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Meningitis

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Meningitis S. Sears, MD * * * * * * * * * * * * * * * * * * * * * * * * * * * Assessment of risk For adverse outcome Death, neurological deficit Baseline clinical ... – PowerPoint PPT presentation

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Title: 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
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