Meningitis

Acute Bacterial
 Introduction
• ABM is a common cause of the fever with features
suggestive of involvement of CNS.
• Bacterial meningitis - potentially serious infections of the
brain associated with
– High rate of acute complications,
– Long term morbidity & mortality.
 Etiology
• Causative organisms are determined by
– Age (neonatal period & post neonatal period)

– Immune status

– Environment of the child.

 Etiology
• Neonatal period: • Post neonatal period:
– Group B streptococcus. – Streptococcus pneumonia.
– Gram - ve enteric – N. meningitidis.
organisms. – H.influenza.
– Listeria monocytogenes. – Less commonly
– H.influenza. – Staph.aureus.
– Coagulase negative
Staphylococcus.
– Salmonella.
 Risk Factors
• Lack of immunity - specific to the age & organisms.
• Close contact with invasive disease caused by
H.influenza, N.meningitidis.
• Overcrowding, improvised living conditions - favors the
persons to person contact with respiratory secretions.
• Occult bacteremia in the infants - predisposes to
meningitis.
 Risk Factors – Contd..
• Specific host defense deficits leads to recurrent & severe meningitis
– Hypo/agammaglobemia,
– Defects in the complement & properidine systems Splenic dysfunctions may
lead to recurrent Hib & meningococcal meningitis.
– T cell defects, HIV infection
• CSF leak like fracture skull, cranial midline defects, fracture of
cribriform plate, fracture of stapedial foot process - associated with
pneumococcal meningitis.
• VP shunt, meningocele, lateral sinus thrombus - associated with
Staph.aureus meningitis.
 Risk Factors – Contd..
• Streptococcus infections
– Invasive disease in children of 0-2 yrs of age
– Prevalence of 2-2.5 per lakh populations.
– In patients with host defense defects, risk increases by 100 folds.
– Additional risk factors are
• Otitis media,
• Sinusitis,
• Pneumonia,
• CSF otorrhea or rhinorrhea.
 Risk Factors – Contd..
• N.minigitidis
– Sporadically & epidemically.
– Strains, A, B, C & Y are known to cause human disease.
– On exposure to index cases, the risk increases by 1000 folds.
• H.influenza
– Occurs commonly in infants of 2mo to 2 yrs of age with peak
incidence of 6-9mo.
– 50% of cases occurs in the first 2 yrs of life.
– Risk is high in day care centers & overcrowded environment.
 Pathology
• Three main pathological changes that determine
clinical features in ABM are
– Exudates.
– Subplial toxemia leading to parenchymal
disease.
– Vasculitis & Thrombosis of veins.
 Pathology – Contd..
• Exudates present
– Around the cerebral vessels & venous sinuses,
– Base and surface of the brain,
– Sylvian fissures, cerebellum &
– Subdural space
• Lead to
– Hydrocephalous,
– Signs of meningeal irritation,
– Signs of raised intra cranial tension &
– Cerebral ischemia resulting in neurodeficits.
 Pathology – Contd..
• Vascular changes:
– Subintimal changes occur in the small vessels & arteries.
– Thrombosis of small cortical veins, occlusion of major venous
sinuses, necrotizing arteritis,
– Subarachnoid hemorrhage, cerebral cortical necrosis, cerebral
infarction.
– Vasospasm, thrombosis of venules may lead to hemiparesis,
cranial nerve palsies, convulsions & coma.
 Pathology – Contd..
• Subplial toxemia:
– Subplial toxemia may lead to cerebral edema.
– Cytokine induces
• Increased vascular permeability &
• Increased hydrostatic pressure
• Leads to cerebral edema
• In turn produces irritability, signs of ICP, altered mental status, coma &
convulsions.
• Other contributing factor for the raised ICP is SIADH.
– Hydrocephalous can be communicative or obstructive which is
due to obstruction at foramen of Magendie or Lushka.
 Pathology – Contd..
• Pathogenesis:
– ABM commonly results from the hematogenous spread from the
distant infection.
– Bacteremia precedes meningitis.
– Colonization of nasopharyx is the usual source.
– Prior or concomitant viral infections may predispose to meningitis.
– The following events takes place in the pathogenesis of ABM
• Attachment to the epithelial cells leads to breach of mucosa &
access to circulation & bacteremia.
• Virulence of the organism & host defense mechanism
interaction determines the infection.
 Nasopharyngeal colonization

Pathology Local invasion

Bacteremia

Meningeal invasion

Bacterial replication in the subarachnoid space

Release of the bacterial components (cell wall & LOS)

Cerebral microvascular endothelium Macrophges, neutrophils & other CNS cells

Cytokines

Subarachnoid space Cerebral vasculitis

Papilledema &/or focal neurological inflammation
deficits
(excluding ophthalmoplegia
Mass lesion
Obtain blood culture & perform LP

No mass lesion
Obtain blood culture
Suspicion of bacterial meningitis
CT scan of the head

CSF consistent with ABM

Dexamethasone + emphirical
antibiotics
 Pathology – Contd..
• Bacteria gain entry into CSF through choroids plexus of
the lateral ventricles & the meninges & then reach the
subarachnoid space.
• Multiply rapidly - complement & antibody levels in CSF is
less compare to that of serum.
• Inflammatory response leads to production of TNF,
interleukins, PGE & other cytokine inflammatory
mediators.
Clinical Features
• Bacterial meningitis is characterized by
– Fever & Headache,
– Restlessness, irritability,
– Vomiting,
– Seizures,
– Altered sensorium varying from obtundation to coma.
• Two types of presentation is known
– Hyperacute - 1-2 days.
– Acute presentation – 2-7 days.
 Clinical Features – Contd..
• Clinical features in the neonates may not be classical
– Irritability,
– Temperature instability,
– Lethargy,
– High pitched cry, fretfulness, refusal of feeds, week suck,
– Jaundice, vomiting & respiratory distress.
– Altered mental status is an important sign.
• Classical signs of meningitis are absent.
• Bulging AF (30%), seizures (40%) & altered mental status
(60%) are common features.
 Clinical Features – Contd..
• Seizures are due to
– Cerebritis,
– Infarction, and
– Electrolyte disturbances.
– Occurs usually within 4 days of onset of fever.
• Seizures occurring after 4 days & resistant to treatment
carry a poor prognosis.
• Altered sensorium is due to raised ICP & cerebritis &
coma carries a poor prognosis.
 Clinical Features – Contd..
Signs & symptoms Frequency (%)
Fever 88-100
Vomiting 68-94
Headache 47-88
Salivary gland swelling 47-62
Meningismus 43-93
Lethargy 28-69
Abdominal pain 14-23
Seizures 14-18
 Diagnosis
CSF analysis:
• Diagnosis rests on CSF examination by lumbar puncture.
• CSF pressure should be recorded where ever is feasible.
• CSF is turbid or opalescent with elevated opening
pressure.
– Turbidity is seen when cells are >300/mm3.
 Diagnosis – Contd..
CSF analysis:
• Cells may be 1000-5000 cells/mm3 with a neutrophilic
predominance (75-98%).
• Absence of pleocytosis carries poor prognosis.
• Pleocytosis is absent in premature & young infants of
<4wks.
• CSF glucose of <40% is seen in 60% of the cases.
• CSF to blood glucose ratio of <0.3 is seen in 70% of
cases
 Diagnosis – Contd..
CSF parameter Typical finding
Opening pressure 200-500 mm H2O
WBC 1000-5000/mm3 (range <100 to
>10,000)
% of neutrophils >80%
Protein 100-500mg/dl
Glucose <40mg/dl
CSF to serum glucose ratio <0.4
Gram stain Positive in 60-90%
Culture Positive in 70-85%
PCR Promising
 Diagnosis – Contd..
• Role of repeat CSF analysis:
– In 1970, routine repeat LP used to be advocated at the
conclusion of treatment.
– The current trend is routine CSF analysis NOT INDICATED in
uncomplicated cases.
– But indicated in case where at the end of the treatment WBC
count, protein & glucose has not normalized.
– Repeat LP is also needed in neonate with Gram –ve meningitis &
organisms resistant to beta lactums.
 Diagnosis – Contd..
• Gram stain:
– Gram staining of CSF - rapid & accurate identification
of organisms in 60-90% of the patients.
– It is directly related to the
• Number of organisms in the CSF,
• Type of organism.
• Previous antibiotic therapy.
 Diagnosis – Contd..
• Gram stain:
– If CSF contains
• <1000 organisms on gram stain is 25%
• >1000 organisms - yield is >90%.
– Highest yield on gram staining is seen with
• Strep (90%)
• H.influenza (85%),
• Gram +ve organism (50%) & L.monocytogenes (50%).
– Children who has received previous antibiotics the yield on
gram staining is <50%.
– CSF becomes sterile with in 2-3 days after initiating the
antibacterial therapy.
 Diagnosis – Contd..
• Other investigations:
– Rapid test: Latex agglutination techniques to detect the antigens for
H.influenza, Strep.pneumoniae, meningococcus, E.coli.
– PCR - may be sensitive in the 91% of the cases.
• May be useful in the partially treated meningitis.
– CRP
• Elevated in blood as well as CSF.
• Useful test when bacteriological parameters are –ve & clinical & biochemical
parameters are suggestive of the ABM.
• Also helpful in ruling out viral meningitis.
– Neuro imaging like CT or MRI does not aid in the diagnosis.
 Diagnosis – Contd..
• Indication for NEUROIMAGING
– Subdural effusion.
– Hydrocephalus.
– Focal neurological signs
– Emergency CT
• Papilloedema
• Before LP
 Diagnosis – Contd..
• Indication for EEG
– Focal seizures.

– Persistent convulsions for >72hrs.

– Seizures occurring after 3 days.

– Subdural effusion.
 Diagnosis – Contd..
• DD:
– Other causes of meningitis should be differentiated in
a child who presents with fever & CNS manifestation.
• Viral meningitis,
• TB meningitis,
• Fungal meningitis - cryptococcal meningitis
• Toxoplasma meningitis.
– In cases of partially treated meningitis
• Concentration of glucose & protein & neutrophil profile are
not altered.
• Gram stain & culture may be –ve.
 Diagnosis – Contd..
• Complications:
– SIADH is seen in 88% of bacterial meningitis.
• Should not be diagnosed in presence of dehydration.
• If SIADH is diagnosed,
– Monitor Serum electrolytes for hyponatremia &
– Daily body weight &
– Serum ADH.
• Treated by restricting fluids intake.
– Subdural effusion as indicated by focal seizures & persistent or
reappearance of fever.
– May present with shock which should be treated aggressively to
prevent multi-organ dysfunction.
• Isotonic fluids to maintain BP >90mm of Hg
• Monitor Urine output 500ml/m2/24hrs.
• Dopamine & dobutamine may be needed.
 Diagnosis – Contd..
• Complications:
– Causes for prolonged fever may include
• Pyogenic complications
– Intra-cranial – subdural effusion & abscess.
– Extra-cranial – pericarditis, empyema, thrombophelbitis.
• Drug fever.
• Poor therapeutic response.
• Drug resistant organisms.
 Management – Contd..
• Treatment components are
– Specific
• Antibiotics
– Supportive
• Monitoring & Stabilization – shock & dehydration
• Fever care & Control of seizures.
• Fluids, electrolytes & nutrition.
• Reduction of raised ICP.
• Management of complications.
– Adjuvant therapy.
– Other therapy.
– Chemoprophylaxis.
– Prevention.
 Treatment of ABM
• Prompt therapy with appropriate antibiotics is critical.
• Initial antibiotics are given before definitive culture results are
available.
• Selection depends on
– Local incidence & susceptibility patterns.
– Causative pathogens.
– Ability of drugs to penetrate the blood brain barrier to achieve bactericidal
concentration in CSF.
– Age of the child.
– Onset – hyperacute/ acute.
 Empirical therapy
• Regimens are selected to cover the most likely
etiological agents.
• Therapy modified as soon as culture reports are
Available.
Infants 0 – 2 months
 Causative organisms
• Neonates - In developing countries
– Gram –ve organisms – 64%.
– Gram +ve organisms – 36%.
Gram –ve % Gram +ve %
E.coli 16 CONS 18
Klebsiella 16 Stap.aureus 10

Pseudomonas 5 GBS 5
Hib 1 Listeria 1
Nesseria 1 Strep.pneumoniae <1
Others 16
 Recommended drugs
• Ampicillin + gentamycin/ cefotaxime – Drug of
choice.
• Repeat CSF in 24-36hrs.
• No advantage of
– Intra-thecal antibiotics.
– Intra-venticular antibiotics –chances of ventriculitis are
high.
• If pseudomonas is suspected
– Ceftazidime should be used.
 Recommended drugs
• Premature infants –
– Stap. Enterococci, β-lactamase resistant organisms.
– Combination of nafcillin/oxacillin, amikacin.
• MRSA – Vancomycin + amikacin / cefotaxime.
• Multidrug resistant gram –ve bacteria.
– Meropenam, cefipime, fluroquinolones.
– Requires greater experience for their usage.
 Recommended drugs – Contd..
• After C/S report -Single or combination of drugs
should be used.

GBS Ampicillin / penicillin.

Listeria Ampicillin
Enterococci Ampicillin + aminoglycoside
Pseudomonas Caftazidime, ticarcillin +
aminoglycoside
Coliform organisms Cefotaxime
 Duration of treatment
• Depends on the organisms.
– Gram +ve – 2wks after bacteriological cure.
– Gram –ve – minimum 3 -6wks
• Final decision
– Depends on the clinical course of the illness.
– CSF findings at the time of decision.
• Dexamethasone – no sufficient data available –
routine use is not recommended.
Beyond 2 months of age
 Empirical therapy
• Ampicillin & chloramphenicol – preferred drugs in the past.
• For empirical therapy – III generation cephalosporines – Drug of
choice.
– Have excellent antibactericidal activity against
• Hib, meningococcal, & pneumococcal infections.

– Penetrate BBB & attains sufficient MIC in CSF.

 Empirical therapy – Contd..
• Cefotaxime / ceftriaxone are comparable to Ampicillin &
chloramphenicol.
• Add vancomycin 60mg/kg/day in 4 divided doses when
drug resistant pneumococcus is suspected.
• When culture reports are available – Penicillin/Ampicillin in
susceptible cases of streptococcus/ meningococcus.
 Duration
• Individualized
• Complicated or uncomplicated course.
• Causative organisms
Uncomplicated meningitis 5 – 7 days
GBS 14 – 21 days
Listeria 10 – 14 days
Gram –ve >3 wks
Hib 7 -10 days
Streptococcus 10 – 14 days
 Home management
• Initial treatment should be in hospital for 6 days.
• Should be afebrile for 48-72hrs.
• No neurological deficits.
• No seizures.
• Clinically stable.
• Able to take oral feeds.
• Examination should be done daily.
• Drugs should be administered by qualified medical
personnel with all precautions
• Reliable parents
• Communication – transport & telephone must be
available.
 Supportive therapy
• Fluid therapy.
– If dehydration is present
• Adequate fluid to treat the dehydration.
• No restriction of fluids.
– If no dehydration
• Restriction of fluids to 50-75% of maintenance.
– Later – liberalize the fluid intake once serum Na+ level is
normalized.
 Supportive therapy – Contd..
• Corticosteroids
– Anti-inflammatory agents – may decrease the degree of
tissue injury.
– Decrease the ICP by decreasing meningeal
inflammation of decrease brain water content.
– Modulate the production of cytokines thereby reducing
the meningeal inflammatory response.
– Decrease the incidence of sensori-neural hearing loss.
 Supportive therapy – Contd..
• Corticosteroids
– Recommended by red book committee & infectious
diseases committee of AAP in
• Pneumococcal meningitis in children of > 6wks of age.
• Hib meningitis.
– Should not be used in
• Aseptic meningitis.
• Partially treated meningitis.
– Should be used in all cases irrespective of severity.
– Dosage –
• Dexamethasone – 0.15mg/kg/day every 6th hrly for 4 days.
• Initial dose should be given 1-2hr before initial antibiotics.
 Supportive therapy
• As important as specific antibiotic therapy.
• Careful monitoring is crucial.
• TPR & BP monitored initially hrly & later 4th hrly.
• Neurological examination id done repeatedly
everyday
• Head circumference in children <18mo every day.
• Weight once in 3 days.
• Intake out put.
 Chemoprophylaxis - H.influenzae
• All members of the household with
– >1contact <4yr old incompletely immunized.
– Immuno-compromised >4yr old & fully immunized
– All susceptible nursery/ childcare center contact when >2 cases
of Hib invasive disease with in 60 days
– Index cases being treated with Ampicillin or cholramphenicol if
<2yrs of age or with a susceptible household contact.
• Recommended regimen
– Rifampicin 20mg/kg orally once daily for 4 days.
– For infants of <1mo dose is 10mg/kg.
 Chemoprophylaxis – N.meningitidis
• All household contacts nursery/ childcare center contacts
during 7days before onset of illness.
• Direct exposure to index case’s secretions – kissing,
sharing of eating utensils, tooth brushes, close social
contact - during 7days before onset of illness.
• Recommended regimen
– Rifampicin 10mg/kg orally once daily for 2 days, for infants of
<1mo dose is 5mg/kg.
– Ceftriaxone 125mg for <15yrs old or 250mg for >15yr old IM
single dose.
– Ciprofloxacin 500mg orally in >18yr old single dose.
 Prognosis
• Prompt diagnosis, Appropriate antibiotics, Supportive care
– is important
• Determinant of prognosis
– Type of onset,
– Age,
– Organisms,
– Selection of antibiotics, dosage, route of antibiotics.
– Comorbidity like malnutrition
 Prognosis – Contd..
• Poor prognostic factors.
– Age < 6mo.
– Seizures & coma.
– Focal neurological deficits at presentation or lasting for >
4 days.
 Summary
• Prompt accurate diagnosis is important.
• Adequate treatment
– Appropriate drugs.
– Appropriate dose.
– Appropriate route.
– Adjuvant therapy.
– Supportive therapy – as essential as antibiotics.