Prognostic indicators in bacterial meningitis: a case-control study

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

w w w . e l s e v i e r . c o m / l o c a t e / b j i d

Original

article

Prognostic

indicators

in

bacterial

meningitis:

a

case–control

study

Maria

de

Fátima

Magalhães

Acioly

Mendizabal

_,

_Phelipe

_Cunha

_Bezerra

_,

Diego

Lins

Guedes

_,

_Diogo

_Buarque

_Cordeiro

_Cabral

_,

Demócrito

de

Barros

Miranda-Filho

a_{HospitalUniversitárioOswaldoCruz,UniversidadedePernambuco(UPE),Recife,PE,Brazil} b_{FaculdadedeCiênciasMédicas,UPE,Recife,PE,Brazil}

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Articlehistory:

Received15October2012 Accepted8January2013 Availableonline5July2013

Keywords:

Bacterialmeningitis Prognosticindicators Case–controlstudy

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Thiswasacase–controlstudytoidentifyprognosticindicatorsofbacterialmeningitisina referencehospitalinPernambuco/Brazil.Thedatawerecollectedfromchartsof294patients withbacterialmeningitisbetweenJanuary2000andDecember2004.Variablesweregrouped inbiological,clinical,laboratoryandetiologicagent/treatment.Variablesselectedineach stepweregroupedandadjustedforage.Twomodelswerecreated:onecontainingclinical variables(clinicalmodel)andothercontaininglaboratoryvariables(laboratorymodel).Inthe clinicalmodelthevariablesassociatedwithdeathduetobacterialmeningitisweredyspnea (p=0.006),evidenceofshock(p=0.051),evidenceofalteredmentalstate(p=0.000),absence ofheadache(p=0.008),absenceofvomiting(p=0.052),andage≥40yearsold(p=0.013).In thelaboratorymodel,thevariablesassociatedwithdeathduetobacterialmeningitiswere positivebloodcultures(p=0.073)andthrombocytopenia(p=0.019).Identificationof progno-sticindicatorssoonafteradmissionmayallowearlyspecificmeasures,likeadmissionof patientswithhigherriskofdeathtoIntensiveCareUnits.

©2013 ElsevierEditoraLtda.Allrightsreserved.

Introduction

Bacterialmeningitisisaworldwidemedical,neurologicaland, sometimes,neurosurgical emergency.1,2 _{Mostpatients with} bacterialmeningitispresentclassicsignsandsymptoms,such asheadache,fever,vomitingandneckstiffness.Somepatients developaseriousclinicalprofile,withagitation,torpor,motor disorders,convulsionsandevencoma.3,4

Studiesofprognosticindicatorsforbacterialmeningitisin adultsarerareinBrazil.Giventheriskofsequelaeanddeath in patients with bacterial meningitis, the identification of

∗ _{Correspondingauthorat:RuaSantoElias,175,1001,Espinheiro,Recife,PE,52020-090,Brazil.}

E-mailaddress:demofi[email protected](D.deBarrosMiranda-Filho).

prognosticfactorsonadmissiontohospitalcouldminimize theoccurrenceofundesirableevents.Theaimofthisstudy was to investigate the implications ofcertain clinical syn-dromesandlaboratoryfindingsatthetimeofadmissionto hospitalforthe prognosisofadultandadolescent patients withbacterialmeningitis.

Methods

A case–control study was carried out with all patients aged 13 years and over admitted to a public hospital in

1413-8670/$–seefrontmatter©2013 ElsevierEditoraLtda.Allrightsreserved. http://dx.doi.org/10.1016/j.bjid.2013.01.016

Pernambuco/Brazil, Hospital Correia Picanc¸o, between Jan-uary2000andDecember2004,withclinical(headache,fever, vomiting, neckstiffness, alterations in consciousness) and laboratorysymptoms (liquor cell count>5cells/mm3 _{and a}

predominanceofpolymorphonuclearsgreaterthan50%, irre-spectiveofGram orcultureresults)ofbacterialmeningitis, evolvingtodeathduetothediseaseorarelatedcause.The controlgroupconsistedofpatientsaged13yearsandover, withclinicalandlaboratorydiagnosis ofbacterial meningi-tis,whowereeventuallydischargedfromthesamehospital, during the same time period. Thestudy was approved by theResearchEthicsCommitteeoftheHospitalUniversitário OswaldoCruz(no.024/2005).

Thesamplesizewascalculatedonthebasisoftwo pre-viousstudies.5,6_{Theestimatedsamplewas96casesand135} controls.

All patients diagnosed with bacterial meningitis were listedand,oncethenumberofdeaths/year(cases)hadbeen identified,thenumberofcontrols(patientsdischargedfrom hospital) was calculated ataproportion of1:2. Individuals wereselectedrandomlyforthecontrolgroupstratifiedbyage, proportionatetothenumberofcases.

PatientswereexcludediftheyhadarrivedattheHospital CorreiaPicanc¸omorethan24hafterthecommencementof specifictreatment(antibiotics);iftheyhadaliquorfistulaor oneventricular-peritonealderivation;oriftheyhadpreviously undergoneneurosurgery.

Patientstransferredtootherservicesduetocomplications whoseoutcomes(deathordischargefromhospital)couldnot beascertained,evenafteractiveinvestigation,andthose dis-chargedfrom hospital for non-medicalreasons (i.e., those patientswhodischargedthemselves)wereconsideredtobe losses.

First, the association of each variable with death from bacterialmeningitiswasassessedusingunivariateanalysis. Thedegree ofassociation was expressedas anodds ratio. Thesensitivityofthe selectionofvariables for thelogistic regression model was established using a cut-off point of

p<0.20inunivariateanalysis.Thestatisticalsignificanceof theresultsobtainedwasassessedusingconfidenceinterval oftheestimatedoddsratiosandthe chi-squaredtest, with Yates’scorrection,whererecommended.

The variables initially tested using univariate analysis were:age,sex,placeoforigin,timeofdevelopmentof symp-toms,timeelapseduntilthefirstdoseofantibiotics,signsand symptomsgroupedaccordingtoorgansorsystemsaffected, evidenceofshock(circulatoryshock,cyanosis,sweating, pal-lor,alterations in peripheraltissue perfusion), evidence of altered mental state (reduction in level of consciousness, psychomotor agitation, coma, disorientation, listlessness), evidencerelatingtomeningealsigns(neckstiffness;Kernig’s, Brudzinski’s, and Lasègue’s signs), skin and mucusa alter-ations(petechiae,ecchymoses,vascularlesions),neurological signs(aphasia,motordysfunction,anisocoria,strabismus,lip pull, dysarthria), and evidence of infection (fever, myalgia, arthralgia, tachypnea, dyspnea, declinein general state of health,chills,asthenia, dizziness).Someclinicalsigns that have been mostcommonly identified as factors determin-ingprognosisinpreviousstudieswereevaluatedinisolation: vomiting,convulsions,dyspnea, fever,headacheand coma;

1st Block 2nd Block 3rd Block 4th Block

Biological variables

Clinical variables

Selected variables from each block Variables relating to laboratory tests Variables relating to etiological agent and treatment Model (clinical) Model (laboratory)

Fig.1–Multivariateanalysismodel.

initialliquorcellcount;initialglycorrhachia;initial proteinor-rhachia;identificationofetiologicalagentbyGramorculture; bacterialisolate(etiologicalagent)fromblood,fromliquoror both;hemoglobinemiaonadmission;leucometryof periph-eral bloodon admission;platelet countinperipheralblood onadmission;initialantibioticregimenandprevioususeof antibiotics.

The variables selected were grouped in blocks and introducedintothemultiplelogisticregression model.Four distinct blocks ofvariables were created:1st _block:

biologi-calvariables;2nd_{block:clinicalvariables;3}rd_{block:variables}

relating to laboratory tests; 4th _{block: variables relating to}

etiologicalagentandtreatment(Fig.1).Atthisstagethe asso-ciationwasconsideredstatisticallysignificantwhenp<0.05. Thet-testwasusedforcomparisonofmeans.Thecalculation ofthesampleandstorageandanalysisofdatawerecarried outusingtheEPIINFO6.04andSPSS8.0forWindows statis-ticsprograms.Thevariablesineachblockwerethenadjusted according toothersinthe bi-ormultivariate analysis.The variables withastatisticallysignificantassociation(p<0.05) identifiedduringeachstageweregroupedtogetherandthen adjustedforthebiologicalvariablethatwasalsofoundtobe statisticallysignificant (agegroup). Aftermultivariate anal-ysis,twodistinct finalmodelswerecreated,onecontaining variablesfromthe1stand2ndblocks(theclinicalmodel),and asecondcontainingvariablesfromthe1stand3rdand4th blocks(thelaboratorymodel).Theassociationofeachvariable withtheriskofdeathfrombacterialmeningitiswasmeasured usingthelowestriskgroupforcomparison.

Results

Thestudycovered294patientsataproportionofonecase fortwocontrols(98casesand196controls).Ofthese,21(7.1%) weretransferredtootherservicesasaresultofcomplications, andofthese,eight(2.7%)died.

Agerangedfrom13to87years,withameanof30.9years. Inthe controlgroup,themean agewas27.7 yearsand the median22,whilein thecasegroup ageranged from14 to

87years,withameanageof37.4yearsandamedianof31.5. Theriskofdeathfrombacterialmeningitiswasaroundthree timesgreateramongindividualsaged40orover(OR2.78;CI 1.62–4.73;p=0.0002).

Ofthe294patients,173weremale(58.8%).Therewasno statistically significant association between sex and death frombacterialmeningitisinthesamplestudied(p>0.05). Nei-therwas thereanyassociation betweentheplaceoforigin of the patient and death from bacterial meningitis,when comparingthosefromtheStatecapitalandthemetropolitan regionwiththosefromothermunicipalitiesintheState.

Bacteria were found in the liquor of 94 patients, with 33.3%(9/27)ofcasespresentingmeningococcicomparedwith 65.7%(44/67)ofthecontrolgroup;with51.9%(14/27)ofthe casespresentingpneumococci,comparedwith26.9%(18/67) of the control group; staphylococci were isolated in 14.8% (4/27)and7.5%(5/67)ofcaseandcontrolgroupsrespectively. Theproportionofpositivehemocultureamongthecaseswas 49.1%(28/57)comparedto19.5%(26/133)inthecontrolgroup (p<0.0001).

Initialunivariateanalysisshowednostatistically signifi-cantassociationbetweenthevariablesrelatingtothetimeof developmentofsymptoms(timeelapsedbetweenthe emer-genceofsymptomsand admissiontohospital);thetypeof initialantibioticregimenemployed;previous use of antibi-otics;andthetimeelapseduntilthefirstdoseofantibiotics and deathdue to bacterialmeningitis. Nostatistically sig-nificant difference was found between the mean time for the commencement of treatment with antibiotics in case (91.7min)andcontrolgroups(98.3min).

Thevariablesageandsexwereselectedforthe1stblock, and,followingbivariateanalysis,onlyagewasretainedinthe finalmodel(OR2.78;CI1.63–4.74;p=0.0002).

Fig.1sumsupallthestepsintheanalysis.

Table1showstheresultsofanalysisofthevariablesinthe 2ndblock(clinicalvariables)anddeathduetobacterial menin-gitis.Presenceofdyspnea,evidenceofshock,andalterations inmentalstatewereassociatedwithdeathduetobacterial meningitis.Likewise,theabsenceofheadacheandvomiting wasassociatedwithalessfavorableprognosis.

Table2showsthe resultsofanalysisofvariables inthe 3rd block (laboratoryvariables) and death due to bacterial meningitis. The mean of cells in liquor was significantly higher inthe controlgroup (8054.9cells/mm3_{) than among}

cases(5734.0cells/mm3_{), [p=0.02]. Themean glycorrhachia}

amongcaseswas36.8mg/dlcomparedto34.6mg/dl(p=0.66) inthecontrolgroup. Nostatisticallysignificantassociation wasfoundbetweenthe leucometryandriskofdeathfrom bacterial meningitis. Regarding the number of platelets in peripheralblood,ameanof203,343.28cells/mm3_foundinthe

caseswassignificantlylowerthanthe227,878.57cells/mm3_in

thecontrolgroup(p=0.04).

The4thblockcontainedthevariables:identificationof eti-ologicalagentusingGram(Grampositivediplococcus)andthe initialantibioticregimen.Afteradjustmentbybivariate analy-sis,onlytheidentificationofGrampositivediplococcusasthe etiologicalagentofbacterialmeningitiswasassociatedwith athreefoldgreaterriskofdeath(Table3).

Analysisofthevariablesselectedfromthe1stblock(age) andthe2ndblock(clinicalvariables)showedthatbeingaged

Table1–Adjustedoddsratio,confidenceintervaland p-valueoftheassociationbetweendeathdueto bacterialmeningitisanddyspnea,evidenceofshock, meningealsigns,fever,headache,vomiting,alterations inmentalstate,coma,andskinandmucosaalterations in294patientsoftheHospitalCorreiaPicanc¸obetween January2000andDecember2004.

OR 95%CI p-Value Dyspnea Yes 4.03 1.51–10.76 0.0054 No 1.00 Evidenceofshock Yes 2.73 1.02–7.25 0.0444 No 1.00 Headache Yes 1.00 No 5.59 1.74–17.96 0.0038 Vomiting Yes 1.00 No 1.96 1.02–3.77 0.0446

Alterationsinmentalstate

Yes 3.65 2.02–6.58 0.0000

No 1.00

OR,oddsratio;CI,confidenceinterval.

40yearsorolder,thepresenceofdyspnea,evidenceofshockor alteredmentalstate,andtheabsenceofheadachesand vomi-tingwereassociatedwithdeathduetobacterialmeningitis (Table4).

Afteradjustmentofthe3rdblock(laboratory)variablesfor agegroupinthemultiplelogisticregressionmodel,the vari-ablesremaininginthefinalmodelwerepositivehemoculture, cellcountinliquorlessthan2000cells/mm3_{,aplateletcount}

Table2–Adjustedoddsratio,confidenceintervaland p-valueoftheassociationbetweendeathdueto bacterialmeningitisandliquorcellcount,leucometryin peripheralblood,numberofplateletsinperipheralblood andproteinorrhachiain136patientsoftheHospital CorreiaPicanc¸obetweenJanuary2000andDecember 2004.

OR 95%CI p-Value

Hemoculture

Positive 2.69 1.13–6.39 0.0253 Negative 1.00

Liquorcellcount

Upto2000cells/mm3 _{2.72 1.16–6.35 0.0211} >2000cells/mm3 _1.00

Plateletsinperipheralblood

<150,000cells/mm3 _{3.22 1.36–7.63 0.0080} ≥150,000cells/mm3 _1.00

Proteinorrhachia

≤40cells/mm3 _1.00

>40cells/mm3 _{4.51 0.76–26.75 0.0972} OR,oddsratio;CI,confidenceinterval.

Table3–Adjustedoddsratio,confidenceintervaland p-valueoftheassociationbetweendeathduetobacterial meningitisandidentificationoftheetiologicalagentby Gramstain(Grampositivediplococcus)andtheinitial antibioticregimenin130patientsoftheHospitalCorreia Picanc¸obetweenJanuary2000andDecember2004.

OR 95%CI p-Value

Diplococcus Grampositive

Yes 3.20 1.47–6.97 0.0062

No 1.00

OR,oddsratio;CI,confidenceinterval.

inperipheralbloodlessthan150,000cells/mm3_,andage≥40 years(Table5).

Table6shows theresultsoftheadjustmentofthe vari-ablesfromthe1st(agegroup),3rd(laboratoryvariables)and 4th(etiologicalagent)blocks,showingthatapositive hemo-cultureandaplateletcountlessthan150,000cells/mm3_were

associatedwithdeath.

Discussion

Afteradjustmentbymultivariateanalysis,thevariablesthat remained associatedwithgreater riskof deathinpatients with bacterial meningitis were age ≥40 years, absence of headache, absence of vomiting, altered mental state,

Table4–Adjustedoddsratio,confidenceintervaland p-valueoftheassociationbetweendeathduetobacterial meningitisandage,dyspnea,evidenceofshock, meningealsigns,fever,headache,vomiting,alterations inmentalstate,comaandskinandthemucosa alterationsin294patientsoftheHospitalCorreia Picanc¸obetweenJanuary2000andDecember2004.

OR 95%CI p-Value Dyspnea Yes 3.99 1.49–10.67 0.0059 No 1.00 Evidenceofshock Yes 2.69 0.99–7.27 0.0511 No 1.00 Headache Yes 1.00 No 4.79 1.51–15.20 0.0077 Vomiting Yes 1.00 No 1.93 0.99–3.77 0.0522

Alteredmentalstate

Yes 3.35 1.84–6.12 0.0001

No 1.00

Age

<40yearsold 1.00

≥40yearsold 2.14 1.17–3.92 0.0130 OR,oddsratio;CI,confidenceinterval.

Table5–Adjustedoddsratio,confidenceintervaland p-valueoftheassociationbetweendeathdueto bacterialmeningitisandage,hemocultureresult,liquor cellcount,plateletcountinperipheralblood,and proteinorrhachiain137patientsoftheHospitalCorreia Picanc¸obetweenJanuary2000andDecember2004.

OR 95%CI p-Value

Hemoculture

Positive 2.80 1.16–6.79 0.0223 Negative 1.00

Liquorcellcount

Upto2000cells/mm3 _{2.55 1.08–6.01 0.0327} >2000cells/mm3 _1.00 Platelets <150,000cells/mm3 _{2.65 1.11–6.33 0.0238} ≥150,000cells/mm3 _1.00 Age <40yearsold 1.00 ≥40yearsold 3.67 1.47–9.16 0.0053 OR,oddsratio;CI,confidenceinterval.

occurrenceofdyspnea,evidenceofshock,positive hemocul-ture,andthrombocytopenia.

Age has been associatedwithhigher mortalityinother studieswithadults,althoughthisvariableiscategorized dif-ferently in different studies. Duran et al.7 _{in a review of} 493episodesofbacterialmeningitis,foundhighermortality amongthoseaged≥60years,usingunivariateanalysis.vande Beeketal.8_{inaprospectivestudyof696episodesofbacterial} meningitisinindividualsagedover16,reportedanassociation between age ≥42 years and deathfrom bacterial meningi-tis.Inacase–controlstudyexaminingprognosticfactorsfor adultswithbacterialmeningitisadmittedtoanintensivecare unit, it was foundthat age ≥55 yearswas associatedwith the developmentofsequelae anddeath.9 _Another descrip-tivestudyofpatientswithacutebacterialmeningitisadmitted toanICUfoundanassociationbetweenage≥50years and anunfavorable outcome(death orsequelae),using univari-ate analysis.10 _{Inanother seriesofcasesitwas foundthat} patientsagedover60yearshadalessfavorableprognosis.11,12

Table6–Adjustedoddsratio,confidenceintervaland p-valueoftheassociationbetweendeathdueto bacterialmeningitisandage,hemocultureresult,liquor cellcount,plateletcountinperipheralblood,and presenceofGrampositivediplococcusin73patientsof theHospitalCorreiaPicanc¸obetweenJanuary2000and December2004. OR 95%CI p-Value Hemoculture Positive 2.69 0.91–7.90 0.0727 Negative 1.00 Platelets <150,000cells/mm3 _{2.62 1.23–10.60 0.0191} ≥150,000cells/mm3 _1.00

However,aretrospectivestudywithaseriesof255patients with acute meningicoccal meningitis did not find any age differencebetweensurvivorsandthosepatientswhodied.13 Pedersenetal.14_{examiningaseriesof96casesof} meningi-tiscausedbyStaphylococcusaureus,usingunivariateanalysis, likewisedidnotfindagetobeariskfactorfordeath.Thesame occurredwhenassessing202patientsaged≥16years,withno associationbetweenageanddeathduetobacterialmeningitis aftermultivariateanalysis.6_{Thegreaterriskofdeathamong} elderly patientsmay be related tovarious factors,such as comorbidity,alterationsintheimmuneresponseorgreater likelihoodofdevelopingothercomplicationsassociatedwith thediseaseitselforwithhospitalization.14

Theassociationbetweensexand deathdue tobacterial meningitis was not statistically significant in the present study,incontrast tothe findings ofother authors.6,15 _This maybeduetomethodologicaldifferences.Thepresentstudy differed from others in using multivariate analysis, which minimizestheeffectofconfoundingvariables.

Therewasnostatisticallysignificantassociationbetween thetimeelapseduntilthefirstdoseofantibioticsanddeath frombacterialmeningitisinthissample.However,according toAroninetal.16,delayingcommencementoftreatmentwith antibioticsmay resultinabad prognosis, especiallyinthe caseofpatientswhohaveshownmarkedclinical deteriora-tion.Thisconflictingresultfoundinthepresentstudymay beduetotheinitiationofantimicrobialtreatmentwithinan adequatetimeperiodoreventheprobablelowincidenceof infectionbyresistantbacteria.

Someofthe clinicalfindings strongly suggest a diagno-sisofbacterialmeningitisandaresometimesconsideredthe onlycriteriaforcommencementoftreatment.Thesemaybe the mainfeatures foridentification ofmoreserious cases. Theclinical indicatorsmost frequently described for diag-nosisofbacterialmeningitisare fever,headache,vomiting, neck stiffness and an altered mental state. In a series of adultcases,fever,neckstiffnessandanalteredmentalstate wereconsideredtheclassictrioofsymptomsandtheir occur-rence in44%ofthe casesstudiedwas notassociatedwith prognosis.However,whentaken togetherwithheadache,it can be seen that two of these four signs/symptoms were presentin95%ofpatients.8_{Inaseriesofchildrenand} ado-lescentswhichconsidered theclassictriotobefever,neck stiffness and vomiting, it was found that the absence of thesethreesymptomswasassociatedwithaless favorable prognosis.17_{Thepresentstudydidnotconsiderthese} clini-caldatatogether,butnotedthattheabsenceofvomitingand headachewasassociatedwithagreaterriskofdeath.Itmay bethattheabsenceofthesewarningsignsdelaysdiagnosis ofmeningitisandthetimelycommencementofappropriate treatment.

Thepresentstudyidentifiedastrongassociationbetween analteredmentalstateanddeath.Lindvalletal.18 _founda highmortalityrate(33%)inpatientswithbacterialmeningitis admittedtoICUswhowerecomatoseonadmission.Likewise, Vibhaetal.,19_{inastudycovering380casesofbacterial} menin-gitis,havereported thatalowscoreon theGlasgowComa Scaleonadmissionwasanindependentriskfactorfordeath. Aroninet al.20 _{havesuggestedthat patients with bacterial} meningitisandanalteredmentalstateand/orhypotension

and/orconvulsionsshouldbekeptundercloserobservation inintensivecare.Aftermultivariateanalysis,Luetal.6_found thattheinitiallevelofconsciousness,appropriatetreatment withantibioticsandsepticshockwereindependently asso-ciatedwithmortalityafteradjustmentforother potentially confoundingfactors.

Inthepresentstudy,nostatisticallysignificantassociation wasfoundbetweenfocalneurologicalsignsanddeathdueto bacterialmeningitis,asinsomepreviousstudies.7,15_Likewise, inaseriesofpatientswithpneumococcalmeningitis,no asso-ciationwasfoundbetweenthepresenceoffocalsignsandan adverseoutcome.21

Onepeculiarityofthepresentstudywasthefactthat dys-pnea,takeninisolation,wasassociatedwithalessfavorable prognosis,sinceitwasfoundinthemostseriouscases.This associationhasnotbeenpreviouslyreportedinstudies involv-ingadults.Theoccurrenceofdyspneainthesepatientsmight bearesultoftheinfectionorseveresystemicinflammatory response,metabolicacidosis,orevenpulmonaryinjurybythe same agentinvolvedinmeningitis.All thesesituations are presentincriticalpatients.

Thepresentstudyidentifiedevidenceofshockasanother factorofpoorprognosisinbacterialmeningitis.Other stud-ieshavealsoreportedthisfinding.12,22–24_{Evidence ofshock} couldbearesultofsepsisandseveresystemicinflammatory responseorinfection.

Asforlaboratoryfindingsasprognosticindicators,vande Beeketal.8_{havereportedasix-foldgreaterriskofdeathwhen} theorganismcausingbacterialmeningitishadbeenidentified. Theprobabilityofanunfavorableoutcomewashighestamong patients infectedwithStreptococcuspneumoniaethanamong thosewithmeningococcalmeningitis.Inthisstudy,presence of Gram-positive diplococcus was also foundto be signifi-cantlyassociatedwithdeath,althoughafteradjustmentsfor otherlaboratoryvariables,thisassociationwasremovedfrom thefinalmodel.

Lowglycorrhachiaonadmissionhasbeendescribedby var-iousresearchersasafactorassociatedwithalessfavorable prognosis, beit deathor thedevelopmentofcomplications ofbacterialmeningitis.Curiously,thepresentstudydidnot findthisassociationasMcMillanetal.15_{did,Thismayhave} beenbecausethesamplewastoosmallforinvestigatingthis particularvariable.

In a retrospective analysis using the 3:1 case–control methodology(n=192),Eisenhutetal.25_{observedthatintypes} ofbacterialmeningitisotherthan thosecausedbyNeisseria meningitidisand regardlessoftheduration ofsymptomsup todiagnosis,glycorrhachiawaslowerinpatientswho expe-riencedareductioninauditoryandsensory-neuralcapacity compared tothe controls, the difference beingstatistically significant.

McMillan et al.15 _{found alower liquorcell countand a} greaterproportionofpositivehemoculturesamongpatients whodied.Aliquorcellcountlowerthan1000cells/mm3_,a

pos-itiveculture,andareductioninthenumberofplateletswere associatedwithdeathduetobacterialmeningitis.8_Tsaietal.22 described thrombocytopeniaas apoor prognosticfactor in youngadults.Inourstudythrombocytopeniawasalso associ-atedwithhighermortality.Inseriousinfectiousdiseases,like meningococcaldiseaseandsepsis,thrombocytopeniaitselfis

alreadyasignofpoorprognosis,andmaybeareflectionof disseminatedintravascularcoagulation.26

In a prospective series of cases with individuals aged over16yearsdiagnosedwithpneumococcalmeningitis,the diagnosticfactorsidentifiedwereparalysisofcranialnerves, lowerleukocytecountinliquor,hyperproteinorrhachia,and anelevatederythrosedimentationrateonmultivariate anal-ysis.Glycorrhachia waslikewisenotassociatedwith death duetobacterialmeningitis,27_{asinthepresentstudy.Many} patientsinthisseriesdidnotusecorticoids,againasinthe presentstudy.

Anumberoffactorsdifferentiatethepresentstudyfrom othersthathaveprecededitlikeuseofarandomlyselected controlgroup,asithasnotbeenthecaseinprevious stud-ieswithadults.Therandomselectionofcontrolsminimizes selectionbias.Asthiswasaretrospectivestudy,some infor-mation may have been lost due to incomplete filling of admissionforms,eventhoughthesewerestandardizedforall thecasesadmitted,orbytheabsenceofrecordsofbaseline laboratorytestsresults.Itmaynotbepossibletocompletely avoidinformationbias,but,shouldthisoccur,itisprobable thatitfollowsthesamepatterninbothgroups,since,atthe timeofadmissiontohospital,itisnotknownwhichpatients willeventuallydie,makingthisannon-systematicerror.

Conclusion

Theprognosticindicatorsidentifiedinthepresentstudymay serveasatoolforcliniciansprovidinginitialcareforpatients withbacterialmeningitis.Inthisway,specialattentionshould be given to patients aged over 40 years, presenting with alteredmentalstate,dyspnea,evidenceofshock,and throm-bocytopenia. Clinicians should be careful for not delaying thediagnosisofbacterialmeningitisinpatientswithother clinical signs,even inthe absence of headache and vomi-ting,which could resultinanunfavorable prognosis, since mortality among adultswith bacterial meningitis and the frequency ofneurological damage amongsurvivors isstill high.

Conflict

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interest

Theauthorsdeclarenoconflictofinterest.

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