Pathophysiology AndPathophysiology AndTherapeutics Of MeningitisTherapeutics Of MeningitisRobert J. Konop, Pharm.D.Robert J. Konop, Pharm.D.Manager, Clinical Formulary DevelopmentManager, Clinical Formulary DevelopmentPharmacotherapy, Assessment & PolicyPharmacotherapy, Assessment & PolicyPrime Therapeutics Inc.Prime Therapeutics Inc.ObjectivesObjectives••Identify the most common organisms for Identify the most common organisms for both viral and bacterial meningitisboth viral and bacterial meningitis••Understand the difference between viral Understand the difference between viral and bacterial meningitisand bacterial meningitis••Know the composition of normal and Know the composition of normal and abnormal CSFabnormal CSFObjectivesObjectives••List the risk factors for CNS infectionsList the risk factors for CNS infections••Describe the clinical presentation and Describe the clinical presentation and laboratory results of characteristic laboratory results of characteristic meningitismeningitis••Know both empiric and pathogenKnow both empiric and pathogen--specific specific antibiotic regimens in meningitisantibiotic regimens in meningitis••Understand the recommended prophylactic Understand the recommended prophylactic regimens and their indications for useregimens and their indications for useDefinitionsDefinitions1.1.MeningitisMeningitisInflammation of the meninges; abnormal WBC in CSFInflammation of the meninges; abnormal WBC in CSF2.2.Septic versus Aseptic meningitisSeptic versus Aseptic meningitis3. Encephalitis3. EncephalitisInflammation of the brainInflammation of the brain4. Meningoencephalitis4. MeningoencephalitisInflammation of the brain accompanied by meningitisInflammation of the brain accompanied by meningitisMeningesMeningesDura Mater (pachymeninges)Dura Mater (pachymeninges)Directly beneath and is adherent to the skullDirectly beneath and is adherent to the skullPia MaterPia MaterLies directly over the brain tissueLies directly over the brain tissueArachnoidArachnoidThe middle layer between the dura mater and the pia materThe middle layer between the dura mater and the pia materSubarachnoid SpaceSubarachnoid SpaceBetween the pia mater and the arachnoidBetween the pia mater and the arachnoidAnatomy/Physiology of the CNSAnatomy/Physiology of the CNSCerebrospinal FluidCerebrospinal FluidOriginOriginInfants: 40Infants: 40--60ml60mlChildren: 60Children: 60--100ml100mlAdults: 110Adults: 110--160ml160mlViral Meningitis1.1.IncidenceIncidence2.2.Clinical presentationClinical presentationViral MeningitisPathogensPathogensA) Enteroviruses A) Enteroviruses --85%85%B) Mumps VirusB) Mumps Virus--55--10%10%C) Lymphocytic choriomeningitis virusC) Lymphocytic choriomeningitis virusD) Herpes Simplex VirusD) Herpes Simplex VirusHSVHSV--22Viral MeningitisViral MeningitisOther PathogensOther Pathogens10%: adenoviruses, poliovirus, 10%: adenoviruses, poliovirus, rhinoviruses, influenza A&B, rotavirus, rhinoviruses, influenza A&B, rotavirus, CMV, coronavirus, VaricellaCMV, coronavirus, Varicella--Zoster virus, Zoster virus, EpsteinEpstein--Barr virusBarr virusEnterovirusesEnteroviruses••Group A Group A coxsackiecoxsackie23 serotypes23 serotypes14% of the cases14% of the cases••Group B Group B coxsackiecoxsackie6 serotypes6 serotypes12% of the cases12% of the cases••Echoviruses Echoviruses 31 serotypes31 serotypes75 %of the cases75 %of the casesEnterovirusesEnterovirusesRespiratoryRespiratoryCommon coldCommon coldPharyngitisPharyngitisPneumoniaPneumoniaGastrointestinalGastrointestinalVomitingVomitingDiarrheaDiarrheaAbdominal painAbdominal painEyeEyeAcute hemorrhagic Acute hemorrhagic conjunctivitisconjunctivitisHeartHeartMyopericarditisMyopericarditisSkinSkinExanthemExanthemNeurologicNeurologicMeningitisMeningitisEnterovirusesEnterovirusesMost commonMost common--8585--95% of the cases95% of the casesSeasonal Seasonal Late summer to fallLate summer to fallFecal to oral routeFecal to oral routeEffects all age groupsEffects all age groupsTypically < 1 year oldTypically < 1 year oldMumps VirusMumps VirusParotitisParotitisMeningitis occurs in 10Meningitis occurs in 10--30% of the cases30% of the casesEncephalitis is rareEncephalitis is rareSecond most common viral meningitis Second most common viral meningitis 10 to 20%10 to 20%Peak late winter to early springPeak late winter to early springHumans only natural hostsHumans only natural hostsLymphocytic Choriomeningitis Lymphocytic Choriomeningitis VirusVirusNonspecific prodromeNonspecific prodromeMeningitisMeningitisChronic infection of the house mouseChronic infection of the house mouseInfected rodentInfected rodentCommon in the winterCommon in the winterHerpes Simplex VirusHerpes Simplex VirusHSVHSV--2 2 Neonates during birthNeonates during birthSexually active adultsSexually active adultsTreatment Viral MeningitisTreatment Viral MeningitisSUPPORTIVE CARESUPPORTIVE CAREAntibiotics until bacterial meningitis is ruled Antibiotics until bacterial meningitis is ruled outoutSeizure controlSeizure controlSymptom controlSymptom controlAcyclovirAcyclovirBacterial MeningitisIncidence: Incidence: 0.20.2--2.9 cases/100,000/year (1986)2.9 cases/100,000/year (1986)0.20.2--1.1 cases/100,000/year (1995)1.1 cases/100,000/year (1995)Very Young and Very OldVery Young and Very OldDramatic decrease in Dramatic decrease in H. fluH. fluMortality Mortality SequelaeSequelaeIncidence and Mortality RateIncidence and Mortality RateOrganism % of Total Cases Annual Incidence Fatality Rate (%)19861995 1986 1995 1986 1995H. flu 45 7 2.9 0.2 3 6S. pneumo 18 47 1.1 1.1 19 21N. menin. 14 25 0.9 0.6 13 3GBS 5.7 12 0.4 0.3 12 7L. mono 3.2 8 0.2 0.2 22 15other 15 1.0 18* Bacterial Meningitis in the United States in 1995,NJM, October* Bacterial Meningitis in the United States in 1995,NJM, October2, 1997, 337 (14) 9702, 1997, 337 (14) 970--976.976.Bacterial MeningitisMost common organisms by population:Most common organisms by population:00--4 weeks: 4 weeks: GBS, E. coli, L. monocytogenes, other GBS, E. coli, L. monocytogenes, other gram negativesgram negatives44--12 weeks: 12 weeks: GBS, E. coli, L. monocytogenes, H. GBS, E. coli, L. monocytogenes, H. influenzae, S. pneumoniaeinfluenzae, S. pneumoniae3mo3mo--4 4 yrsyrs: : N. meningitidis, S. pneumoniae , H. N. meningitidis, S. pneumoniae , H. influenzaeinfluenzae55--9 9 yrsyrs::N. meningitidis, S. pneumoniae/H. N. meningitidis, S. pneumoniae/H. influenzaeinfluenzaeBacterial