Meningitis and Encephalitis:Meningitis and Encephalitis:Meningitis and Encephalitis:Meningitis and Encephalitis:

Diagnosis and Treatment Update

DefinitionsDefinitions

• Meningitis – inflammation of the meninges

• Encephalitis – infection of the brain parenchyma

• Meningoencephalitis – inflammation of brain + meninges

• Aseptic meningitis – inflammation of meninges with sterile CSF

Symptoms of meningitisSymptoms of meningitis

• Fever

• Altered consciousness, irritability, photophobia

• Vomiting, poor appetite

• Seizures 20 - 30%

• Bulging fontanel 30%

• Stiff neck or nuchal rigidity

• Meningismus (stiff neck + Brudzinski + Kernig signs)

Clinical signs of meningeal irritationClinical signs of meningeal irritation

Diagnosis – lumbar punctureDiagnosis – lumbar puncture

• Contraindications: Respiratory distress (positioning) ICP reported to increase risk of herniation Cellulitis at area of tap Bleeding disorder

CSF evaluationCSF evaluation

Condition WBC Protein (mg/dL)

Glucose (mg/dL)

Normal <7, lymphs mainly 5-45 >50Bacterial, acute 100 – 60K PMN’s 100-500 Low

Bacterial, part rx’d 1 – 10,000 100+ Low to

normalTB 10 – 500 100-500 <50Fungal 25 – 500 25-500 <50Viral <1000 50-100 Normal

CSF Gram stainCSF Gram stain

Hemophilus influenza(H flu)

Strep pneumoniae

Not addressedNot addressed

• Indwelling CNS catheters

• S/P cranial surgery

• Anatomic defects predisposing to meningitis

• Immunocompromised patients

• Abscesses

Bacterial meningitisBacterial meningitis

• 3 - 8 month olds at highest risk

• 66% of cases occur in children <5 years old

Bacterial meningitis - OrganismsBacterial meningitis - Organisms

• Neonates Most caused by Group B Streptococci E coli, enterococci, Klebsiella, Enterobacter,

Samonella, Serratia, Listeria

• Older infants and children Neisseria meningitidis, S. pneumoniae,

tuberculosis, H. influenzae

Bacterial meningitis – Clinical courseBacterial meningitis – Clinical course

• Fever

• Malaise

• Vomiting

• Alteration in mental status

• Shock

• Disseminated intravascular coagulation (DIC)

• Cerebral edema Vital signs Level of mentation

Increased intracranial pressure (ICP)Increased intracranial pressure (ICP)

• Papilledema

• Cushing’s triad Bradycardia Hypertension Irregular respiration

• ICP monitor (not routine)

• Changes in pupils

ICP treatmentICP treatment

• 3% NaCl, 5 cc/kg over ~20 minutes

• May utilize osmotherapy - if serum osms <320

• Mild hyperventilation PaCO2 <28 may cause

regional ischemia Typically keep PaCO2

32-38 torr

• Elevate HOB 30o

Meningitis - Fluid managementMeningitis - Fluid management

• Restore intravascular volume & perfusion

• Monitor serum Na+ (osmolality, urine Na+): If serum Na+ <135 mEq/L then fluid restrict

(~2/3x), liberalize as Na+ improves If severely hyponatremic, give 3% NaCl

• SIADH 4 - 88% in bacterial meningitis 9 - 64% in viral meningitis

• Diabetes insipidus

• Cerebral salt wasting

Meningitis - Treatment durationMeningitis - Treatment duration

• Neonates: 14 – 21 days

• Gram negative meningitis: 21 days

• Pneumococcal, H flu: 10 days

• Meningococcal: 7 days

Bacterial Meningitis - TreatmentBacterial Meningitis - TreatmentNeonatal (<3 mo) Neonatal (<3 mo)

• Ampicillin (covers Listeria)

+

• Cefotaxime High CSF levels

Less toxicity than aminoglycosides

No drug levels to follow

Not excreted in bile not inhibit bowel flora

Meningitis - Acute complicationsMeningitis - Acute complications

• Hydrocephalus

• Subdural effusion or empyema ~30%

• Stroke

• Abscess

• Dural sinus thrombophlebitis

Bacterial meningitis - OutcomesBacterial meningitis - Outcomes

• Neonates: ~20% mortality

• Older infants and children: <10% mortality 33% neurologic abnormalities at discharge 11% abnormalities 5 years later

• Sensorineural hearing loss 2 - 29%

Bacterial meningitis - childrenBacterial meningitis - children

• Strep pneumoniae

• Neisseria meningitidis

• TB

• Hemophilus influenza

Pneumococcal meningitisPneumococcal meningitis

Antibiotic susceptibilityAntibiotic susceptibility

• Susceptible

• Non-susceptible

• Resistant

Pneumococcal resistancePneumococcal resistance• Strep pneumococcus - most common cause of

invasive bacterial infections in children >2 months old

• Incidence of PCN-, cefotaxime- & ceftriaxone-nonsusceptible isolates has ’d to ~40%

• Strains resistant to PCN, cephalosporins, and other -lactam antibiotics often resistant to trimethoprim-sulfamethoxazole (Bactrim™, Septra™), erythromycin, chloramphenicol, tetracycline

Mechanism of resistanceMechanism of resistance

• PCN-binding proteins synthesize peptidoglycan for new cell wall formation

• PCN, cephalosporins, and other -lactam antibiotics kill S pneumoniae by binding irreversibly to PCN-binding proteins located in the bacterial cell wall

• Chromosomal changes can cause the binding affinity for the -lactam antibiotics to decrease

Pneumococcal meningitis – MgmtPneumococcal meningitis – Mgmt

• Vancomycin + cefotaxime or ceftriaxone, if > 1 month old

• If hypersensitive (allergic) to -lactam antibiotics, use vancomycin + rifampin

• D/C vancomycin once testing shows PCN-susceptibility

• Consider adding rifampin if susceptible & condition not improving, or cefotaxime or ceftriaxone MIC high

• Not vancomycin alone

Antibiotic use inAntibiotic use inPneumococcal meningitisPneumococcal meningitis

• PCN-susceptible organism: PenG 250,000 - 400,000 U/kg/day Q 4 - 6 h Ceftriaxone 100 mg/kg/day Q 12 - 24 h Cefotaxime 225 - 300 mg/kg/day Q 8 h Chloramphenicol 50 - 100 mg/kg/day Q 6 h

• Adequate cephalosporin levels in CSF ~2.8 hours after dose administration

Vancomycin use inVancomycin use inpneumococcal meningitispneumococcal meningitis

• Combination therapy since late 90’s

• At initiation- Baseline urinalysis

BUN and creatinine

• Enters the CSF in the presence of inflamed meninges within 3 hours

• Should not be used as solo agent, but with cephalosporin for synergy

Vancomycin use inVancomycin use inpneumococcal meningitispneumococcal meningitis

• Vancomycin 60 mg/kg/day Q 6 h

• Trough levels immediately before 3rd dose

• (10-15 mcg/mL or less)

• Peak serum level 30-60 minutes after completion of a 30-minute infusion

(35-40 mcg/mL)

Other antibiotics inOther antibiotics inpneumococcal meningitis (resistant)pneumococcal meningitis (resistant)

• Rifampin 20 mg/kg/day Q 12

Not a solo agent

Slowly bactericidal

• Meropenem Carbapenem 120 mg/kg/day Q 8 h

seizure incidence, not generally used in meningitis

Resistance reported

Dexamethasone use in meningitisDexamethasone use in meningitis

• Consider if H flu & S pneumo meningitis & > 6 wks old 0.6 mg/kg/day Q 6h x 2d

local synthesis of TNF-, IL-1, PAF & prostaglandins resulting in BBB permeability, meningeal irritation

• Debate if it incidence of hearing loss

• If used, needs to be given shortly before or at the time of antibiotic administration

• May adversely affect the penetration of antibiotics into CSF

Pneumococcal meningitis - TreatmentPneumococcal meningitis - Treatment

• LP after 24-48 hours to evaluate therapy if: Received dexamethasone PCN-non-susceptible MIC’s not available Child’s condition not improving

Infection control precautionsInfection control precautions(invasive pneumococcus)(invasive pneumococcus)• CDC recommends Standard Precautions

• Airborne, Droplet, Contact are NOT recommended

• Nasopharyngeal cultures of family members and contacts is NOT recommended

• No isolation of contacts

• No chemoprophylaxis for contacts

Meningococcal meningitisMeningococcal meningitis

• Neisseria meningitidis

• ~10 - 15% with chronic throat carriage

• Outbreaks in households, high schools, dorms Accounts for <5% of cases

• 2,400 - 3,000 cases occur in the USA each year

• Peaks <2 years of age & 15-24 years

Meningococcal diseaseMeningococcal disease

• Can cause purulent conjunctivitis, septic arthritis, sepsis +/- meningitis

• Diagnose presence of organism (Gram negative diplococci) via: CSF Gram stain, culture Sputum culture CSF (not urine) Latex agglutination Petechial scrapings Buffy coat Gram stain

Meningococcemia - PetechiaeMeningococcemia - Petechiae

Meningococcemia - Purpura fulminansMeningococcemia - Purpura fulminans

Meningococcemia - IsolationMeningococcemia - Isolation

• Capable of transmitting organism up to 24 hours after initiation of appropriate therapy

• Droplet precautions x 24 hours, then no isolation

• Incubation period 1 - 10 days, usually <4 days

Meningococcemia - TreatmentMeningococcemia - Treatment

• Antibitotic resistance rare

• Antibitotics: PCN Cefotaxime or Ceftriaxone

• Patient should get rifampin prior to discharge

Meningococcal disease - Care takersMeningococcal disease - Care takers

• Day care where child attends >25 h/wk, kids are >2 years old, & 2 cases have occurred

• Day care where kids not all vaccinated

• Persons who have had “intimate contact” w/ oral secretions prior & during 1st 24 h of antibiotics

• “Intimate contact” – 300-800x risk(kissing, eating/ drinking utensils, mouth-to-mouth, suctioning,

intubating)

Meningococcemia - ProphylaxisMeningococcemia - Prophylaxis

• No randomized controlled trials of effectiveness

• Treat within 24 hours of exposure

• Vaccinate affected population, if outbreak

Meningococcemia - ProphylaxisMeningococcemia - Prophylaxis

• Rifampin Urine, tears, soft contact lenses orange; OCP’s

ineffective <1 mo 5 mg/kg PO Q 12 x 2 days >1 mo 10 mg/kg (max 600 mg) PO Q 12 x 2 days

• Ceftriaxone 12 y 125 mg IM x 1 dose >12 y 250 mg IM x 1 dose

• Ciprofloxacin 18 y 500 mg PO x 1 dose

Meningococcal meningitis - OutcomesMeningococcal meningitis - Outcomes

• Substantial morbidity: 11% - 9% of survivors have sequelae Neurologic disability

Limb loss

Hearing loss

• 10% case-fatality ratio for meningococcal sepsis

• 1% mortality if meningitis alone

TB meningitisTB meningitis

• Children 6 months – 6 years

• Local microscopic granulomas on meninges

• Meningitis may present weeks to months after primary pulmonary process

• CSF: Profoundly low glucose High protein Acid-fast bacteria (AFB stain) PCR

• Steroids + antimicrobials

Aseptic vs. partially treated bacterial Aseptic vs. partially treated bacterial meningitismeningitis

• Aseptic much more common

• Gram stain positive CSF: 90 - 100% in young patients 50 - 68% positive in older children

• If CSF fails to show organisms in a pretreated patient, then very unlikely that organism is resistant

Viral meningitisViral meningitis

• Summer, fall

• Severe headache

• Vomiting

• Fever

• Stiff neck

• CSF - pleocytosis (monos), NL protein, NL glucose

Etiology viral meningitisEtiology viral meningitis

• Enteroviruses predominate Spring, summer

Oral-fecal route

± initial GI symptoms

Meningitic symptoms appear 7-10 days after exposure

• Less common: Mumps

HIV

Lymphocytic choriomeningitis

HSV-2

Other causes of aseptic meningitisOther causes of aseptic meningitis

• Leptospira Young adults Late summer, fall Conjunctivitis, splenomegaly, jaundice, rash Exposure to animal urine

• Lyme Disease (Borrelia burgdorferi) Spring-late fall Rash, cranial nerve involvement

Viral meningitis - TreatmentViral meningitis - Treatment

• Supportive

• No antibiotics

• Analgesia

• Fever control

• Often feel better after LP

• No isolation - Standard precautions

Viral meningitis - OutcomesViral meningitis - Outcomes

• Adverse outcomes rare

• Infants <1 year have higher incidence of speech & language delay

Meningoencephalitis - etiologyMeningoencephalitis - etiology

• Herpes simplex type 1

• Rabies

• Arthropod-borne St. Louis encephalitis La Crosse encephalitis Eastern equine encephalitis Western equine encephalitis West Nile

Herpes simplex 1 encephalitisHerpes simplex 1 encephalitis

• Symptoms Depressed level of consciousness Blood tinged CSF Temporal lobe focus on CT scan or EEG + PCR Neonates typically will have cutaneous vessicles

• Treatment - IV acyclovir

West Nile VirusWest Nile Virus

• Via bite of infected mosquito

• Incubation period 3 - 14 days

• 1 in 150 infected persons get encephalitis 4% of those are <20 years of age

• H/A, fever, neck stiffness, stupor, coma, convulsions, weakness, & paralysis

• Supportive therapy

• Mortality 9%

West Nile VirusWest Nile Virus

MMWR Dec 2002 51;1129-33

SummarySummary

• Antibiotics ASAP, even if LP not yet done

• Vanco + cephalosporin until some identification known CSF, Latex, exam

• Isolate if bacterial x 24 hours, Universal Precautions

• Monitor for status changes Pupils, LOC, HR, BP, resp Seizures Hemodynamics DIC, coagulopathy Fluid, electrolyte issues