2/28/2017 Management and outcome of sepsis in term and late preterm infants - UpToDate

OfficialreprintfromUpToDate
www.uptodate.com2017UpToDate

Managementandoutcomeofsepsisintermandlatepreterminfants

Author: MorvenSEdwards,MD
SectionEditors: LeonardEWeisman,MD,SheldonLKaplan,MD
DeputyEditor: CarrieArmsby,MD,MPH

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Jan2017.|Thistopiclastupdated:Jan21,2016.

INTRODUCTIONSepsisisanimportantcauseofmorbidityandmortalityamongnewborninfants.
Althoughtheincidenceofsepsisintermandlatepreterminfantsislow,thepotentialforseriousadverse
outcomes,includingdeath,isofsuchgreatconsequencethatcaregiversshouldhavealowthresholdfor
evaluationandtreatmentforpossiblesepsisinneonates.Theapproachdiscussedbelowisconsistentwith
guidelinespublishedbytheAmericanAcademyofPediatrics(AAP)andtheCenterforDiseaseControl
(CDC)[1,2].

Thetreatmentandoutcomeofsepsisintermandlatepreterminfantswillbereviewedhere.The
epidemiology,clinicalfeatures,diagnosis,andevaluationofsepsisintermandlatepreterminfants,neonatal
sepsisinpreterminfants,themanagementofwellappearinginfantsatriskforgroupBstreptococcal
infection,andtheevaluationoffebrileorillappearingnewbornsarediscussedseparately:

(See"Clinicalfeatures,evaluation,anddiagnosisofsepsisintermandlatepreterminfants".)
(See"Clinicalfeaturesanddiagnosisofbacterialsepsisinthepreterminfant(<34weeksgestation)".)
(See"Treatmentandpreventionofbacterialsepsisinthepreterminfant(<34weeksgestation)".)
(See"ManagementoftheinfantwhosemotherhasreceivedgroupBstreptococcalchemoprophylaxis".)
(See"Febrileinfant(youngerthan90daysofage):Management",sectionon'Neonates(28daysofage
andyounger)'.)
(See"Approachtotheillappearinginfant(youngerthan90daysofage)".)

TERMINOLOGYThefollowingtermswillbeusedthroughoutthisdiscussiononneonatalsepsis:

Neonatalsepsisisaclinicalsyndromeinaninfant28daysoflifeoryounger,manifestedbysystemic
signsofinfectionandisolationofabacterialpathogenfromthebloodstream[3].Aconsensusdefinition
forneonatalsepsisislacking[4].(See"Clinicalfeatures,evaluation,anddiagnosisofsepsisintermand
latepreterminfants",sectionon'Diagnosis'.)

Terminfantsarethosebornatagestationalageof37weeksorgreater.

Latepreterminfants(alsocallednearterminfants)arethosebornbetween34and36completed
weeksofgestation[5].(See"Latepreterminfants".)

Preterminfantsarethosebornatlessthan34weeksofgestation[5].

Neonatalsepsisisclassifiedaccordingtotheinfant'sageattheonsetofsymptoms:

Earlyonsetsepsisisdefinedastheonsetofsymptomsbefore7daysofage,althoughsomeexperts
limitthedefinitiontoinfectionsoccurringwithinthefirst72hoursoflife[6].

Lateonsetsepsisisdefinedastheonsetofsymptomsat7daysofage[6].Similarlytoearlyonset
sepsis,thereisvariabilityinitsdefinition,rangingfromanonsetat>72hoursoflifeto7daysofage
[6,7].

https://www.uptodate.com/contents/management-and-outcome-of-sepsis-in-term-and-late-preterm-infants/print?source=search_result&search=neonatal%20seps 1/21
2/28/2017 Management and outcome of sepsis in term and late preterm infants - UpToDate

SUPPORTIVECARESymptomaticinfantsshouldbetreatedinacaresettingwithfullcardiopulmonary
monitoringandsupport,becausetheclinicalcourseoftheseinfantscandeterioraterapidly.Althoughthere
arenodatademonstratingtheimportanceofsupportivecaremeasuresinneonateswithsepsis,itisgenerally
acceptedthatthefollowingsupportivemeasuresarecriticalcomponentsofmanagement:

Maintainingadequateoxygenationandperfusion(see"Oxygenmonitoringandtherapyinthenewborn")
Preventionofhypoglycemiaandmetabolicacidosis(see"Managementandoutcomeofneonatal
hypoglycemia")
Maintenanceofnormalfluidandelectrolytestatus(see"Fluidandelectrolytetherapyinnewborns")

Severelyillpatientsmayrequireventilatory,volume,and/orvasopressorsupporttomaintainadequate
oxygenationandperfusion.(See"Mechanicalventilationinneonates"and"Etiology,clinicalmanifestations,
evaluation,andmanagementofneonatalshock".)

ONGOINGDIAGNOSTICEVALUATION

OtherdiagnosticconsiderationsIninfantswithsuspectedsepsis,additionaltestingforotherconditions
maybewarrantedbasedonclinicalsignsandsymptoms(table1).Itisoftendifficulttodifferentiateneonatal
sepsisfromotherdiseaseshowever,giventhemorbidityandmortalityofneonatalsepsis,empiricantibiotic
therapyshouldbeprovided(afterculturesareobtained)toinfantswithsuspectedsepsispendingdefinitive
culturebaseddiagnosis.Alternativediagnosesshouldbeentertainedwhenaninfantwithsuspectedsepsis
hasnegativecultures.(See"Clinicalfeatures,evaluation,anddiagnosisofsepsisintermandlatepreterm
infants",sectionon'Differentialdiagnosis'.)

LumbarpunctureIfnotdoneduringtheinitialevaluation,alumbarpuncture(LP)shouldbeperformedin
infants,wheneverpossible,withcultureprovenorculturenegativeclinicalsepsis.Clinicalsignssuggesting
meningitiscanbelackingandbloodculturemaybenegativeininfantswithmeningitis.(See"Bacterial
meningitisintheneonate:Clinicalfeaturesanddiagnosis".)

ANTIBIOTICTHERAPY

WhomtotreatThedecisiontostartantibiotictherapyisbasedonassessmentofriskfactors,clinical
evaluation,andlaboratorytests.Indicationsforempiricantibiotictherapyinclude(see"Clinicalfeatures,
evaluation,anddiagnosisofsepsisintermandlatepreterminfants",sectionon'Evaluationandinitial
management'):

Illappearance(see"Approachtotheillappearinginfant(youngerthan90daysofage)")

Concerningsymptoms,includingtemperatureinstability,orrespiratory,cardiocirculatory,orneurologic
symptoms(see"Clinicalfeatures,evaluation,anddiagnosisofsepsisintermandlatepreterminfants",
sectionon'Clinicalmanifestations')

Cerebrospinalfluid(CSF)pleocytosis(whitebloodcell[WBC]cellcountof>20to30cells/microL)(table
2)(see"Bacterialmeningitisintheneonate:Clinicalfeaturesanddiagnosis",sectionon'Interpretationof
CSF')

Confirmedorsuspectedmaternalchorioamnionitis(see"Clinicalfeatures,evaluation,anddiagnosisof
sepsisintermandlatepreterminfants",sectionon'Maternalriskfactors')

Positiveblood,urine,orCSFculture(see"Clinicalfeatures,evaluation,anddiagnosisofsepsisinterm
andlatepreterminfants",sectionon'Bloodculture')

InitialempirictherapyTheinitialchoiceofparenteralantimicrobialsforsuspectedsepsisintermandlate
pretermneonatesisbasedontheinfant'sage,likelypathogens,thesusceptibilitypatternsoforganismsina
particularnursery,andthepresenceofanapparentsourceofinfection(eg,skin,joint,orboneinvolvement)
(table3).

https://www.uptodate.com/contents/management-and-outcome-of-sepsis-in-term-and-late-preterm-infants/print?source=search_result&search=neonatal%20seps 2/21
2/28/2017 Management and outcome of sepsis in term and late preterm infants - UpToDate

EarlyonsetsepsisTherecommendedempiricregimenforsuspectedearlyonsetsepsisinatermor
latepreterminfantisampicillin150mg/kgperdoseintravenously(IV)every12hoursandgentamicin4mg/kg
perdoseIVevery24hours[7,8].Wegenerallyobtainbaselinerenalfunctiontests(ie,bloodureanitrogen
andcreatininelevels)attheinitiationoftreatmentwithgentamicin.Serumgentamicinlevelsshouldbe
obtainedininfantsreceivingafullcourseofantibiotics,butarenotrequiredifatreatmentcourseofonly48
hoursisanticipatedandrenalfunctionisnormal[3,7].

Thecombinationofampicillinandgentamiciniseffectiveintreatingmostcommonpathogensthatcause
earlyonsetsepsis,includinggroupBStreptococcus(GBS),Listeria,Enterococcus,andmostisolatesof
Escherichiacoli(E.coli)(table4)[1,9].

Inanationalsurveillancestudy(2006to2008),94percentofallisolatesinneonatesweresusceptibletothe
combinationofpenicillinandgentamicin[10].Ina10yearreviewfromasinglecenter,90percentofearly
onsetsepsispathogensintermandlatepreterminfantsweresusceptibletoampicillinand/orgentamicin[11].
AmongsixinfantswithearlyonsetS.aureusbacteremiathatwasnotsusceptibletoampicillinand
gentamicin,therewerenocomplicationsbeforeorafterantibiotictherapywasadjustedbaseduponantibiotic
susceptibility.

Ampicillinandgentamicinarepreferredoverampicillinandathirdgenerationcephalosporin(eg,cefotaxime)
baseduponthefollowing:

Theregimenofampicillinandathirdgenerationcephalosporinisnotmoreeffectivethanthecombination
ofampicillinandgentamicin[12].

Theemergenceofcephalosporinresistantgramnegativeorganisms(eg,Enterobactercloacae,
Klebsiella,andSerratiaspecies)canoccurwhencefotaximeisusedroutinely[1,13].

AmpicillinandgentamicinaresynergisticintreatinginfectionscausedbyGBSandListeria
monocytogenes.CephalosporinsarenotactiveagainstL.monocytogenes.

Inalargecohortstudy,infantswhoreceivedampicillinpluscefotaximehada1.5foldincreasein
mortalitycomparedwiththosetreatedwithampicillinplusgentamicin(4.2versus1.9percent,adjusted
oddsratio1.5,95%CI1.41.7)[12].

Ceftriaxoneishighlyboundtoalbuminandappearstodisplacebilirubin[14,15].Althoughdisplacement
offreebilirubinbyceftriaxonehasnotbeenreported,avoidanceofceftriaxoneinneonatesatriskfor
acutebilirubinencephalopathyisrecommended[1].(See"Clinicalmanifestationsofunconjugated
hyperbilirubinemiaintermandlatepreterminfants",sectionon'Neurologicmanifestations'.)

Theadditionofathirdgenerationcephalosporintotheregimenofampicillinandgentamiciniswarrantedfor
infantswithsuspectedmeningitisandcriticallyillneonateswithriskfactorsassociatedwithampicillinresistant
infections(ie,prolongedruptureofmembranesand/orprolongedantenatalmaternalampicillintreatment).

LateonsetsepsisThechoiceofempirictherapyforlateonsetsepsisdependsuponwhethertheinfant
isadmittedfromthecommunity,andthusisatlowerriskforinfectioncausedbyamultidrugresistant
pathogen,orishospitalizedsincebirthandthusatahigherrisk.

AdmittedfromthecommunityNeonatesadmittedfromthecommunityareatlowerriskfor
infectioncausedbyamultidrugresistantpathogenthanareinfantswhoremainhospitalizedsincebirth.The
combinationofampicillinandgentamicinorampicillinandcefotaximeareregimensforempirictreatmentof
sepsiswithoutanapparentfocusofinfectioninthissetting(table3)[6].

Ampicillinandgentamicinisgenerallythepreferredregimenhowever,localantibioticresistancepatterns
mustbeconsidered.Thedosingforampicillinis75mg/kgperdoseintravenously(IV)everysixhoursthe
dosingofgentamicinis4mg/kgperdoseIVevery24hours[7,8].Wegenerallyobtainbaselinerenalfunction
tests(ie,bloodureanitrogenandcreatininelevels)attheinitiationoftreatmentwithgentamicin.Serum

https://www.uptodate.com/contents/management-and-outcome-of-sepsis-in-term-and-late-preterm-infants/print?source=search_result&search=neonatal%20seps 3/21
2/28/2017 Management and outcome of sepsis in term and late preterm infants - UpToDate

gentamicinlevelsshouldbeobtainedininfantsreceivingafullcourseofantibiotics,butarenotrequiredifa
treatmentcourseofonly48hoursisanticipatedandrenalfunctionisnormal[3,7].

Inanationalsurveillancestudy(2006to2008),96percentofisolatesfromlateonsetbacteremiawere
susceptibletothecombinationofamoxicillinandgentamicin[10].Theadditionofathirdgeneration
cephalosporintoanampicillinandgentamicinregimeniswarrantedforneonateswithsuspectedmeningitis.
(See'Specialcircumstances'below.)

HospitalizedsincebirthInfantswhocontinuetobehospitalizedsincebirthareathigherriskfor
multidrugresistantorganisms,andthereforevancomycinissubstitutedforampicillin(table3).Forterm
infants>7daysoflife,thedosingofvancomycinisdependentonserumcreatinine(Scr)[16]:

Scr<0.7mg/dL:15mg/kg/doseIVevery12hours
Scr0.7to0.9mg/dL:20mg/kg/doseIVevery24hours
Scr1to1.2mg/dL:15mg/kg/doseIVevery24hours
Scr1.3to1.6mg/dL:10mg/kg/doseIVevery24hours
Scr>1.6mg/dL:15mg/kg/doseIVevery48hours

Alternativeweightdirectedneonataldosingrecommendationsforvancomycininarealsoavailable(referto
Lexicomppediatricdruginformation).

SpecialcircumstancesAlternativeregimensbaseduponspecificclinicalcircumstancesincludethe
following(table3):

SuspectedmeningitisInneonateswithlateonsetsepsis,cefotaximeshouldbeincludedintheregimen
iflumbarpuncturesuggestsmeningitis(eg,CSFpleocytosis).Cefotaximeshouldalsobeaddedtothe
empiricregimenforearlyonsetmeningitisiftheCSFGramstainrevealsgramnegativebacilli.
Cefotaximeprovidesextendedspectrumforentericgramnegativerodsandhasoptimalactivityinthe
CSFagainstpneumococci.Treatmentofbacterialmeningitisinneonatesisdiscussedindetail
separately.(See"Bacterialmeningitisintheneonate:Treatmentandoutcome",sectionon'Empirical
therapy'.)

SuspectedpneumoniaEmpiricregimensfortreatmentofinfantswithapulmonaryfocusofinfection
includeampicillinandgentamicin,ampicillinandcefotaxime,vancomycinandcefotaxime,orvancomycin
andgentamicin.Treatmentofpneumoniainneonatesisdiscussedindetailseparately.(See"Neonatal
pneumonia",sectionon'Treatment'.)

Ifthereisafocusofinfectioninvolvingthesofttissues,skin,joints,orbones(inwhichcaseS.aureusisa
likelypathogen),vancomycinshouldbesubstitutedforampicillin[17].Inatoxicappearinginfant,nafcillin
shouldalsobeadded.

Ifintravascularcatheterrelatedinfectionisaconcern,treatmentshouldbeinitiatedwithvancomycinand
gentamicintoprovideempiriccoverageforcoagulasenegativestaphylococci,S.aureus,andgram
negativebacteria.

Ifinfectionisthoughttoarisefromthegastrointestinaltract(eg,anaerobicbacteria),clindamycinor
anothersuitableagent,suchasmetronidazole,shouldbeaddedtothetherapeuticregimentoimprove
coverageforthesepathogens.

CultureprovensepsisInneonateswithcultureprovensepsis,theusualcourseoftherapyis10days
[1,3,13,18,19].Longertreatmentcoursesmaybewarrantedifaspecificfocusofinfectionisidentified(eg,
meningitis,osteomyelitis,orsepticarthritis).Antimicrobialtherapyshouldbealteredbaseduponthe
susceptibilityprofileofthepathogenisolated.

PathogenspecifictherapyGuidelinesforthetreatmentofthemostcommoncausativeorganismsof
neonatalsepsisare(table3):
https://www.uptodate.com/contents/management-and-outcome-of-sepsis-in-term-and-late-preterm-infants/print?source=search_result&search=neonatal%20seps 4/21
2/28/2017 Management and outcome of sepsis in term and late preterm infants - UpToDate

GroupBstreptococcusThedrugofchoiceforGBSispenicillin.Thus,whenGBSisidentified,and
resolutionofbacteremiaisdocumentedbyarepeatbloodcultureand,ininfantswithmeningitis,theCSFis
sterile,werecommenddiscontinuinggentamicinandcontinuingtherapywithpenicillinGalone(table5AB).
(See"GroupBstreptococcalinfectioninneonatesandyounginfants",sectionon'Definitivetherapy'.)

EscherichiacoliInpatientswithEscherichiacoli(E.coli)sepsissensitivetoampicillinwhohave
improvedclinicallyandinwhommeningitishasbeenexcluded,ampicillinmonotherapyisadministeredfora
10daycourse.

ForpatientswithampicillinresistantE.coli,thechoiceofdefinitivetherapyisbaseduponthesusceptibility
profile.Cefotaximeisoftenemployediftheisolateissusceptible.

OthergramnegativebacilliNonmeningealinfectionscausedbyE.coli,Klebsiella,Proteus,
Salmonella,orShigellashouldbetreatedwithasingleagent,basedupontheantimicrobialsusceptibility
profile.

AntimicrobialtreatmentforinfectionscausedbyEnterobacter,Serratia,orPseudomonasshouldbeselected
baseduponthesusceptibilityprofileoftheorganism.

Infectionscausedbymultidrugresistantgramnegativebacilli,includingthosecausedbyextendedspectrum
betalactamaseproducingorganisms,orthosewithhyperproductionofbetalactamases,shouldbetreated
withmeropenem.

ListeriamonocytogenesThecombinationofampicillinandgentamicinisusedforinitialtherapy.
TreatmentwithbothagentsismoreeffectivethanampicillinaloneinvitroandinanimalmodelsofListeria
infection.CephalosporinsarenotactiveagainstL.monocytogenes.Durationoftherapyusuallyis10days.
(See"Treatment,prognosis,andpreventionofListeriamonocytogenesinfection",sectionon'Antibiotic
regimens'.)

StaphylococcusspeciesDirectedtherapyforinfectioncausedbystaphylococciisdeterminedby
thesensitivityoftheisolatetospecificantibioticagents:

S.aureusVancomycinor,inatoxicappearinginfant,vancomycinplusnafcillinshouldbeemployedfor
S.aureusinfectionuntilthesusceptibilityprofileisavailable.Theregimenthenshouldbeadjusted
accordingtothesusceptibilityprofile:

MethicillinsusceptibleS.aureus(MSSA)TreatmentofMSSAinfectionshouldbecompletedwith
nafcillin.CefazolinisanalternativefortreatmentofmostMSSAinfectionsoutsidethecentral
nervoussystem(CNS)andnotinvolvingendocarditis.(See"Staphylococcusaureusbacteremiain
children:Managementandoutcome".)

MethicillinresistantS.aureus(MRSA)Treatmentshouldbecompletedwithvancomycin.(See
"MethicillinresistantStaphylococcusaureusinchildren:Treatmentofinvasiveinfections",sectionon
'Treatmentofneonates'.)

CoagulasenegativestaphylococciCoagulasenegativestaphylococcalinfectionsrequiretreatmentwith
vancomycin.

ProbablebutunprovensepsisIninfantswithanegativebloodculturebutaclinicalstatusthatremains
concerningforasystemicinfection(eg,ongoingtemperatureinstabilityongoingrespiratory,cardiocirculatory,
orneurologicsymptomsnotexplainedbyotherconditionsorlaboratoryabnormalitiessuggestiveofsepsis),
antibiotictherapycanbeextendedforaslongasatotalof5to10days.

After48hours,theempiricregimenisalteredbaseduponwhetherornotmeningitishasbeenexcluded:

Ifmeningitishasbeenexcluded,theampicillinregimencanbechangedto75mg/kgevery12hours.

https://www.uptodate.com/contents/management-and-outcome-of-sepsis-in-term-and-late-preterm-infants/print?source=search_result&search=neonatal%20seps 5/21
2/28/2017 Management and outcome of sepsis in term and late preterm infants - UpToDate

Iflumbarpuncturehasnotbeenperformed,ampicillinshouldbecontinuedatameningiticdose.

Managementofinfantswithcerebrospinalfluid(CSF)pleocytosisand/orpositiveCSFcultureis
discussedseparately.(See"Bacterialmeningitisintheneonate:Treatmentandoutcome".)

Alternativediagnosesshouldalsobeentertainedwhenaninfantwithsuspectedsepsishasnegativecultures
(table1).Antibioticsshouldbediscontinuedwhenanotherdiagnosisisestablished.(See"Clinicalfeatures,
evaluation,anddiagnosisofsepsisintermandlatepreterminfants",sectionon'Differentialdiagnosis'.)

InfectionunlikelyEmpiricantibioticsareinitiatedinmanyinfantswithmaternalriskfactors,abnormal
laboratoryvalues,and/ormildtomoderatesymptomsthatsubsequentlyresolve.Sepsisisunlikelyinthese
infantsiftheyremainwellandthebloodcultureissterileat48hours.Empiricantibiotictherapyshouldbe
discontinuedafter48hoursintheseneonates[1,20].

ResponsetotherapyInmostcases,symptomaticinfantswithprovensepsisimproveclinicallywithin24
to48hours.

Ininfantswithbacteremia,arepeatbloodcultureshouldbeobtainedafter24to48hoursoftherapyto
documentsterility.Failuretosterilizethebloodstreamsuggeststhattheantimicrobial(s)chosenarenotactive
againsttheinfectingpathogenorthatthereisanunrecognizedfocusofinfection.Consultationwithapediatric
infectiousdiseasespecialistmaybewarranted.

ADJUNCTIVETHERAPIESThefollowingadjunctiveimmunotherapeuticinterventionshavebeenstudied
inneonatalsepsis,butshouldNOTberoutinelyadministeredastheyhavenotbeenshowntoconclusively
improveoutcomes[18,19,21]:

Intravenousimmunoglobulin(IVIG)infusions[22,23]
Granulocytetransfusions[24]
Granulocyteandgranulocytemacrophagecolonystimulatingfactor(GCSFandGMCSF)[25,26]
Pentoxifylline[27]
Lactoferrin[28]

PREVENTIONTheprimaryinterventiontopreventneonatalsepsisistheuseofintrapartumantibiotic
prophylaxis(IAP)inmotherswithgroupBstreptococcal(GBS)colonizationandotherriskfactors.Although
IAPhasresultedinadecreaseintheincidenceofearlyonsetGBSinvasiveneonatalinfection,ithasnothad
asimilarimpactontherateoflateonsetGBSdisease.(See"NeonatalgroupBstreptococcaldisease:
Prevention"and"GroupBstreptococcalinfectioninneonatesandyounginfants",sectionon'Epidemiology'.)

Comprehensivepreventionofneonatalsepsiswillrequireamultiinterventionalprogramincludingeffective
maternalvaccination,reductioninpretermdelivery,andlimitedexposureofterminfantstopotential
pathogens.(See"VaccinesforthepreventionofgroupBstreptococcaldisease".)

OUTCOMEOverallmortalityintermandlatepreterminfantswithneonatalsepsisisapproximately2to4
percent[12,29].Mortalityestimatesvarydependingongestationalageoftheinfant(lowergestationalageis
associatedwithhighermortality),pathogen(E.coliisassociatedwithhighermortalitythanGBS),andsepsis
definition(lowermortalityratestendtobereportedifinfantswithculturenegativeclinicalsepsisareincluded
comparedwithcasesofcultureprovensepsisonly).

MortalityratesforGBSsepsisinterminfantsaftertheintroductionofIAPandroutineuseofempirical
antibiotictherapyrangefrom2to3percentforearlyonsetdiseaseand1to2percentforlateonsetdisease.
Theriskofmortalityishigherininfantswithbirthweightlessthan2500g,absoluteneutrophilcountlessthan
1500cells/microL,hypotension,apnea,andpleuraleffusion[30].(See"GroupBstreptococcalinfectionin
neonatesandyounginfants",sectionon'Outcome'.)

TheriskofmortalityisparticularlyhighinneonateswithearlyonsetsepsiscausedbyE.coli.Estimated
mortalityratesfortermneonateswithE.colisepsisare6to10percent[9,29,31].
https://www.uptodate.com/contents/management-and-outcome-of-sepsis-in-term-and-late-preterm-infants/print?source=search_result&search=neonatal%20seps 6/21
2/28/2017 Management and outcome of sepsis in term and late preterm infants - UpToDate

INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"
and"BeyondtheBasics."TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6th
gradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagiven
condition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easyto
readmaterials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmore
detailed.Thesearticlesarewrittenatthe10thto12thgradereadinglevelandarebestforpatientswhowant
indepthinformationandarecomfortablewithsomemedicaljargon.

Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremail
thesetopicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsby
searchingon"patientinfo"andthekeyword(s)ofinterest.)

Basicstopics(see"Patienteducation:Sepsisinnewbornbabies(TheBasics)")

SUMMARYANDRECOMMENDATIONS

Althoughtheincidenceofsepsisintermandlatepreterminfantsislow,thepotentialforseriousadverse
outcomes,includingdeath,isofsuchgreatconsequencethatcaregiversshouldhavealowthresholdfor
evaluationandtreatmentforpossiblesepsis.(See'Introduction'above.)

Supportivecareforsymptomaticinfantsisdeliveredinanintensivecaresettingtoensureadequate
oxygenation,perfusion,andmaintenanceofnormalfluidandelectrolytebalance,especiallyinseverely
affectedpatients.(See'Supportivecare'above.)

Indicationsforempiricantibiotictherapyincludeanyofthefollowing:

Illappearance(see"Approachtotheillappearinginfant(youngerthan90daysofage)")

Concerningsymptoms,includingtemperatureinstability,orrespiratory,cardiocirculatory,or
neurologicsymptoms(see"Clinicalfeatures,evaluation,anddiagnosisofsepsisintermandlate
preterminfants",sectionon'Clinicalmanifestations')

Cerebrospinalfluid(CSF)pleocytosis(whitebloodcell[WBC]cellcountof>20to30cells/microL)
(table2)(see"Bacterialmeningitisintheneonate:Clinicalfeaturesanddiagnosis",sectionon
'InterpretationofCSF')

Confirmedorsuspectedmaternalchorioamnionitis(see"Clinicalfeatures,evaluation,anddiagnosis
ofsepsisintermandlatepreterminfants",sectionon'Maternalriskfactors')

Positiveblood,urine,orCSFculture(see"Clinicalfeatures,evaluation,anddiagnosisofsepsisin
termandlatepreterminfants",sectionon'Bloodculture')

Werecommendsuspectedneonatalsepsisbetreatedinitiallywithempiricantibiotictherapy(table3)that
providesbroadcoverageforthemostlikelypathogens(groupBStreptococcus[GBS]andgramnegative
entericorganisms,includingEscherichiacoli[E.coli])(table4)(Grade1B).

Theempiricregimenforearlyonsetsepsiswithoutanapparentfocusconsistsofampicillinand
gentamicin.(See'Earlyonsetsepsis'above.)

Empiricantibioticregimensforlateonsetsepsiswithoutanapparentfocusareasfollows(see
'Lateonsetsepsis'above):

Forneonatesadmittedfromthecommunity,wesuggestampicillinandgentamicin.

Forinfantswhocontinuetobehospitalizedfrombirth,wesuggestvancomycinandgentamicin.

Empiricantibioticregimensforsuspectedneonatalsepsis(earlyorlateonset)withcertainspecial
circumstancesareasfollows(see'Specialcircumstances'above):
https://www.uptodate.com/contents/management-and-outcome-of-sepsis-in-term-and-late-preterm-infants/print?source=search_result&search=neonatal%20seps 7/21
2/28/2017 Management and outcome of sepsis in term and late preterm infants - UpToDate

Ifthereisconcernoflateonsetmeningitis,wesuggestaddingcefotaximetotheregimen.(See
"Bacterialmeningitisintheneonate:Treatmentandoutcome",sectionon'Empiricaltherapy'.)

Ifthereisconcernforpneumonia,wesuggestaregimenofampicillinandcefotaximeor
vancomycinandcefotaxime.

Ifthereisafocusofinfectioninvolvingthesofttissues,skin,joints,orbones(inwhichcaseS.
aureusisalikelypathogen),wesuggestsubstitutingvancomycinor,intoxicappearinginfants,
vancomycinplusnafcillinforampicillin.

Ifintravascularcatheterrelatedinfectionisaconcern,wesuggestvancomycinandgentamicin.

Ifanintestinalsourceforsepsisissuspected,wesuggestaddingclindamycin,orothersuitable
antibioticsuchasmetronidazole.

Antibiotictherapyisalteredbaseduponisolationofthecausativeagentanditsantimicrobial
susceptibilitypattern.(See'Pathogenspecifictherapy'above.)

Ininfantswithcultureprovensepsis,theusualcourseoftherapyis10days.Longertreatmentis
warrantedifaspecificfocusofinfectionisidentified(eg,meningitis,osteomyelitis,orsepticarthritis).
(See'Cultureprovensepsis'above.)

Inwellappearinginfantswithnegativeculturesafter48hours,empiricantibiotictherapyshouldbe
discontinuedassepsisisunlikelyintheseinfants.(See'Infectionunlikely'above.)

Mostinfantswithcultureprovensepsisimproveclinicallywithin24to48hoursafterappropriateantibiotic
treatmentisstarted.Theresponsetoantibiotictherapyisassessedbyarepeatbloodculture24to48
hoursafterinitiationofantibiotictherapy.Failuretosterilizethebloodstreamsuggestseitherthatthe
antimicrobial(s)chosenarenotactiveagainsttheinfectingpathogenorthatthereisanunrecognized
focusofinfection.(See'Responsetotherapy'above.)

Themortalityofneonatalsepsisinterminfantsislessthan10percent.(See'Outcome'above.)

Theprimaryinterventiontopreventneonatalsepsisistheuseofintrapartumantibioticprophylaxisin
motherswithdocumentedGBScolonization,apreviousbirthofaninfantwithGBSdisease,orGBS
bacteriuriaduringthecurrentpregnancy.(See"NeonatalgroupBstreptococcaldisease:Prevention".)

UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.

REFERENCES

1.PolinRA,CommitteeonFetusandNewborn.Managementofneonateswithsuspectedorprovenearly
onsetbacterialsepsis.Pediatrics2012129:1006.
2.VeraniJR,McGeeL,SchragSJ,DivisionofBacterialDiseases,NationalCenterforImmunizationand
RespiratoryDiseases,CentersforDiseaseControlandPrevention(CDC).Preventionofperinatalgroup
BstreptococcaldiseaserevisedguidelinesfromCDC,2010.MMWRRecommRep201059:1.
3.Edwards,MS,Baker,CJ.SepsisintheNewborn.In:Krugman'sInfectiousDiseasesofChildren,11th
ed,Gershon,AA,Hotez,PJ,Katz,SL(Eds),Mosby,Philadelphia2004,p.545.
4.WynnJL,WongHR,ShanleyTP,etal.Timeforaneonatalspecificconsensusdefinitionforsepsis.
PediatrCritCareMed201415:523.
5.RajuTN,HigginsRD,StarkAR,LevenoKJ.Optimizingcareandoutcomeforlatepreterm(nearterm)
infants:asummaryoftheworkshopsponsoredbytheNationalInstituteofChildHealthandHuman
Development.Pediatrics2006118:1207.

https://www.uptodate.com/contents/management-and-outcome-of-sepsis-in-term-and-late-preterm-infants/print?source=search_result&search=neonatal%20seps 8/21
2/28/2017 Management and outcome of sepsis in term and late preterm infants - UpToDate

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:theburdenofgroupB
StreptococcalandE.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,compared
withampicillinandgentamicin,forneonatesatriskforsepsisisassociatedwithanincreasedriskof
neonataldeath.Pediatrics2006117:67.
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.AmericanAcademyofPediatrics.Tablesofantibacterialdrugdosages,Table4.2.In:RedBook:2015
ReportoftheCommitteeonInfectiousDiseases,30thed,KimberlinDW(Ed),AmericanAcademyof
Pediatrics,ElkGroveVillage,IL2015.p.882.
17.FortunovRM,HultenKG,HammermanWA,etal.CommunityacquiredStaphylococcusaureus
infectionsintermandneartermpreviouslyhealthyneonates.Pediatrics2006118:874.
18.NizetV,KleinJO.Bacterialsepsisandmeningitis.In:InfectiousdiseasesoftheFetusandNewborn
Infant,7thed,RemingtonJS,etal(Eds),WBSaunders,Philadelphia2010.p.222.
19.GerdesJS.Diagnosisandmanagementofbacterialinfectionsintheneonate.PediatrClinNorthAm
200451:939.
20.PolinRA,WatterbergK,BenitzW,EichenwaldE.Theconundrumofearlyonsetsepsis.Pediatrics
2014133:1122.
21.CohenWolkowiezM,BenjaminDKJr,CapparelliE.Immunotherapyinneonatalsepsis:advancesin
treatmentandprophylaxis.CurrOpinPediatr200921:177.
22.INISCollaborativeGroup,BrocklehurstP,FarrellB,etal.Treatmentofneonatalsepsiswithintravenous
immuneglobulin.NEnglJMed2011365:1201.
23.OhlssonA,LacyJB.Intravenousimmunoglobulinforsuspectedorproveninfectioninneonates.
CochraneDatabaseSystRev2015:CD001239.
24.PammiM,BrocklehurstP.Granulocytetransfusionsforneonateswithconfirmedorsuspectedsepsis
andneutropenia.CochraneDatabaseSystRev2011:CD003956.
25.SchiblerKR,OsborneKA,LeungLY,etal.Arandomized,placebocontrolledtrialofgranulocytecolony
stimulatingfactoradministrationtonewborninfantswithneutropeniaandclinicalsignsofearlyonset
sepsis.Pediatrics1998102:6.
https://www.uptodate.com/contents/management-and-outcome-of-sepsis-in-term-and-late-preterm-infants/print?source=search_result&search=neonatal%20seps 9/21