Meningitis

1
Meningitis

• S. Sears, MD

2
Meningitis

• Inflammatory disease of the leptomeninges ( the
  tissues surrounding the brain and spinal cord)
• Meninges consist of
• Pia
• Arachnoid
• Dura maters

3
Meningitis

• Infection of the arachnoid mater and
  cerebrospinal fluid
• In both the subarachnoid space and in the
  cerebral ventricles

4
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

5
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

6
Community-acquired meningitis

• Adults up to the age sixty
• Streptococcus pneumonia
• Neisseria meningitidis
• Haemophilus influenza
• Listeria monocytogenes
• Group B streptococcus
• Adults age sixty and above
• Streptococcus pneumonia
• Listeria monocytogenes
• Neisseria meningitidis
• Group B streptococcus
• Haemophilus influenza

7
Nosocomial meningitis

• Meningitis that developed
• more than 48 hours after hospitalization
• within one week of hospital discharge
• Risk factors
• Neurosurgery
• Head trauma within the past month
• Neurosurgical device
• CSF leak

8
Nosocomial meningitis

• Causative agents
• Gram-negative bacilli
• Streptococcus
• Staphylococcus aureus
• Coagulase-negative staphylococci

9
Recurrent meningitis

• Community-acquired meningitis
• Streptococcus pneumonia
• Nosocomial-acquired meningitis
• Gram-negative bacilli

10
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
• From contiguous spread (sinuses, mastoid)
• Trauma
• Neurosurgery
• CSF leak
• Medical devices ( shunts, ICP monitors, cochlear
  implants)

11
Predisposing factors to meningitis

• Host factors
• 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
  (Africa-meningococcemia )

12
Mechanism of disease

• Colonization and invasion
• Evasion of the complement system
• Alternate pathway outside the CNS
• Stimulation of the classic complement system
  inside the CNS
• Inadequate humoral immunity in the CSF
• Rapid replication of the bacteria in the CNS
• Cell wall components of the bacteria cause
  inflammation in CNS
• 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

13
Clinical features

• Presenting manifestation
• Fever
• Nuchal rigidity
• Change in mental status
• Headache

14
Clinical features

• Other
• Photophobia
• Seizures
• Cranial nerve palsies
• Papilledema
• Petechiae
• Palpable purpura
• Arthritis
• Otitis
• Sinusitis

15
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

16
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

17
Lumbar puncture

• Opening pressure
• 350 mm H20 (normal up to 200 mm H20)
• CSF analysis
• 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)
• White cell count above 1000/microliter (N-no
  cells)
• Traumatic tap
• CSF clears between 1 to 3 tubes
• Blood pigments-present hemorrhage gt12 hours,
  absent hemorrhage or traumatic tap lt12 hours
• CSF cortisol level greater than 46.1 nmol/L
• Latex agglutination test
• Detects antigens to common bacteria

18
Gram-positive diplococci-pneumococcal meningitis
19
Gram-negative diplococci-meningococcal meningitis
20
meningococcemia
21
Gram-positive cocci-clusters-staphylococcus
meningitis
22
Gram-negative coccobacilli-haemophilus influenza
meningitis
23
Gram-positive rods-listeria monocytogenes
meningitis
24
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

25
Treatment failures

• Not covering the appropriate bacteria for the
  clinical situation
• Resistance in bacteria
• Immunocompromised patient
• Resistant bacteria are selected from under-dosing
• Antibiotics chosen do not penetrate the CSF
• Aminoglycosides
• Diagnosis is not meningitis

26
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 gt 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

27
Antibiotics-for specific bacteria

• S. Pneumonia
• Vancomycin 1g IV bid plus Ceftriaxone 2g IV bid
  for 14 days
• Discontinue Vancomycin if strepto not
  cephalosporin-resistant
• N. Meningitis
• 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

28
Adjuvant therapy

• Dexamethasone
• Approved for children with H. influenza type b
  meningitis
• Significant reduction in hearing loss
• 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
• Add rifampin 600mg per day (for adults only)
• IV fluids
• Limiting resulted in increased spasticity,seizures
  and chronic severe neurologic sequelae
• Treatment of raised intracranial pressure
• Raise the head of the bed, possible sedation if
  ventilated,hyperosmolar agents, hyperventilation
  acutely only

29
Neurologic complications

• Cerebrovascular abnormalities
• Thrombosis
• Vasculitis
• Acute cerebral hemorrhage
• Aneurysm formation
• Seizures
• Poor prognostic sign
• Status epilepticus-permanent neurologic
  impairment
• Recurrent seizures within 5 years in survivors

30
Sagittal sinus thrombosis
31
Neurologic complications

• Focal neurologic deficit
• Cranial nerve palsy
• Monoparesis
• Hemiparesis
• Gaze preference
• Visual field defects
• Aphasia
• Ataxia
• Sensorineural hearing loss
• Intellectual impairment
• Visuospatial reasoning
• Speed in attention
• Executive functioning
• Reaction speed

32
Neurologic complications

• Altered mental status
• Cerebral edema/coma
• Increased intracranial pressure
• Measured by Glasgow coma scale
• (verbal,eyes,motor)
• Increased intracranial pressure
• Vasogenic cerebral edema, cytotoxic factors,
  inflammation
• Bradycardia and hypertension (cushing reflex)
• Papilledema
• Cranial nerve palsy-VI
• Herniation leading to death

33
Unusual complications

• Subdural empyema
• Mandatory drainage
• Spinal cord
• Transverse myelitis
• Spinal cord infarction
• Brain abscesses
• Severe permanent hydrocephalus

34
Assessment of risk

• For adverse outcome
• Death, neurological deficit
• Baseline clinical features
• Hypotension
• Altered mental status
• Seizures

35
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

36
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

37
Chemprophylaxis

• Basilar skull fracture-underlying dural tears
• Prophylactic antibiotics not proven to reduce
  meningitis
• H.influenza
• 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
• Household contacts,intimate contacts,children,cowo
  rkers,young adults in dormitories
• Rifampin
• 2 days -oral bid -max 600mg (adults), lt1 year
  5mg/kg, gt1year 10mg/kg
• Not if pregnant,reduces oral contraceptives,discol
  ors urine,tears-orange
• Ciprofloxacin
• Adults- 500mg oral one dose
• Not if under 18, pregnant, lactating
• Ceftriaxone
• Single IM dose-under 15 years 125mg, over 15
  years 250mg

38
Viral Meningitis

• Causes
• 85 enterovirus,HIV,HSV2,EBV,varicella zoster
  virus,mumps,lymphocytic choriomeningitis (LCV)
• Presents
• Intense headache,fever,malaise,myaglia,photophobia
  
• Clinically
• Nuchal rigidity, look for focal signs, less
  likely to have altered mental status
• Lumbar puncture
• 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
• HIV test in 2-3 months
• Treatment
• supportive

39
Aseptic meningitis

• Causes
• 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
• Travel history,exposure to animals,ticks,
  TB,sexual history, others that are
  sick,medication usage
• Physical exam
• New rashes, enlarged parotids,vesicles, ulcers,
  lymphadenopathy, opportunist infections-candida,pa
  ralysis
• CT if focal signs
• LP
• Results depend upon etiology, will be gram stain
  negative,

40
Aseptic meningitis

• Management
• Supportive
• Suspected bacterial meningitis
• Empiric antibiotic therapy
• Suspected viral meningitis
• Empiric antibiotic therapy for 48 hours if
• lt 1 year age, elderly, immunocompromised,
  received antibiotics prior to presentation
• Suspected HSV
• Start acyclovir-10mg/kg IV q 8 hrs
• Unclear etiology
• 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

41
Brucellosis

• Organisms of the genus Brucella
• Small, gram negative, aerobic coccobacilli

42
Epidemiology

• Animal infection
• Cattle (B. abortus), sheep and goats (B.
  melitensis), swine (B.suis)
• Human infection
• Most common in US (B. melitensis), in California
  (B. abortus)
• Acquired
• Direct inoculation-handling animal carcasses
  (open wounds)
• Conjunctiva
• Inhaled infected aerosols
• Ingestion of contaminated food
• Raw milk
• Cheese (from unpasteurized milk)
• Raw meat

43
Clinical manifestation

• Symptoms
• Fever of unknown origin
• Night sweats
• Malaise
• Anorexia
• Arthralgias
• Fatigue
• Weight loss
• Depression
• Localized disease
• Osteoarticular
• Sacroiliitis
• Genitourinary
• Epididymoorchitis
• Neurobrucellosis
• Meningitis
• Papilledema,optic neuropathy,radiculopathy,stroke,
  ICH
• Endocarditis
• Hepatic abscess

44
Diagnosis

• Culture
• Blood
• Localized sites
• bone marrow and liver
• Serologic tests
• To detect antibody
• Serum agglutination
• Complement fixation
• Antibrucella coombs
• ELISA (enzyme-linked immunosorbent assay)
• To detect DNA
• PCR
• Recommended
• PCR-ELISA

45
Treatment

• Regime A
• Doxycycline 100 mg po bid for 6 weeks
• Streptomycin 1g IM daily for 14-21 days
• Regime B
• 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

46
Prevention

• Vaccination of domesticated herds
• Serologic testing of animals
• Slaughter of infected animals
• Protection of slaughter house workers
• Pasteurization of milk