Berhanu .E (M.

D)

08/02/20 bacterial meningitis for C-I student 1

Objectives:
Identify concept of meningitis.
Discuss etiology & epidemiology of meningitis.
Explain pathogenesis & risk factors of meningitis.
Discuss diagnosis & differential diagnosis of meningitis.
Outline complications & prognosis of meningitis.
Discuss treatment & prevention of meningitis.

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 DEFINITION
Acute inflammation of the membranes covering the brain
& spinal cord with evidence of bacteria &
polymorphonuclear leukocytes in the cerebrospinalfluid.

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 Meningitis

Bacterial Aseptic
)Septic(
Tuberculous

Viral
Fungal
Non-infectious

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ETIOLOGY
● Pathogen is influenced by :
-Age of the host
-Immune status of the host
-Epidemiology of the pathogen
a) Birth - 2 months
 Group B Streptococci (Streptococcus agalactiae)

 Gram –negative enteric bacilli(E.coli,klebsiella)

 Listeria Monocytogenes

 Group D streptococci (Enterococcus)

b) 2 month - 12 years
 S. Pneumoniae

 N. Meningitidis

 H.. influenza type B ( 70% of cases of meningitis in <5 yr of age )

c) Other less common pathogens

- P. aeruginosa , S. aureus , CONS , Salmonella spp. , L.monocytogenes
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 EPIDEMIOLOGY
 Risk factors
 Lack of immunity to specific pathogens
associated with young age
 Recent colonization with pathogenic bacteria
 Close contact
 Black race
 Male sex
 Crowded living conditions
 Poverty
 Splenic dysfunction
 CSF leak ( congenital or acquired )……Pneumococcal meningitis
 T-lymphocyte defects ( congenital or acquired )
- Listeria Monocytogenes
 Lumbosacral dermal sinus and meningomyelocele
- Staphylococcal and gram negative enteric bacterial meningitis
 CSF shunt infections
- Staphylococci (especially CONS)
- Low virulence bacteria that colonize the skin
 Mode of transmission
 Person to person contact through respiratory tract secretions or droplets

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 H. influenzae
 Invasive infections occur primarily in the 1st 2mth -2 yrs of life
 Peak incidence 6 - 9 mth of age
 Risk factors :
-Family or day care center contacts of patients with H . inf type b disease
-Unvaccinated individuals
-Individuals with blunted immunologic response to vaccine
e.g. child with HIV infection

 S. Pneumoniae
 Invasive infection peaks during the first 2 yrs of life
 Risk factors :
-Age < 2 yrs
-Asplenia (functional or anatomic )
-HIV infection
-Otitis media ,sinusitis,pneumonia
-CSF otorrhea or rhinorrhea

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N. meningitidis
-Serogroups A ,B ,C,,W135,Y
 Epidemic disease serogroup A

-Cases are common in winter & spring

-Nasopharyngeal carriage …1-15 % of adults
-Attack rate in family…..1 %
-Most infections of children are acquired from :
 Contact in a day care facility

 Colonized adult family member

 Ill patient with meningococcal disease

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PATHOLOGY AND PATHOPHYSIOLOGY
-Meningeal exudates ( with variable thickness )
-Ventriculitis
-Subdural effusions
-Occurs in later phase ; because of transudation of fluid .
-Subdural empyema
-Perivascular inflammatory infiltrates
-Ependymal membrane disruption
-Vascular and parenchymal cerebral changes

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-Cerebral infarction
-Inflammation of the spinal nerves and roots
 Produces meningeal signs
-Inflammation of the cranial nerves
 Produces cranialneuropathies(2,3,7,8)
-Increased ICP
 Types of cerebral edema :
a) cytotoxic cerebral edema -Cell death
b) vasogenic cerebral edema -Cytokine-induced increased capillary
permeability
c) Interstitial cerebral edema -Increased hydrostatic pressure
-SIADH
 Excessive water retention ……Increased risk of elevated ICP
 Hypotonicity of brain extra cellular spaces……..cell swelling and
lysis……Cytotoxic edema

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-Hydrocephalus
 Communicating

- Most common form

- Due to adhesive thickening of the arachnoid villi
around the cisterns at the base of the brain
 Obstructive

- Less common form

- Due to fibrosis and gliosis of the aqueduct of sylvius or
the foramina of magendie and luschka

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-Raised CSF proteins

 Increased vascular permeability of the blood brain barrier

……..loss of albumin rich fluid from the capillaries and veins
traversing the subdural space .

-Hypoglycorrhachia (reduced CSF glucose level)

 Due to decreased glucose transport by the cerebral tissue

-Damage to the cerebral cortex

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PATHOGENESIS
a) Bacterial meningitis most commonly results from
hematogenous dissemination of microorganisms from a
distant site of infection .
 Bacteremia usually precedes meningitis or occurs concomitantly

b)Meningitis rarely follows bacterial invasion from a

contiguous focus of infection
 Para nasal sinusitis , otitis media , mastoiditis,orbital cellulitis ,
cranial or vertebral osteomyelitis

c )Meningitis may occur after direct introduction of bacteria

in to subarachnoid space
 Penetrating cranial trauma ,dermal sinus tracts , meningomyeloceles

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Development of meningitis is influenced by
interaction of :

Host factors : Age, Sex (more in males) ,

Underlying disorder e.g.. Immunodeficiency

The organism
- The organism must have an essential bacterial
virulent factor disclosed by having
polyribophosphate (capsular )antigen.

The environment
- Children living in crowded areas are at high risk
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CLINICAL MANIFESTATIONS
Two patterns of onset :
a ) Dramatic onset (less common )

Shock , purpura ,DIC ,reduced level of

consciousness, death with in 24 hour.

b )Gradual onset (more common )

Meningitis is preceded by several days of fever

accompanied by URT or GI symptoms
-followed by nonspecific signs of CNS
infection like increased lethargy &
irritability .
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 Non-specific findings
- Fever ,anorexia ,poor feeding ,symptoms of
URTI, myalgias , arthralgias , tachycardia,
hypotension, petechiae , purpura ,
erythematous macular rash

Signs of meningeal irritation

- Back pain ,neck stiffness , kernig sign,
brudzinski sign.

Papilledema , photophobia
Focal neurologic signs
10 - 20% of cases
Cranial
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  Signs of increased ICP
- Headache ,emesis ,bulging fontanel , diastasis
(widening ) of the sutures
- Oculomotor or abducens nerve palsy
- HTN with bradycardia ; stupor ,coma
- Apnea or hyper ventilation ,signs of herniation
- Decorticate or decerebrate posturing
 Seizures
- Focal or generalized
- 20 -30 % of cases
- Causes : cerebritis ,infarction ,or electrolyte disturbance
 Alteration of mental status
- Common
- Causes : increased ICP , cerebritis ,hypotension
- Manifestations : irritability,lethargy,stupor,coma.
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DIAGNOSIS
1) Lumbar puncture
 Between L2 & L3 or L3 & L4
 Confirms DX of meningitis
 CSF
 Pressure …..usually elevated to 100-300 mmH2O ( Nl =50-80 mmH2O
)
 Gross appearance……turbid (WBC >200-400 /mm3)
 WBC count (Nl =less than 5 , lymphocyte > 75% or monocytes )
 Usually elevated to >1000/mm3 (100 – 10,000/mm3 or more )
 Neutrophil predominance ( 75- 95% )
 In 20 % of cases WBC < 250/mm3
 Absent pleocytosis …….sever overwhelming sepsis

with meningitis
 Pleocytosis with lymphocyte predominance…….during

early stages
 Elevated protein …usually 100-500 mg/dl (Nl = 20 - 45 mg/dl )
 Reduced glucose….usually <40 mg/dl (or <75% of serum glucose )
( Nl =>50mg/dl or 75 %of serum glucose )
 Gram stain : positive in 70-90 % of cases
 Culture

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 microbio WBC/ml Glucose PROTEIN Pressure Gross
logy (mg/dl) (mg/dl) (mmH2O) appearanc
e
<5 40-80
sterile ≥ 75% >75% 20-45 50-80 clear Normal CSF
L.cytes of RBG
Gm stain
↑ 100- ↓ <40
& bacterial
10,000 <66% 100-500 ↑ 100-300 cloudy
Culture mng
PMN of RBG
+ve
10-
10,000
Partially
Culture PMN but
↓ or N 100-500 N or ↑ ± clear treated
+ve ±
bacterial
lymphoc
ytes
AFB 10-500 100-500
culture PMN → <50 ± ↑↑ in Usually ↑ opalescent T.B mng
+ve L.cyte obstr.
Rarely >
1000 N or slight
PCR N 50-200 clear viral
PMN → ↑
L.cyte
25-500
culture PMN → <50 20-500 Usually ↑ ----- fungal
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  Contraindications for LP
- Increased ICP
- Sever cardiopulmonary compromise
- Infection of the skin overlying the site of the LP
- Thrombocytopenia( < 20,000/mm3 ) : Relative c/I
 Traumatic LP
- Affects CSF WBC & protein concentration
- Does not affect G/S , culture & Glucose level
- Repeat LP after sometime
2) Latex particle agglutination
- Highly sensitive but less specific
3) Blood culture : Positive in 80 -90 % of cases

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4. CNS imaging
It is considered when another brain pathology is suspected:
*Prolonged coma
*Persistent irritability.
*Persistent (>4d) or focal seizures
*focal neurological deficits
*Enlarging head circumference
*Persistent ↑ in CSF PTN & PMN
*Recurrent disease

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DIFFERENTIAL DIAGNOSIS
A) INFECTIONS
1) Generalized infection of the CNS
 Bacteria

M . Tuberculosis (Tb meningitis)

 T . Pallidum (Syphilis )

 Fungi

 Histoplasma ,Candida ,Cryptococcus , Aspergillus

 Parasites

 T .godii , Cysticercosis

 Viruses

 Enteroviruses , HSV( Viral meningoencephalitis )

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 2) Focal infections of the CNS
 Brain abscess
 Para meningeal abscess

 Subdural empyema

 Cranial epidural empyema

 Spinal epidural empyema

B) NON-INFECTIOUS ILLNESSES
-Cause generalized inflammation of the CNS
-Uncommon
 Malignancy

 Collagenvascular syndromes
 Exposure to toxins

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TREATMENT
A) Antibiotics
Always use high dose ,parenteral (IV) antibiotics.
 Initial (empirical )choice of therapy
Vancomycin 60 mg/kg/24 hr, given every 6 hr

OR
Ceftriaxone 100 mg /Kg /24 hr once per day or

50 mg/Kg /dose every 12 hrs for 7 – 10 days

OR
Cefotaxime 200 mg /Kg /24 hr every 6 hr for 7- 10

days
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 Patientallergic to b-lactam antibiotics
-CAF 100 mg /Kg /24hr given every 6 hr
OR
- Patient can be desensitized to the
antibiotic
 If patient is immuno compromised
-Ceftazidime and aminoglycoside need to be
included because of risk of gram –ve bacterial
meningitis e.g. P.aeruginosa ,E .coli
Duration of antibiotic therapy

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 a) Generally total of 10 days
b) Specific ( based on etiologic agent ) in
uncomplicated cases
N .meningitidis…….5 -7 days

H .influenzae type b……….7 10 days

S .Pneumoniae………..10-14 days

CSF culture –ve………7- 10 days

Gram –ve bacilli……03 weeks or 2 weeks after

CSF sterilization
( usually after 2 – 10 days of treatment )
Neonates ……..03 weeks

** N.B. In complicated cases of meningitis ,give

antibiotics for 10-14 days
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 PRACTICE IN ETHIOPIA

- Crystalline Na penicillin G 250,000 IU

/Kg IV stat…..loading dose
Then, 500,000 IU /Kg/24hr in 8 divided
doses for 10 days .
PLUS

CAF 50 mg/Kg IV stat …….loading dose

Then, 100 mg /Kg /24 hr in 4 divided doses
for 10 days
OR
- Ceftriaxone 50 mg /Kg /dose every 12 hrs
for 7- 10 days
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B) Corticosteroids
Dexamethasone 0.15 mg/Kg/dose every 6 hrs for 2

days
Maximum benefit if given 1-2 hours before

antibiotics are initiated

Limit inflammatory mediators that worsen

neurologic injury and CNS symptoms & signs

C) Supportive care
Repeated medical and neurologic assessment esp.

during the 1st 72 hrs

(Use neuro-sign chart)
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 IV fluid
- Restrict to 1/ 2 - 2/3 of the maintenance
(800 -1000ml/m2 /24hr )
till we rule-out increased ICP or SIADH
- When serum Na is normal…… change IV fluid to
normal (1500-1700ml/m2/24hr)
- Systemic hypotension or shock……Rx aggressively
with IV fluids
- Septic shock…..add also vasoactive agents

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 Lab Ix
- BUN ,serum Na, Cl ,K ,HCO3
- Urine ….output &Specific gravity ,CBC
- PT ,PTT, fibrinogen level for bleeding diathesis
Increased ICP

- Elevate head to 30 degree

- Endotracheal intubation & hyperventilation
(To maintain pCO2 at around 25 mmHg)
- Furosemide 1mg/Kg IV…..diuresis & venodilation
- Mannitol 20% 0.5 -1 gm/Kg/dose IV to run in 30
min , repeat 6 hourly if needed

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 Seizure control
- IV diazepam 0.1 -0.2 mg/Kg /dose or
IV lorazepam 0.05 – 0.1 mg/Kg /dose
- Monitor serum glucose ,Na ,Ca
- Phenytoin 15 -20 mg/Kg loading dose .
- Then 5 mg /Kg /24 hr maintenance dose
OR
- Phenobarbitone 20 mg /Kg IV loading dose
- Then 5 mg/Kg /24 hr maintenance dose
** Phenytoin causes less CNS depression & permits
assessment of level of consciousness
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COMPLICATIONS
1.Acute complications
Seizures
Increased ICP
Cranial nerve palsies
Stroke
Cerebral or cerebellar herniation
Thrombosis of the dural venous sinuses
Subdural effusions
-In 10 -30 % of patients
-Asymptomatic in 85-90 % of cases
- CT or MRI confirms the DX
-Increased or depressed level of consciousness i.e.
symptomatic
-Subdural tap
Hydrocephalus

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SIADH
- Occurs in majority of patients

- In 30 - 50 %of patients
- Hyponatremia
- Decreased serum osmolality

-Its effects are :

- Exacerbation of cerebral edema
- Independently produces hyponatremic seizures

Pericarditis or arthritis occurs during RX of meningitis

-Infectious (bacterial dissemination )

-Immune mediated (immune complex deposition )

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COMPLICATIONS ( CONT ‘D )
2.Chronic complications

Sensorineural hearing loss

Visual impairment
Behavioral problems
Mental retardation
Delay in acquisition of language

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PROGNOSIS
Mortality …< 10 % with antibiotic therapy and supportive
care
Sever neurodevelopmental sequalae …10 -20 % of cases
Neurobehavioral morbidity ….50 % of cases
POOR PROGNOSTIC FACTORS
 Pneumococcal meningitis
 Age < 6 months
 >106 colony – forming units of bacteria / ml of CSF
 Seizure occurring after 4days of therapy
 Coma or focal neurological signs on presentation
Most common neurologic sequalae
 Hearing loss
 Mental retardation , delay in acquisition of language
 Seizures
 Visual impairment , behavioral problems

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PREVENTION

A ) Chemoprophylaxis
-Antibiotic prophylaxis of susceptible at-risk
contacts
B ) Vaccination
N. MENINGITIDIS
a) Chemoprophylaxis

-All close contacts of patients with meningococcal

meningitis regardless of age or immunization status
-Rifampin 10 mg /kg /dose every 12 hr (max.600 mg) for
2 days
-Close contacts
 House hold ,day care center ,nursery school contacts,
health care workers
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 b) Vaccination
-Meningococcal quadrivalent vaccine against serogroups
A,C, Y,W 135
A) 11-12 year old adolescents

B) High risk children older than 2 years

- Anatomic or functional asplenia

- Deficiencies of terminal complement proteins

C) Adjunct with chemoprophylaxis for exposed

contacts and during epidemics of meningococcal
disease

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H . INFLUENZAE

a) Chemoprophylaxis

-House hold contacts ,including adults

If any close family member < 48 months has
not been fully immunized
If an immuno compromised child resides in
the house hold

-Rifampin 20 mg /kg /24 hr (max .600 mg )

given once daily for 4 days

Definition of house hold contact

- person who spent a minimum of 4 hr with the
index case for at least 5- 7 days preceding the
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patients hospitalization
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 b) Vaccination
-Conjugate vaccines

 Efficacy rates 70 - 100 % against invasive infections

 All
children should be immunized with H .influenza
type b conjugate vaccine beginning at 2 mo of age
S .PNEUMONIAE

a) Chemoprophylaxis

-Not indicated

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 b) Vaccination

-Heptavalent conjugate vaccine

-The initial dose is given at 2 month of age ( 2 , 4 , 6 & 12 - 15 mth
of age )
-Indications :
a)Routinely for all children < 2yr of age
b) High risk of invasive pneumococcal infection :
- Functional / anatomic asplenia
- Underlying immunodeficiency
.HIV
.Primary immunodeficiency
. Immunosuppressive therapy

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 THANK YOU!!!

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