hhh

2. Treatment: General Principle
• Avoidance of delay
• Emperical antibiotic

3. • 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

4. 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

5. 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

6. • 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 ?

7. 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

8. 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

9. Antibiotic Therapy
• Certainly Bacterium
– Once the pathogen has been identified and the
antibiotic sensitivities determined, the most
appropriate drugs should selected.
• N meningitidis : penicillin, tert- cephalosporin
• S pneumoniae: penicillin, tert- cephalosporin,
vancomycin
• H influenzae: ampicillin, tert- cephalosporin
• S aureus: penicillin, nefcillin, vancomycin
• E coli: ampicillin, chloramphenicol, tert-
cephalosporin

10. Dexamethasone
• Animal studies:hearing 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
• > 6 weeks of age
• 0.15 mg/kg per dose) every 6 hours for 2 to 4 days

11. 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 >30 percent,
– or CSF glucose concentration <20 mg/dL

12. Bacterial Meningitis -
Treatment
Neonatal (<3 mo)
• Ampicillin (covers Listeria)
+
• Cefotaxime
– High CSF levels
– Less toxicity than aminoglycosides
– No drug levels to follow
– Not excreted in bile ∴ not inhibit bowel
flora

13. Pneumococcal meningitis

14. Antibiotic susceptibility
• Susceptible
• Non-susceptible
• Resistant

15. Pneumococcal resistance
• Strep pneumococcus - most common
cause of invasive bacterial infections in
children >2 months old
• Incidence of PCN-, cefotaxime- &
ceftriaxone-nonsusceptible isolates has
↑’d to ~40%
• Strains resistant to PCN,
cephalosporins, and other β-lactam
antibiotics often resistant to
trimethoprim-sulfamethoxazole
(Bactrim™, Septra™), erythromycin,
chloramphenicol, tetracycline

16. Mechanism of resistance
• PCN-binding proteins synthesize
peptidoglycan for new cell wall
formation
• PCN, cephalosporins, and other β-
lactam antibiotics kill S pneumoniae
by binding irreversibly to PCN-binding
proteins located in the bacterial cell
wall
• Chromosomal changes can cause the
binding affinity for the β-lactam

17. Pneumococcal meningitis –
Mgmt
• Vancomycin + cefotaxime or
ceftriaxone, if > 1 month old
• If hypersensitive (allergic) to β-lactam
antibiotics, use vancomycin +
rifampin
• D/C vancomycin once testing shows
PCN-susceptibility
• Consider adding rifampin if
susceptible & condition not improving,
or cefotaxime or ceftriaxone MIC high
• Not vancomycin alone

18. • PCN-susceptible organism:
– PenG 250,000 - 400,000 U/kg/day ÷
Q4-6h
– Ceftriaxone 100 mg/kg/day ÷ Q 12 -
24 h
– Cefotaxime 225 - 300 mg/kg/day ÷ Q 8
h
– Chloramphenicol 50 - 100 mg/kg/day
÷Q6h
• Adequate cephalosporin levels in
CSF ~2.8 hours after dose
administration

19. ROLE OF VANCOMYCIN
• Combination therapy since late
90’s
• At initiation-
– Baseline urinalysis
– BUN and creatinine
• Enters the CSF in the presence
of inflamed meninges within 3
hours
• Should not be used as solo
agent, but with cephalosporin for
synergy

20. Vancomycin use in
pneumococcal meningitis
• Vancomycin 60 mg/kg/day ÷ Q 6 h
• Trough levels immediately before 3rd
dose
• (10-15 mcg/mL or less)
• Peak serum level 30-60 minutes
after completion of a 30-minute
infusion
(35-40 mcg/mL)

21. RESISTANT CASES
• Meropenem • Rifampin
– Carbapenem – 20 mg/kg/day ÷ Q
– 120 mg/kg/day ÷ Q 12
8h – Not a solo agent
↑ seizure – Slowly
incidence, ∴ not bactericidal
generally used in
meningitis
– Resistance
reported

22. Dexamethasone Role
• Consider if H flu & S pneumo
meningitis & > 6 wks old 0.6
mg/kg/day ÷ Q 6h x 2d
∀ ↓ local synthesis of TNF-α, IL-1, PAF
& prostaglandins resulting in ↓ BBB
permeability, ↓ meningeal irritation
• Debate if it ↓ incidence of hearing loss
• If used, needs to be given shortly
before or at the time of antibiotic
administration
• May adversely affect the penetration of
antibiotics into CSF

23. Pneumococcal meningitis -
Treatment
• LP after 24-48 hours to evaluate
therapy if:
– Received dexamethasone
– PCN-non-susceptible
– MIC’s not available
– Child’s condition not improving

24. Infection control precautions
• CDC recommends Standard
Precautions
• Airborne, Droplet, Contact are NOT
recommended
• Nasopharyngeal cultures of family
members and contacts is NOT
recommended
• No isolation of contacts
• No chemoprophylaxis for contacts

25. Meningococcemia - Isolation
• Capable of transmitting organism up
to 24 hours after initiation of
appropriate therapy
• Droplet precautions x 24 hours, then
no isolation
• Incubation period 1 - 10 days,
usually <4 days

26. Meningococcemia - Treatment
• Antibitotic resistance rare
• Antibitotics:
– PCN
– Cefotaxime or Ceftriaxone
• Patient should get rifampin prior to
discharge

27. Meningococci – Care Takers
• Day care where child attends >25 h/
wk, kids are >2 years old, & 2 cases
have occurred
• Day care where kids not all
vaccinated
• Persons who have had “intimate
contact” w/ oral secretions prior &
during 1st 24 h of antibiotics
• “Intimate contact” – 300-800x risk
(kissing, eating/ drinking utensils, mouth-to-
mouth, suctioning, intubating)

28. Meningococcemia - Prophylaxis
• No randomized controlled trials of
effectiveness
• Treat within 24 hours of exposure
• Vaccinate affected population, if
outbreak

29. • Rifampin
– Urine, tears, soft contact lenses orange;
OCP’s ineffective
– <1 mo 5 mg/kg PO Q 12 x 2 days
– >1 mo 10 mg/kg (max 600 mg) PO Q 12 x
2 days
• Ceftriaxone
≤12 y 125 mg IM x 1 dose
– >12 y 250 mg IM x 1 dose
• Ciprofloxacin
≥18 y 500 mg PO x 1 dose

30. Meningococcal meningitis -
Outcomes
• Substantial morbidity: 11% - 9% of
survivors have sequelae
– Neurologic disability
– Limb loss
– Hearing loss
• 10% case-fatality ratio for
meningococcal sepsis
• 1% mortality if meningitis alone

31. Summary
• Antibiotics ASAP, even if LP not yet done
• Vanco + cephalosporin until some
identification known
– CSF, Latex, exam
• Isolate if bacterial x 24 hours, Universal
Precautions
• Monitor for status changes
– Pupils, LOC, HR, BP, resp
– Seizures
– Hemodynamics
– DIC, coagulopathy
– Fluid, electrolyte issues

32. Meningitis - Treatment duration
• Neonates: 14 – 21 days
• Gram negative meningitis: 21 days
• Pneumococcal, H flu: 10 days
• Meningococcal: 7 days

33. 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.

34. 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)

35. Repeat CSF
• Poor clinical response after 24-36 hours of
antibiotics
• Persistence or recurrence of fever
• Gram –ve meningitis

36. Neuroimaging
• Focal neurologic signs, increasing head
circumference, or prolonged obtundation,
irritability, or seizures (>72 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

37. Prognosis
• Mortality:meta-analysis: 4520 children
4.8 %in developed countries and 8.1 % in
developing countries
• Hib:3.8 %, N. meningitidis: 7.5 %, S.
pneumoniae: 15.3 %
• Neurological sequele:16% 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

38. Poor prognostic factors
• Etiology: more with pneumocaccal
• Seizure after 72 hours
• CSF sugar < 20 mg per dl at admission
• Delayed sterlization of CSF : > 24 hours

39. Meningitis - Acute complications
• Hydrocephalus
• Subdural effusion
or empyema
~30%
• Stroke
• Abscess
• Dural sinus
thrombophlebitis

40. Complications of meningitis in infants and
children.
- Hearing loss is the most encountered sequelae; it occurs
* in 30% cases of S. pneumoniae meningitis,
* in 20% of H. influenzae meningitis,
* in 10% of N. meningitidis meningitis.
– Mental retardation, seizures, delay in language acquisition,
visual impairment, behavioural problems and hydrocephalus.

41. • Thrombocytosis, eosinophilia, and anemia may
develop during therapy for meningitis. Anemia
may be due to hemolysis or bone marrow
suppression.
• DIC is most often associated with the rapidly
progressive pattern of presentation and is noted
most commonly in patients with shock and
purpura.
• The combination of endotoxemia and severe
hypotension initiates the coagulation cascade;
the coexistence of ongoing thrombosis may
produce symmetric peripheral gangrene.

42. Bacterial meningitis - Outcomes
• Neonates: ~20% mortality
• Older infants and children:
– <10% mortality
– 33% neurologic abnormalities at
discharge
– 11% abnormalities 5 years later
• Sensorineural hearing loss 2 - 29%