BACTERIAL MENINGITIS
DEFINITION:
Inflammation of the meninges that is identified by an abnormal
number of white blood cells (WBCs) in the cerebral spinal fluid (CSF)
and evidence of a bacterial pathogen in the CSF.
EPIDEMIOLOGY:
- incidence:
- newborn: 0.5/1000 live births
- childhood: ?
- age of onset:
- highest age-specific attack rates are in the newborn period
and between 3-8 months of age
- 90% of all cases before the age of 5 years
- risk factors:
- sepsis with hematogenous spread to meninges:
- incidence of bacterial meningitis is about 1/4 cases of
sepsis
- blood usually invaded from a colonized site -
respiratory tract or umbilical cord
- rarely contamination from neural tube defects, congenital
sinus tracts, penetrating scalp wounds
2. Genetic
- Inuit, Navajo, Alaskan Eskimos
- HLA-B12, absence of Bw40
- M > F
3. Environment
- closed communities - households, day-care centres,
classrooms, institutions
4. Host Factors
- congenital/acquired deficiencies in host defense
mechanisms:
2. Complement Deficiencies
3. Splenic Deficiencies
- following splenectomy
- congenital asplenia or splenosis
4. Others
- sickle cell anemia & other hemoglobinopathies
- malignancies
CLINICAL FEATURES:
- minimal and subtle (high index of suspicion)
- fever (50%)
- seizure (40%)
- bulging fontanelle (33%)
- irritable +/- change in consciousness & poor muscle tone
(33%)
- others:
- apnea and bradycardia, cyanosis, diarrhea, disinterest in
feeding, jaundice, lethargy, respiratory distress, temperature
instability (hypothermia or fever), vomiting
2. Children
- fever, headache, photophobia
2. Others
- irritability, lethargy, mental confusion, nausea and
vomiting
- change in affect or state of alertness
2. Signs
- Kernig and Brudzinski signs
2. Others
- erythematous maculopapular rash -> purpura and
petechiae (Neisseria)
- Tache Cerebrale - stroke skin with a blunt instrument
-> 30-60 sec -> raised red rash
2. Central Nervous System
- seizures (20-30% of cases):
- focal, generalized, or subtle, febrile
- due to abscess, cerebritis, SIADH, subdural
effusion, vascular thrombosis, ventriculitis
- focal neurologic signs:
- cranial nerve +/- facial palsies
- hemiparesis, quadriparesis
- visual signs:
- endophthalmitis, papilledema
- visual field defects (due to cortical venous or
arterial thrombosis)
- auditory signs:
- ataxia & hearing loss (due to labyrinthitis)
- altered state of consciousness:
- obtunded, semicomatose, comatose
3. Systemic Conditions
- cellulitis, septic arthritis, otitis media, pneumonia,
etc which act as the source of infection
INVESTIGATIONS:
- high index of suspicion (only 10-16% of LP's are positive)
- any patient with sepsis or bacteremia
- repeat LP within hours to days if clinical signs and
symptoms persist
- +/- febrile seizures (although only 5% have underlying
meningitis)
2. Contraindications
- cardiorespiratory compromise
- increased intracranial pressure (ICP)
- infection in the area of needle insertion
- bleeding diathesis
3. Adverse Reactions
- bleeding into CSF, headache, herniation of brainstem and
cerebellar tonsils, pain
4. CSF Analysis (in patients >6 weeks of age)*
- <5 WBC/uL
- <40 mg/dl protein
- 2.5-3.6 mmol/L glucose (<67%)
2. Bacterial
- 200-2000 WBC/uL (PMN)
- >130 mg/dl protein
- <2.5 mmol/L glucose (<67%)
3. Viral
- 0-200 WBC/uL (LYM)
- <40 mg/dl protein
- 2.5-3.6 mmol/L glucose (<67%)
4. Tumor
- 0-200 WBC/uL (LYM)
- 50-500 mg/dl protein
- 2.5-3.6 mmol/L glucose (<67%)
- *Bonadia, W.A. (1992), Pediatric Infectious Disease J. 11:
423-432
- *FN rates can be as high as 47% but there appears to be a
less than 1% chance that a patient with meningitis will have a
completely normal CSF exam, ie., have to look at everything
- risk factors for bacterial meningitis:
- Pleocytosis
- ANC >1 neutrophil/uL (with neutrophil predominance)
- Hypoglycorrhachia (with a CSF:serum ratio <0.4)
- Elevated CSF [Protein]
- Positive Gram stain
- CSF collection:
- Tube #1 - cell count with differential - looking for
pleocytosis and ANC
- Tube #2 - glucose - looking for hypoglycorrhachia
- Tube #2 - protein - looking for elevated [protein]
- Tube #3 - gram stain, C&S - looking for organisms
- Tube #4 - viral cultures - looking for virus
5. Pleocytosis (WBC Count)
- Normal CSF WBC Count (WBC/uL):
- Term - 8.2 (mean); 22 (upper limit of normal [+2SD])
- 0-4 weeks - 11.0 (mean); 35 (upper limit of normal
[+2SD])
- 4-8 weeks - 7.1 (mean); 25 (upper limit of normal
[+2SD])
- >6 weeks - 2.3 (mean); 5 (upper limit of normal
[+2SD])
- CSF mean total WBC count is inversely proportional to
patient age
2. Abnormal
- vast majority of paediatric patients with bacterial
meningitis are associated with CSF pleocytosis:
- 0-4 weeks - 83% of cases
- >4 weeks - 98% of cases
- school-age - 100% of cases
- CSF becomes opalescent when there are between 200-500
WBC/uL
- magnitude depends upon invading organism:
- N. meningitidis - 5476 (WBC/uL)
- H. influenzae b - 4612 (WBC/uL)
- S. pneumoniae - 1136 (WBC/uL)
- time coure:
- slight pleocytosis may persist 18-36 hours after
initiating antibiotic therapy
- significant reduction in WBC count within 48-72 hours
after initiating antibiotic therapy
- there may be a persistence of pleocytosis after the
full antibiotic course
6. CSF Absolute Neutrophil Count (Neutrophils/uL)
- ANC = total WBC count x % neutrophils x 0.01
- normal CSF = <1 neutrophil/uL
- normal % CSF neutrophils = <35% (in those <4 weeks)
2. Abnormal
- abnormal CSF = >1 neutrophil/uL
- CSF neutrophil (>50%) predominance in patients with
bacterial meningitis:
- 0 to 4 weeks of age - 100% of cases
- >4 weeks of age - 99% of cases
- no difference in CSF mean % neutrophil count associated
with the 3 major pathogens (>3 months)
7. Hypoglycorrhachia
- Normal Values of CSF Glucose (mmol/L):
- Term - 2.9 (mean); 1.9-6.6 (range)
- 0-4 weeks - 2.6 (mean); 2.0-3.4 (range)
- 4-8 weeks - 2.6 (mean); 1.6-3.4 (range)
- >6 weeks - 3.4 (mean); 2.5-3.6 (range)
- CSF glucose characteristics:
- derived from serum via a carrier-facilitated transport
of glucose into the CSF
- removed by bulk flow into the venous circulation and
through utilization as a fuel source
- CSF [glucose] usually < serum [glucose]
- reaches adult CSF values by 4-8 weeks of life
2. Abnormal
- majority of paediatric patients with bacterial
meningitis are associated with hypoglycorrhachia:
- 0-4 weeks - 61% of cases
- >4 weeks - 78% of cases
- school-age - 45% of cases
- CSF glucose ranges from 1.1-1.7 mmol/L in the majority
of cases of hypoglycorrhachia
- mechanisms of hypoglycorrhachia:
- increased rate of transport out of CSF
- increased glycolysis by WBC and bacteria
- increased metabolic rate of brain and spinal cord
- decreased transport of glucose into the CSF due to
inhibition of the membrane carrier system
- in 70% of cases, the hypoglycorrhachia resolves after 48
hours of antibiotic therapy
- CSF:serum glucose concentration ratio:
- value of <0.4 is highly accurate in defining
hypoglycorrhachia in bacterial meningitis
- in children with bacterial meningitis >2 months,
hypoglycorrhachia is 80% sensitive and 98% specific
- may range from .2-.52 after complete course of
antibiotics
8. Gram Stain
- reveals bacteria in more than 90% of cases except in older
(school-age) children where the rate of positive Gram stain is
only 50%
- rate of positive Gram stain is not associated with
different pathogens
- after 24-48 hours of adequate antibiotic therapy, 98% of
cases convert to no organisms visualized on repeat CSF
sampling
- Neisseria and Listeria are most apt to be missed
9. Elevated CSF Protein Concentration
- Normal Values of CSF Protein (mg/dl):
- Term - 90 (mean); 20-170 (range)
- 0-4 weeks - 84 (mean); 35-189 (range)
- 4-8 weeks - 59 (mean); 19-121 (range)
- >6 weeks - 28 (mean); 20-45 (range)
- CSF protein content is age-dependent being greatest at
birth because of increased permeability of the blood-brain
barrier to protein at this time
- two main components of CSF protein are albumin (70%) and
gamma-globulin (10-15%) with an overall albumin:globulin
ratio of about 5:1
- very low CSF/serum protein ratio due to:
- exclusion of high molecular weight proteins from the
CSF
- protein exit rate from CSF is 200-300x greater than
the entrance rate into the CSF
2. Abnormal
- majority of paediatric patients with bacterial
meningitis are associated with elevated CSF [protein]:
- 0-4 weeks of age - 55% of cases
- >4 weeks of age - 93% of cases
- school-age - 60% of cases
- elevated CSF protein in bacterial meningitis usually
ranges from 130-300 mg/dl but can reach levels 500-1000
mg/dl (14%) and >1000 mg/dl (8% of cases)
- usually elevated within 16-18 hours after bacterial
invasion
- mechanisms of elevated CSF [Protein]:
- opening of tight junctions of cerebral capillaries
during the inflammatory process
- complement and antibodies enter the CSF with other
serum proteins
- after appropriate antibiotic therapy, the CSF protein
concentration may decrease by 75% from initial values
- an abnormally low CSF [protein] (<20 mg/dl) may occur
with conditions in which there is an elevated ICP (increases
bulk flow reabsorption of protein out of the CSF)
10. Other
- normally 14 mg/dl
- in bacterial meningitis is usually <25 mg/dl
2. Intracranial Pressure
- elevated in bacterial meningitis particularly during the
first two days of illness
2. Serum
- positive in 85% of patients with GBS meningitis
- positive in 75% of patients with gram negative meningitis
2. Blood Cultures
- 70-85% of neonates with meningitis will have positive
blood culture
3. Complete Blood Count
3. Imaging Studies
- brain abscesses
- subdural effusions or empyemas
- ventriculitis
- hydrocephalus
MANAGEMENT:
- empiric Ampicillin and Gentamicin
- Ampicillin or Penicillin for 14-21 days
2. E. coli
- Gentamicin +/- Cefotaxime for 21 days
3. Listeria monocytogenes
- Ampicillin and Gentamicin for 14-21 days
- resistant to all cephalosporins
4. Others covered
- Enterococcus sp., Klebsiella pneumoniae, Salmonella sp.
2. Infant (1-3 months)
- empiric Ampicillin and Cefotaxime
3. Infant (older than 3 months)
- 50% of isolates Ampicillin resistant
- treatment for 7-10 days
2. N. meningitids
- penicillin resistant strains appearing
- treatment for 7 days
3. S. pneumoniae
- 5-15% of isolates Penicillin resistant
- treatment for 7-10 days
2. Steriod Therapy
- use in patients older than 6 weeks of age
- give prior to first dose of antibiotic
- dexamethasone 0.6 mg/kg/day IV q6h for 4 days
- reduces incidence of neurologic sequelae, i.e., hearing loss
3. Supportive
- sepsis +/- complications
- elevated ICP
- seizures
- electrolyte abnormalities - SIADH
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