It include etiology, pathophysiology ,diagnosis and treatment..

1. R.MADHURI
ROLL N0:5
PHARM-D III YEAR
MENINGITIS

2. Our brain, the spinal cord and its surrounding structures could become infected by a
large spectrum of microorganisms . Central nervous system (CNS) infections are
caused by various pathogens, including bacteria, viruses, fungi, and parasites.
Depending on the location of the infection, different names are given to the diseases.
• MENINGITIS
• Encephalitis
• Myelitis
• Abscess
INTRODUCTION

3. • Meningitis is a serious and potentially life-threatening disease, involves an
inflammation of the membranes that cover the brain and spinal cord, called the meninges.
• If not treated, meningitis can lead to brain swelling and cause permanent disability,
coma , and even death.
• Most cases of meningitis are caused by bacteria and virus.
• Acute bacterial meningitis develops within hours or days and can be rapidly fatal or
lead to serious, permanent complications if not recognized and treated immediately.
 Pyogenic meningitis: With evidence of pathogenic bacteria in CSF.
 Aseptic meningitis: Without the usual evidence of pathogenic bacteria in CSF.

4. TYPES
 Acute pyogenic (bacterial) meningitis
 Acute aseptic (viral) meningitis
 Fungal meningitis
 Chronic bacterial infection (tuberculosis).
EPIDEMIOLOGY
 Approximately 1.2 million cases of acute bacterial meningitis, excluding epidemics,
occur every year around the world, resulting in 135,000 deaths.
 Overall mortality rates for patients with meningitis range from 2% to 30% depending
on the causative microorganism, approaching 20% in most cases of bacterial meningitis.
 Generally, 30% to 50% of patients who survive meningitis may develop neurologic
disabilities.

5. ETIOLOGY
Bacterial
meningitis
Streptococcus pneumoniae (pneumococcus)
Most common cause It more commonly causes pneumonia or ear or sinus
infections.
Neisseria meningitidis (meningococcus)
Commonly occurs when bacteria from an upper respiratory infection enter
bloodstream.
This infection is highly contagious.
Haemophilus influenzae (haemophilus).
Before the 1990s, Haemophilus influenzae type b (Hib) bacterium was the leading
cause of bacterial meningitis in children. HiB vaccination greatly reduced the number
of cases
There are various types of bacterial meningitis, but the two types

6. VIRAL MENINGITIS
Can also follow and develop after
chicken pox or mumps.
some cases of viral meningitis are
caused from mosquito-born viruses.
CAUSATIVE AGENT:
• Enterovirus
• polioviruses types 1,2,&3
• coxsackievirus type A and B
• HIV
• measles
• variola virus
• rubella viruses
• rhinovirus
• varicella zooster virus

7. • Fungal meningitis is rare and usually the result of spread of a fungus
through blood to the spinal cord
• people with weak immune system like those with AIDS or cancer,
are at risk
FUNGAL MENINGITIS Cryptococcus
Histoplasma
Blastomyces
Caused by the bacterium Mycobacterium tuberculosis. Infection with
this bacterium begins usually the lungs, but in about 2% of cases the
bacteria travel via the bloodstream to the meninges and cause TB
meningitis.
TUBERCULAR MENINGITIS
Can also result from
Polluted water Poor hygiene

8. ANATOMY

9. Subarachnoid space
BACTERIAL LYSIS
by a hematogenous
route reach the meninges
Bacterial cell wall
component release
Endothelial cells CNS macrophage cells
an intense host inflammatory
response triggered
Cytokine
release
(IL-1, PGE2,
TNF,
PAF, etc.)
Inflammatory response Neurologic damage
PATHOPHYSIOLOGY

10. Inflammatory response Neurologic damage
Cont’d…
Coagulation
cascade
Thrombosis
Vasogenic
edema
Increased ICP Decreased CBF
swelling and
proliferation of the
endothelial cells
of arterioles
veins, causing
mural thrombi and
obstruction of flow
an increase in intracellular
sodium and intracellular water
Affecting
cortical vessels
Cytotoxic
and
interstitial
edema
oxygen
depletion
Increased
CSF protein Decreased CSF
glucose
Increased
CSF lactate
development of brain edema
further compromises cerebral
circulation
ICP secretion of
ADH
These factors contribute to the development
of focal or generalized seizures
(SIADH) with
meningitis causes
further retention of
free water

11. CLINICAL PRESENTATION
PHYSICALLY DEMONSTRABLE SIGNS
BRUDZINSKI’S NECK SIGN
Severe neck stiffness causes a patient's
hips and knees to flex when the neck is
flexed.
KERNIG’S SIGN
Severe stiffness of the hamstrings causes
an inability to straighten the leg when the
hip is flexed to 90 degrees.
SEPTICAEMIC RASH/ PURPURIC RASH
Watch out for tiny red or brown pin prick
marks which can change into purple
blotches or blood blisters.

12.  Nuchal rigidity
 Lethargy
 Irritability
 Apnea
 Apathy
 Jaundice
 Pallor
 Shock
 Hypoglycemia
 Convulsions
 Anorexia
 Coma
 Fever
 Tachycardia
 Diaphoresis
 Weakness
 Photophobia
 Seizures
 Headache
 Aching
muscles
OTHER SYMPTOMS

13. Blood and other specimens culture:
A minimum of 20 mL of blood in each of two to three separate
cultures per each 24- hour period is necessary for the detection of most
bacteremias.
Gram stain and culture of the CSF
Most important laboratory tests performed for bacterial
meningitis. When performed before antibiotic therapy is initiated, Gram stain
is both rapid and sensitive and can confirm the diagnosis of bacterial
meningitis in 75% to 90% of cases.
Polymerase chain reaction (PCR)
Used to diagnose meningitis caused by N. meningitidis, S. pneumoniae,
and H. influenzae type b (Hib). PCR is considered to be highly sensitive and
specific. PCR testing of the CSF is the preferred method of diagnosing most
viral meningitis infections.
Latex fixation, latex coaglutination, and enzyme immunoassay
For the rapid identification of several bacterial causes of
meningitis, including
S. pneumoniae, N. meningitidis, and Hib. The rapid antigen tests should be
used in situations in which the Gram stain is negative.

14. A lumbar puncture
Or spinal tap, is a procedure to collect
cerebrospinal fluid to check for the presence
of disease or injury.
A spinal needle is inserted, usually between
the 3rd and 4th lumbar vertebrae in the
lower spine. Once the needle is properly
positioned in the subarachnoid space (the
space between the spinal cord and its
covering, the meninges), pressures can be

15. Glucose
(mg/dL):
40–85 < 40
<40
<40
Normal
(> 40)
Protein
(mg/dL)
15 - 45 > 250 25 - 500 50 - 500 <100
WBCs
(cells/µL)
0–5/µL (usually >
1000).
Early: May
be < 100
Variable
(10 -1000)
< 500
Variable
(10 -1000)
< 500
< 100
Cell
differenti
al:
60–70% L
30% M
macrophage
other cells
2% or less.
Neutrophils Lymphocyte
s
Lymphocyte
s
Early:
Neutrophils
Late:
Lymphocyte
s
Culture: sterile +ve +ve +ve -ve
Opening
Pressure
50–180 Elevated Variable
Variable Usually
normal
NORMAL BACTERIAL FUNGAL TUBERCULAR
VIRAL
CSFANALYSIS

16.  The choice of antibiotic depends on the organism isolated. In most cases
the initial treatment has to be empirical.
 Animal studies have shown that a bactericidal effect is necessary for
sterilisation of the CSF and survival
There are three factors affecting antibiotic activity:
• Ability to penetrate the CSF
•Concentration
•Intrinsic activity in infected fluid.
In a child with suspected meningitis
• urgent transfer to hospital
• Followed by concurrent microbiological investigation and antibiotic
treatment are the cornerstones of management.
 Lack of adequate blood and CSF culture may result in difficulty deciding
on the duration of treatment and uncertainty over the antimicrobial
susceptibility of organism.

17. Duration of treatment and choice of antibiotic
 The duration of antibiotic therapy depends on the organism isolated.
• For S.pneumoniae and H.influenzae, 10–14 days recommended
• N.meningitidis a seven day course is sufficient.
• In Listeria monocytogenes and group B streptococcal meningitis, antibiotics should be
given for 14–21 days.
• For Gram negative bacilli a minimum of three weeks is needed.
 A broad spectrum cephalosporin (cefotaxime or ceftriaxone) is the most
appropriate empirical choice in children over 3 months old.
 Ampicillin should be added in young infants (less than 3 months old) to
cover Listeria monocytogenes.
 Ceftriaxone may be effective when given as a single daily dose (80–100
mg/kg) to treat serious bacterial infections including meningitis in children

18. Drug Dose Frequency Maximum total daily
dose
Penicillin G 50 mg/kg 4–6 14.4 g
Cefotaxime 50 mg/kg 4 3 g
Ceftriaxone 80–100 mg/kg 1 4 g
Ampicillin 100 mg/kg 4 3 g
Ceftazidime 50 mg/kg 3 6 g
Vancomycin 15 mg/kg then
10 mg/kg
4 2 g
Dosages and frequency of the common antibiotics used in bacterial
meningitis

19.  Antibiotic therapy may need to be modified once a pathogen is cultured and
antibiotic susceptibility testing becomes available.
 If pneumococcal meningitis is high on the differential diagnosis and there is
a clear history of anaphylaxis to beta lactams
vancomycin + chloramphenicol
 For more complicated cases such as immunosuppressed patients or those
with recent history of head trauma or neurosurgery and those with
cerebrospinal fluid shunts.
vancomycin + ceftazidime
 Studies comparing the use of rifampicin with ceftriaxone in experimental
S.pneumoniae meningitis support the use of rifampicin because of
•A reduction in the release of proinflammatory mediators
•Decreased secondary brain injury
•A lower early mortality rate
followed by addition of a beta lactam may result in reduction of
tissue damage and a better outcome.
 Other less frequently used carbapenem antibiotics, such as imipenem and
meropenem, are very active in vitro against most isolates of S.pneumoniae,
although some penicillin resistant strains have shown reduced susceptibility

20. Fluroquinolones,
such as trovafloxacin, gatifloxacin, and moxifloxacin are potentially effective
in the treatment of multiple resistant pneumococcal isolates because of their
activity and CSF penetration, even when dexamethasone is also given.
The resistance of S.pneumoniae to penicillin and other beta lactam antibiotics
is caused by either alteration in
• penicillin binding proteins
• production of beta lactamase
American Academy of Pediatrics recommended combination therapy, initially
with vancomycin and either cefotaxime or ceftriaxone for all children 1 month
of age or older with definite or probable bacterial meningitis.
In the case of N meningitidis isolates, the great majority are susceptible to
penicillin and ampicillin

21. This reduces the likelihood of the syndrome of
inappropriate secretion of antidiuretic hormone
(SIADH). The incidence of SIADH reported in studies
varies considerably, from
4% to 88%
SIADH leads to hyponatraemia and fluid retention, which
may worsen cerebral oedema.
Hyponatraemia has been correlated with an increased
risk of seizures and neurological abnormalities. Although
hyponatraemia can occur as a result of excessive fluid
administration or SIADH, it can also occur in children
with dehydration.
However, a significant proportion of meningitis cases
present with dehydration or hypovolaemia and are in
clinical need of fluid resuscitation.
It is therefore important that the degree of hydration
is carefully assessed in order to correctly manage the

22. o Empiric antimicrobial therapy should be instituted as soon as possible to
eradicate the causative organism.
o Antimicrobial therapy should last at least 48 to 72 hours or until the diagnosis
of bacterial meningitis can be ruled out.
Continued therapy should be based on the assessment of
• clinical improvement
• Cultures
• susceptibility testing results.
o Once a pathogen is identified, antibiotic therapy should be tailored to the
specific pathogen.
With increased meningeal inflammation, there will be greater antibiotic
penetration
Problems of CSF penetration may be overcome by direct instillation of
antibiotics by
• intrathecal
• intracisternal
• Intraventricular

23. Dexamethasone as an Adjunctive Treatment
for Meningitis
commonly used therapy for the treatment of pediatric meningitis.
MOA : causes a significant improvement in CSF concentrations of
proinflammatory cytokines, glucose, protein, and lactate as well as a significantly
lower incidence of neurologic sequelae commonly associated with bacterial
meningitis.
The American Academy of Pediatrics suggests that the use of dexamethasone be
considered for infants and children aged 2 months or older with pneumococcal
meningitis and that it be given to those with H. influenzae meningitis.
IV dexamethasone dose
• 0.15 mg/kg every 6 hours for 4 days. Alternatively,
• 0.15 mg/kg every 6 hours for 2 days or 0.4 mg/kg every 12 hours for 2 days
is equally effective and a potentially less toxic regimen.

24. Neisseria meningitidis (Meningococcus)
Aggressive, early intervention with high-dose IV crystalline penicillin G 50,000
units/kg every 4 hours
Several third generation cephalosporins (e.g., cefotaxime, ceftizoxime,
ceftriaxone,
& cefuroxime)
Meropenem and fluoroquinolones are suitable alternatives for treatment of
penicillin
non-susceptible meningococci.
Prophylaxis of contacts should be started only after consultation with the local
health department.
• Adult patients -600 mg of rifampin orally every 12 hours for four doses.
• 1 month to 12 years of age -10 mg/kg of rifampin orally 12 hours for four
doses
• younger than 1 month - 5 mg/kg orally every 12 hours for four doses.

25. The treatment of choice until susceptibility of the organism is the
combination of vancomycin + ceftriaxone.
Penicillin may be used for drug-susceptible isolates.
A high percent of S. pneumoniae is either intermediately or highly resistant
to penicillin.
A heptavalent conjugate vaccine is available for use in infants between 2
months and 9 years of age.
For all healthy infants younger than 2 years of age to be immunized with the
heptavalent vaccine at 2, 4, 6, and 12 to 15 months.
Streptococcus pneumoniae
(Pneumococcus
or Diplococcus)

26. 30% to 40% of H. influenzae are ampicillin resistant. For this reason, many
clinicians use a third-generation cephalosporin (cefotaxime or ceftriaxone) for
initial antimicrobial therapy.
Cefepime and fluoroquinolones are suitable alternatives regardless of β-
lactamase activity.
Prophylaxis of close contacts
• children 20 mg/kg (maximum 600 mg)
• adults 600 mg daily in one dose for 4 days.
Fully vaccinated individuals should not receive prophylaxis.
Vaccination with Hib conjugate vaccines is usually begun in children at 2
months.
The vaccine should be considered in patients older than 5 years with sickle cell
disease, asplenia, or immunocompromising diseases.
Haemophilus influenzae

27. Listeria monocytogenes
The combination of penicillin G or ampicillin with an aminoglycoside results in
a bactericidal effect.
Patients should be treated for 2 to 3 weeks after defervescence to prevent
the possibility of relapse.
Trimethoprim-sulfamethoxazole may be an effective alternative because
adequate CSF penetration is achieved with these agents.

28. Gram-Negative Bacillary Meningitis
Meningitis caused by Pseudomonas aeruginosa is initially treated with
• ceftazidime or cefepime,
• piperacillin + tazobactam, (or )
• meropenem + aminoglycoside, usually tobramycin.
If resistance developed…
An intraventricular aminoglycoside should be considered along with IV AG
(0.03mg of tobramycin or gentamicin per mL of CSF and 0.1 mg of amikacin per
mL of CSF every 24 hours)
Gram-negative organisms, other than P. aeruginosa
• 3rd generation or 4th generation cephalosporin
•In adults, daily
doses of 8 to 12 g/day of these third-generation cephalosporins or 2 g of
ceftriaxone twice daily should produce CSF concentrations of 5 to 20 mg/L.

29. Mycobacterium tuberculosis
A regimen of four drugs
 Isoniazid, rifampin, pyrazinamide, and ethambutol,
15 to 20 mg/kg/day (maximum 1.6 g/day) for the first 2 months generally
followed by isoniazid plus rifampin for the duration of therapy.
In children, the usual dose of isoniazid is 10 to 15 mg/kg/day (max 300 mg/day).
Adults usually receive 5 mg/kg/day or a daily dose of 300 mg.
Concurrent administration of rifampin is recommended at doses of
• 10 to 20 mg/kg/day (maximum 600 mg/day) for children
• 600 mg/day for adults.
The addition of pyrazinamide to the regimen of isoniazid and rifampin is
recommended.
(children and adults, 15 to 30 mg/kg/ day; maximum in both, 2 g/day)

30. Patients with M. tuberculosis meningitis should be treated for a duration of 9
months or longer with multiple-drug therapy, and patients with rifampin-
resistant strains should receive 18 to 24 months of therapy.
The use of glucocorticoids for tuberculous meningitis remains controversial.
The administration of steroids such as
oral prednisone, 60 to 80 mg/ day (1 to 2 mg/kg/day in children),
(or) 0.2 mg/kg/day of IV dexamethasone, tapered over 4 to 8 weeks,
• Improves neurologic sequelae and survival in adults & decrease mortality,
• Prevents Long-term neurologic complications, and permanent sequelae in
children.

31. Cryptococcus neoformans
Amphotericin B is the drug of choice for treatment of acute C. neoformans
meningitis.
 Amphotericin B, 0.5 to 1 mg/kg/day, combined with flucytosine,100 mg/kg/day,
is more effective than amphotericin alone.
In the (AIDS) population,
flucytosine is often poorly tolerated, causing bone marrow suppression and GI
distress.
Due to the high relapse rate following acute therapy…
AIDS patients require lifelong maintenance or suppressive therapy. The
standard of care for AIDS-associated cryptococcal meningitis is primary therapy
of generally using amphotericin B with or without flucytosine followed by
maintenance therapy with fluconazole for the life of the patient.

32. •Nonpolio enteroviruses such as coxsackievirus A and B, echoviruses, and
enterovirus 70 and 71 cause approximately 85% of all viral encephalitis cases.
•The remaining 10% to 15% of viral encephalitis cases are caused by a variety of
pathogens, such as arboviruses, adenoviruses, influenzae virus A and B, rotavirus,
corona virus, cytomegalovirus, varicella-zoster, herpes simplex virus
•Acyclovir is the drug of choice for herpes simplex encephalitis. In patients with
normal renal function, acyclovir usually is administered 10 mg/kg intravenously
every 8 hours for 2 to 3 weeks.
•Herpes virus resistance to acyclovir has been reported with increasing incidence,
particularly from immunocompromised patients with prior or chronic exposures to
acyclovir.
•The alternative treatment of acyclovir-resistant herpes simplex virus is
foscarnet. The major toxicity of foscarnet is renal impairment, and doses must be
individualized for renal function.
•For patients with normal renal function is 40 mg/kg infused over 1 hour every 8
to 12 hours for 2 to 3 weeks. Ensuring adequate hydration is imperative. Monitor
for seizures related to alterations in plasma electrolyte levels.
VIRAL MENINGITIS

33. Acute complications
•Seizures
•Syndrome of inappropriate antidiuretic hormone (SIADH)
secretion
•Hemodynamic instability
•Increased intracranial pressure
•Subdural effusions
•Focal neurologic deficits
Chronic complications
•Deafness
•Seizure disorders
•Motor deficits
•Language deficits
•Behavior disorders
•Mental retardation

34. REFERENCE
•Text Book of Pharmacotherapy, By Joseph T.Dipiro.
•http://emedicine.medscape.com/article/1165557-differential
•http://www.rightdiagnosis.com/v/viral_meningitis/intro.htm
•http://bacmen.weebly.com/pathophysiology.html
•http://www.jaapa.com/meningitis-distinguishing-the-benign-from-the-serious/article
•http://bacmen.weebly.com/pathophysiology.html
•http://www.nlm.nih.gov/medlineplus/meningitis.html
•http://www.globalrph.com/cerebrospinal_fluid.htm

35. THANK YOU