Bacterial Meningitis in Children

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Bacterial Meningitis in Children
Dr Rajesh KumarMD (PGI), DM (Neonatology) PGI,
Chandigarh, IndiaRani Children Hospital, Ranchi
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• Inflammatory disease of the leptomeninges
• three parts the pia, arachnoid, and dura maters
• Meningitis reflects inflammation of the arachnoid
  mater and the cerebrospinal fluid (CSF) in both
  the subarachnoid space and in the cerebral
  ventricles.
• Suspected bacterial meningitis is a medical
  emergency,

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Organisms

• 1 month to 2 years The major causes were S.
  pneumoniae (45 percent), Neisseria meningitidis
  (30 percent), and group B streptococcus (18
  percent).
• 2 through 18 years N. meningitidis was the most
  common cause, accounting for 59 percent of cases,
  followed by S. pneumoniae (approximately 25
  percent) and Hib (approximately 8 percent).

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Organisms

• H influnzae
• Pneumococcus
• N meningitidis
• In lt3 months E.coli, Listeria

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Clinical Features

• Two patterns
• Develops progressively over one or several days
  and may be preceded by a febrile illness.
• Acute and fulminant, with manifestations of
  sepsis and meningitis developing rapidly over
  several hours. The rapidly progressive form is
  frequently associated with brain edema

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Symptoms

• Depends upon age
• Infants, 1-5 years, gt5 years
• Fever
• Symptoms and signs of meningeal inflammation
  (nausea, vomiting, irritability, anorexia,
  headache, confusion, back pain, and nuchal
  rigidity)

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Clinical features

• In one review of 1064 cases of acute bacterial
  meningitis in children older than 1 month, 16
  (1.5 percent) had no meningeal signs during their
  entire period of hospitalization
• Kernig sign With the hip and knee flexed at
  90º, cannot extend the knee more than 135º and/or
  there is flexion of the opposite knee
• Brudzinski sign Brudzinski sign is present if
  the patient, while in the supine position, flexes
  the lower extremities during attempted passive
  flexion of the neck
• Signs of meningeal irritation are present in 60
  to 80 percent of children with bacterial
  meningitis at the time of presentation and in
  approximately 25 percent of children with normal
  CSF findings
• Bulging fontanel was present in 20 percent of
  infants with meningitis, but also in 13 percent
  of infants with normal CSF and viral infections
  other than meningitis

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Clinical features

• Papilledema, which takes several days to become
  apparent, is an uncommon finding in acute
  bacterial meningitis. The finding of papilledema
  should prompt evaluation for venous sinus
  occlusion, subdural empyema, or brain abscess,
  TBM
• Signs of increased intracranial pressure that may
  occur in bacterial meningitis include palsies of
  the third, fourth, and sixth cranial nerves
• Seizures Seizures, typically generalized, occur
  before admission to the hospital or within the
  first 48 hours of admission in 20 to 30 percent
  of patients with meningitis. Seizures later in
  the course are more often focal and may indicate
  cerebral injury

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• Focal findings In one review of 235 children
  with bacterial meningitis, focal neurologic
  findings (hemiparesis, quadriparesis, facial
  palsy, visual field defects) were present at the
  time of admission in 16 percent of patients
  overall and in 34 percent of those with
  pneumococcal meningitis. The presence of focal
  neurologic signs at the time of admission
  correlated with persistent abnormal neurologic
  examination one year after discharge and with
  cognitive impairment.

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History

• The course of illness
• The presence of symptoms consistent with
  meningeal inflammation.
• The presence of seizures, an important prognostic
  finding.
• The presence of predisposing factors
• Immunization history
• Recent use of antibiotics, which may affect the
  yield of blood and/or CSF culture.

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Examination

• Vital signs volume status, presence of shock,
  and the presence of increased intracranial
  pressure. The constellation of systemic
  hypertension, bradycardia, and respiratory
  depression (Cushing triad) is a late sign of
  increased intracranial pressure.
• Head circumference should be measured at the time
  of admission in children younger than 18 months
  of age
• Elicitation of meningeal signs
• Cutaneous examinations are discussed above.
• Other bacterial infections (eg, facial
  cellulitis, sinusitis, otitis media, arthritis,
  pneumonia).

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Lab evaluation

• Blood cultures positive in at 50 of patients.
  Among children who were not pretreated with
  antibiotics.
• Contraindications to LP
• cardiopulmonary compromise,
• increased intracranial pressure,
• papilledema,
• altered respiratory effort,
• focal neurologic signs,
• skin infection over the site for LP
• CSF culture may be positive in the absence of
  pleocytosis

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CSF

• TLCtypically gt1000 WBC/microL, with a
  predominance of neutrophils .A CSF WBC count
  gt6/microL is considered abnormal in children
  older than 3 months of age
• Traumatic LP should be treated presumptively for
  meningitis pending results of CSF culture.
• The presence of a single neutrophil in the CSF is
  considered abnormal
• Glucose lt40 mg/dL in gt 50 cases. ratio of the
  CSF to blood glucose concentration is usually
  depressed (lt0.66)
• Protein100 to 500 mg/dL

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CSF CRP

• 100 sensitive and 96-100 specific
• -ve CRP rules out bacterial meningitis

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Role of urine culture

• Urine cultures should be obtained in infants (lt12
  months of age) who present with fever and
  nonspecific symptoms and signs of meningitis
  since urinary tract infection may be the primary
  source of the meningitis pathogen in such
  patients

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Neuroimaging

• Indications for imaging before LP in children
  with suspected bacterial meningitis include
• Coma
• The presence of a CSF shunt
• History of hydrocephalus
• Recent history of CNS trauma or neurosurgery
• Papilledema
• Focal neurologic deficit (with the exception of
  palsy of cranial nerve VI abducens nerve or VII
  facial nerve)

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Bacterial Meningitis Score

• Positive CSF Gram stain
• CSF absolute neutrophil count of lt1000
  cells/microL
• CSF protein of at least 80 mg/dL
• Peripheral blood ANC of at least 10,000
  cells/microL
• History of seizure before or at the time of
  presentation

Absence of all these excludes bacterial meningitis
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Treatment General Principle

• Avoidance of delay
• Emperical antibiotic

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• Drug entry into CSF Most drugs reach peak
  concentrations in the CSF that are only 10 to 20
  percent of peak concentrations in the serum. This
  is because the blood-brain barrier blocks
  macromolecule entry into the CSF, with small,
  lipophilic molecules penetrating most easily.
• The peak concentration of drugs in CSF increases
  with inflammation of the blood-brain barrier. The
  mean CSF/serum ratio two hours after
  administration of the same intravenous dose of
  penicillin was 42 percent on the first day of
  therapy but fell to less than 10 percent on the
  tenth day, when the inflammatory changes had
  subsided

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Immediate management

• Assurance of adequate ventilation and cardiac
  perfusion.
• Initiation of hemodynamic monitoring
• Establishment of venous access.
• Administration of fluids as necessary to treat
  septic shock, if present.
• Administration of dexamethasone if warranted.
  before or immediately after the first dose of
  antimicrobial therapy.
• Administration of the first dose of empiric
  antibiotics
• Administration of glucose (0.25 g/kg) for
  documented hypoglycemia (serum glucose
  concentration less than 40 mg/dL
• Treatment of acidosis and coagulopathy

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Supportive care

• Fluid and electrolyte management
• Isotonic fluid to maintain blood pressure and
  cerebral perfusion.
• Children who are hypovolemic, but not in shock,
  should be rehydrated with careful and frequent
  attention to fluid status.
• For children who are neither in shock nor
  hypovolemic, moderate fluid restriction (1200
  mL/m2 per day) initially, especially if the serum
  sodium is less than 130 meq/L. Fluid
  administration can be liberalized gradually as
  the serum sodium reaches 135 meq/L. Most children
  can receive maintenance fluid intake within 24
  hours of hospitalization.
• Monitoring
• increased intracranial pressure, seizure
  activity, development of infected subdural
  effusions, particularly during the first two to
  three days of treatment,
• Heart rate, blood pressure, and respiratory rate
  should be monitored regularly with a frequency
  appropriate to the care setting.
• A complete neurologic examination should be
  performed daily rapid assessment of neurologic
  function should be performed several times per
  day for the first several days of treatment.
• Head circumference should be measured daily in
  children younger than 18 months

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• In US (nelson)
• 25-50 S.pneumoniae resistant to penicillin
• 25 S Pneumoniae resistant to cefotax or
  ceftraixone
• 30-40 Hib resistant to ampicillin
• In INDIA ?

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JIPMER Study

• Organisms were isolated from the cerebrospinal
  fluid (CSF) in 35 of cases. Among infants and
  children, the two major pathogens were H.
  influenzae (17) and S. pneumoniae (12).
  RESULTS The illness at presentation was mild in
  13 and severe in 36 of cases. The

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Emperic Therapy

• empiric regimen should include coverage for Hib,
  penicillin resistant S. pneumoniae and N.
  meningitidis. E.coli in young infants
• High dose of 3rd generation cephalosporin
  Vancomycin

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Dexamethasone

• Animal studieshearing loss is associated with
  the severe inflammatory changes
• RCT and meta-analyses indicate that dexamethasone
  therapy provides no survival advantage in
  children, but reduces the incidence of deafness
  and severe neurologic complications in selected
  children, predominantly those with meningitis
  caused by Hib. The data are insufficient to
  demonstrate a clear benefit in children with
  pneumococcal meningitis
• before or within one hour of the first dose of
  antibiotic therapy
• concern that the CSF concentration of vancomycin
  may be diminished when administered with
  dexamethasone
• gt 6 weeks of age
• 0.15 mg/kg per dose) every 6 hours for 2 to 4
  days

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Duration of treament

• S. pneumoniae 10-14 days
• N. meningitidis 5-7 days
• Hib 7-10 days
• Gram ve 3 weeks
• CSF analysis near the end of therapy,
  particularly in young infants, needs longer
  therapy if
• Percentage of neutrophils gt30 percent,
• or CSF glucose concentration lt20 mg/dL

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Out patient therapy

• Completion of at least 6 days of inpatient
  therapy
• Afebrile for at least 24 to 48 hours before
  initiation of outpatient therapy.
• No significant neurologic dysfunction or focal
  findings.
• No seizure activity.
• Clinical stability.

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Response to therapy

• duration of fever is typically four to six days
  after the initiation of adequate therapy
• Persistence of fever beyond 8 days and secondary
  fever have a number of causes, including
• Inadequate treatment
• Development of nosocomial infection
• Discontinuation of dexamethasone
• Development of a suppurative complication
  (pericarditis, pneumonia, arthritis, subdural
  empyema)
• Drug fever (a diagnosis of exclusion)

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Repeat CSF

• Poor clinical response after 24-36 hours of
  antibiotics
• Persistence or recurrence of fever
• Gram ve meningitis

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Neuroimaging

• Focal neurologic signs, increasing head
  circumference, or prolonged obtundation,
  irritability, or seizures (gt72 hours after the
  start of treatment)
• Persistently positive CSF cultures despite
  appropriate antibiotic therapy
• Persistent elevation of CSF neutrophils at the
  completion of standard duration of therapy (more
  than 30 to 40 percent)
• Recurrent meningitis

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Prognosis

• Mortalitymeta-analysis 4520 children 4.8 in
  developed countries and 8.1 in developing
  countries
• Hib3.8 , N. meningitidis 7.5 , S. pneumoniae
  15.3
• Neurological sequele16 in developed and 26 in
  developing countries
• Deafness 11 percent, including bilateral severe
  or profound deafness in 5 percent
• Mental retardation 4 percent
• Spasticity and/or paresis 4 percent
• Seizures 4 percent

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Poor prognostic factors

• Etiology more with pneumocaccal
• Seizure after 72 hours
• CSF sugar lt 20 mg per dl at admission
• Delayed sterlization of CSF gt 24 hours

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Untreated meningitis as hydrocephalus

• infantile hydrocephalus due to clinically
  unsuspected meningitis.
• 8 year study period 54.2 (39/72) of
  hydrocephalus were found to be due to infection,
  far higher than what is reported from developed
  nations
• it may be a good practice to sample the CSF in
  every infant with hydrocephalus before a shunting

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Long-term Disability Following Neonatal and
Infantile Meningitis -results at 5 years of age
Disability Neonates Infants Controls
n274() n1304()
n1391() Severe 20 (7.3) 72 (5.5)
1 (0.1) plt0.0001 Moderate 50 (18.2)
103 (7.9) 20 (1.4) plt0.0001 Mild
66 (24.1) 392 (30.1) 275 (19.8) None
138 (50.4) 737 (56.5) 1095 (78.7)  
not significant. plt0.001
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Meningococcal Vaccination

• Currently licensed vaccine is composed of
  elements of polysaccharide coat of the bacteria
• Serogroups A, C, W-135, and Y
• Recommended for control of serogroup C
  meningococcal disease outbreaks although its not
  guaranteed to control them
• Recommended for use among certain high
  risk-groups

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• Vaccine may benefit travelers to countries in
  which disease is hyperendemic or epidemic
• A poor vaccine in children lt18-24 months
• Immunity of limited duration, especially in young
  children. Only 2-3 years at best.
• Vaccine confers effective protection
• Protective levels of antibody are usually
  achieved within 7-10 days