meningitis and encephalitis: diagnosis and treatment update
TRANSCRIPT
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