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8/12/2019 Meningitis pathophysiology.pdf
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Pathophysiology AndPathophysiology AndTherapeutics Of MeningitisTherapeutics Of Meningitis
Robert J. Konop, Pharm.D.Robert J. Konop, Pharm.D.
Manager, Clinical Formulary DevelopmentManager, Clinical Formulary DevelopmentPharmacotherapy, Assessment & PolicyPharmacotherapy, Assessment & Policy
Prime Therapeutics Inc.Prime Therapeutics Inc.
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ObjectivesObjectives
•• Identify the most common organisms forIdentify the most common organisms forboth viral and bacterial meningitisboth viral and bacterial meningitis
•• Understand the difference between viralUnderstand the difference between viraland bacterial meningitisand bacterial meningitis
•• Know the composition of normal andKnow the composition of normal andabnormal CSFabnormal CSF
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ObjectivesObjectives
•• List the risk factors for CNS infectionsList the risk factors for CNS infections•• Describe the clinical presentation andDescribe the clinical presentation and
laboratory results of characteristiclaboratory results of characteristicmeningitismeningitis
•• Know both empiric and pathogenKnow both empiric and pathogen --specificspecific
antibiotic regimens in meningitisantibiotic regimens in meningitis•• Understand the recommended prophylacticUnderstand the recommended prophylactic
regimens and their indications for useregimens and their indications for use
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DefinitionsDefinitions
1.1. MeningitisMeningitis
Inflammation of the meninges; abnormal WBC in CSFInflammation of the meninges; abnormal WBC in CSF2.2. Septic versus Aseptic meningitisSeptic versus Aseptic meningitis
3. Encephalitis3. EncephalitisInflammation of the brainInflammation of the brain
4. Meningoencephalitis4. MeningoencephalitisInflammation of the brain accompanied by meningitisInflammation of the brain accompanied by meningitis
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MeningesMeningesDura Mater (pachymeninges)Dura Mater (pachymeninges)
Directly beneath and is adherent to the skullDirectly beneath and is adherent to the skull
Pia MaterPia MaterLies directly over the brain tissueLies directly over the brain tissue
ArachnoidArachnoid
The middle layer between the dura mater and the pia materThe middle layer between the dura mater and the pia materSubarachnoid SpaceSubarachnoid Space
Between the pia mater and the arachnoidBetween the pia mater and the arachnoid
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Anatomy/Physiology of the CNSAnatomy/Physiology of the CNS
Cerebrospinal FluidCerebrospinal FluidOriginOrigin
Infants: 40Infants: 40 --60ml60mlChildren: 60Children: 60 --100ml100mlAdults: 110Adults: 110 --160ml160ml
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Viral Meningitis
1.1. IncidenceIncidence2.2. Clinical presentationClinical presentation
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Viral Meningitis
PathogensPathogensA) EnterovirusesA) Enteroviruses -- 85%85%
B) Mumps VirusB) Mumps Virus -- 55--10%10%C) Lymphocytic choriomeningitis virusC) Lymphocytic choriomeningitis virusD) Herpes Simplex VirusD) Herpes Simplex Virus
HSVHSV --22
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EnterovirusesEnteroviruses•• Group AGroup A coxsackiecoxsackie
23 serotypes23 serotypes
14% of the cases14% of the cases
•• Group BGroup B coxsackiecoxsackie6 serotypes6 serotypes
12% of the cases12% of the cases•• EchovirusesEchoviruses
31 serotypes31 serotypes75 %of the cases75 %of the cases
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EnterovirusesEnteroviruses
RespiratoryRespiratoryCommon coldCommon coldPharyngitisPharyngitis
PneumoniaPneumonia
GastrointestinalGastrointestinal
VomitingVomitingDiarrheaDiarrheaAbdominal painAbdominal pain
EyeEyeAcute hemorrhagicAcute hemorrhagicconjunctivitisconjunctivitis
HeartHeartMyopericarditisMyopericarditis
SkinSkinExanthemExanthem
NeurologicNeurologic
MeningitisMeningitis
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EnterovirusesEnteroviruses
Most commonMost common -- 8585 --95% of the cases95% of the casesSeasonalSeasonal
Late summer to fallLate summer to fallFecal to oral routeFecal to oral route
Effects all age groupsEffects all age groupsTypically < 1 year oldTypically < 1 year old
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Mumps VirusMumps Virus
ParotitisParotitisMeningitis occurs in 10Meningitis occurs in 10 --30% of the cases30% of the cases
Encephalitis is rareEncephalitis is rareSecond most common viral meningitisSecond most common viral meningitis
10 to 20%10 to 20%Peak late winter to early springPeak late winter to early spring
Humans only natural hostsHumans only natural hosts
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Herpes Simplex VirusHerpes Simplex Virus
HSVHSV --22Neonates during birthNeonates during birth
Sexually active adultsSexually active adults
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Treatment Viral MeningitisTreatment Viral Meningitis
SUPPORTIVE CARESUPPORTIVE CAREAntibiotics until bacterial meningitis is ruledAntibiotics until bacterial meningitis is ruled
outoutSeizure controlSeizure control
Symptom controlSymptom controlAcyclovirAcyclovir
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Bacterial Meningitis
Incidence: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 Old
Dramatic decrease inDramatic decrease in H . flu H . f lu MortalityMortality
SequelaeSequelae
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Incidence and Mortality RateIncidence and Mortality Rate
Organism % of Total Cases Annual Incidence Fatality Rate (%)
1986 1995 1986 1995 1986 1995 H. flu 45 7 2.9 0.2 3 6S. pneumo 18 47 1.1 1.1 19 21
N. menin. 14 25 0.9 0.6 13 3GBS 5.7 12 0.4 0.3 12 7
L. 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, October 2, 1997, 337 (14) 9702, 1997, 337 (14) 970 --976.976.
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Bacterial Meningitis
Most common organisms by population:Most common organisms by population:00--4 weeks:4 weeks: GBS, E. coli, L. monocytogenes, otherGBS, E. coli, L. monocytogenes, othergram negativesgram negatives
44--12 weeks:12 weeks: GBS, E. coli, L. monocytogenes, H.GBS, E. coli, L. monocytogenes, H.influenzae, S. pneumoniaeinfluenzae, S. pneumoniae
3mo3mo --44 yrsyrs :: N. meningitidis, S. pneumoniae , H.N. meningitidis, S. pneumoniae , H.influenzaeinfluenzae
55--99 yrsyrs :: N. meningitidis, S. pneumoniae/H.N. meningitidis, S. pneumoniae/H.influenzaeinfluenzae
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Bacterial Meningitis
99--18 years:18 years: N. meningitidis, S. pneumoniae, H.N. meningitidis, S. pneumoniae, H.influenzaeinfluenzae
1818 --60 years:60 years: S. pneumoniae, N. meningitidisS. pneumoniae, N. meningitidis
> 60 years:> 60 years: S. pneumoniae, N. meningitidis, L.S. pneumoniae, N. meningitidis, L.monocytogenes, other gram negativesmonocytogenes, other gram negativesNeurosurgNeurosurg :: S. aureus, S. epidermidis, gramS. aureus, S. epidermidis, gram
negativesnegativesClosed Head:Closed Head: S. pneumoniae, H. influenzaeS. pneumoniae, H. influenzaeOpen Head:Open Head: S. aureus, gram negativesS. aureus, gram negatives
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Pathogenesis
Bacterial InvasionBacterial InvasionParameningeal focus/colonizationParameningeal focus/colonization
Adhesions, binding receptors, piliAdhesions, binding receptors, piliHematogenous spreadHematogenous spreadParameningeal seedingParameningeal seedingColonization of hardwareColonization of hardwareDirect inoculationDirect inoculation
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Pathogenesis
Bacterial elementsBacterial elements -- inflammatory responseinflammatory response
Endotoxin/LipopolysaccharideEndotoxin/LipopolysaccharidePeptidoglycanPeptidoglycanLipoteichoic acidLipoteichoic acid
Release of inflammatory mediators byRelease of inflammatory mediators byastrocytes, microglial/endothelial cellsastrocytes, microglial/endothelial cells
TNF alphaTNF alphaILIL --11
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Pathophysiology
•• Reduced cerebral perfusion secondary to edemaReduced cerebral perfusion secondary to edema•• Cerebral ischemia secondary to thrombosisCerebral ischemia secondary to thrombosis•• VasculitisVasculitis•• Alteration of cerebral blood flowAlteration of cerebral blood flow•• Direct neuronal cell damage secondary toDirect neuronal cell damage secondary to
bacterial elements, activated leukocytes,bacterial elements, activated leukocytes,cytokines, and other inflammatory mediatorscytokines, and other inflammatory mediators
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Pathophysiology
Increased intracranial pressureIncreased intracranial pressureVasogenic edemaVasogenic edema ---- cytokines act oncytokines act onendothelial cells to damage the BBBendothelial cells to damage the BBB
Cytotoxic edemaCytotoxic edema ---- direct damage to cells allowingdirect damage to cells allowingbuildup of intracellular waterbuildup of intracellular water
Interstitial edemaInterstitial edema ---- obstruction of CSF flow and removalobstruction of CSF flow and removal
Brain herniationBrain herniation
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Risk Factors
1. Respiratory tract infection1. Respiratory tract infection2. Otitis media2. Otitis media3. Mastoiditis3. Mastoiditis4. Head trauma4. Head trauma5. Splenectomy5. Splenectomy6. Sickle cell disease6. Sickle cell disease7. Immunosuppressive therapy7. Immunosuppressive therapy8. Immunocompromised host8. Immunocompromised host9. Alcoholic patients9. Alcoholic patients10.Patients with hardware (shunts, etc.)10.Patients with hardware (shunts, etc.)
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Clinical Presentation
Physical signs/symptoms:Physical signs/symptoms:FeverFeverHeadacheHeadachePhotophobiaPhotophobiaNausea/vomitingNausea/vomitingMental status changesMental status changesStiff neck/backStiff neck/backPositive Brudzinski's signPositive Brudzinski's sign
Positive Kernig's signPositive Kernig's signDeafnessDeafnessSeizuresSeizures
Focal neurologic deficitFocal neurologic deficitHydrocephalusHydrocephalus
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Laboratory StudiesLaboratory Studies
Lumbar PunctureLumbar PunctureCSF cell countCSF cell countCSF chemistriesCSF chemistries
CSF gram stainCSF gram stainCSF cultureCSF culture
Blood CultureBlood CultureSputum Culture/Urine CultureSputum Culture/Urine Culture
Peripheral CBC and ElectrolytesPeripheral CBC and Electrolytes
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Clinical Presentation and Diagnosis
Abnormal CSF-findings by type of meningitis
ProteinProtein GlucoseGlucoseTypeType WBC(mm2)WBC(mm2) Diff Diff . (%). (%) (mg/L)(mg/L) (mg/ (mg/ dLdL ))
NMLNML < 10< 10 >50 lymphs>50 lymphs < 50< 50 3030--7070BactBact .. 400400 --100,000100,000 >90>90 PMN'sPMN's 8080--500500 < 35< 35ViralViral 55--500500 >50 lymphs>50 lymphs 3030--150150 NML/lowNML/lowFungalFungal 4040--400400 >50 lymphs>50 lymphs 4040--150150 NML/lowNML/lowT.B.T.B. 100100 --1,000 >50 lymphs1,000 >50 lymphs 4040--400400 NML/lowNML/low
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Clinical Presentation and Diagnosis
Bacterial antigen detection testsBacterial antigen detection tests69% accurate when positive cultures69% accurate when positive culturesUseful when antibiotics were given before the CSF culture wasUseful when antibiotics were given before the CSF culture was
takentaken
May react to other organismsMay react to other organisms
Other testsOther tests
Counterimmunoelectrophoresis (CIE) and latex fixationCounterimmunoelectrophoresis (CIE) and latex fixation(encapsulated organisms)(encapsulated organisms)Limulus lysate assay (gramLimulus lysate assay (gram --negative endotoxin)negative endotoxin)
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Common Bacterial Organisms
Haemophilus influenzaeHaemophilus influenzaePeak incidence: 6Peak incidence: 6 --12 months of age: declines after 2412 months of age: declines after 24
months of agemonths of age
Deafness = 6%Deafness = 6%Coma/seizures commonComa/seizures commonClose contacts are 200Close contacts are 200 --1000 x risk1000 x risk
Resistance pattern is growing throughout the U.S.Resistance pattern is growing throughout the U.S.Dramatic decrease in cases since 1990Dramatic decrease in cases since 1990
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Common Bacterial Organisms
Neisseria meningitidisNeisseria meningitidisUsually occurs winter/springUsually occurs winter/springFive main serogroups: A, B, C, Y, and WFive main serogroups: A, B, C, Y, and W --135 (A135 (A
and Cand C ----epidemics; Bepidemics; B ---- individual cases; Yindividual cases; Y ----pneumonia)pneumonia)
May present with a characteristic immuneMay present with a characteristic immune
reaction 10reaction 10 --14 days after infection (fever,14 days after infection (fever,arthritis, pericarditis). Rx with NSAID'sarthritis, pericarditis). Rx with NSAID's
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Common Bacterial Organisms
Streptococcus pneumoniaeStreptococcus pneumoniaeGram positive diplococciGram positive diplococci"Pneumococcus""Pneumococcus"Deafness = 31%Deafness = 31%Coma and seizures are more commonComa and seizures are more commonResistance is becoming a problemResistance is becoming a problem
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Common Bacterial Organisms
Listeria monocytogenesListeria monocytogenesPeak incidence in summer/early fallPeak incidence in summer/early fallGram positive rod (coccobacilli)Gram positive rod (coccobacilli)
Most common ages:Most common ages:Very young (< 3 months)Very young (< 3 months)
Older (> 60 years)Older (> 60 years)Susceptible to ampicillinSusceptible to ampicillin
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Antibiotic TherapyAntibiotic TherapyFactors Enhancing Antimicrobial PenetrationFactors Enhancing Antimicrobial Penetration
Small MWSmall MWUnionized at physiologic pHUnionized at physiologic pH
Lipid solubleLipid solubleLarge Free FractionLarge Free Fraction
Factors Reduce Antibiotic ActivityFactors Reduce Antibiotic ActivityLow pH of fluidLow pH of fluidHigh concentration of protein in fluidHigh concentration of protein in fluid
High temperature of fluidHigh temperature of fluid
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Needs InflammationNeeds InflammationPenicillinPenicillinAmpicillinAmpicillinCarbenicillinCarbenicillinCiprofloxacinCiprofloxacinTicarcillin (clavulanate)Ticarcillin (clavulanate)
QuinolonesQuinolonesPiperacillin (tazobactam)Piperacillin (tazobactam)
CefuroximeCefuroximeCeftizoximeCeftizoximeCeftazidimeCeftazidimeMezlocillinMezlocillinImipenemImipenemAztreonamAztreonamVancomycinVancomycin
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Questionable concentrationsQuestionable concentrations
AminoglycosidesAminoglycosidesGentamicinGentamicinStreptomycinStreptomycinAmikacinAmikacinKanamycinKanamycin
TobramycinTobramycinPolymyxinPolymyxin
T
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TreatmentTreatment
Empiric choice of antibiotic:Empiric choice of antibiotic:00--4 weeks: ampicillin/cefotaxime or4 weeks: ampicillin/cefotaxime or
ampicillin/gentamicinampicillin/gentamicin44--12 weeks: ampicillin/cefotaxime12 weeks: ampicillin/cefotaxime3mo3mo --4 years: vancomycin/ceftriaxone or4 years: vancomycin/ceftriaxone or
cefotaximecefotaxime
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TreatmentTreatment
55
--9 years: vancomycin/ceftriaxone or cefotaxime9 years: vancomycin/ceftriaxone or cefotaxime
99--18 years: vancomycin/ceftriaxone or18 years: vancomycin/ceftriaxone orcefotaximecefotaxime
1818--60 years: vancomycin/ceftriaxone or60 years: vancomycin/ceftriaxone orcefotaximecefotaxime
> 60 years: ampicillin/ceftriaxone or> 60 years: ampicillin/ceftriaxone orampicillin/cefotaximeampicillin/cefotaxime
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Treatment
Definitive Choice of AntibioticDefinitive Choice of Antibiotic
H. influenzae:H. influenzae:ßß --lactamase (lactamase ( --) ampicillin) ampicillin
ßß --lactamase (+) cefotaxime orlactamase (+) cefotaxime orceftriaxoneceftriaxone
N. meningitidis: penicillin G or ampicillinN. meningitidis: penicillin G or ampicillinL. monocytogenes: ampicillinL. monocytogenes: ampicillin
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TreatmentTreatment
Enterobacteriaceae: cefotaximeEnterobacteriaceae: cefotaximeP. aeruginosa: ceftazidime/tobramycinP. aeruginosa: ceftazidime/tobramycinS. aureus:S. aureus:
MSSA: nafcillinMSSA: nafcillinMRSA: vancomycinMRSA: vancomycin
S. epidermidis: vancomycin/rifampinS. epidermidis: vancomycin/rifampin
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h
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DexamethasoneDexamethasone
•• Blocks TNF alpha and ILBlocks TNF alpha and IL --1 release1 release
•• Decreases ICP, CNS edema, fever duration, andDecreases ICP, CNS edema, fever duration, andCSF lactate and protein levelsCSF lactate and protein levels
•• Increased CSF glucose levelIncreased CSF glucose level•• Decreases neurologic complications (e.g. ataxia,Decreases neurologic complications (e.g. ataxia,
seizures, focal deficit) and hearing loss byseizures, focal deficit) and hearing loss byapproximately 50%approximately 50%
Children withChildren with H . inf luenzae H . inf luenzae typetype BB
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DexamethasoneDexamethasone
Indication: > 6 weeks of age, and clinical CSFIndication: > 6 weeks of age, and clinical CSFfindings of H. flu meningitisfindings of H. flu meningitis
0.15 mg/kg/dose IV Q6H x 4 days0.15 mg/kg/dose IV Q6H x 4 daysFirst dose given with/before antibioticsFirst dose given with/before antibiotics
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Dexamethasone/Antibiotic InteractionSignificant reduction of vancomycin/BBBSignificant reduction of vancomycin/BBB
penetrationpenetrationSomewhat lower CSF concentrations ofSomewhat lower CSF concentrations of
ceftriaxoneceftriaxone
D h /A ibi iD th /A tibi ti
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Dexamethasone/AntibioticDexamethasone/Antibiotic
InteractionInteraction
Paris et.al.Paris et.al.S. pneumoniae susceptibility in areaS. pneumoniae susceptibility in areaIf resistant is a probability then use ceftriaxoneIf resistant is a probability then use ceftriaxone
or cefotaxime andor cefotaxime and vancomycinvancomycin withwithdexamethasonedexamethasone
Found vancomycin significant for killingFound vancomycin significant for killingbacteria (4 times MIC )bacteria (4 times MIC )
Treat for minimum of 10 daysTreat for minimum of 10 days
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PreventionVaccinesVaccines
a.a. N. meningitidisN. meningitidiscovers serotypes A, C, Y, Wcovers serotypes A, C, Y, W --135135
type B causes 50% of casestype B causes 50% of casescompliment deficiency, aspleniacompliment deficiency, asplenia
b.b. H. influenzaeH. influenzaeall children at 2 monthsall children at 2 months
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PreventionPrevention
Vaccine (cont.)Vaccine (cont.)
c.c. S. pneumoniaeS. pneumoniae1) Capsular polysaccharide vaccine1) Capsular polysaccharide vaccineCovers 23 serotypes (88% of cases)Covers 23 serotypes (88% of cases)
patients with chronic disease (e.g. CHF, COPD,patients with chronic disease (e.g. CHF, COPD,diabetes, alcoholism, cirrhosis, > 65diabetes, alcoholism, cirrhosis, > 65 yrsyrs , asplenia,, asplenia,sickle cell disease, lymphoma, chronic renal failure,sickle cell disease, lymphoma, chronic renal failure,
HIV, transplant patients)HIV, transplant patients)2) Heptavalent Conjugate Vaccine2) Heptavalent Conjugate VaccineCovers 7 serotypesCovers 7 serotypes
Standard immunizationStandard immunization
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ProphylaxisProphylaxis
A.A. Neisser ia meningitidis Neisser ia meningitidis Close contacts of index caseClose contacts of index caseIndex caseIndex case
RifampinRifampin
B. Haemophilus influenzae type BB. Haemophilus influenzae type B
Close contacts of index caseClose contacts of index caseIf a contact is 4 yo and not immunizedIf a contact is 4 yo and not immunized
C. Streptococcus PneumoniaeC. Streptococcus PneumoniaeNot recommendedNot recommended
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Case PresentationCase Presentation
EB was a 8 mo femaleEB was a 8 mo female
– – 2 days PTA pt became “ill” with “cold”2 days PTA pt became “ill” with “cold” Sx’sSx’s – – 1 day PTA pt went into the clinic and was Dx1 day PTA pt went into the clinic and was Dx
with a ROM;with a ROM; Rx’dRx’d with Amoxicillin andwith Amoxicillin andAPAP prnAPAP prn
– – Morning of admission dad was holding herMorning of admission dad was holding herand she started cough. EB started to shakeand she started cough. EB started to shakeand then went into a GTCand then went into a GTC SzSz
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Case PresentationCase Presentation
EB was brought into the ER with GTCEB was brought into the ER with GTC SzSz – – SzSz was stopped with multiple doses ofwas stopped with multiple doses ofmidazolam, diazepam, and phenobarbitalmidazolam, diazepam, and phenobarbital
•• Lasted 30 minutesLasted 30 minutes
– – Sx’sSx’s : Cough, anorexia, rhinorrhea, fussy, temp: Cough, anorexia, rhinorrhea, fussy, temp
(102 F)(102 F) – – Labs: CBC, ABG, CSF,Labs: CBC, ABG, CSF, LytesLytes , UA/UC, UA/UC
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Clinical Presentation
Physical signs/symptoms:Physical signs/symptoms:FeverFeverHeadacheHeadacheNausea/vomitingNausea/vomitingMental status changesMental status changes
Stiff neck/backStiff neck/backPositive Brudzinski's signPositive Brudzinski's signPositive Kernig's signPositive Kernig's sign
DeafnessDeafnessSeizuresSeizuresFocal neurologic deficitFocal neurologic deficit
HydrocephalusHydrocephalusAnorexiaAnorexia
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Case Presentation: LabsCase Presentation: LabsCSFCSF
WBC: 217WBC: 217RBC: 31RBC: 31
Glu: 57Glu: 57Protein: 118Protein: 118Gram stain (+) for GPCGram stain (+) for GPCAG + for S. pneumoAG + for S. pneumoCxCx pendingpending
CBCCBCWBC: 14.5WBC: 14.5HGB: 8.2HGB: 8.2
PLTsPLTs : 244: 244LytesLytes : NL: NL
Glu: 244Glu: 244
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Clinical Presentation and Diagnosis
Abnormal CSF-findings by type of meningitis
ProteinProtein GlucoseGlucoseTypeType WBC(mm2)WBC(mm2) Diff Diff . (%). (%) (mg/L)(mg/L) (mg/ (mg/ dLdL ))
NMLNML < 10< 10 >50 lymphs>50 lymphs < 50< 50 3030--7070BactBact .. 400400 --100,000100,000 >90>90 PMN'sPMN's 8080--500500 < 35< 35ViralViral 55--500500 >50 lymphs>50 lymphs 3030--150150 NML/lowNML/lowFungalFungal 4040--400400 >50 lymphs>50 lymphs 4040--150150 NML/lowNML/lowT.B.T.B. 100100 --1,000 >50 lymphs1,000 >50 lymphs 4040--400400 NML/lowNML/low
8/12/2019 Meningitis pathophysiology.pdf
http://slidepdf.com/reader/full/meningitis-pathophysiologypdf 56/59
8/12/2019 Meningitis pathophysiology.pdf
http://slidepdf.com/reader/full/meningitis-pathophysiologypdf 57/59
8/12/2019 Meningitis pathophysiology.pdf
http://slidepdf.com/reader/full/meningitis-pathophysiologypdf 58/59
Case StudyCase Study
Vancomycin was stoppedVancomycin was stoppedEB continued to improveEB continued to improve
Never had another seizure to dateNever had another seizure to dateCT did reveal a small bilateral subdural effusionCT did reveal a small bilateral subdural effusionFollow up CT: present but decreasing in sizeFollow up CT: present but decreasing in size
No neurological deficits were noted to dateNo neurological deficits were noted to datePt got a total of 14 days of antibioticsPt got a total of 14 days of antibioticsRepeat LP was WNLRepeat LP was WNL
8/12/2019 Meningitis pathophysiology.pdf
http://slidepdf.com/reader/full/meningitis-pathophysiologypdf 59/59
CNS-macrophage
Decreased Cerebral
CSF lactate
Bacterial Components
Endothelial Cells
I L-1
PGE 2
Increased BBBPermeability
Vasogenic Edema
IncreasedCSF protein
Endothelium-leukocyte TNF and IL-1
PAF
Thrombosis
Blood FlowIncreased
ICP
OxygenDepletion
Decreased
CSF glucose
Increased
CSF pleocytosis
CSF outflow
resistanceInterstitial
Edema
CytotoxicEdema