacoli
+++
++
Klebsiellaspp.
Enterobacterspp.
Listeriamonocytogenes
Otherentericgramnegatives
Nonentericgramnegatives*
Viridansstreptococci
Staphylococcusaureus
+++
Citrobacterspp.
Salmonellaspp.
Coagulasenegativestaphylococci
Enterococcusspp.
+++:commonlyassociated++:frequentlyassociated+:occasionallyassociated0:rarely
associated.
*IncludesnontypableHemophilusinfluenzaeandNeisseriameningitidis.
Adaptedfrom:EdwardsMS,BakerCJ.Bacterialinfectionsintheneonate.In:PrinciplesandPracticeof
PediatricInfectiousDisease,4thed,LongSS,PickeringLK,ProberCG.ElsevierSaunders,Philadelphia
2012.
18/22
17/9/2015
IntravenoustreatmentofearlyonsetgroupBstreptococcal
infections
Site(s)ofinfection
Bacteremia/sepsis/pneumonia
Empiricaltherapy
Ampicillin150mg/kgevery12
hours
PLUS
Gentamicin4mg/kgevery24
hoursforinfantsbornat35
weeksgestation3mg/kgevery
24hoursforinfantsbornat
<35weeksgestation
Meningitis
Definitive
therapy*
PenicillinG:
50,000to
PenicillinG:
every8hours
250,000to
450,000
units/kgperday
dividedevery8
hours
Gentamicin4mg/kgevery24
hoursforinfantsbornat35
weeksgestation3mg/kgevery
24hoursforinfantsbornat
<35weeksgestation
10days
100,000
units/kgperday
dividedevery12
hours
Ampicillin100to150mg/kg
PLUS
Duration
of
therapy
14to21
days
GBS:GroupBstreptococcusCSF:cerebrospinalfluid.
*DefinitivetherapyshouldnotbestarteduntilGBSisidentifiedbycultureclinicalimprovementis
evidentandformeningitis,CSFissterileat24to48hoursoftherapy.
14daysissufficientforuncomplicatedcasesofGBSmeningitis.
References:
1. Medications.In:GuidelinesforAcuteCareoftheNeonate,22ndEd,AdamsJM,FernandesCJ
(Eds),BaylorCollegeofMedicine,Houston,TX2014.p.89.
3. AmericanAcademyofPediatrics.Tablesofantibacterialdrugdosages,Table4.2.In:RedBook:
2015ReportoftheCommitteeonInfectiousDiseases,30thed,KimberlinDW(Ed),American
AcademyofPediatrics,ElkGroveVillage,IL2015.p.882.
4. RaoSC,SrinivasjoisR,HagenR,etal.Onedoseperdaycomparedtomultipledosesperdayof
gentamicinfortreatmentofsuspectedorprovensepsisinneonates.CochraneDatabaseSystRev
2011Nov9(11).
19/22
17/9/2015
IntravenoustreatmentoflateonsetgroupBstreptococcalinfections
inneonatesandyounginfants
Site(s)of
infection
Bacteremiawithouta
focus
Empirical
therapy*
Definitive
therapy
Ampicillin,nafcillin,or
vancomycin
PenicillinG
PLUS
units/kgperday
dividedevery8hours
Gentamicinor
Durationof
therapy
10days
75,000to150,000
cefotaxime
Meningitis
Ampicillinand/or
vancomycin
PLUS
Gentamicinor
PenicillinG
14to21days
450,000to500,000
units/kgperday
dividedevery6hours
cefotaxime
Cellulitis/adenitis
Nafcillinorvancomycin
PenicillinG
PLUS
cefotaxime
75,000to150,000
units/kgperday
dividedevery8hours
PenicillinG
PLUS
Cefotaxime
75,000to150,000
units/kgperday
dividedevery8hours
PenicillinG
PLUS
75,000to150,000
units/kgperday
Gentamicinor
Septicarthritis
Osteomyelitis
Cefotaxime
Urinarytractinfection
Ampicillin,nafcillin,or
vancomycin
PLUS
Gentamicinor
cefotaxime
10to14days
14to21days
21to28days
dividedevery8hours
PenicillinG
10days
75,000to150,000
units/kgperday
dividedevery8hours
Theantibioticdoseslistedaboveareforuseinneonatesandyounginfantsage>1weekand
bodyweight1kgwithnormalrenalfunction.Foradditionaldosingdetail,refertothe
LexicomppediatricandneonataldruginformationmonographsincludedwithinUpToDate.
GBS:groupBstreptococcusCSF:cerebrospinalfluid.
*Selectionwilldependonageandpresumedsourceofinfection(maternal,hospital,orcommunity).
DefinitivetherapyshouldbestartedonceGBSisidentifiedbycultureclinicalimprovementisevident
andformeningitis,CSFissterileat24to48hoursoftherapy.
References:
20/22
17/9/2015
2. AmericanAcademyofPediatrics.Tablesofantibacterialdrugdosages,Table4.2.In:RedBook:
2015ReportoftheCommitteeonInfectiousDiseases,30thed,KimberlinDW(Ed),American
AcademyofPediatrics,ElkGroveVillage,IL2015.p.882.
21/22
17/9/2015
Disclosures
Disclosures:MorvenSEdwards,MDGrant/Research/ClinicalTrialSupport:PfizerInc.[GroupB
Streptococcus].Consultant/AdvisoryBoards:NovartisVaccines[GroupBStreptococcus].LeonardE
Weisman,MDConsultant/AdvisoryBoards:GlaxoSmithKline[Malariavaccine]NIAID[Staphylococcus
aureus(Mupirocin)].PatentHolder:BaylorCollegeofMedicine[Ureaplasma
diagnosis/vaccines/antibodies,processforpreparingbiologicalsamples].EquityOwnership/Stock
Options:VaxImmune[Ureaplasmadiagnosis,vaccinesandantibodies].SheldonLKaplan,MD
Grant/Research/ClinicalTrialSupport:Pfizer[vaccine(PCV13)]ForestLab[antibiotic(Ceftaroline)]
Optimer[antibiotic(fidaxomicin)].Consultant/AdvisoryBoards:Pfizer[vaccine(PCV13)].CarrieArmsby,
MD,MPHNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseare
addressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobe
providedtosupportthecontent.Appropriatelyreferencedcontentisrequiredofallauthorsandmust
conformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy
22/22

Management and Outcome of Sepsis in Term and Late Preterm Infants

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Management and Outcome of Sepsis in Term and Late Preterm Infants

Uploaded by

Copyright:

Available Formats

17/9/2015

You might also like