Meningitis is the inflammation of the meninges which covers the brain and the spinal cord. It may be caused due to various viruses, bacteria, and other microorganisms

1. MENINGITIS
By: DR. ZEEL NAIK

4. DISCUSSION
 DEFINITION
 CLASSIFICATION AND
CAUSATIVE AGENTS
 EPIDEMIOLOGY
 PATHOPHYSIOLOGY
 SIGNS AND SYMPTOMS
 DIAGNOSIS
 TREATMENT

5. MENINGES
 The skull and vertebrae protect the CNS from blunt
or penetrating trauma .
 The brain is suspended in these structures by
cerebrospinal fluid (CSF) and is surrounded by the
meninges.
 The meninges are made up of three separate
membranes:
 dura mater,
 arachnoid,
 and pia mater.

6. MENINGES
 Dura mater directly
beneath and is adherent to
the skull.
 The other two membranes
are referred to collectively
as leptomeninges.
 Pia mater lies directly over
brain tissue.
 Arachnoid, the middle
layer, lies between the
dura mater and the pia
mater.
 The subarachnoid space,
located between the
arachnoid and the pia
mater, is the conduit for
CSF.

7. Cerebrospinal fluid
 Cerebrospinal fluid (CSF) is a clear, colorless
liquid composed primarily of water that protects the
brain and spinal cord from chemical and physical
injuries.
 The total volume of CSF is 80 to 150 mL(3 to 5 oz)
in an adult.
 CSF contains small amounts of glucose, proteins,
lactic acid, urea, cations (Na, K, Ca2, Mg2), and
anions (Cl– and HCO3-) it also contains some
white blood cells.
 The CSF production is from the choroid
plexuses, networks of blood capillaries in the walls
of the ventricles

8. Formation of csf
 The CSF formed in the choroid plexuses
of each lateral ventricle flows into the third
ventricle through two narrow, oval
openings,the interventricular foramina .
 More CSF is added by the choroid plexus
in the roof of the third ventricle.
 The fluid then flows through the aqueduct
of the midbrain (cerebral aqueduct)
which passes through the midbrain, into
the fourth ventricle.
 The choroid plexus of the fourth ventricle
contributes more fluid.
 CSF enters the subarachnoid space
through three openings in the roof of the
fourth ventricle: a single median aperture
and paired lateral apertures, one on
each side.
 CSF then circulates in the central canal of
the spinal cord and in the subarachnoid
space around the surface of the brain and
spinal cord.
 CSF is gradually reabsorbed into the
blood through arachnoid villi, fingerlike
extensions of the arachnoid that project
into the dural venous sinuses, especially
the superior sagittal sinus.

9. DEFINITION
 Meningitis is the inflammation of the
meninges which covers the brain and
the spinal chord.
 It may be caused due to various viruses
, bacteria and other microorganisms.

26. DEFINITION
 With meningitis, mening- refers to the meninges which are
three protective membranes that cover the brain and spinal
cord, and -itis refers to inflammation; so meningitis is an
inflammation of the meninges.
 More specifically, it refers to the inflammation of the two inner
layers which are called the leptomeninges.
 The outer layer of the meninges is the dura mater, the middle
layer is the arachnoid mater, and the inner layer is the pia
mater.
 These last two, the arachnoid and pia maters, are the
leptomeninges.
 Between the leptomeninges there’s the subarachnoid space,
which houses cerebrospinal fluid, or CSF.
 CSF is a clear, watery liquid which is pumped around the
spinal cord and brain, cushioning them from impact and
bathing them in nutrients.
 In one microliter or cubic millimeter, there are normally a few
white blood cells, up to 5.

27. DEFINITION
 If we look at a bigger sample, like say a decilitre, then
around 70% of those will be lymphocytes, 30%
monocytes, and just a few polymorphonuclear cells --
PMNs -- like neutrophils.
 That same volume will contain some proteins, as well,
about 15-50 mg as well as some glucose, about 45-100
mg, which is close to two thirds of the glucose we’d find
in the same volume of blood.
 The CSF is held under a little bit of pressure, below 200
mm of H2O, which is just under 15 mm of mercury --
which is less than a fifth of the mean arterial pressure.
 Now at any given moment, there’s about 150 ml of CSF
in the body.
 This is constantly replenished, with around 500 ml of
new CSF produced everyday and the excess, or 500
minus 150 mL or 350 mL, is absorbed into the blood.

28. DEFINITION
 But for any nutrients to enter and leave the CSF, and
the brain itself for the matter, they have to go through
the tightly regulated blood-brain barrier(BBB or B3).
 The blood brain barrier is the special name given to the
blood vessels in the brain.
 That’s because the endothelial cells in the blood
vessels are so tightly-bound to one another that they
prevent leakage and only allow certain molecules to slip
through them.
 Meningitis is the inflammation of the leptomeninges,
which remember are the inner two membranes around
the brain and spinal cord.
 It is not the inflammation of the brain itself,
that’s encephalitis; but sometimes they can occur
together and when that happens it’s called
meningoencephalitis.

29. DEFINITION
 So meningitis needs some kind of trigger
for the inflammation, and could be an
autoimmune disease, where the body
attacks itself, like lupus, or the body
having an adverse reaction to some
medication, which can happen with
intrathecal therapy, when medication is
injected directly into the CSF.
 But, by far, infection is the most common
trigger for meningitis across all age
groups, like with the Neisseria
meningitidis bacteria or herpes simplex
virus for example.

30. DEFINITION
 Now there are two routes that an infection can take to reach the CSF
and leptomeninges.
 The first way is direct spread, which is when a pathogen gets inside
the skull or spinal column, and then penetrates the meninges,
eventually ending up in the CSF.
 Sometimes the pathogen will have come through the overlying skin
or up through the nose, but it’s more likely that there’s an anatomical
defect to blame.
 For example, it could be a congenital defect like spina bifida, or an
acquired one like a skull fracture, where there might be CSF leaking
through the sinuses.
 The second way is hematogenous spread, which is when a
pathogen enters the bloodstream and moves through the endothelial
cells in the blood vessels making up the blood-brain barrier and gets
into the CSF.
 To do this, the pathogens typically have to bind to surface receptors
on the endothelial cells in order to get across.
 Otherwise, they have to find areas of damage or more vulnerable
spots like the choroid plexus.

31. DEFINITION
 Once the pathogen finds a way into the CSF it can start
multiplying.
 Soon enough, the handful of white blood cells surveilling the
CSF identify the pathogen and release cytokines to recruit
additional immune cells.
 Over time, a microliter of CSF might go on to contain up to
thousands of white blood cells, but any more than five usually
defines meningitis.
 In most bacterial cases, there’ll be above 100 white blood
cells per microliter, and more than 90% PMNs.
 In most viral cases, there’ll be 10 to 1000 white blood cells;
over 50% lymphocytes and under 20% PMNs.
 In most fungal cases, there’ll be 10-500 white blood cells,
with over being 50% lymphocytes.
 In most cases of tuberculous meningitis there’ll be 50-500
white blood cells with over 80% being lymphocytes.
 The additional immune cells attract more fluid to the area and
start causing local destruction as they try to control the
infection.

32. DEFINITION
 As a result the CSF pressure typically rises above 200 mm of H2O.
 The immune reaction also causes the glucose concentration in the CSF to fall, to below two thirds of
the concentration in the blood, and makes the protein levels increase to over 50 mg per decilitre.
 When it comes to the causes of meningitis, viruses and bacteria usually cause acute meningitis,
whereas fungi usually cause chronic meningitis.
 Now for bacteria there are a lot of possibilities. In newborns, the most common causes are Group B
streptococci, E coli, and Listeria monocytogenes.
 In children and teens, the most common causes are Neisseria meningitidis and Streptococcus
pneumoniae.
 In adults and the elderly, the most common causes are Streptococcus pneumoniae and Listeria
monocytogenes.
 There are also tick-borne causes of meningitis like Borrelia burgdorferi bacteria - which the cause
of Lyme disease.
 As for viruses, the main culprits are enteroviruses, especially coxsackie virus, and herpes simplex
virus.
 HIV is usually contracted through body fluids and can also cause viral meningitis.
 Less common causes include mumps virus, varicella zoster virus, and lymphocytic choriomeningitis
virus.
 There’s also the fungi, like those from the Cryptococcus and Coccidioides genuses, which mainly affect
immunocompromised individuals.
 And then of course there’s tubercular meningitis is caused by the Mycobacterium tuberculosis bacteria,
and finally parasitic causes of meningitis like P. falciparum which is the main cause of malaria.
 Now, the classic triad of meningitis symptoms are headaches, fevers, and nuchal rigidity, or neck
stiffness.

33. DEFINITION
 The diagnosis of meningitis starts with a physical exam.
 One maneuver is when a person lies flat on their back facing upwards, and one of their legs is raised with the
knee flexed to a 90 degree angle.
 Then, the leg is supported and slowly straightened at the knee.
 If this causes back pain, then it’s called the Kernig’s sign.
 Another maneuver, is when a person lies flat on their back facing upwards, and has their neck supported and
flexed.
 If this causes them to automatically flex their knees or hips, then it’s called the Brudzinski’s sign.
 If meningitis is suspected, a lumbar puncture can be done.
 This is when a needle goes through the lower lumbar vertebral levels of the spinal cord, between L3 and L4 for
example.
 The needle penetrates into the subarachnoid space and a few milliliters of CSF is taken.
 The opening pressure can be measured, and the CSF can be analyzed for white blood cells, protein, and
glucose.
 Polymerase chain reaction, or PCR, might be used to find specific causes like HIV, enterovirus, HSV,
or tuberculosis.
 If a particular infection seems like an obvious cause, then a test for that might be used, like the Western blot
for Borrelia burgdorferi bacteria, or a thin blood smear for malaria.
 The treatment of meningitis depends on the underlying cause.
 For bacterial meningitis, it’s common is to administer steroids and then antibiotics, to prevent massive injury to
the leptomeninges from the inflammation caused as the antibiotics destroy the bacteria.
 In general the treatment - antivirals, antibacterials, antifungals, or antiparasitic drugs are aimed at the specific
cause of meningitis.
 Prevention with a vaccine, is appropriate for some causes like Neisseria meningitidis, but also for mumps and for
disseminated tuberculosis.
 Prophylactic antibiotics can also be administered, to avoid outbreaks of bacterial meningitis like in households
where individuals haven’t been vaccinated against Neisseria meningitidis.

34. EPIDEMIOLOGY
 A variety of factors influence the suspected cause of
meningitis.
 Age, underlying risk factors(e.g. immuocompromised)
and seasonal variations can be useful in directing
empirical therapy.
 In adults 3 organisms- Neisseria Meningitidis ,
streptococcus pneumoniae, and Haemophilus Influenza
are most responsible for meningitis.
 Gram negative meningitis is extremely rare in adults,
except when postneurosurgical meningitis occurs.
 However, meningitis due to enteric organisms, most
frequently Eschrichia coli (E.coli), is common in
neonates.
 Gastric patients are most likely to develop meningitis
due to Listeria monocytogenes, although S.pneumoniae
and N.meningitidis are still the most common
pathogens in this age group.

35. EPIDEMIOLOGY
 Age cannot be used as the only criterion for empirical
antibiotic treatment selection.
 Several other factors should influence the decision making
process.
 Nosocomial meningitis or status post open head trauma
increases the index of suspicion for gram negative bacilli and
staphylococcal infections.
 Specifically, patients with indwelling shunts may develop
Staphylococcus epidermis meningitis(frequently mithicillin
resistant).
 Other risk factors can also predispose patients to certain
types of meningitis.
 Alcoholism, asplenia, bacterial pneumonia, sinusitis, head
trauma, immunosuppression, and sickle cell disease
increases the likelihood of S.pneumoniae meningitis.
 Lyme meningitis due to Borrelia burgdorferi(neuroborreliosis)
is becoming more common in areas endemic for LYME
disease.
 Meningitis can also occur due to syphilis and leptospriosis.

37. PATHOPHYSIOLOGY
 Pathogens are thought to infect
meningitis through 3 pathways:
 1. Hematogenous seeding.
 2. Direct inoculation(trauma,
neurosurgery, direct spread from
nasopharynx)
 3. Contiguous spread from a
parameningeal focus(e.g.
sinusitis,dental surgery)

38. PATHOPHYSIOLOGY
 Virulence factors may also play a role
for certain meningeal pathogens.
 Encapsulated organism such as
S.Pneumoniae and H.influenza type B
are easily able to cross the BBB into
the CNS, and they are also resistant
to phagocytois in the bloodstream.
 N.meningitidis use pili on their cell
surface to breach and attach to
mucosal barrier.

39. PATHOPHYSIOLOGY
 When pathogens have entered the CNS, a cascade of
events occurs.
 The presence of bacterial cell wall products trigger the
production of cytokines, including IL-1, TNF, and
prostaglandin E2, which initially leads to increased blood
flow to the brain.
 These cytokines also increase BBB permeability by
interfering with the integrity of capillary tight junctions,
allowing cerebral edema to occur.
 Cytotoxins released from the neutrophils, and possibly
bacteria themselves, also contribute to the development of
cerebral edema.
 Intracranial pressure rises secondary to increased blood flow
and edema, resulting in decreased cerebral perfusion.
 The inflammatory process may cause vasculitis and
thrombotic events that contribute to overall cerebral

40. CLASSIFICATION &
CAUSATIVE AGENTS
 TYPES OF MENINGITIS
1. Acute pyogenic meningitis
2. Aseptic meningitis
3. Chronic meningitis
 TB
 Fungal
 Syphyllitic
 Protozoal
 Helminthe

41. Causative agents
1.ACUTE PYOGENIC MENINGITIS
 NEONATES -- E.COLI ,GROUP B
STREPTOCOCCI ,LISTERIA MONOCYTOGENES
,STREPTOCCOCUS PNEUMONIAE
 CHILDREN AND ADULTS -- N .MENINGITIS,
S.PNEUMONIAE ,H.INFLUENZAE
 ELDERLY -- LISTERIA SPECIES
2.ASEPTIC MENINGITIS
 COMMON -- ENTEROVIRUSES,HSV2,HIV
 LESS COMMON -- VZV,EBV

42. Causative agents
 CHRONIC MENINGITIS
1. TB MENINGITIS- M
TUBERCULOSIS
2. SYPHILICTIC MENINGITIS-
T.PALLIDUM
3. FUNGAL MENINGITIS-CANDIDA
ALBICANS,C.NEOFORMANS
4. PROTOZOAL- TOXOPLASMA
GONDI,TRYPANOSOMA.

43. PATHOPHYSIOLOGY
 The neurologic sequelae occur due to
activation of the host’s inflammatory
pathways, which is induced by the pathogens
or their products.
 Bacterial cell death can cause the release of
cell wall components, such as
lipopolysaccharide, lipid A (endotoxin),
lipoteichoic acid, teichoic acid, and
peptidoglycan,depending on whether the
pathogen is gram-positive or gram-negative
 These cell wall components cause capillary
endothelial cells and CNS macrophages to
release cytokines (interleukin 1 [IL-1], tumor
necrosis factor [TNF]) and other inflammatory
mediators(IL-6, IL-8, platelet-activating factor
[PAF], nitric oxide, arachidonic acid
metabolites [e.g., prostaglandin and
prostacyclin], macrophage derived proteins).
Proteolytic products and toxic oxygen radicals
are released from the capillary endothelium,
causing an alteration in the permeability of the
blood–brain barrier. PAF activates the
coagulation cascade, and arachidonic acid
metabolites stimulate vasodilation.
 These events propagate other sequential
events that lead to cerebral edema, elevated
intracranial pressure (ICP), CSF pleocytosis,
decreased cerebral blood flow, cerebral
ischemia, and death.

44. CLINICAL PRESENTATION
 Symptoms of meningitis may occur acutely, within 24
hours, or insidiously, over 1-7 days.
 Acute meningitis is associated with a higher mortality
rate (50%) and is most commonly caused by bacteria.
 Subacute meningitis may be caused by virus,
mycobacterial, or fungal, and is generally associated
with a lower mortality rate (<25%).
 A patient with acute or subacute menigitis may have
symptoms of meningeal inflammation such as vomiting,
head ache, lethargy, confusion, or neck stiffness.
 Fever, rigors, myalgias, and photophobia are also
seen.
 Patients also experience focal symptoms such as
seizures, cranial nerve palsies, or hemiparesis.
 The clinical presentation in neonates and in older adults
is more insidious.

45. CLINICAL PRESENTATION
 Neonates and young infants lack the
meningeal signs and symptoms but may
display hypothermia or hyperthermia,
listlessness, lethargy, high-pitched crying,
nausea, vomiting, anorexia, poor eating habits,
irritability, and seizures.
 Late clinical manifestations in infants include
neck stiffness and a full fontanella.
 Classic triad that is the fever& headche, neck
stiffness and a change in mental status and
are found in 95% patients of acute bacterial
meningitis.

46. DIAGNOSIS
 On physical examination, patients may
have nuchal rigidity or meningismus, a
positive Kernig or Brudzinski sign, and
papilledema.
 The Kernig sign is elicited by placing the
patient in the supine position, then flexing
the thigh perpendicular to the abdomen
with the knee also in the flexed position.
 As the leg is extended, the patients with
meningitis resists leg extension.

47. CLINICAL PRESENTATION
 The Brudzinski sign is evident when
forward neck flexion results in flexion of the
hips and knees.
 A petechial or purpuric rash predominantly
on the extremities is consistent with
N.meningitidis, although it may occur with
streptococcus or H. Influenza infection but
rarely.

48. SIGNS AND SYMPTOMS
 Fever,
 Nuchal rigidity.
 Altered mental status
 Chills,
 Vomiting,
 Photophobia, phonophobia and severe
headache.
 Irritability, and delirium.
 Drowsiness, lethargy, and coma.
 ■ Clinical signs in children also may include
 Bulging fontanelle, apneas, purpuric rash,
convulsions and cold extremeties.
 Nausea ,vomiting, and diarrhea.

50. Brudzinski sign
 A, B. Brudzinski
neck signs. Hip and
knee flexion occur as
a result of flexion of
the neck (B).
 C–E. Brudzinski leg
signs.
 C. Patient’s leg is
flexed by examiner
(arrow).
 D. Contralateral leg
begins to flex—
identical
contralateral sign.
 E. Contralateral leg
now begins to
extend
spontaneously,
resembling a little

51. Kernig sign

 Kernig sign.
 A. Knees are
raised to form a 90-
degree angle
relative to the
trunk, and the
examiner attempts
to extend the
knees.
 B. Once the knee
angle reaches
approximately 135
degrees,
contracture or

52. DIAGNOSIS
 It is imperative that a rapid diagnosis of meningitis
be made to ensure prompt, appropriate therapy.
 A lumbar puncture (LP) is used to confirm the
diagnosis and identify the pathogen.
 The goal is to obtain and evaluate CSF within 30
minutes of presentation.
 However, it must first be determined whether it is
safe to perform the LP(i.e., rule out CI to performing
an LP, such as mass lesion, brain abscess, or
subdural empyema).
 The patient should also be evaluated for
papilledema, hemiparesis, aphasia, ataxia , and
visual field defects, which may suggest an extreme
increase in intracranial pressure.
 If papilledema or neurologic sign are present, an LP
is CI because of the risk of brain herniation.

53. DIAGNOSIS
 CT scan or MRI may be performed before an
LP is done, to help in assessment process.
 When an LP is delayed so that a CT scan
can be obtained, blood cultures should be
obtained for culture and empiric antibiotics
should be initiated, along with any adjunctive
therapy.
 A delay in start of therapy can lead to
increased mortality.

54. DIAGNOSIS
 Before the CSF is removed, opening
pressure can be measured.
 In meningitis, pressures generally exceed
200 mm H20(normal : <150 mm H2O in
supine position).
 Pressures greater than 600 mm H2O may be
consistent with intracranial masses.
 A repeat LP may be necessary if treatment
response is inadequate.

55. DIAGNOSIS
 The CSF is also evaluated for gross visual
turbidity, cell analysis, glucose and protein
concentrations, and gram stain and culture.
 A pleocytosis(increased number of WBC) with a
predominance of neutrophils is consistent with
bacterial meningitis.
 A lymphocytic pleocytosis is consistent with
fungal, mycobacterial, or viral infection, although
viral meningitis may have initial neutrophilic
predominance.
 An elevated protein concentration is a sign of
disruption of the BBB.

58. DIAGNOSIS
LUMBAR PUNCTURE TEST
 ALSO KNOWN AS SPINAL TAP
 Is a diagnostic and therapeutic procedure
that is performed in order to collect a sample
of csf for chemistry, microbiologic, and
hematologic tests.
 CSF should not be refrigerated or stored on
ice therpeutically to relieve increased
intracranial pressure.

60. Csf analysis
The total csf producad per day is 500 ml .but is present in the
subarachnoid space about 80-150 ml.contains around 0.3 %of plasma
proteins.

61. DIAGNOSIS
 Other diagnostic tests include
 In patients presenting with new-onset
seizures, signs of space occupying lesions,
or moderate-to-severe impairment of
consciousness, cranial imaging via
magnetic resonance imaging or cranial
computed tomography (CT) should precede
a lumbar puncture.

62. DIAGNOSIS
 Blood and other specimens should be
cultured according to clinical judgment
because meningitis frequently can
arise via hematogenous dissemination
or can be associated with infections at
other sites.
 A minimum of 20 mL of blood in each
of two to three separate cultures per
each 24-hour period is necessary for
detection of most bacteremias.

63. DIAGNOSIS
 Gram stain and culture of the CSF are the
most important laboratory tests performed
for bacterial meningitis..
 ■ Polymerase chain reaction (PCR)
techniques can be used to diagnose
meningitis caused by N. meningitidis, S.
pneumoniae,and H.influenza B.
 ■ Latex fixation or agglutination, and
enzyme immunoassay tests provide for
rapid identification of several bacterial
causes of meningitis.

64. Latex fixation or agglutination
test
 Latex fixation test is an agglutination
test used to detect antigens produced
in response to rubella virus or
rheumatoid factor.
 It is used in diagnosis of group A
streptococcus.
 In latex fixation test , a sample is
mixed with latex beads coated with
antibodies ,if antigen is present it will
react with the antibody causing the

65. DIAGNOSIS
 Diagnosis of tuberculosis meningitis uses acid-fast
staining, culture, and PCR of the CSF.
 ■ PCR testing of the CSF is the preferred method
for diagnosing most viral meningitis infections.
 ■ The standard diagnostic tests for fungal
meningitis include culture, direct microscopic
examination of stained and unstained specimens of
CSF, antigen detection of cryptococcal or
histoplasmal antigens, and antibody assay of
serum and/or CSF.

66. TREATMENT
 ANTIBACTERIALS
1. Penicillins
2. Cephalosporins
3. Chloramphenicol
4. Fluroquinolones
5. Aminoglycosides,and macrolides.
 SULPHONAMIDES
 ANTI TB DRUGS
 ANTIFUNGALS
 ANTIVIRALS

67. GOAL OF TREATMENT
 Diagnose and initiate therapy promptly. A
delay in therapy of a few hours may
result in increased morbidity and
mortality.
 Base treatment on the suspected
pathogens and their anticipated
susceptibilities, and individual patient
characteristics.
 Use only antimicrobials that have
bactericidal MOA, include all agents in a
combination regimen.
 Select antimicrobials that have good
penetration through the BBB and
achieve adequate CSF drug

71. TREATMENT OF BACTERIAL
MENINGITIS
SR.NO AGE GROUP 1st Choice Drug Alternative Therapy
1 Neonates
<7 days
Ampicillin, 50mg/kg twice daily or
Amoxicillin 25 mg/kg twice daily or
Cefotaxime 50 mg/kg twice daily or
Ceftazidime 50mg/kg twice daily.
Benzyl penicillin 50mg
twice daily and
Ampicillin 50 mg/kg
twice daily or
amoxicillin 25mg/kg
twice daily and
Gentamicin 2.5 mg/kg
twice daily
2 Neonates 8-28
days
Ampicillin, 50mg/kg 4 times daily or
Amoxicillin 25 mg/kg 3 times daily
or Cefotaxime 50 mg/kg 3 times
daily or
Ceftazidime 50mg/kg 3 times daily.
Benzyl penicillin 50mg
4 times daily and
Ampicillin 50 mg/kg 3
times daily or
amoxicillin 25mg/kg 4
times daily and
Gentamicin 2.5 mg/kg
3 times daily

72. TREATMENT OF BACTERIAL
MENINGITIS
SR.NO AGE GROUP 1st Choice Drug Alternative Therapy
3. Infants 1-3
months
Ampicillin, 50mg/kg 4 times daily or
Amoxicillin 25 mg/kg 3 times daily
or Cefotaxime 50 mg/kg 3 times
daily or
Ceftazidime 75-100 mg once daily.
4 Infants,
>3 months
Cefotaxime 50 mg/kg 3 times daily
or
Ceftazidime 75-100 mg once daily.
Ampicillin 50mg/kg
daily 4 times.
Amoxicillin 25 mg/kg 4
times.
Chloramphenicol
25mg/kg 4 times daily

73. TREATMENT OF BACTERIAL
MENINGITIS
SR.NO AGE GROUP 1st Choice Drug Alternative Therapy
5 Adults Cefotaxime 2g 3 times daily or
Ceftazidime 2-4 g once daily.
Benzyl penicillin 2.4 g-
4 hours.
Ampicillin 2-3 g 4
times daily or
amoxicillin 2g 3 or 4
times daily and
chloramphenicol 25
mg/kg 4 times daily.

74. TREATMENT

76. Dosing of antibacterials

77. STREPTOCOCCUS
PNUMONIAE MENINGITIS
 Streptococcus penumoniae, commonly called pneumococcus, is a gram
positive coccus seen on Gram stain.
 In 40-50% cases, the patient has a concomitant pneumococcal pneumonia or
otitis media infection.
 Additionally, patients may have a contiguous or distant focus of infection
such as pneumonia, mastoiditis, sinusitis, or endocarditis.
 Empiric treatment for patients with S.Pneumoniae include penicillin or
ampicillin.
 As there is an increase in the rate of penicillin resistance.
 Cephalosporins such as ceftriaxone or cefotaxime are therefore currently
used as first line agents.
 Empiric therapy may sometimes include the use of adjuvant dexamethasone.
 It is recommended that dexamethasone(0.15 mg/kg q6H for 2-4 days) with
the first dose of antibiotics should be given.
 Dexamethasone should be given to all adults with pneumococcal meningitis.

78. NEISSERIA MENINGITIDIS
Meningitis
 It is a gram negative bacteria.
 Because of success of H. Influenza type B vaccination , N.meningitidis has
become the leading cause of bacterial meningitis.
 Clinical features of N.meningitidis infection include rapid onset, with
meningococcemia, of fever, chills, malaise, and rash.
 The rash may be maculopapular, petechial, or urticaria.
 In fulminant disease, the rash may become puerperal and is associated with a
syndrome of disseminated intravascular coagulation(DIC), shock, coma , and
death(Waterhouse Friderichsen syndrome).
 The drug of choice for N.menigitidis meningitis is Penicillin G administered as 4
million units every 4 hours for 7 days for adults with normal renal function.
 Cefotaxime(2 g every 4-6 hours) and ceftriaxone (2g every 12-24 hours) are used
if the bacteria is penicillin resistant.
 Chloramphenicol may be used in patients with allergy to both penicillin and
cephalosporins.
 Other alternatives include sulfonamides and fluoroquinolones.
 Corticosteroids should not be given in this meningitis.
 A quadrivalent N.meningitidis vaccine is commercially available.
 Vaccination should be considered in children older than 2 years of age.

79. Haemophilus Influenzae Type B
Meningitis.
 It is a gram negative organism.
 Approximately 30-50% of children carry H.influenzae
asymptomatically in the nasopharynx.
 80% of patients with this meningitis also have otitis
media, sinusitis, and brochitis(any 1 or all).
 Children younger than 2 years old are at higher risk of
developing infection with this organism, as are adults
with predisposing factors such as sickle cell anemia,
asplenia, immunodeficiency disease, malignancy, head
trauma, neurosurgery, sinusitis, otitis media.
 Patients commonly develops this meningitis after an
upper respiratory tract infection or otitis media.
 Complications of this meningitis include deafness,
blindess, seizure disorders, behaviour disorders , and a
decrease in school performance.

80. Haemophilus Influenzae Type B
Meningitis.
 The first choice of drug is ampicillin.
 Presently , ceftriaxone and cefotaxime
are the first line drugs.
 Since the development of the vaccine,
the incidence of H.Influenzae type B
meningitis has dramatically declined
by more than 90%.

81. Listeria Monocytogenes
Meningitis
 It is a gram positive aerobic bacillus.
 Pregnant women, newborns, older adults, and immunocompromised
persons are predisposed to get this meningitis.
 Listeria is the cause of 8% of cases of menigitis.
 The incidence of Listeria infection is greatest in summer and early
fall.
 Contaminated coleslaw, milk, cheese, raw vegetables, turkey franks,
alfaalfa tablets, and processed meat are associated with listeria food
poisoning.
 Antibiotics that have activity against listeria include penicillin G,
ampicillin, erythromycin, trimethoprim-sulfamethoxazole,
chloramphenicol, tetracyclines and aminoglycosides.
 The treatment of choice for patients with Listeria meningitis include
ampicillin in combination with an aminoglycosides given
intravenously or intrathecally.
 Trimethoprim-sulfamethoxazole is an alternative therapy for patients
with penicillin allergy.
 Meropenem can also be used.

82. Gram Negative Bacillary
Meningitis
 Gram-negative bacilli are very uncommon cause of
meningitis.
 Enterobacteriaceae(especially E.coli and Klebsiella species)
and pseudomonas species are most commonly implicated
gram-negative pathogens.
 The best drug for gram negative infections is cefotaxime and
ceftazidime.
 The usual dosage of cefotaxime is 2 g every 4 hours.
 If pseudomonas is implicated, ceftazidime 2 g every 6-8
hours or cefepime 2 g every 8 hours plus systemic
aminoglycosides therapy may be used.
 Ventriculitis is commonly associated with gram-negative
meningitis and require intraventricular aminoglycoside
administration.
 Meropenem can be used if resistant develops in the above
mentioned antibiotics.
 Trimethoprim-sulfamethoxazole can be used.
 Fluoroquinolones and aztreonam are other possible
alternatives.

83. FUNGAL MENINGITIS
 The 2 most common cause of fungal meningitis are
Cryptococcus Neoformans and Coccidioidomycosis.
 Bird droppings, rotten fruits and vegetable, wood rot, and
soil contain cryptococcus.
 Infection occurs through inhalation of the aerosolized
spores which results in primary pulmonary disease that
dessiminates to the CNS.
 The onset of disease is gradually, generally over 4 or more
weeks, and is more prevalent in immunosuppressed.
 Patients most commonly experience head ache along with
alteration in mental status, nuchal rigidity, fever and
papilledema.
 Diagnosis is made by India Ink stain, culture, latex
agglutination test, which identifies the circulating antigen in
the serum of CSF.

84. FUNGAL MENINGITIS
 The preferred treatment regimen in persons who donot have HIV
infections is amphotericin B 0.5 to 1 mg/kg/day and flucytosine 100-
150 mg/kg/day for 6 weeks.
 A total of 2 g amphotericin B should be administered.
 The combination of amphotericin and flucytosine has been found to
be superior to amphotericin alone in patients who do not have HIV
infection, leading to successful outcome in 75 % of treated patients.
 In HIV infected patient, FLUCONAZOLE achives good CNF
concentration, is available as an oral agent and is better tolerated
than amphotericin B.
 The usual regimen for cryptococcal meningitis in HIV infected
patients is amphotericin B 0.7-1 mg/kg/day for 2 weeks followed by
fluconazole 800 mg per day orally for 2 days, then 400 mg per day
for 8 weeks and 200 mg per day indefinetly.
 Therapy with amphotericin B causes significant ADRs, including
nephrotoxicity, electrolyte abnormalities, anemia, thrombocytopenia,
and phlebitis.

85. FUNGAL MENINGITIS
 COCCIDIOIDOMYCOSIS is caused by
Coccidioidesimmitis.
 Infection occurs through inhalation of the aerosolized
spores.
 When inhaled, the infection disseminates within 3-6
months to the skin, musculoskeletal system and
meninges.
 People at increased risk include immunocompromised
patients, infants, older adults, males, and pregnant
women.
 Head ache is the most common symptom.
 Approximately 90% of patients dies within 12 months
without active treatment.
 Amphotericin is given intrathecally or intravenously.

86. VIRAL MENINGITIS OR
ASEPTIC MENINGITIS
 Aseptic meningitis is defined as the presence of meningeal signs
and symptoms, as well as CSF abnormalities consistent with
meningitis, with stains and cultures that are negative for bacteria or
fungi.
 The most common causes of aseptic meningitis are viruses,
particularly enterovirus, herpes, lymphocytic choriomenigitis, and
mumps.
 Drugs have also been implicated as a cause of aseptic meningitis .
 West Nile Virus may cause aseptic meningitis or asymmetric flaccid
paralysis, although encephalitis is more common.
 Enterovirus are members of the picornavirus family and consist of
poliovirus, coxsackievirus A and B, and echovirus and the most
common causes of aseptic meningitis.
 Transmission of these viruses occur via fecal-oral and respiratory
routes.
 Infants, children and young adult are at risk.
 Symptoms are similar to bacterial meningitis.
 These infections are self limiting and do not require any treatment.
 Patients are given supportive care , including hydration and pain
control.

87. VIRAL MENINGITIS OR
ASEPTIC MENINGITIS
 Herpes simplex virus types 1 and 2
have both been associated with
meningitis.
 Herpes simplex virus type 1 has been
associated with meningoencephalitis,
which is potentially fatal.
 Herpes Simplex Virus Type 2 is
predominantly associated with
meningitis, which is self-limiting.

88. DRUGS WHICH CAUSES
ASEPTIC MENINGITIS
 IBUPROFEN
 TRIMETHOPRIM-
SULFAMETHOXAZOLE.
 SULINDAC
 NAPROXEN
 DICLOFENAC
 CARBAZEPINE
 VACCINES- MUMPS AND RUBELLA

89. Pharmacology
 Antibacterials :
 Penicillins ,cephalosporins,bacitracin and vancomycin
 Moa :
Inhibitors of Cell Wall Synthesis: In most bacteria, a cell wall surrounds
thecell like a rigid shell that protects against noxious outside influences
and prevents rupture of the plasma membrane from a high internal
osmotic pressure. The structural stability of the cell wall is due mainly to
the murein (peptidoglycan) lattice. This consists of basic building blocks
linked together to form a large macromolecule. Each basic unit contains
the two linked aminosuga rN-acetylglucosamine and N-
acetylmuramicacid; the latter bears a peptidechain. The building blocks
are synthesizedin the bacterium, transported outward through the cell
membrane. The enzym etranspeptidase cross-links the peptidechains of
adjacent aminosugar chains.
 b lactam antibiotics act by inhibiting the tranpeptidase enzyme-so that
cross linking does not take place.
 Adrs :
 Local irritancy ,hypersensitivity,super infections,nausea ,vomiting
,diarrhea,nephrotoxicity,bleeding,neutropenia,thrombocytopenia,pain
after im injection.
 Uses :infections caused by streptococcal, pneminococcal,
staphylococcal, meningococcal species .

90. Pharmacology
 Inhibitors of protein synthesis:
 chloramphenicol ,macrolides and
aminoglycosides.
 Chloramphenicol
 Moa :it inhibits bacterial protein synthesis by
interfering with transfer of elongating peptide
chain to the newly attached amino acyl t rna at
the ribosome –mrna complex.it specifically
attaches to the 50s ribosome and prevents the
binding of aminoacyl t rna to the accceptor site
for aminoacid incorporation.
 Adrs:bone marrow toxicity,neonatal
toxicity,hypersensitivity,superinfections,nausea,v
omiting,depression delirium.neuritis.
 Uses: meningitis caused by h.influenzae.

91. Pharmacology
 Macrolides
 Moa:
Inhibits the bacterial protein synthesis it
binds reversibly with 50s sub unit of
bacterial ribosome . They can inhibit the
elongation of protein by the peptidyl
tranferase ,the enzyme that forms peptide
bonds btw the amino acids.
ADRS:nausea ,vomiting,allergic reactions
dermatitis lymphadenopathy ,jaundice.
Uses: infections caused by pnemonia
species

92. Pharmacology
 Aminoglycosides
 Moa :
Irreversible inhibition of protein syntesis
 Three mechanisms of protein synthesis inhibition which
results in cell death.
 The drug may interfere with the initiation of ps
 Misreading of m rna that leads to incorrect aminoacids
being integrated into the peptide chains resulting in non
functional proteins.
 They reduce polysomes into non functional monosomes
 Adrs :nephrotoxicity,ototoxicity,neuromuscular
blockage,super infection,nausea,vomiting,neuritis.
 Uses:infections caused by various gram –ve bacteria .

93. Pharmacology
 Sulphonamides:
 Moa:
 They are bacteriostatic drugs which act by inhibiting the
folic acid synthesis in the bacteria .they are competitive
antagonists of paba.they prevent the utilization of paba
in the synthesis of folic acid .
 Sulphonamides act by inhibiting the enzyme
dihydropteorate synthase .-prevents the formation of
dihydrofolic acid .
 The trimethoprime inhibits the dihydrofolate reductase –
prevents the formation of tetrahydrofolic acid –this
prevents formation of purine bases for synthesis of dna
.
 Adrs :nausea ,vomiting,abdominal
pain,hypersensitivity,skin rash fever steven jonson
syndrome,blood
dyscriasis,neuritis,tinnitus,ataxia,confusion ,depression
 Uses: meningococcal infections.

94. Pharmacology
 Cotrimoxazole :combination of
trimethoprime and sulphamethoxazole
in 1:5 ratio.
 Individually bacteriostatic ,when
combined they become bacteriocidal.
 Moa and adrs same as that of
sulphonamides.
 Uses:infections caused by e coli
bacteria.

95. Anti tubercular drugs
 Drugs of choice are isoniazid, rifampin, and ethambutol, along with streptomycin
and pyrazinamide. Less well tolerated, secondline agents include p-
aminosalicylic acid, cycloserine, viomycin, kanamycin, amikacin, capreomycin,
and ethionamide.
 Isoniazid is bactericidal against growing M. tuberculosis. Its mechanism of
action remains unclear. In the bacterium it is converted to isonicotinic acid,
which is membrane impermeable and hence likely to accumulate intracellularly.
Isoniazid is rapidly absorbed after oral administration. In the liver, it is
inactivated by acetylation. Notable adverse effects are peripheral neuropathy,
optic neuritis preventable by administration of vitamin B6 (pyridoxine), and liver
damage.
 Rifampin. . Although mostly well tolerated,this drug may cause several adverse
effects including hepatic damage, hypersensitivity with flulike symptoms,
disconcerting but harmless red/orange discoloration of body fluids, and enzyme
induction (failure of oral contraceptives)
 Pyrazinamide exerts a bactericidal action by an unknown mechanism. It is
given orally. Pyrazinamide may impair liver function; hyperuricemia results from
inhibition of renalurate elimination.
 Streptomycin must be given i.v. like other aminoglycoside antibiotics . It
damages the inner ear and the labyrinth. Its nephrotoxicity is comparatively
minor.
 Ethambutol. The cause of ethambutol’s specific antitubercular action is
unknown. It is given orally. It is generally well tolerated,but may cause dose-

96. Antifungal drugs
 Moa of imidazole derivatives :
 Imidazole derivatives inhibit synthesis of ergosterol, an integral
constituent of cytoplasmic membranes of fungal cells. Fungi
stop growing (fungistatic effect) or die (fungicidal effect). The
spectrumof affected fungi is very broad.
 Flucytosine is converted in candidal fungi to 5-fluorouracil by
the action of a specific fungal cytosine deaminase. As an
antimetabolite,this compound disrupts DNAand RNA
synthesis,resulting in a fungicidal effect.
 Griseofulvin:inhibits the biosynthesis of microtubules of
the fungal cells leading to stoppage of the spindle
formation during mitosis.leading to fungal cell death.
 Amphotericin b :polyene antibiotic –it associates with ergosterol
forming a transmembrane channel .through this channel
intracellular monovalent ions move out leading to fungal cell
death.
 Adrs : nausea ,vomiting headache,fever ,vertigo skin
rashes,convulsions,nephrotoxicity,myalgia ,neuritis.
 Uses: fungal infections

97. Antiviral drugs
 Moa: The organism can disrupt viral
replication with the aid of cytotoxic T-
lymphocytes that recognize and
destroy virus-producing cells or by
means of antibodies that bind to and
inactivate extracellular virus particles.
 Adrs:headache,nausea.vomiting
,malice,tremors hypotension ,skin
rashes .
 Uses: viral infections caused by
enteroviruses,hiv ,vzv.