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1. Fentahun A(MD, Asst. Professor of pediatrics )
4/23/2023
1
Bacterial Meningitis Beyond
Neonatal Age

2. Outline
2
 Introduction
 Definition
 Etiology
 Risk factors
 Pathology and pathogenesis
 Clinical manifestations
 Diagnosis
 Management
 Complication
 Prognosis

3. Acute Bacterial Meningitis
3
 Definition-Inflammation of the leptominges
surrounding the brain and spinal cord: pia,
arachnoid and subarachnoid matter
 Occurs at all ages but is commonest during
infancy (greatest risk 6-12 months)

4. ETIOLOGY
4
Neonatal period
 Groups B streptococci
 Gram-negative enteric bacilli (E. coli,
Klebsiella), and
 Listeria monocytogenes

5. ETIOLOGY…..
5
Children 2 mo to 12 yr of age
 N. meningitidis
 H. influenzae type b
 S. pneumoniae

6. Etiology…
6
 Alterations of host defense
 Pseudomonas aeruginosa
 Staphylococcus aureus, Coagulase-negative
staphylococci
 Salmonella spp
 L. monocytogenes

7. EPIDEMIOLOGY
7
Predisposing Factors
Major risk –Lack of immunity to specific pathogens
associated with young age
Additional risk factors
 Recent colonization with pathogenic bacteria
 Close contact with patients having invasive
disease caused by N. meningitidis and H.
influenzae type b,
 Crowding
 Poverty
 Male sex
 Person to person contact through respiratory

8. 8
Congenital or acquired CSF leak
 Cranial or midline facial defects (cribriform plate)
 Middle ear or inner ear fistulas
 Basal skull fracture into the cribriform plate or
paranasal sinus- increased risk of pneumococcal
meningitis.
 Lumbosacral dermal sinus and meningomyelocele:
staphylococcal and gram-negative enteric meningitis.
 VP shunts-increase the risk staphylococcal meningitis
(especially CONS) and other low virulence bacteria
that typically colonize the skin.

9. Streptococcus pneumonia
9
 Commonly occurs during the first 2yrs of life
 Peak 6-12 months
 Highest in children with
 HIV- infection
 Anatomic or functional asplenia
 Other risk factors include
 Otitis media
 Sinusitis
 Pneumonia
 CSF otorrhea or rhinorrhea

10. Neisseria Meningitides
10
Occurs
 Sporadically or as epidemics
 Serogroups A,B,C,Y, W-135,X are responsible
 Common in the winter and spring
 Nasopharyngeal carriage occurs in adults
 Contact infection
 Epidemics is defined as the occurrence of 3 cases in
3 months time with attack rate of 10 cases per
100,000 population in the same community
 Epidemics is usually caused by serogrup A

11. The “meningitis belt”
11

12. Haemophilus influenza type B
12
 Primarily occurs in infants 2month to 2 yrs
 50% of cases occur in the 1st year of life
 Peak at 6-9 months of age
 Risk increased
among family or day care center contacts of patients
with HIB disease.
unvaccinated and
those with blunted immunologic responses to vaccine
( HIV- Infection)

13. Pathogenesis
Routes of infection
13
 Hematogenous dissemination of micro-organisms
from a distant site of infection-Most common
route.
 Direct invasion of the CNS from
 contiguous focus of infection: otitis media, mastoditis,
sinusitis,osteomyelitis (cranial,vertebral)
through anatomic abnormalities
head trauma
neurosurgical procedures

14. Pathogenesis…..
14
 Bacteria gain entry to the CSF
 Multiply rapidly and incite local inflammatory response,
with poly morphonuclear cell infiltration.
 Marked inflammatory response with local production of
TNF, IL-1, and other cytokines
 Inflammatory response in characterized by
 Neutrophilic infiltration
 Altered BBB
 Increased vascular permeability
 Vascular thrombosis and vasculitis
 Inflammation of spinal nerves and roots produces
meningeal signs
 Inflammation of the cranial nerves produces cranial
neuropathies

15. Nasopharyngeal colonization
Local invasion
Bacteremia
Meningeal invasion
Bacterial replication in the subarachnoid space
Release of bacterial components (cell wall, LOS)
Cerebral microvascular endothelium Macrophages, neutrophils, other CNS Cells
Cytokines
Subarachnoid space inflammation
Cerebral
vasculitis
Increased CSF outflow resistance
Hydrocephalus
Interstitial edema
Increased intracranial pressure
Decreased cerebral blood flow and loss of cerebrovascular autoregulation
Cytotoxic edema
Cerebral
infarction
Increased BBB
permeability
Vasogenic edema
15

16. Clinical manifestations
16
Infants
 Fever
 Poor feeding
 Projectile Vomiting
 Altered level of consciousness
 Convulsions
 Neck stiffness ( hyper extension)
 Bulging fontanel
 Rash (Purpuric)
 Meningeal signs are not consistently
present

17. Clinical manifestations…..
17
Older children
 Classic signs are preceded upper respiratory or GIT
symptoms
 Fever
 Headache
 Projectile Vomiting
 Poor feeding
 Seizures are common-20-30% of patients before or
during the first 3 days after diagnosis

18. P/E
18
 Neck stiffness
 Positive Kerning’s sign
 Positive Brudzinski’s sign
 Altered state of consciousness
 CN palsies
 Meningococcal meningitis
-generalized purpuric rash
-Peripheral cyanosis
-Toxic and comatose
-Tachycardia, Hypotension
- DIC

19. 19
 Alterations of mental status
 Irritability, lethargy to coma may be due to:
 Increased ICP
 Cerebritis
 Hypotension
 Factors that lead to Death or Brain Damage in
Meningitis
 SIADH secretion With resultant Hyponatremia
 Brain edema → Acute Brainstem Compression
 Subdural Effusion/Empyema/Brain Abscess
 Seizures

20. Kerning Vs Brudzinski signs
20

21. Diagnosis
21
Lumbar Puncture- CSF analysis
 Leukocyte count (>1000/mm3) with neutrophilic
predominance (75–95%).
 Turbid CSF when WBC count is >200–400/mm3.
 <250/mm3in as many as 20% of patients
 pleocytosis may be absent in severe overwhelming
sepsis and meningitis and is a poor prognostic sign
lymphocyte predominance may be present during
the early stage
 Elevated protein
 Hypoglycorrhachia
 Gram stain-positive in 70–90% of untreated
patients
 Culture

22. 22
Condition
s
Pressure
(mmH2O)
Leukocyte
(mm3)
Protein
(mg/dl)
Glucose
(mg/dl)
Normal 50-80 <5, ≥75%
Lymphocytes
20-45 >50 (or 75%
Serum
Glucose)
Acute
Bacterial
Usually
elevated
(100 -300)
>100-10,000 ;
usually 300-2,000;
PMNs
Usually
100-500
usually <40
(or <50%
serum
glucose)
Partially
Rxed Bact.
Normal or
elevated
5-10,000; PMNs
early/Mon dominate
most of the course
Usually
100-500
Normal or
decreased
Viral Normal/slightl
y (80-150)
Rarely >1,000, Mon
predominate
Usually 50-
200
Generally
normal; but
mumps
Tuberculou
s
Usually
elevated
10–500;lymp
predominate
through most of the
100-3,000;
may be
higher
<50 in most
cases

23. Diagnosis……
23
 CBC- Leukocytosis, with polymorph
predominance
 Blood culture- reveals organisms in ~80-
90% of cases
o CXR if pneumonia or TB is suspected

24. Contra-indications for Lumbar Puncture
24
 Elevated ICP and focal Neurologic deficit
 Severe cardio respiratory compromise –
postpone LP
 Infection of the overlying skin
 Thrombocytopenia ( relative)

25. DDX
25
 Aseptic meningitis
 Tuberculous meningitis
 Cerebral malaria
 Brain abscess
 Brain tumor

26. Management
26
I. Supportive Measures
 Vital Signs _ 15-30 min.
 Frequent Neurologic assessment -Follow patient with
neurosign chart
 Level of consciousness(GCS)
 Pupillary size and reactivity
 Pattern of breathing
 Posture
 Occulocephalic reflex
 Seizure
 Cranial nerve palsies or focal Neurologic deficits
 Daily HC measurement –for children<18 months

27. Management…..
27
 Strict input/output recording
 Serum electrolytes
 Body weight
 Antipyretics ,Cold sponging
 Fluid restriction to 2/3rd maintenance for fear of
syndrome of inappropriate ADH secretion
- fluid restriction should be avoided in the presence of
hypotension
 Coma care- bowel, bladder, skin, air way
 Seizure control
 Active SZ –arrest with diazepam 0.1 -0.3 mg/kg/IV
or PR
 Prevention of recurrence of seizure
o Phenytoin- 20mg/kg loading then 5mg/kg/
24 hrs – bid
 Phenobarbitone can be added for refractory
SZ

28. Management…..
II. Specific Measures
28
 Shock
 in meningo coccemia or due to
vomiting
 IV NS/RL /Plasma
 Antibiotic therapy

29. Antibiotic therapy
29
Empirical treatment
 Cyst.pencillin plus
 Chloramphenicol or
 Ceftriaxone 100mg/kg/24hrs Bid
 Vancomycin – penicillin/ceftriaxone resistant
S.pneumoniae
 According to culture and sensitivity result

30. Antibiotics
30
 Duration of therapy
 5-7 days for meningococcal meningitis
 7-10 days for H. influenzae meningitis
 10-14 days for pneumococcal meningitis
 Gram-negative meningitis should be treated for
3 wk or for at least 2 wk after CSF sterilization

31. Corticosteroids
31
 Corticosteroid:
decrease ICP by decreasing meningeal
inflammation and brain water content
modulate the production Of cytokines,
lessens the meningeal inflammatory
response
decrease incidence of sensorineural
hearing loss or other neurologic
complications
 Dexamthasone
• 0.15 mg/kg/dose Qid for 2 days before the
1st dose of antibiotic for those older than

32. Complications
32
Increased Intracranial pressure(ICP)-
 Common acute complication
 Increase ICP is due to:-
 Cytotoxic cerebral edema- due to cell swellingcell death
 Vasogenic cerebral edema- due to cytokine induced increased
capillary vascular permeability
 Interstitial cerebral edema- increased hydrostatic pressure
after impaired reabsorption or obstruction of CSF flow
(Hydrocephalus)

33. 33
Management of Increased ICP
 Elevating head by 300
 20%Manitol 0.5-1g/kg/dose over 30min, Q6hrs or
Frusemide 1mg/kg or hypertonic saline(3% Saline)
 Dexamethasone 0.25 -0.5mg/kg QID
 Endotracheal intubation and hyperventilation (Pco2 25-
30mmHG)
 Treat fever aggressively

34. 34
Hydrocephalus
 Communicating
 Ocurrs most commonly
 due to adhesive thickening of arachnoid villi around
the cisterns - impaired CSF reabsorption
 Obstructive
 Less often
 due to fibrosis and gliosis of the aqueduct of sylvius

35. Intracranial cavity Vs CSF
35

36. 36
Subdural effusion/empyema
 10-30% & 1% of cases respective
 Highest in infants ,and H.influenzae
meningitis(45% of cases)
 85-90% are asymptomatic
 C/Fs
o bulging fontanel
o diastasis of sutures
o enlarging HC
o Persistence /recurrence of emesis
o Persistent/focal seizures
o persistence of fever
 Symptomatic - subdural tap

37. Complications…..
37
Cranial nerve palsies
 Inflammation of cranial nerves results cranial
neuropathies of Optic ,Oculomotor, Facial ,Auditory
Nerves
 Increased ICP Produces oculomotor and abducens nerve
palsies
 Seizure
 focal or generalized
 20–30% of patients
 occurs due to cerebritis, infarction, or
electrolyte disturbances
_ on presentation or within the 1st 4 days of
onset is usually of no prognostic
significance

38. Complications…..
38
 Syndrome of inappropriate ADH secretion
 Cerebral herniation
 Stroke

39. Sequelae /chronic complications
39
 Sensorineural hearing loss– mainly cochlear injury
 Ataxia
 Hemiparesis/Quadriparesis
 Epilepsy
 Spinal cord infarction
 Cortical blindness - Optic arachnoiditis
 Diabetes insipidus
 Hydrocephalus
 Behavior disorder
 Intellectual deficits

40. Prognosis
Poor prognostic factors
40
 Infants <6 months
 Delayed/Late presentation
 >106 CFU/ml of CSF
 Seizure that persist after 4 days of illness and
difficult to treat/control
 Coma or focal Neurologic signs at presentation.
 pneumococcal meningitis
 Delayed sterilization of CSF

41. Prevention
41
Chemoprophylaxis /vaccination
Neisseria meningitides
Chemoprophylaxis
 All close contacts regardless of age & immunization
 Meningococcal quadrivalent vaccine
( Serogroups A,C,Y,W-135)

42. Prevention…
42
H. Influenza
 Rifampin 20mg/kg/daily for 4 day for all close
contacts
if any close family member younger than 48 mo has
not been fully immunized or if an
immunocompromised person, of any age, resides in
the household
 HIB vaccine - Prevents development of HIB
Infection – If given for all < 2yrs
Pneumococcal
 Conjugate vaccine against S.pneumoniae (
PCV10) for all younger than 2 yrs.

43. References
43
 Nelson Text book of pediatrics, 19th ed
 Mandell, Bennett, & Dolin: Principles and
Practice of Infectious Diseases, 6th ed
 Feigin and Cherry’s Text book of pediatrics
infectous disease
 UpTodate 21.2

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