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ManagementofBacterialMeningitis:NewGuidelinesfromthe
IDSA
LIZSMITH
AmFamPhysician.2005May1571(10):20032008.

TheInfectiousDiseasesSocietyofAmerica(IDSA)hasissuednewguidelinesforthediagnosisandtreatmentofbacterialmeningitis.Recommendationsarebasedon
resultsfromclinicaltrialsanddatafromanimalexperimentationpublishedthroughMay2004.TheguidelineswerepublishedintheNovember1issueofClinical
InfectiousDiseases,andcanbeaccessedonlineathttp://www.journals.uchicago.edu/CID/journal/issues/v39n9/34796/34796.text.html.Definitionsofstrengthof
recommendationsandqualityofevidencearelistedinTable1.

TABLE1
IDSAUnitedStatesPublicHealthServiceGradingSystemforRankingRecommendationsinClinicalGuidelines
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InitialManagementSteps
Whenapatientpresentswithsuspectedacutebacterialmeningitis,thephysicianshouldbeginantimicrobialtherapyassoonaspossible.Bacterialmeningitisisa
neurologicemergencyprogressiontomoreseverediseasereducesthepatientslikelihoodofafullrecovery.

Abloodcultureandlumbarpunctureshouldbeperformedimmediatelytoconfirmthediagnosis.Becausecomplicationsassociatedwithlumbarpunctureincludelife
threateningbrainherniation,atriskpatients(e.g.,thosewhoareimmunocompromised,hadaseizurewithinthepreviousweek[adultsonly],havepapilledema,orhave
aspecificneurologicabnormality)shouldhaveacomputedtomographic(CT)scanbeforeundergoingtheprocedure(BII).Lumbarpuncturealsomaybedelayed
pendingCTscanresultsifitmaybelikelythatsymptomsarecausedbyincreasedintracranialpressurefrom,forexample,acentralnervoussystemmasslesion.
Bloodsamplesstillshouldbeobtainedfrompatientsimmediately,andappropriateempirictherapyadministered.OnceanegativeCTscanresultisobtained,patients
canproceedtolumbarpuncture.

Empirictherapy
Empirictherapyshouldbeginassoonasbacterialmeningitisisthoughtlikely.Widespreadresistancetopenicillinsandsulfonamideshasforcedaconsiderationofnew
agentsforthetreatmentofbacterialmeningitis,suchascephalosporins,vancomycin(Vancocin),rifampin(Rifadin),carbapenems,andfluoroquinolones.Choiceof
agentsforempirictherapyshouldbedeterminedbythepatientsageandthepresenceofpredisposingconditions,andshouldassumeantimicrobialresistance.
RecommendationsarelistedinTable2(AIII).

AdjunctiveDexamethasoneTherapy
Theadditionofdexamethasonealsoshouldbeconsidered.Adjunctivedexamethasonecanreducethesubarachnoidspaceinflammatoryresponseamajorfactorin
morbidityandmortalitycausedbybacterialmeningitisandmaythereforealleviatemanyofthepathologicconsequencesofbacterialmeningitis(e.g.,cerebraledema,
cerebralvasculitis,changeincerebralbloodflow,increaseinintracranialpressure,neuronalinjury).Thereissomeconcernthatadjunctivedexamethasonetherapy
mayinhibittheefficacyofcerebrospinalfluid(CSF)vancomycinandwouldthereforebeharmfultopatientswithpenicillinorcephalosporinresistantstrains.However,
intheabsenceofdatafromclinicaltrials,adjunctivedexamethasoneisrecommendedforalladultswithsuspectedorprovenpneumococcalmeningitis,andininfants
andchildrenwithHaemophilusinfluenzaetypebmeningitis(AI),eveniftheisolatesubsequentlyisfoundtobehighlyresistanttopenicillinoracephalosporin.
Patientsshouldbeobservedcloselyinfollowuptocheckforanyadverseoutcomes.Recommendeddosageofdexamethasoneis0.15mgperkgadministeredevery
sixhoursfortwotofourdays,beginning10to20minutesbefore(oratleastconcomitantwith)thefirstantimicrobialdose(AI).Patientsreceivingadjunctive
dexamethasoneforthetreatmentofsuspectedpneumococcalmeningitismaybenefitfromtheadditionofrifampintothecombinationofvancomycinandathird
generationcephalosporin.

Theuseofdexamethasoneininfantsandchildrenwithpneumococcalmeningitisiscontroversial,andthereareinsufficientdatatosupportitsuseinneonatesorin
adultswithmeningitiscausedbyotherpathogens.Patientswhoalreadyhavereceivedantimicrobialtherapyshouldnotbegivendexamethasonetherapy,asitis
unlikelytoimprovetheiroutcome(AI).DexamethasonetherapyshouldbecontinuedfollowingtestresultsonlyifgrampositivediplococciarefoundintheCSFGram
stain,orifculturesrevealStreptococcuspneumoniae.

TABLE2
RecommendationsforEmpiricAntimicrobialTherapyforPurulentMeningitisBasedonPatientAgeandSpecificPredisposingCondition
Therightsholderdidnotgrantrightstoreproducethisiteminelectronicmedia.Forthemissingitem,seetheoriginalprintversionofthispublication.

Diagnosis
DiagnosisofbacterialmeningitisisdependentonCSFexaminationfollowinglumbarpuncture.Inbacterialmeningitis,openingpressuregenerallyisbetween200and
500mmH2O(lowerinchildren)whitebloodcellcountandproteinconcentrationareelevatedglucoseconcentrationmaybelowandtheremaybeaneutrophilor
lymphocytepredominance.

Becausedeterminingthebacterialetiologycantakeupto48hourswithCSFcultures,analternativediagnostictestshouldbeconsidered.

GramstainexaminationofCSFisrecommendedforallpatientsinwhommeningitisissuspected(AIII).Itisfast,inexpensive,andaccuratein60to90percentof
patients,althoughmisinterpretationandcontaminationmaycausefalsepositiveresults.

PolymeraseChainReaction(PCR)isusefulforexcludingadiagnosisofbacterialmeningitisandmayeventually,withfurtherrefinement,beusedfordetermining
etiology(BII).

Latexagglutination,whilequick,simple,andsensitive,isnotrecommendedforroutineuseaspathogenscannotberuledoutbyanegativetestresult(DII).Itismost
usefulforpatientswhohavebeguntherapyandhavenegativeGramstainandCSFcultureresults.

Limuluslysateassay,thoughsensitive,alsoisnotrecommendedforroutineuse(DII)asitdoesnotdistinguishbetweenorganismsorruleoutgramnegative
meningitis,anditisnotwidelyavailable.

WhenCSFfindingssuggestbacterialmeningitisbutCSFGramstainandcultureresultsarenegative,acombinationoflaboratorytestsisnecessarytodistinguish
bacterialfromviralmeningitis.(AlthoughthereisavalidatedCSFresultmodel,itsclinicalutilityhasnotyetbeenproven,anditshouldnotbeusedtodetermine
initiationofantimicrobialtherapy.)ThemoststronglyrecommendedtestsarePCR,whichismoresensitivethanviralcultureandfasterthancellcultureforthe
detectionofenterovirus,anddeterminationofCreactiveprotein(CRP)concentration,whichhasahighnegativepredictivevalueforbacterialmeningitiswhenresults
arenormal(BII).

Lactateconcentrationisnotrecommended(DIII)sinceresultsgenerallyarenonspecificandmaybeconfoundedbyotherfactors(althoughaCSFlactate
concentrationof4.0mmolperLorgreatermaybeusedasanindicationforempiricaltherapyinpostoperativeneurosurgicalpatients[BII]).

Procalcitoninconcentrationmeasurementisuseful,butcannotberecommendeduntilitbecomesmorewidelyavailable(CII).

Management
TargetedantimicrobialtherapycanbegininadultsfollowingapositiveCSFGramstainresult.(Notethatempiricantibiotictherapyshouldnotbedelayedpendingthe
resultsofGramstainorotherdiagnostictests.)Childrenshouldnotbegiventargetedtherapyuntilbloodcultureresultsconfirmthediagnosis,sinceCSFGramstain
interpretationissubjecttoexpertise.Inthemeantime,theyshouldreceiveempirictherapywithvancomycinpluseitherceftriaxone(Rocephin)orcefotaxime(Claforan).
PatientswhoseGramstainresultisnegativealsoshouldcontinuewithempirictherapy.

Antimicrobialtherapyshouldbemodifiedassoonasthepathogenhasbeenisolatedandinvitrotestshavebeenperformed.Durationoftherapydependsonindividual
patientresponse,thoughgeneralizedguidelinesaccordingtotheresponsiblepathogenareasfollows:NeisseriameningitidisorH.influenzae,sevendaysS.
pneumoniae,10to14daysStreptococcusagalactiae,14to21daysaerobicgramnegativebacilli,21days(twoweeksbeyondthefirststerileCSFculturein
neonates)Listeriamonocytogenes,21daysorlonger.IntravenoustherapyisrecommendedthroughouttomaintainsufficientCSFconcentrations.

Inneonateswithmeningitiscausedbygramnegativebacilli,thedurationoftherapyshouldbedeterminedinpartbyrepeatedlumbarpuncturesdocumentingCSF
sterilization(AIII).Patientswhohavenotrespondedclinicallyafter48hoursofappropriatetherapyalsoshouldbemonitoredwithrepeatedCSFanalysis(AIII),
particularlythosewithmeningitiscausedbyresistantstrainsandthosewhohavereceivedadjunctivedexamethasonetherapy.RepeatedCSFanalysisisnot
recommendedonaroutinebasis.

Becauseanycomplicationsofbacterialmeningitisusuallyoccurwithinthefirsttwoorthreedaysoftreatment,carefullyselectedpatientsmaybeeligibleforoutpatient
management,withclosefollowup.Criteriaforoutpatienttherapyareinpatientantimicrobialtherapyforsixormoredaysnofeverforatleast24to48hoursno
significantneurologicdysfunction,focalfindings,orseizureactivitystableorimprovingconditionabilitytotakefluidsbymouthsafeenvironmentwithaccesstoa
telephone,arefrigerator,food,utilities,andhomehealthnursingreliableintravenouslineandinfusiondevice,ifnecessaryphysicianavailabledailyandan
establishedplanforphysicianandnursevisits,laboratorymonitoring,andemergencies.

AntimicrobialAgents
Cephalosporins
Thirdgenerationcephalosporins(cefotaximeorceftriaxone)arerecommendedforthetreatmentofchildhoodbacterialmeningitis(AI)andforpneumococcaland
meningococcalmeningitiscausedbypenicillinresistantstrains(AIII).TheyarethedrugsofchoiceforempirictherapyinthetreatmentofH.influenzaetypeb
meningitis,becauseresistancetochloramphenicolhasdeveloped.Thirdgenerationcephalosporinshaveshowngreaterefficacythanchloramphenicol(Chloromycetin)
andthesecondgenerationcephalosporincefuroxime(Ceftin).Theyareeffectiveinmeningitiscausedbyaerobicgramnegativebacilli(AII),butincreasingresistance
makesinvitrosusceptibilitytestingcrucial.Ceftazidime(Ceptaz)hasprovedeffectiveinthetreatmentofPseudomonasmeningitis(AII).Cefepime(Maxipime),a
fourthgenerationcephalosporin,hasprovedsafeandeffectiveinthetreatmentofinfantsandchildrenwithbacterialmeningitis,andhasbeenusedsuccessfullyin
patientswithbacterialmeningitiscausedbyEnterobacterspeciesandPseudomonasaeruginosa(AII).

Vancomycin
Theuseofvancomycinisnotrecommendedinpatientswithbacterialmeningitiscausedbynonresistantstrains(EII).Inpatientswithmeningitiscausedbypenicillin
orcephalosporinresistantstrainsitmaybeusedincombinationwithathirdgenerationcephalosporinbutshouldnotbeusedalone(AIII).Ifapatientisunresponsive
toparenteraladministration,intrathecaladministrationmaybeconsidered.

Rifampin
Rifampinshouldbeusedonlyincombinationwithotherantimicrobialagentsasresistancedevelopsrapidlywhenitisusedalone.Ithasbeenusedincombinationwith
athirdgenerationcephalosporinwithorwithoutvancomycinfortreatmentofpneumococcalmeningitiscausedbypenicillinorcephalosporinresistantstrains,though
dataonitsefficacyarelacking.Theadditionofrifampinisrecommendedonlyifclinicalorbacteriologicresponsetoasusceptiblepathogenisdelayed(AIII).
Carbapenems
Imipenem(Primaxin)hasprovedsuccessful,butisnotrecommendedfortreatmentofmeningitisinmostpatientsbecauseofthepotentialforseizureactivity(DII).
Meropenem(Merrem)haslesspotentialforseizureandisrecommendedasanalternativetocefotaximeandceftriaxoneinthetreatmentofpatientswithbacterial
meningitis(AI),andforuseinthetreatmentofmeningitiscausedbycertaingramnegativebacilli(AIII).Althoughmeropenemiseffectiveintreatingpatientswith
pneumococcalmeningitiscausedbypenicillinorcephalosporinresistantstrains,theprevalenceofstrainswithsharedresistancemayundermineitsusefulness(DII).

Fluoroquinolones
Theuseoffluoroquinolonesinthetreatmentofbacterialmeningitisisrecommendedwhenpatientsareunresponsivetoorcannotbegivenstandardantimicrobial
therapy,orwhenmeningitisiscausedbygramnegativebacillithatareresistanttomultipleagents(AIII).Newerfluoroquinolones,suchasgatifloxacin(Tequin)and
moxifloxacin(Avelox),potentiallyareusefulintreatingbacterialmeningitis,butshouldbeusedonlyasalternativeagentsuntilmoreevidenceisproduced(BII).There
arenodataontheuseoftheseagentsinnewbornsandchildren,althoughtheymaybeconsideredinthesepatientswhenstandardtherapyisineffective.
Trovafloxacin(Trovan)nolongerisusedowingtopossiblelivertoxicity.

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