MeningitisMeningitis

Hai Ho, MDHai Ho, MD

Department of Family PracticeDepartment of Family Practice

Riverside County Regional Medical CenterRiverside County Regional Medical Center

Easy ConceptEasy Concept

Treat empirically with medications that Treat empirically with medications that kill the organisms involvedkill the organisms involved

Therefore, if you know the organisms Therefore, if you know the organisms involved, you could choose the right involved, you could choose the right

medicationsmedications

Organisms involvedOrganisms involved

BacteriaBacteria VirusesViruses FungiFungi ParasitesParasites

The most common organisms The most common organisms involved in meningitis?involved in meningitis?

Depend on the age and the clinical situations Depend on the age and the clinical situations

Neonates to 2 months of ageNeonates to 2 months of age4,74,7??•VirusesViruses

•Herpes SimplexHerpes Simplex

•EnterovirusesEnteroviruses

•Cytomegalovirus (CMV)Cytomegalovirus (CMV)

•BacteriaBacteria

•Group B StreptococcusGroup B Streptococcus

•Escherichia Coli Escherichia Coli

•Listeria monocytogenesListeria monocytogenes

Listeria monocytogenesListeria monocytogenes4,54,5

Risk groupsRisk groups– Extreme ageExtreme age– Impaired immunityImpaired immunity– PregnancyPregnancy

PresentationsPresentations– Subacute Subacute – Ataxia and myoclonic seizure – small abscesses in Ataxia and myoclonic seizure – small abscesses in

cerebellum and brainstemcerebellum and brainstem Treatment – aminoglycoside (poor CSF Treatment – aminoglycoside (poor CSF

penetration) synergistic with ampicillinpenetration) synergistic with ampicillin

Antibiotics for infants 0 to 2 Antibiotics for infants 0 to 2 months of age?months of age?

Third-generation cephalosporins Third-generation cephalosporins (cefotaxime or ceftriaxone)(cefotaxime or ceftriaxone)

AmpicillinAmpicillin

Should corticosteroid be used in Should corticosteroid be used in meningitismeningitis44??

ControversialControversial Reduce deafness in children with H. Reduce deafness in children with H.

influenzainfluenza Give before or at the time of initiation of Give before or at the time of initiation of

antibiotics x 2 to 4 daysantibiotics x 2 to 4 days Lack evidences of beneficial effects in Lack evidences of beneficial effects in

adultsadults

Greater than 3 months to 60 years of age?Greater than 3 months to 60 years of age?

Streptococcus pneumoniaeStreptococcus pneumoniae

Neisseria meningitidisNeisseria meningitidis

Antibiotics for patients greater Antibiotics for patients greater than 2 months to 60 years of age?than 2 months to 60 years of age?

Third-generation cephalosporins Third-generation cephalosporins (cefotaxime or ceftriaxone)(cefotaxime or ceftriaxone)

VancomycinVancomycin

VancomycinVancomycin4,54,5

Not to use as monotherapy because of its Not to use as monotherapy because of its poor CSF penetrationpoor CSF penetration

Added to cover resistant pneumococciAdded to cover resistant pneumococci If corticosteroid is used, need to add If corticosteroid is used, need to add

rifampin because corticosteroid decrease rifampin because corticosteroid decrease CSF penetration of vancomycinCSF penetration of vancomycin

Greater 60 years of ageGreater 60 years of age

Streptococcus pneumoniaeStreptococcus pneumoniae

Neisseria meningitidisNeisseria meningitidis

Listeria monocytogenesListeria monocytogenes

Antibiotics for patients greater Antibiotics for patients greater than 60 years of age?than 60 years of age?

Third-generation cephalosporins Third-generation cephalosporins (cefotaxime or ceftriaxone)(cefotaxime or ceftriaxone)

VancomycinVancomycin

AmpicillinAmpicillin

Nosocomial meningitisNosocomial meningitis

Most cases from neurosurgical procedures Most cases from neurosurgical procedures or CSF shunt placementor CSF shunt placement

Common bacteriaCommon bacteria– Gram negative rods: Gram negative rods: E. Coli, Klebsiella, E. Coli, Klebsiella,

pseudomonas, Acinotobacter, Enterobacter, pseudomonas, Acinotobacter, Enterobacter, SerratiaSerratia species species

– Staphylococci: Staphylococci: Staphylococcus aureus, Staphylococcus aureus, staphylococcus epidermidisstaphylococcus epidermidis

Antibiotics for nosocomial Antibiotics for nosocomial meningitismeningitis4,54,5

Ceftazidime or cefepime and VancomycinCeftazidime or cefepime and Vancomycin ImipenemImipenem

– Resistant Gram negative rodsResistant Gram negative rods– Associated with seizureAssociated with seizure

AminoglycosideAminoglycoside– Indicated in patients with poor response to IV Indicated in patients with poor response to IV

antibioticsantibiotics– Intrathecal Intrathecal

Aseptic meningitisAseptic meningitis88

CSF analysis not consistent with CSF analysis not consistent with bacterial infectionbacterial infection

Infectious aseptic meningitisInfectious aseptic meningitis9,109,10??

VirusesViruses Bacteria – Bacteria – mycobacterium tuberculosis, mycobacterium tuberculosis,

treponema pallidum, borerrelia burgdorferitreponema pallidum, borerrelia burgdorferi Fungi – Fungi – cryptococcus neoforman, coccidioides cryptococcus neoforman, coccidioides

immitis, histoplamaimmitis, histoplama capsulatumcapsulatum

ParasitesParasites

Non-infectious aseptic Non-infectious aseptic meningitis?meningitis?

DrugsDrugs– PenicillinPenicillin– Trimethoprim/sulfamethoxazoleTrimethoprim/sulfamethoxazole– NSAIDsNSAIDs– CarbamezepineCarbamezepine

GranulomaGranuloma NeoplasmNeoplasm IdiopathicIdiopathic

Treatment for aseptic meningitis?Treatment for aseptic meningitis? Viral causesViral causes

– Mainly supportive careMainly supportive care– EnterovirusEnterovirus

» Most common Most common » Diverse group of RNA viruses including coxsackieviruses, Diverse group of RNA viruses including coxsackieviruses,

echoviruses, and poliovirusesechoviruses, and polioviruses

– HIV – anti-HIV meds, but most resolve spontaneouslyHIV – anti-HIV meds, but most resolve spontaneously

– Herpes simplex – acyclovirHerpes simplex – acyclovir– CMV – ganciclovir (not approved for CNS)CMV – ganciclovir (not approved for CNS)

Syphilis – Penicillin GSyphilis – Penicillin G Fungi – amphotericinFungi – amphotericin Tuberculosis – Isoniazid, pyazinamide, rifampin, Tuberculosis – Isoniazid, pyazinamide, rifampin,

steptomycicin, ethambutolsteptomycicin, ethambutol

Clinical presentations in children?Clinical presentations in children?

NonspecificNonspecific

General toxic appearanceFeverDecreased PO intakeDecreased alertness

Clinical presentations in adults?Clinical presentations in adults?

Classic triadClassic triad– Fever, neck stiffness, and altered mental statusFever, neck stiffness, and altered mental status

– Fever is the most sensitive, followed by neck stiffnessFever is the most sensitive, followed by neck stiffness

– Mental statusMental status» High sensitivity – normal rules out meningitis in low-risk High sensitivity – normal rules out meningitis in low-risk

patientspatients

» More common in bacterial than viral meningitisMore common in bacterial than viral meningitis

Kernig and Brudzinski - Kernig and Brudzinski - Low sensitivity but high specificityLow sensitivity but high specificity

Jolt accentuation of headache – Jolt accentuation of headache – negative test excludes negative test excludes meningitismeningitis

Diagnostic testsDiagnostic tests4,54,5??

Lumbar punctureLumbar puncture Head CT prior to lumbar punctureHead CT prior to lumbar puncture

– Should NOT delay treatment – blood culture Should NOT delay treatment – blood culture and antibioticsand antibiotics

– Indicated if patients have altered mental status, Indicated if patients have altered mental status, focal neurological deficits, and signs of focal neurological deficits, and signs of intracranial pressure such as papilledemaintracranial pressure such as papilledema

CSF analysisCSF analysis

ComponentsComponents Normal Normal NewbornNewborn

Normal Normal ChildrenChildren

Bacterial Bacterial MeningitisMeningitis

Viral Viral MeningitisMeningitis

Herpes Herpes MeningitisMeningitis

Glucose (mg/dL)Glucose (mg/dL) 32-12132-121 40-8040-80 <30<30 >30>30 >30>30

Protein (mg/dL)Protein (mg/dL) 19-14919-149 20-3020-30 >100>100 50-10050-100 >75>75

Leukocytes/Leukocytes/LL 0-300-30 0-60-6 >1,000>1,000 100-500100-500 10-1,00010-1,000

Neutrophils (%)Neutrophils (%) 2-32-3 00 >50>50 <40<40 <50<50

Erythrocytes/Erythrocytes/LL 0-20-2 0-20-2 0-100-10 0-20-2 10-50010-500

True CSF WBC = Measured CSF WBC x (1 – CSF RBC blood RBC)

In bloody tap, if WBC/RBC in CSF < that of blood

Bacterial invasion of CNS

Ventriculitis

CSF flow resistance

Increased ICP

Leptomengitis

IL1 & TNF production

Endothelial injury

Increased blood brain barrier permeability

Cerebral edema

Increased CSF protein

Vascular thrombosis

Decreased blood flow

Cerebral hypoxia

Glycolysis

Decreased CSF glucose

Increased CSF lactate

Infarction

SeizureAbscesses

CSF analysisCSF analysis

Bacterial antigens by Bacterial antigens by counterimmunoelectrophesis and latex counterimmunoelectrophesis and latex agglutination – helpful when patients are agglutination – helpful when patients are already on antibioticsalready on antibiotics

CultureCulture PCR for viruses and tuberculosisPCR for viruses and tuberculosis VDRLVDRL

Repeat CSF analysisRepeat CSF analysis44??

Consider in all infants and children with Consider in all infants and children with bacterial meningitis – 24-36 hours after bacterial meningitis – 24-36 hours after treatmenttreatment

Adults Adults – Penicillin-resistant pneumococci or Gram Penicillin-resistant pneumococci or Gram

negative rodnegative rod– Poor clinical responsePoor clinical response

Complications of meningitis?Complications of meningitis? SeizureSeizure Subdural effusionSubdural effusion

– 20-30% of infants with meningitis20-30% of infants with meningitis– Commonly with H. influenza type b & pneumococcal Commonly with H. influenza type b & pneumococcal

meningitismeningitis– Drain only with neurological symptoms from mass effectDrain only with neurological symptoms from mass effect

Subdural empyema – Subdural empyema – drainage & prolonged antibioticsdrainage & prolonged antibiotics Hearing lossHearing loss SIADH SIADH – very cautious with fluid restriction because – very cautious with fluid restriction because

cerebral vascular autoregulation is compromised in cerebral vascular autoregulation is compromised in meningitismeningitis

Loss of cognitive functionsLoss of cognitive functions

Prevention of meningitisPrevention of meningitis44

VaccinesVaccines– H. influenzae in childrenH. influenzae in children

ChemoprophylaxisChemoprophylaxis– Rifampin x 4 daysRifampin x 4 days– Neisseria meningitidisNeisseria meningitidis

» Index case to eradicate pharyngeal carriageIndex case to eradicate pharyngeal carriage» Members in same householdMembers in same household» Prolonged close contactsProlonged close contacts» Direct exposure to respiratory secretion (suction, intubation)Direct exposure to respiratory secretion (suction, intubation)

– Haemophilus influenzae type bHaemophilus influenzae type b» Children <4 years of age with close contactChildren <4 years of age with close contact» All household members with children < 4 years of ageAll household members with children < 4 years of age

ReferencesReferences1.1. Smith AL. Bacterial Meningitis. Pediatrics in Review 1993;14:11-Smith AL. Bacterial Meningitis. Pediatrics in Review 1993;14:11-

18.18.2.2. Attia J, et al. Does This Adult Patients Have Acute Meningitis?Attia J, et al. Does This Adult Patients Have Acute Meningitis?3.3. Uchihara T, Tsukagoshi H. Jolt Accentuation of Headache: the Most Uchihara T, Tsukagoshi H. Jolt Accentuation of Headache: the Most

Sensitive Sign of CSF Pleocytosis. Headache 1991; 31: 167-171.Sensitive Sign of CSF Pleocytosis. Headache 1991; 31: 167-171.4.4. Thomas F. Prevention and Treatment of Bacterial Meningitis. Thomas F. Prevention and Treatment of Bacterial Meningitis.

www.uptodate.comwww.uptodate.com 2002. 2002.5.5. Mathisen GE. Bacterial Meningitis: 11 Questions Physicians Often Mathisen GE. Bacterial Meningitis: 11 Questions Physicians Often

Ask. Consultant 2001.Ask. Consultant 2001.6.6. Wubbel L, McCracken GH. Management of Bacterial Meningitis: Wubbel L, McCracken GH. Management of Bacterial Meningitis:

1998. Pediatrics in Review 1998;19:78-84.1998. Pediatrics in Review 1998;19:78-84.7.7. Prober CG. Central Nervous System Infections. In: Behrman ER, Prober CG. Central Nervous System Infections. In: Behrman ER,

ed. Textbook of Pediatrics. Philadelphia: W.B Saunders Company; ed. Textbook of Pediatrics. Philadelphia: W.B Saunders Company; 2000:751-757.2000:751-757.

8.8. Ryan ME, Brendlinger J, Scott T, Metrishyn L. Aseptic Meningitis. Ryan ME, Brendlinger J, Scott T, Metrishyn L. Aseptic Meningitis. Cortlandt Forum 2000. Cortlandt Forum 2000.