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Microbiology: Meningitis (Brown)
BACTERIAL MENINGITIS:
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Basics:
Definition: inflammation of the meninges; can have both infectious and non-infectious causes
Epidemiology:
o Bacterial: 0.2 cases/100,000 population
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More common in adults than children
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Incidence much higher in DEVELOPING world
o Viral: 10.9 cases/100,000 populations
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More common in children in adults
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Pathogenesis of Meningitis:
Disease Process:
1. Mucosal invasion
2. Local invasion/bacteremia (may be able to make presumptive diagnosis based on blood culture)
3. Meningeal invasion across BBB or BCB (most important step- serious 100% of the time)
4. Bacterial replication in subarachnoid space
5. Release of bacterial components (cell wall, lipo-oligosaccharide), which has direct effects on:
Cerebral microvascular endothelium
-Increases BBB permeability
- Results in vasogenic edema
-Overall Result is INCREASED ICP
Macrophages
-Release IL-1 and TNF
-Act on cerebral microvascular endothelium (see
left) AND result in subarachnoid space
inflammation
-Inflammation of subarachnoid space has 2
effects:
1. Interstitial edema: caused by increased
resistance to CSF outflow
2.Cytotoxic edema: caused by host response to
inflammation
-Overall result is INCREASED ICP
Note: subarachnoid space inflammation may also
lead to cerebral vasculitis, which can cause
cerebral infarction
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Effects of Increased ICP:
o Decreased cerebral blood flow
o Loss of cerebrovascular autoregulation
Pathogenic and Host Factors of Importance During Invasion Events:
Event
Pathogenic Factors
Mucosal Colonization
Fimbriae
Polysaccharide capsule
IgA protease
Intravascular Survival
Polysaccharide capsule
Meningeal Invasion
Fimbriae
Association with monocytes
Survival in Subarachnoid Space
Polysaccharide capsule
Host Protective Factors
Mucosal epithelium
Secretory IgA
Ciliary activity
Anti-capsular Abs
Complement activation
Organism specific Abs
BBB/BCB
Note: once infection is established,
this is to our disadvantage because
it prevents Abx from entering
Poor opsonic activity of CSF
Once the infection gets here, not a
lot we have in the way of defense
Microbiology of Meningitis:
<1 month:
o Group B Streptococcus (S.agalactiae)

Note: can decrease early onset disease by intrapartum prophylaxis of maternal carriers

o E.coli
o Listeria monocytogenes
1-23 months:
o Group B Strep
o E.coli
o Streptococcus pneumoniae
o Haemophilus influenza (may see it before vaccine series is complete)
o Neisseria meningitidis
24 months to 18 years:
o Neisseria meningitidis (most common)
o S.pneumoniae
o H.influenzae (only if unvaccinated or immunocompromised for some reason)
18-50 years:
o S.pneumoniae (most common)
o N.meningitidis
≥50 years:
o S.pneumoniae
o N.meningitidis
o L.monocytogenes (considered in immunocompromise or pregnancy)
o Aerobic gram negative bacilli (E.coli, Klebsiella)
Head trauma/post neurosurgery:
o Staphylococcus aureus
o Staphylococcus epidermidis
o Aerobic gram negative bacilli (including Pseudomonas)
Basilar skull fracture/CSF leak: head trauma occurs, and during recover patient notices clear drainage out of
nose (can be tested for glucose to diagnose as CSF leak); may also be less noticeable (ie. no leakage), and should
always be considered in cases of recurrent bacterial meningitis
o S.pneumoniae
o H.influenzae
o Group A, B-hemolytic streptococci
Clinical Presentation:
Symptoms:
o Headache (due to increased ICP)
o Fever (systemic response to infection- not meningitis specific)
o Neck stiffness (due to inflammation of meninges)
o Photophobia (due to inflammation of meninges)
o N/V (due to increased ICP)
o Change in mental status (generally depressed status)
Clinical Findings:
o Adults: from most common to least common

Neck stiffness (nuchal ridgidity)
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Fever

Mental status change
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Focal neurological finding (often due to cerebral vasculitis and infarction)
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Rash (petechial rash seen classically with N.meningitidis, but can be seen with others)
o Children:

Older Children: similar to adults
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Neonates/Infants/Non-Verbal Children: much more subtle presentation
 Fever
 Irritability
 Poor-feeding
 Bulging fontanel (occurs late in infection; want to diagnose before this occurs)
Underlying conditions that can predispose to the development of bacterial meningitis:
o Acute/chronic otitis media/mastoiditis (S.pneumo)
o Sinusitis (S.pneumo)
o Pneumonia (S.pneumo)
o Endocarditis (continuous bacteremia)
o Recent/remote head trauma (CSF leak)
o
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Immunsuppression
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Particularly humoral immunity defects or splenic dysfunction (encapsulated organisms)
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Deficiency of terminal components of complement
Alcoholism (suppresses the immune system; at risk for Gram negative meningitis- E.coli, Klebsiella)
o
Diagnosis:
Bacterial meningitis is a medical emergency: need to move quickly; the diagnosis is made by lumbar puncture
CSF parameters that need to be evaluated:
o Opening pressure (normal is 20 cm)
o Cell count (RBCs, WBCs, differential)
o Protein
o Glucose (with simultaneous serum glucose)
o Bacterial Ag detection (latex agglutination is best, but sensitivity varies); often just do a Gram stain!
o Gram stain and culture (sensitivity lower for Gram negative bacilli and L.monocytogenes; better for
S.pneumo, N.meningitidis, H.influenzae)
o In some cases (when rarer causes are suspected)
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VDRL (neurosyphilis?)
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Cryptococcal Ag (AIDS)
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Acid fast bacilli stain and culture (Mycobacterium)
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Fungal stain and culture
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Cytology
Blood cultures
Management:
Antibiotics: must be chosen based on spectrum of causative agents and CSF penetration (cetriaxone is the go to)
Corticosteroids: anti-inflammatory (shown to be beneficial in adults with bacterial meningitis in the developed
world; controversial in pediatric patients)
Supportive care with management of complications
Early
Late (After Recovery)
Septic shock
Behavioral/learning disabilities (children)
DIC
Hearing loss (especially GBS infection in adults)
Respiratory failure (ARDS)
Seizures
Cerebral edema
Hydrocephalus
Prognosis:
Overall mortality for CA-meningitis: 25%
Pathogen specific mortality: from highest to lowest
o L.monocytogenes (28.5%)
o S.pneumoniae (19-26%)
o GBS (7-27%)
o N.meningitidis (10%)
o H.influenzae (6%)
Risk factors for mortality:
o Age >60
o Obtunded mental status (depressed mental capacity)
o Seizures within first 24 hours of admission
o Otitis/sinusitis
o Absence of rash
o Bacteremia
o Thrombocytopenia
o Low CSF WBC count (because that means the host immune response isn’t what it should be)
Prevention:
o Antibiotic prophylaxis for close contacts
o Meningococcal vaccine (however, does not cover serotype B)
o HIB conjugate vaccine
o 23 or 13-valent pneumococcal conjugate vaccine
o Management of GBS colonization during pregnancy
ASEPTIC MENINGITIS:
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Basics:
Lymphocyte predominant pleocytosis with negative bacterial stains/cultures
Most common cause is enteroviruses:
o Most common in infants and young kids, but may also occur in adults
o Presentation similar to bacterial meningitis but LESS SEVERE
o Disease occurs commonly in late summer and early fall (often associated with community epidemics)
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Examination of CSF (in comparison to bacterial meningitis):
Bacterial
Aseptic
Protein
Increase (>100mg/dl)
Normal or slight increase
Glucose
Decrease (<50% serum glucose)
Generally normal
WBC
Increase (>1000 cells/mm3)
Less of an Increase (<500 cells/mm3)
Majority are PMNs
Majority are lymphocytes
% PMNs
>50%
<50%
Note: can have >50% PMNs in viral
meningitis if LP is done very early in the
course of disease
**Note: NORMAL neonates may have up to 30 WBC/mm3 and protein levels up to 150mg/dl in their CSF**
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Differential diagnosis of the aseptic meningitis syndrome:
IMPORTANT: not exclusively caused by infections
Other causes:
o Carcinomatous meningitis
o Autoimmune diseases (lupus, RA, Kawasaki’s disease etc.)
o Drugs (NSAIDs, TMP/SMX, IVIG, carbamazepine, etc.)