Meningitis
S. Sears, MD
Meningitis
Inflammatory disease of the leptomeninges ( the
tissues surrounding the brain and spinal cord)
Meninges consist of
• Pia
• Arachnoid
• Dura maters
Meningitis
• Infection of the arachnoid mater and
cerebrospinal fluid
• In both the subarachnoid space and in the
cerebral ventricles
Causative organisms-site of entry
Neisseria meningitidis
• Nasopharynx
Streptococcus pneumonia
• Nasopharynx,direct extension across skull fracture
Listeria monocytogenes
• GI tract,placenta
Coagulase-negative staphylococcus
• Dermal of foreign body
Staphylococcus aureus
• Bacteremia,dermal,or foreign body
Gram negative rods
• Various
Haemophilus influenza
• Nasopharynx
Community-acquired meningitis
Newborns
• Group B stretpococcus
• Listeria monocytogenes
• Streptococcal pneumonia
One month to two years
• Streptococcal pneumonia
• Neisseria meningitidis
• Group B streptococcus
Age two through age eighteen
• Neisseria meningitidis
• Streptococcus pneumonia
• Haemophilus influenza
Community-acquired meningitis
Adults up to the age sixty
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Streptococcus pneumonia
Neisseria meningitidis
Haemophilus influenza
Listeria monocytogenes
Group B streptococcus
Adults age sixty and above
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Streptococcus pneumonia
Listeria monocytogenes
Neisseria meningitidis
Group B streptococcus
Haemophilus influenza
Nosocomial meningitis
Meningitis that developed:
• more than 48 hours after hospitalization
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within one week of hospital discharge
Risk factors
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Neurosurgery
Head trauma within the past month
Neurosurgical device
CSF leak
Nosocomial meningitis
Causative agents
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Gram-negative bacilli
Streptococcus
Staphylococcus aureus
Coagulase-negative staphylococci
Recurrent meningitis
Community-acquired meningitis
• Streptococcus pneumonia
Nosocomial-acquired meningitis
• Gram-negative bacilli
Mechanism for developing meningitis
Colonization of the nasopharynx
• Bloodstream invasion and subsequent CNS invasion
Invasion of the CNS following bacteremia
• Localized source ( endocarditis ) or urinary tract infection
Direct entry of organisms into the CNS
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From contiguous spread (sinuses, mastoid)
Trauma
Neurosurgery
CSF leak
Medical devices ( shunts, ICP monitors, cochlear implants)
Predisposing factors to meningitis
Host factors
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Asplenia
Complement deficiency
Corticosteroid excess
HIV infection
Recent infection (respiratory, otic )
Recent exposure to someone with meningitis
IV drug use
Recent head trauma
Otorrhea or rhinorrhea
Travel to an endemic meningitis area (Africameningococcemia )
Mechanism of disease
Colonization and invasion
Evasion of the complement system
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Alternate pathway outside the CNS
Stimulation of the classic complement system inside the
CNS
Inadequate humoral immunity in the CSF
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Rapid replication of the bacteria in the CNS
Cell wall components of the bacteria cause inflammation in
CNS
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Leads to disruption of the blood-brain barrier
Results in vasogenic brain edema, loss of cerebrovascular
autoregulation, increased intracranial pressure
Results in brain ischemia, cytotoxic injury and neuronal loss
Clinical features
Presenting manifestation
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Fever
Nuchal rigidity
Change in mental status
Headache
Clinical features
Other
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Photophobia
Seizures
Cranial nerve palsies
Papilledema
Petechiae
Palpable purpura
Arthritis
Otitis
Sinusitis
Examination of nuchal rigidity
Passive or active flexion of the neck
• Patient unable to touch chin to chest
Brudzinski sign
• Passive flexion of the neck from a supine position results
in spontaneous flexion of the hips and knees
Kernig sign
• In the supine position with the hips and knees flexed at 90
degrees, resistance to extension of the knee
Jolt accentuation of headache
• Patient rotates head 2-3 times per second and reports
exacerbation of the headache
Investigations
Blood cultures- 50-75 % positive
CT scan of the brain-especially if has a
risk factor for mass lesion
• Immunocompromised state ( HIV,transplant,
chemo therapy)
• History of CNS disease (mass lesion, stroke,
focal infection)
• New onset seizures
• Papilledema
• Abnormal level of consciousness
• Focal neurologic deficit
Lumbar puncture
Opening pressure
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350 mm H20 (normal up to 200 mm H20)
CSF analysis
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Gram stain and culture
Protein above 250 mg/dL (N-less than 50 mg/dL)
Glucose below 45 mg/dL (N-greater then 45 mg/dL)
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White cell count above 1000/microliter (N-no cells)
Traumatic tap
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CSF clears between 1 to 3 tubes
Blood pigments-present hemorrhage >12 hours, absent
hemorrhage or traumatic tap <12 hours
CSF cortisol level greater than 46.1 nmol/L
Latex agglutination test
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Detects antigens to common bacteria
Gram-positive diplococci-pneumococcal meningitis
Gram-negative diplococci-meningococcal meningitis
meningococcemia
Gram-positive cocci-clusters-staphylococcus meningitis
Gram-negative coccobacilli-haemophilus influenza meningitis
Gram-positive rods-listeria monocytogenes meningitis
Treatment
Initiated as soon as possible
Delay of therapy associated with increased
mortality
Delay associated with increased complications
If LP delayed due to needing a CT-blood cultures
and start empiric therapy
LP as soon as it is safe-longer the time between
antibiotics and the LP-decreased return of the
CSF culture results
Treatment failures
Not covering the appropriate bacteria for the
clinical situation
• Resistance in bacteria
• Immunocompromised patient
Resistant bacteria are selected from underdosing
Antibiotics chosen do not penetrate the CSF
• Aminoglycosides
Diagnosis is not meningitis
Antibiotics-empiric therapy
Age 18 to 60 years
• Ceftriaxone 2 g IV bid plus Vancomycin 1 g IV bid (if
resistant pneumococci in community)
Age > 60 years
• As above plus Ampicillin 200mg/kg IV in 6 divided doses
Impaired cellular immunity
• Ceftazidime 2 g IV q8hrs plus Ampicillin 2 g IV q4hrs
• Add Vancomycin 1 g IV bid (if resistant pneumococci in
community)
Nosocomial meningitis
• Ceftazidime 2 g IV q8hrs plus Vancomycin 1 g IV bid
Antibiotics-for specific bacteria
S. Pneumonia
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Vancomycin 1g IV bid plus Ceftriaxone 2g IV bid for 14 days
Discontinue Vancomycin if strepto not cephalosporin-resistant
N. Meningitis
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Penicillin G 4 million units IV q4hrs for 7 days
H. Influenza
• Ceftriaxone 2g IV q12hrs for 7 days
L. Monocytogenes
• Ampicillin 2g IV q4hrs for 2-4 weeks if immunocompetent, for 6-8 weeks if
immunocompromised
• PLUS Gentamicin 1-2mg/kg IV q8hrs until patient improves for 10-14
days, monitoring of ototoxicity and nephrotoxicity
Group B Streptococci (agalactiae)
• Penicillin G 4 million units IV q4hrs for 2-3 weeks
Enterobacteriacae
• Ceftriaxone 2g IV q12hrs plus Gentamicin 1-2mg/kg IV q8hrs for 3 weeks
Pseudomonas
• Ceftazidime 2g IV q8hrs plus Gentamicin 1-2mg/kg for 3 weeks
Adjuvant therapy
Dexamethasone
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Approved for children with H. influenza type b meningitis
– Significant reduction in hearing loss
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Approved for adults with S.pneumonia meningitis with Glasgow
coma scale 8-11 ( dose-10mg IV q6hrs- 4 days)
– Reduced mortality from septic shock, pneumonia, adult respiratory
distress syndrome
If using dexamethasone
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Add rifampin 600mg per day (for adults only)
IV fluids
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Limiting resulted in increased spasticity,seizures and chronic
severe neurologic sequelae
Treatment of raised intracranial pressure
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Raise the head of the bed, possible sedation if
ventilated,hyperosmolar agents, hyperventilation acutely only
Neurologic complications
Cerebrovascular abnormalities
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Thrombosis
Vasculitis
Acute cerebral hemorrhage
Aneurysm formation
Seizures
• Poor prognostic sign
• Status epilepticus-permanent neurologic impairment
• Recurrent seizures within 5 years in survivors
Sagittal sinus thrombosis
Neurologic complications
Focal neurologic deficit
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Cranial nerve palsy
Monoparesis
Hemiparesis
Gaze preference
Visual field defects
Aphasia
Ataxia
Sensorineural hearing loss
Intellectual impairment
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Visuospatial reasoning
Speed in attention
Executive functioning
Reaction speed
Neurologic complications
Altered mental status
• Cerebral edema/coma
• Increased intracranial pressure
• Measured by Glasgow coma scale
(verbal,eyes,motor)
Increased intracranial pressure
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Vasogenic cerebral edema, cytotoxic factors, inflammation
Bradycardia and hypertension (cushing reflex)
Papilledema
Cranial nerve palsy-VI
Herniation leading to death
Unusual complications
Subdural empyema
• Mandatory drainage
Spinal cord
• Transverse myelitis
• Spinal cord infarction
Brain abscesses
Severe permanent hydrocephalus
Assessment of risk
For adverse outcome
• Death, neurological deficit
Baseline clinical features
• Hypotension
• Altered mental status
• Seizures
For adverse outcome
Low risk
• No clinical risk factors - 9 % adverse outcome
Intermediate risk
• One clinical risk factor - 33 % adverse outcome
High risk
• Two or three risk factors - 57 % adverse outcome
Prevention
Vaccines
• Pneumococcal vaccine
– Over age 65 and for chronically ill
• Meningococcal vaccine
– Not warranted postexposure unless serotype not represented in
vaccine ( type A,C,Y,W-135)
• H. influenza vaccine
– For children (routine), adults prior to splenectomy
Chemprophylaxis
Basilar skull fracture-underlying dural tears
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Prophylactic antibiotics not proven to reduce meningitis
H.influenza
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Young children less than 4 years of age in the house
Plus child-and household contacts
Rifampin 20mg/kg (max 600mg) po daily-4 days
N.Meningitidis
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Household contacts,intimate contacts,children,coworkers,young adults in
dormitories
Rifampin
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Ciprofloxacin
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2 days -oral bid -max 600mg (adults), <1 year 5mg/kg, >1year 10mg/kg
Not if pregnant,reduces oral contraceptives,discolors urine,tears-orange
Adults- 500mg oral one dose
Not if under 18, pregnant, lactating
Ceftriaxone
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Single IM dose-under 15 years 125mg, over 15 years 250mg
Viral Meningitis
Causes
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85% enterovirus,HIV,HSV2,EBV,varicella zoster
virus,mumps,lymphocytic choriomeningitis (LCV)
Presents
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Intense headache,fever,malaise,myaglia,photophobia
Clinically
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Nuchal rigidity, look for focal signs, less likely to have altered mental
status
Lumbar puncture
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Negative gram stain, WBC 10-1000/mm3, normal glucose,protein up to
150mg/dL
Send for nested PCR (two loci primers)
Can send for direct viral cultures ( only 6% return)
Blood
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HIV test in 2-3 months
Treatment
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supportive
Aseptic meningitis
Causes
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Same as viral meningitis
Some viruses than cause arthropod encephalitis
Lyme disease
Syphilis
Tick- borne diseases
Fungal infections (cryptococcal )
Tuberculosis
Abscess in CNS ( tissues and endocarditis)
Neoplasms (metastatic, leukemia,lymphoma)
Drug-induced (NSAIDS, Septra,Vioxx,OKT3 antibodies)
Partially treated bacterial meningitis
History
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Travel history,exposure to animals,ticks, TB,sexual history, others that are
sick,medication usage
Physical exam
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New rashes, enlarged parotids,vesicles, ulcers, lymphadenopathy, opportunist
infections-candida,paralysis
CT if focal signs
LP
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Results depend upon etiology, will be gram stain negative,
PCR and special staining depending on clinical suspicion required
Aseptic meningitis
Management
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Supportive
Suspected bacterial meningitis
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Empiric antibiotic therapy
Suspected viral meningitis
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Empiric antibiotic therapy for 48 hours if
< 1 year age, elderly, immunocompromised, received antibiotics prior to
presentation
Suspected HSV
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Start acyclovir-10mg/kg IV q 8 hrs
Unclear etiology
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Obtain blood and CSF cultures
Start empiric antibiotics or repeat LP in 6 hours
Patient improved-cultures negative discontinue antibiotics (usually 72hrs)
Repeat LP in patient with progressive symptoms or unclear diagnosis
Brucellosis
Organisms of the genus Brucella
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Small, gram negative, aerobic coccobacilli
Epidemiology
Animal infection
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Cattle (B. abortus), sheep and goats (B. melitensis), swine
(B.suis)
Human infection
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Most common in US (B. melitensis), in California (B. abortus)
Acquired
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Direct inoculation-handling animal carcasses (open wounds)
Conjunctiva
• Inhaled infected aerosols
• Ingestion of contaminated food
– Raw milk
– Cheese (from unpasteurized milk)
– Raw meat
Clinical manifestation
Symptoms
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Fever of unknown origin
Night sweats
Malaise
Anorexia
Arthralgias
Fatigue
Weight loss
Depression
Localized disease
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Osteoarticular
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Genitourinary
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Epididymoorchitis
Neurobrucellosis
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Sacroiliitis
Meningitis
Papilledema,optic neuropathy,radiculopathy,stroke, ICH
Endocarditis
Hepatic abscess
Diagnosis
Culture
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Blood
Localized sites
– bone marrow and liver
Serologic tests
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To detect antibody
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Serum agglutination
Complement fixation
Antibrucella coombs
ELISA (enzyme-linked immunosorbent assay)
To detect DNA
– PCR
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Recommended
– PCR-ELISA
Treatment
Regime A
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Doxycycline 100 mg po bid for 6 weeks
Streptomycin 1g IM daily for 14-21 days
Regime B
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Doxycycline 100 mg po bid and rifampin 600 mg po daily for
6 weeks
Osteoarticular disease
• Regime B and streptomycin-treat up to 5 months
Neurobrucellosis
• Three drugs to cross the blood-brain barrier
• Regime B and septra-treat until CSF returns to normal
Endocarditis
• Treat for months-three drugs
• Valve replacement
Accidental animal vaccine exposure
• Full course of antibiotic treatment
Prevention
Vaccination of domesticated herds
Serologic testing of animals
Slaughter of infected animals
Protection of slaughter house workers
Pasteurization of milk