Meningitisunderthreemonthsbefore37weeksofgestationbutallbeendischargedfromaneonatalunitbeforetheiradmissionwithmeningitisTwentynineinfantsweredirectlyadmittedtoourhospitaloneofwhomwasreadmitteda ID: 944224
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PostgradMedj1995;71:36-38C)TheFellowshipofPostgraduateMedicine,1995BacterialmeningitisinthefirstthreemonthsoflifeFAIRiordan,APJThomson,JASills,CAHartUniversityofLiverpool,Liverpool,UKInstituteofChildHealthFAIRiordanAPJThomsonJSillsDepartmentofMedicalMicrobiologyFAIRiordanCAHartCorrespondencetoDrFAIRiordan,InstituteofChildHealth,RoyalLiverpoolChildren'sNHSTrust(AlderHey),EatonRoad,LiverpoolL122AP,UKAccepted27July1994SummaryAretrospectivestudyofinfantswithbacterialmeningitisadmittedtoourhos-pitalduring1949-52,highlightedthelackof'classical'signsofmeningitisintheseinfants.1Wecarriedoutasimilarreviewof44infantsagedlessthanthreemonths,admittedduring1982-91.Wealsodeter-minedthecausativeorganismsandtheirantiobioticsensitivities.Symptomsandsignsweresimilarinthetwoseries.Fortyinfantsinthelaterserieswereeitherfebrile,irritableorhadseizuresonthedayofadmission.Overallmortalityfellfrom30%to11%.Between1982and1991GroupBStrep-tocococcusandNeisseriameningitidiswerethecommonestcausesofmenin-gitis.Allorganisms,exceptone,weresensitivetoampicillinandlorcefotaxime.Bacterialmeningitisshouldbesuspectedinyounginfantswhoarefeb-rile,irritableorhavingseizures.Initialtreatmentwithampicillinandcefotax-imeisappropriate.Keywords:bacterialmeningitis,infantsIntroductionBacterialmeningitisinthefirstfewmonthsoflifepresentsanumberofdifficultclinicalproblemsindiagnosisandtreatment.Thesymptomsandsignsofmeningitismaybenon-specific,anddiagnosisreliesheavilyonahighindexofsuspicion.FortyyearsagoHaworth'notedthatthe'classical'signsofmeningitis(neckstiffnessand/oraraisedanteriorfontanelle)occurredlessoftenininfantslessthanthreemonthsofage.Hereportedon13infantsunderthreemonthsofagewithbacterialmeningitisadmit-tedtoourhospitalbetweenJuly1949andApril1952.Thediagnosisofmeningitiswasdelayedinfourinfants,allofwhomdied.Sincethisstudy,groupBStreptococcushasbecomeamajorpathogenforyounginfants.2WeaimtoseeiftheclinicalpresentationofbacterialmeningitisinyounginfantshaschangedsinceHaworth'sstudy.Wealsoaimtodeterminewhetherdelayindiagnosisstilloccurs.Controversyalsoexistsoverthemostappro-priateinitialantibioticregimenforyounginfantswithmeningitis.Theorganismsthatcausebacterialmeningitisininfantsvarywiththeageofthechild.IntheneonatalperiodGram-negativebacteria(particularlyEscherichiacolt),andmorerecentlyGroupBStreptococcus(GBS),andListeriamonocyto-genes,arecommoncauses.InchildrenoverthreemonthsofageNeisseriameningitidis,Haemophilus'influenzaetypeb(Hib)andStreptococcuspneumoniaecausealmostallcommunity-acquiredcases.3Infantsbetweenoneandthreemonthsofagecandevelopmeningitiswitheithertheneonatalorthechildhoodgroupofpathogens.Anti-bioticguidelinesbasedonknowledgeofthecommonpathogensrecommendacombinationofcefotaximeandampillicin.4Beforeadoption,theseguidelinesneedvalidatinginaclinicalsetting.Neonatalmeningitishasahighmortality,especiallyinprematureandlowbirthweightinfants.3Initialtreatmentwithpenicillin,cefotaximeandgentamicinisrecommended.5Almosthalfofallcasesofneonatalmenin-gitisareadmittedtohospitaldirectlyfromhome3andwillthereforenotbetreatedonaneonatalunitbutonapaediatricward.Anantibioticregimentocovermeningitisinallchildrenunderthreemonthsofageadmittedtopaediatricwardsmayhelptosimplifytreat-ment.Wehavereviewedinfantsunderthreemonthsofagewithbacterialmeningitisadmit-tedtoourhospitalovera10-yearperiod.Ouraimwastoexaminetheinitialclinicalpresenta-tionandtodeterminethecausativeorganismsandtheirantibioticsensitivities.Anappropri-ateinitialantibioticregimencouldthenbesuggested.PatientsandmethodsThecase-notesofallchildrenlessthanthreemonthsofagewithpositivecerebrospinalfluid(CSF),cultures,admittedtoourhospitalbetweenJanuary1982andDecember1991,werereviewed.Caseswereidentifiedfrommicrobiologyrecordsandwardadmissionbooks.Thecase-notesforallbutthreechildrenwereeventuallytraced,andinformationfrompreviousresearchwasavailableontwoofthesechildren.Infectionscomplicatingmyelomen-ingocoeles,ventricularshunts,oroccurringaftersurgerywereexcluded.Forty-fiveepisodesofmeningitisoccuredin44childrenoverthe10-yearperiod.(Onechildwasre-admittedfollowingpartiallytreatedEcolimeningitis.)Sixinf
antshadbeenborn Meningitisunderthreemonthsbefore37weeksofgestation,butallbeendischargedfromaneonatalunitbeforetheiradmissionwithmeningitis.Twenty-nineinfantsweredirectlyadmittedtoourhospital,oneofwhomwasre-admitted,and15weretertiaryreferrals.Fivechildrendied,threeofwhomhadneonatalmeningitis(seetable1).ResultsSYMPTOMSANDSIGNSPresentingsymptomsandsignswerenotedfromcase-notes,referrallettersandcasualtycardsandcomparedwiththosefoundbyHaworth'(table2).Symptomsandsignsdidnotdifferbetweenthetwogroupsexceptfortheincidenceofpoorfeeding.Fortychildreninourseriespresentedwitheitherfever,irritabilityorseizuresonthedayofadmission.Twofurtherinfantshadpoorperipheralperfusionandcyanosis.The'clas-sical'signsofmeningitis(neckstiffnessand/orTable1Causativeorganismofmeningitisininfantsunderthreemonths,AlderHeyChildren'sHospital1982-91.FiguresaregivenasthenumberofadmissionswiththenumberofdeathsinparenthesesAgeincompletedweekOrganism0-34-89-13TotalNmeningitidis8513Hinfluenzae11(1)2Spneumoniae12(1)14GroupBStrep8(2)4315GroupAStrep3(1)3Listeria22Escherichiacoli22*4*Other**112*OnechildwithrelapsedEcolimeningitisre-admittedagedfiveweeks.**Streptococcusmilleri(oneweekold)andEnterobacteragglomerans(10weeksold).Table2Presentingsymptomsandsignsandoutcomeofinfantslessthanthreemonthswithbacterialmeningitis1949-521982-91Symptoms(n=13)(n=42)Poorfeeding5(38%)32(76%)*FeverNA29(69%)Irritable7(54%)25(60%)Lethargic1(8%)14(33%)Vomiting5(38%)13(31%)Signs(n=13)(n=40)Temperature)38TCNA28(70%)IrritableNA28(70%)Seizuresday1NA14(35%)Fullfontanelle5(38%)18(45%)Neckstiffness3(23%0,)5(13%o)No'classical'signs7(56%)22(55%)Outcome(n=13)(n=45)Delayindiagnosis4(30%)7(15%)Deaths4(30%)5(11%)NA=informationnotavailable*Significantatp0.05bychi2.araisedanteriorfontanelle)wereabsentinover5000ofinfantsinbothseries.Aclinicaldiag-nosisofmeningitiswasmadeinonly430OoftheseinfantsinHaworth'sseries,butin810oftheseinfantsinourseries.DelayindiagnosisoccurredinfourchildreninHaworth'sseries.Theseinfantswereinitiallythoughttohavepneumonia(two),jaundice,orfailuretothrive.Allthesechildrendied.Inourseriesdelayindiagnosisoccurredinsevencases.Fivechild-renwereinitiallyreferredtootherspecialitiesbecauseofpresumedsurgical(three)orcardiac(two)symptoms,onechildpresentedwithafebrileseizures,andonewithstomatitis.Noneofthesechildrendied.Therewasanoveralldecreaseinmortalityfrom30°/0to110%,butthisfailedtoachievestatisticalsignificance.ORGANISMSTheorganismsgrownfromtheCSFofthechildrenadmittedbetween1982and1991arelistedintable1.Teninfantsagedbetweenoneandthreemonths(36%)hadinfectionswith'neonatal'organisms.Bothcasesofcoliformmeningitisinthisagegroupwereduetoarelapseofinfection.(Onechildhadpreviouslybeentreatedatourhospitalandoneatareferringhospital.)Antimicrobialsensitivitieswereavailablefor41organisms,28ofwhichwereseenonmicro-scopyoftheCSF.Ofthe17organismsisolatedfromneonates,11weresensitivetoeitherpenicillinorcefotaximeandfourorganisms(EcoliandLmonocytogenes,twoeach)weresen-sitivetogentamicin.(SensitivitieswereunavailablefortwocasesofGBSmeningitis.)Howeverall15organismswithknownsen-sitivitiesweresensitivetoeitherampicillinorcefotaxime,makingtheadditionofgentamicinunnecessary.Amongstthe26organismswithknownsen-sitiviesintheonetothreemonthagegroup,allexceptoneweresensitivetoeitherampicillinorcefotaximeorboth.TheexceptionwasacaseofrelapsedmeningitisduetoEcoliresistanttoampicillin.Thisorganismwassensitivetocefuroxime,butsensitivitytocefotaximewasnottested.(Thiscaseoccurredin1982.)(Sen-sitivitieswereagainunavailablefortwocasesofGBSmeningitis.)DiscussionSymptomsandsignsofbacterialmeningitisinyounginfantsappearnottohavechangedoverthepast40yearsdespitechangesinthecausativeorganisms.2(TherewerenocasesofGBSmeningitisinHaworth'sseries.)Ahighindexofsuspicionisstillnecessaryasoverhalfthecasesdonotshowthe'classical'signsofbacterialmeningitis.Mostcasesinourseries,however,wereeitherfebrile,irritableorhadseizuresonthedayofadmission.Otherstudieshavefoundthatfeverandirritabilityarethecommonestsignsofbacterialmeningitisinyounginfants.6'7Awarenessofthesenon-specificsymptomsofmeningitisappearstobeincreasing,asadelay
indiagnosisoccurredinamuchsmallerproportionofcasesinourseries(310%inHaworth'sseries,16%inours).There37 38Riordan,Thomson,Sills,Hartisnoroomforcomplacency,however,asthefiveinfantsinitiallyreferredtooursurgicalandcardiaccolleaguesdemonstrate.Ourstudydemonstratesthewidenumberofpathogenscausingmeningitisinthefirstthreemonthsoflife,withGBSandmeningococcipredominating.Allexceptoneoftheseorganismsweresensitivetoeitherampicillinorcefotaxime,orboth.(TheexceptionbeingarelapsedcaseofmenigitisduetoEcolisensitivetocefuroxime,andthuslikelytobesensitivetocefotaxime,althoughnottested.)ThefourcaseswheresensitivitieswereunavailablewereallcausedbyGBS.Thesewouldalmostcer-tainlybesensitivetoampicillinandcefotaxime.StudiesfromtheUSfoundthatHib8orGBS6werethecommonestcausesofmeningitisininfantsagedbetweenoneandthreemonths,andrecommendedtreatmentwithampicillincombinedwitheitherchloramphenicol8orcefotaxime.6NosimilarstudyfromtheUK,focusingonthisagegroup,hasbeenpublishedalthoughdeLouvoisetalhavestudiedmenin-gitisinchildrenunderoneyearofage.3Inthisstudy,10%ofneonatalmeningitiswascausedbythecommonchildhoodorganisms,and5%ofmeningitisbetweenthesecondandsixthmonthoflifewascausedbyneonatalorganisms.Penicillinandchloramphenicolwerethemostcommonlyusedantibioticsforbothneonatesandolderinfants.Chloramphenicolandgentamicinbothhaveseriousside-effectsandrequiremonitoringofbloodlevels.9Theefficacyandsafetyofampicillinandcefotaximemakethemanattractivechoiceforyounginfantswithbacterialmeningitis.4Thiscom-binationisincreasinglypopularamongstdirec-torsofprogrammesinpaediatricinfectiousBacterialmeningitisininfants*classicalsignsoftenlacking*groupBStreptococcusandNmeningitidisaretheusualcauses*highindexofsuspicionfordiagnosis*treatinitiallywithampicillinandcefotaximediseaseintheUS.10OurstudyshowsthatthiscombinationcouldbeusedintheUKastheinitialtreatmentofmeningitisininfantsagedbetweenoneandthreemonths.Neonatesadmit-tedtoachildren'swardwithmeningitiscouldalsobetreatedwiththisregimen,insteadofoneusinggentamicincombinedwithcefotaximeandpenicillin.5Ourstudycannotmakeanyrecommenda-tionsabouttreatingmeningitisontheneonatalunit,althoughacombinationofampicillinandcefotaximehasbeenrecommendedbyothers.""2Inconclusion,thediagnosisofbacterialmeningitisinyounginfantscontinuestorequireahighindexofsuspicion.Meningitisshouldbesuspectedinanyinfantlessthanthreemonthsofagewhoisfebrile,irritable,hasseizuresorisinapoorcondition.Initialtreatmentonapaediatricwardwithampicillinandcefotaximeisappropriateuntilthecausativeorganismisidentified.WewouldliketothankDrOmniaMarzoukandDrHuwThomasforprovidingdata,PaulaThomasforhelpintracingcase-notes,andtheJohanneHollyTrustforfinancialsupport.1HaworthJC.Thediagnosisofacutemeningitisininfancy.Lancet1953;i:911-4.2ReidTMS.EmergenceofgroupBstreptococciinobstetricandperinatalinfections.BMJ1975;2:533-6.3deLouvoisJ,BlackbournJ,HurleyR,HarveyD.InfantilemeningitisinEnglandandWales:atwoyearstudy.ArchDisChild1991;66:603-7.4KleinNJ,HeydermanRS,LevinM.Antibioticchoicesformeningitisbeyondtheneonatalperiod.ArchDisChild1992;67:157-61.5GandyG,RennieJ.Antibiotictreatmentofsuspectedneonatalmeningitis.ArchDisChild1990;65:1-2.6BaumgartnerET,AugustineA,SteeleRW.Bacterialmeningitisinolderneonates.AmJDisChild1983;137:1052-4.7ValnariP,PeltolaH,Ruuskanen0,KorvenrantaH.Childhoodbacterialmeningitis:initialsymptomsandsignsrelatedtoage,andreasonforconsultingaphysician.EurJPediatr1987;146:515-8.8EnzenauerRW,BassJW.Initialantibiotictreatmentofpurulentmeningitisininfants1to2monthsofage.AmJDisChild1983;137:1005-6.9Marzouk0,NunnAJ,ThomsonAPJ,SillsJA,HartCA.Chloramphenicollevelsinchildrenwithmeningococcaldisease.PediatricRevCommun1993;7,47-53.10KlassPE,KleinJO.Therapyofbacterialsepsis,meningitisandotitismediaininfantsandchildren:1992pollofdirectorsofprogramsinpediatricinfectiousdiseases.PediatrInfectDisJ1992;11:702-5.11FeiginRD,McCrakenGHJr,KleinJO.Diagnosisandmanagementsofmeningitis.PediatrInfectDisJ1992;11,785-814.12RennieJM.Infectionofthenervoussysteminthenewborn.In:CampbellAGM,McIntoshN,eds.ForfarandArneil'sTextbookofPaediatrics.Edinburgh:ChurchillLivingstone,1992;p273